研究者情報

マスター

アカウント（マスター）

• 氏名

  山田　崇弘(ヤマダ　タカヒロ), ヤマダ　タカヒロ

所属（マスター）

• 北海道大学病院

所属（マスター）

• 北海道大学病院

researchmap

プロフィール情報

所属

• 北海道大学病院, 臨床遺伝子診療部

学位

• 博士（医学）（北海道大学大学院）

プロフィール情報

• 姓

  山田

• 名

  崇弘

• ID各種

  201301070851181490

所属

• 北海道大学病院, 臨床遺伝子診療部

業績リスト

研究キーワード

• 医療倫理学   二次的所見   がんゲノムプロファイリング   ゲノム医療   遺伝カウンセリング   CVS   NIPT   骨系統疾患   分子細胞遺伝学   臨床遺伝学   出生前診断   胎盤   オートファジー   妊娠高血圧腎症   NOS3   p57KIP2   子宮内胎児発育遅延   遺伝子多型   妊娠高血圧症候群   フォーカスグループ面接   相互作用   妊娠中のストレス   マウスモデル   薬剤耐性遺伝子   疫学   ABCC11遺伝子   耳垢   

研究分野

• 人文・社会 / 哲学、倫理学
• ライフサイエンス / 胎児医学、小児成育学
• ライフサイエンス / 医療管理学、医療系社会学
• ライフサイエンス / 遺伝学
• ライフサイエンス / 産婦人科学
• ライフサイエンス / 医化学

経歴

• 2017年06月 - 2022年11月 京都大学医学部附属病院遺伝子診療部 特定准教授
• 2016年09月 - 2017年05月 北海道大学大学院医学研究科総合女性医療システム学講座 特任准教授
• 2013年04月 - 2016年08月 北海道大学大学院 総合女性医療システム学講座 特任講師
• 2009年08月 - 2013年03月 北海道大学 大学病院 助教

学歴

• 1996年04月 - 2002年03月   北海道大学   大学院   医学研究科
• 1989年04月 - 1995年03月   北海道大学   医学部   医学科

委員歴

• 2020年09月 - 現在   日本遺伝子診療学会   COI委員会
• 2020年09月 - 現在   日本遺伝子診療学会   ELSI委員会
• 2020年09月 - 現在   日本人類遺伝学会   Journal of Human Genetics編集委員( Editorial Board)
• 2020年07月 - 現在   日本遺伝性腫瘍学会   専門医制度小委員会
• 2020年01月 - 現在   日本遺伝性腫瘍学会   評議員
• 2020年 - 現在   日本人類遺伝学会   利益相反委員会
• 2018年09月 - 現在   日本人類遺伝学会   臨床遺伝専門医制度委員会
• 2018年09月 - 現在   日本遺伝カウンセリング学会   臨床遺伝専門医制度委員会
• 2017年09月 - 現在   日本人類遺伝学会   国際化推進委員会
• 2017年04月 - 現在   日本遺伝カウンセリング学会   倫理問題検討委員会
• 2015年12月 - 現在   日本産科婦人科遺伝診療学会   代議員
• 2014年04月 - 現在   日本周産期・新生児医学会   評議員
• 2013年04月 - 現在   日本遺伝カウンセリング学会   遺伝学的検査委員会
• 2013年04月 - 現在   日本遺伝カウンセリング学会   評議員
• 2012年11月 - 現在   日本人類遺伝学会   評議員
• 2012年09月 - 現在   日本人類遺伝学会   遺伝医学セミナー実行委員会
• 2012年08月 - 現在   日本人類遺伝学会   遺伝医学セミナー実行委員会
• 2010年04月 - 現在   日本先天異常学会   評議員
• 2013年04月 - 2021年03月   日本遺伝カウンセリング学会   研修委員会
• 2015年04月 - 2017年03月   日本遺伝カウンセリング学会   出生前遺伝カウンセリング検討委員会
• 2011年04月 - 2017年03月   日本産科婦人科学会   周産期委員会
• 2013年04月 - 2015年03月   日本遺伝カウンセリング学会   編集委員会

受賞

• 2018年12月 East Asian Union of Human Genetics Societies 東アジア人類遺伝学会連合2018年度優秀ポスター賞
  
• 2013年08月 北海道産科婦人科学会 北海道産科婦人科学会賞
  
• 2011年08月 日本産科婦人科学会 学会ボランティア活動賞
  
• 2007年11月 財団法人武田科学振興財団 財団法人武田科学振興財団研究助成金
   胎盤の発生発達及び周産期疾患におけるオートファジーの機能的役割の解明 

  受賞者: 山田崇弘
• 2004年10月 The Hospital For Sick Children, Research Institute トロント小児病院研究トレーニングコンペティション
   NOS3AS, the overlapping antisense transcript with endothelial nitric oxide synthase (NOS3), encodes a putative mammalian autophagy protein highly expressed in placenta. 

  受賞者: 山田崇弘

論文

• Nationwide survey of the secondary findings in cancer genomic profiling: survey including liquid biopsy.

  Saki Shimada, Takahiro Yamada, Akari Minamoto, Manami Matsukawa, Ichiro Yabe, Hiroshi Tada, Katsutoshi Oda, Arisa Ueki, Satomi Higashigawa, Maki Morikawa, Yuki Sato, Akira Hirasawa, Masanobu Ogawa, Tomohiro Kondo, Masahiro Yoshioka, Masashi Kanai, Manabu Muto, Shinji Kosugi

  Journal of human genetics 2024年09月17日 

  We surveyed the status of the secondary finding (SF) disclosure in comprehensive genome profiling (CGP) in 2020. The situation has changed: increase in the number of hospitals that provide CGP, an update to the Comprehensive Tumor Genomic Profiling: Materials for Review of Secondary Findings (CTGPMRSF), and the addition of a liquid biopsy test, FoundationOne® Liquid CDx (F1L). Moreover, the actual situation was unclear because the 2020 survey did not include all designated and cooperative hospitals. Herein, we conducted a questionnaire survey of all designated-core, designated, and cooperative hospitals to identify the current status and challenges concerning SF in the CGP in 2022. A total of 82.1% of the hospitals responded and 77.7% of the response was from cooperative hospitals. Approximately 80% of the hospitals used CTGPMRSF. SF disclosure, confirmatory test implementation, and SF confirmation rates were 12.4%, 31.6%, and 46.6% for FoundationOne® CDx (F1CDx), respectively, and 6.8%, 31.8%, and 70.7% for F1L, respectively. The implementation rate of the confirmatory test was substantially higher in hospitals with genetic experts and in hospitals that could conduct confirmatory tests on the same day. Our survey provides insight into how SF is handled in Japan. The percentage of cases leading to confirmatory tests has gradually increased, although challenges such as insurance coverage limitations and varied understanding of SF among patients and healthcare providers persist. With the increasing use of whole-genome analysis, our findings will provide valuable insights into establishing an effective SF disclosure system.
• Dyssegmental dysplasia Rolland-Desbuquois type is caused by pathogenic variants in HSPG2 - a founder haplotype shared in five patients.

  Paniz Farshadyeganeh, Takahiro Yamada, Hirofumi Ohashi, Gen Nishimura, Hiroki Fujita, Yuriko Oishi, Misa Nunode, Shuku Ishikawa, Jun Murotsuki, Yuri Yamashita, Shiro Ikegawa, Tomoo Ogi, Eri Arikawa-Hirasawa, Kinji Ohno

  Journal of human genetics 2024年02月29日 

  Dyssegmental dysplasia (DD) is a severe skeletal dysplasia comprised of two subtypes: lethal Silverman-Handmaker type (DDSH) and nonlethal Rolland-Desbuquois type (DDRD). DDSH is caused by biallelic pathogenic variants in HSPG2 encoding perlecan, whereas the genetic cause of DDRD remains undetermined. Schwartz-Jampel syndrome (SJS) is also caused by biallelic pathogenic variants in HSPG2 and is an allelic disorder of DDSH. In SJS and DDSH, 44 and 8 pathogenic variants have been reported in HSPG2, respectively. Here, we report that five patients with DDRD carried four pathogenic variants in HSPG2: c.9970 G > A (p.G3324R), c.559 C > T (p.R187X), c7006 + 1 G > A, and c.11562 + 2 T > G. Two patients were homozygous for p.G3324R, and three patients were heterozygous for p.G3324R. Haplotype analysis revealed a founder haplotype spanning 85,973 bp shared in the five patients. SJS, DDRD, and DDSH are allelic disorders with pathogenic variants in HSPG2.
• 遺伝性乳癌卵巣癌患者の血縁者に対する遺伝カウンセリング受診勧奨のために克服すべき課題

  大高 理生, 中島 健, 吉田 晶子, 鳥嶋 雅子, 川崎 秀徳, 山田 崇弘, 和田 敬仁, 小杉 眞司

  遺伝性腫瘍 23 3 84 - 93 (一社)日本遺伝性腫瘍学会 2023年12月 

  遺伝性腫瘍診療では,診断後発端者に血縁者への情報共有を推奨するが,困難な場合がある.欧米では受診勧奨の研究があるが,本邦の実態は不明である.2020年より遺伝性乳癌卵巣癌(hereditary breast and ovarian cancer;HBOC)は遺伝学的検査が保険収載され,血縁者への対応も求められる.本研究はHBOC患者血縁者への情報共有と受診勧奨の施設での課題抽出を目的とし,乳房悪性腫瘍の治療実績国内上位100施設を対象に質問紙調査を行った.初回調査で回答を得た44施設(44%)のうち5例以上のHBOC診断数の31施設を対象とし29施設(94%)から二次調査回答を得た.26施設(90%)で血縁者のリスク説明は実施だが,発端者家系に特化した資料配布は17施設(59%)で未実施であった.課題は,「未発症血縁者のサーベイランスが保険適用外」「血縁者と疎遠な関係性」であった.受診勧奨支援は施設間差を認め,その解決には多角的な検討が必要と考えられた.(著者抄録)
• 神経難病の発症前遺伝カウンセリングの在り方は変化しつつある

  松島 理明, 柴田 有花, 山田 崇弘, 矢部 一郎

  日本難病医療ネットワーク学会機関誌 11 1 127 - 127 日本難病医療ネットワーク学会 2023年11月
• ヒト遺伝子研究最新動向 骨系統疾患の改訂国際分類について

  池川 志郎, 山田 崇弘

  遺伝子医学 13 4 99 - 104 (株)メディカルドゥ 2023年10月 

  骨系統疾患は,骨格に異常をもつ疾患の総称で,ほとんどが単一遣伝子病である。本年(2023年)2月に発表された骨系統疾患の分類・命名法,いわゆる国際分類の改訂版について解説した。改訂に加わったメンバー,分類のコンセプト,疾患グループ,疾患の組み入れ基準,疾患情報の記載法などについての今回の分類における変更点を示し,分類の問題点を指摘した。分類に記載されている疾患の96%で原因遺伝子がすでに同定されており,パーソナルゲノム時代,精密医療の時代に向けて,骨系統疾患の国際分類は,表現型,X線像による分類から,原因遺伝予,分子病態を中心とする分類へと向かっている。(著者抄録)
• Change in client choice under multiple prenatal genetic testing options including noninvasive prenatal testing (NIPT) after genetic counseling in a Japanese maternity hospital.

  Katsuhiko Naruse, Ritsuko K Pooh, Yutaka Kyukawa, Taihei Tsunemi, Takahiro Yamada

  The journal of obstetrics and gynaecology research 49 9 2337 - 2342 2023年09月 

  OBJECTIVE: This study examined how clients' selection and preference for noninvasive prenatal testing (NIPT) for aneuploidy changed with genetic counseling (GC) performed by certified geneticists at a primary hospital specializing in obstetrics, where other multiple prenatal genetic tests options were available. METHODS: A total of 334 couples who underwent GC between 2017 and 2019 were included in the study. The average age of the pregnant women who underwent GC was 35.1 years. RESULTS: Among the 95 couples (28.4%) who wanted NIPT at the start of GC, 10 (10.5%) switched to other tests, and 4 (4.2%) chose not to undergo any test. Among the 106 (31.7%) couples who wanted the combination of ultrasonography and the serum marker test, 12 (11.3%) chose not to undergo the test. Among the 92 (27.5%) couples who were undecided before GC, 21 (22.8%) wanted NIPT, 31 (33.7%) selected combined tests, and 18 (19.6%) did not undergo any test. CONCLUSION: We have demonstrated the significance of GC before prenatal genetic testing under widespread use of NIPT. Ideally, obstetric facilities should provide GC, or at least, pre-counseling at their own facilities, and offer multiple prenatal genetic testing options or refer to other facilities for the same.
• 【図説 産婦人科医のための臨床遺伝学必修知識I】Secondary Findingsの取り扱い方

  島田 咲, 洪本 加奈, 山田 崇弘

  産婦人科の実際 72 8 793 - 801 金原出版(株) 2023年08月 

  ＜文献概要＞網羅的遺伝子解析は,がん領域では治療薬探索を目的に,難病領域では疾患診断を目的に実施されている。これらの解析では,本来の検査の目的ではないものの,受検者の健康管理に貢献しうる情報としての二次的所見が得られることがある。ここで得られる二次的所見は生殖細胞系列の遺伝情報であり,患者本人だけでなく血縁者においても有益な情報となる。網羅的遺伝子解析を実施する際は,本来の検査目的との説明のバランスに配慮しつつ,二次的所見が検出される可能性を念頭におき,検査前から患者本人や血縁者へ説明しておくことが重要である。
• 【図説 産婦人科医のための臨床遺伝学必修知識I】Secondary Findingsの取り扱い方

  島田 咲, 洪本 加奈, 山田 崇弘

  産婦人科の実際 72 8 793 - 801 金原出版(株) 2023年08月 

  ＜文献概要＞網羅的遺伝子解析は,がん領域では治療薬探索を目的に,難病領域では疾患診断を目的に実施されている。これらの解析では,本来の検査の目的ではないものの,受検者の健康管理に貢献しうる情報としての二次的所見が得られることがある。ここで得られる二次的所見は生殖細胞系列の遺伝情報であり,患者本人だけでなく血縁者においても有益な情報となる。網羅的遺伝子解析を実施する際は,本来の検査目的との説明のバランスに配慮しつつ,二次的所見が検出される可能性を念頭におき,検査前から患者本人や血縁者へ説明しておくことが重要である。
• 当院におけるHBOC症例のフォローアップに関する調査

  佐々木 佑菜, 三田村 卓, 松本 隆児, 桑谷 将城, 細田 充主, 安部 崇重, 柴田 有花, 松島 理明, 矢部 一郎, 山田 崇弘

  日本遺伝カウンセリング学会誌 44 2 137 - 137 (一社)日本遺伝カウンセリング学会 2023年06月
• 難病領域における次世代シークエンサーを用いた網羅的遺伝子解析受託施設の二次的所見開示の現状と困難 アンケート調査

  洪本 加奈, 山田 崇弘, 土屋 実央, 川目 裕, 難波 栄二, 後藤 雄一, 小杉 眞司

  日本遺伝カウンセリング学会誌 44 2 88 - 88 (一社)日本遺伝カウンセリング学会 2023年06月
• がん遺伝子パネル検査の二次的所見開示プロセスに関する現状調査 多施設対象アンケート調査

  島田 咲, 山田 崇弘, 源 明理, 松川 愛未, 矢部 一郎, 青木 洋子, 織田 克利, 植木 有紗, 東川 智美, 森川 真紀, 佐藤 友紀, 平沢 晃, 小川 昌宣, 近藤 知大, 吉岡 正博, 金井 雅史, 武藤 学, 小杉 眞司

  日本遺伝カウンセリング学会誌 44 2 92 - 92 (一社)日本遺伝カウンセリング学会 2023年06月
• 常染色体優性遺伝性脊髄小脳変性症(AD-SCD)の疾患構成

  柴田 有花, 松島 理明, 山田 崇弘, 矢部 一郎

  臨床神経学 63 5 326 - 326 (一社)日本神経学会 2023年05月
• 常染色体優性遺伝性脊髄小脳変性症(AD-SCD)の疾患構成

  柴田 有花, 松島 理明, 山田 崇弘, 矢部 一郎

  臨床神経学 63 5 326 - 326 (一社)日本神経学会 2023年05月
• Fundamental knowledge taught in compulsory education for effective genetic counseling: a qualitative study of descriptions in textbooks.

  Eri Sakai, Takahiro Yamada, Tomomi Funaki, Miho Iwakuma, Harumo Osawa, Kana Morimoto, Shinji Kosugi

  Journal of community genetics 14 3 263 - 274 2023年02月28日 

  In genetic counseling, information must be provided in ways that the client and general public can understand to ensure that decisions are made autonomously. To realize this, we must assess the extent of knowledge held by the general public regarding genetics. To identify the client's original knowledge before genetic counseling, we explored the fundamental knowledge related to genetic counseling that is taught in Japanese compulsory education. A qualitative study was conducted. We selected 50 textbooks for compulsory education (Japanese, social studies, science, health and physical education, technology and home economics, morality, and life) that had been used in more than half of the districts in Japan. The text data were analyzed using qualitative content analysis, and quantitative data were analyzed for methodological triangulation. Codes, subcategories, and categories were generated from the contexts that met the following criteria: the contents included in the official textbook for clinical geneticists, contents derived from such descriptions that were related to genetic counseling, and contents clearly related to genetics. Among the 50 textbooks, 33 textbooks contained fundamental knowledge regarding genetic counseling. A qualitative content analysis identified four major categories: (1) basics of genetics, (2) understanding and control of diseases, (3) efforts and barriers to the realization of a harmonious society, and (4) technology and humans. We found that fundamental knowledge related to genetic counseling is directly or indirectly taught in compulsory education. Our results are an important resource for understanding the client's knowledge baseline and will be helpful for effective genetic counseling.
• 高度生殖補助医療(ART)経験の有無による出生前検査の知識や意識についての検討

  坂本 美和, 白土 なほ子, 宮上 景子, 池本 舞, 和泉 美希子, 廣瀬 達子, 水谷 あかね, 池袋 真, 佐村 修, 山田 崇弘, 清野 仁美, 吉橋 博史, 鈴森 伸宏, 山田 重人, 奥山 虎之, 澤井 英明, 左合 治彦, 関沢 明彦, 成育疾患克服等次世代育成基盤研究事業白土班

  日本産科婦人科学会雑誌 75 臨増 S - 307 (公社)日本産科婦人科学会 2023年02月
• Reproductive decision-making following the diagnosis of an inherited metabolic disorder via newborn screening in Japan: a qualitative study.

  Kana Hiromoto, Masakazu Nishigaki, Shinji Kosugi, Takahiro Yamada

  Frontiers in reproductive health 5 1098464 - 1098464 2023年 

  INTRODUCTION: The aim of the study was to describe the factors influencing the reproductive decision-making of carrier parents after the diagnosis of an inherited metabolic disorder in newborn screening in Japan. METHODS: We conducted a semi-structured interview with 12 parents and analyzed data based on content analysis methodology. RESULTS: We identified 11 factors, including personal evaluation of recurrence risk, understanding of hereditary phenomena, concerns and desires for future planned children, concerns for older siblings, perceptions of diseases, degree of acceptance and denial of diseases, the opinions of others on having another child, optimism/faith in positive outcomes, self-evaluation of parental capability, factors unrelated to the disease, and the "right" time to expand the family. DISCUSSION: Perceptions and acceptance of disease are both important factors in reproductive decision-making, though these factors fluctuate continuously during the childbearing period. Therefore, effective reproductive genetic counseling will be considerate of the parents' fluctuating perceptions on reproduction. To ensure that the decision-making process is for the benefit of the parents and future children, long-term involvement of health care professionals is needed to assess the client's acceptance of the disease and their understanding of genetic phenomena and recurrence rates.
• Challenges of secondary finding disclosure in genomic medicine in rare diseases: A nation-wide survey of Japanese facilities outsourcing comprehensive genetic testing.

  Kana Hiromoto, Takahiro Yamada, Mio Tsuchiya, Hiroshi Kawame, Eiji Nanba, Yuichi Goto, Shinji Kosugi

  Journal of human genetics 68 1 1 - 9 2022年10月03日 

  Comprehensive genome analysis may reveal secondary findings (SFs) including pathogenic variants of genes other than those originally targeted. Comprehensive genetic analysis of rare diseases is generally performed as research in Japan. Therefore, the status and difficulties in SF disclosure remain unclear. To obtain information for the appropriate disclosure of SFs in rare diseases, we conducted a survey on how SFs are handled in clinical practice by facilities that outsource comprehensive genetic testing to other facilities. The response rate was 66.7% (40/60). Among the responding facilities, 55% had a policy of disclosing SFs with clinical utility and considered targeting actionable SFs with high penetrance. These facilities had difficulties in determining the disclosure targets (51%) and in genetic counseling (38%). Improving genetic literacy, establishment of surveillance systems, and providing insurance coverage for medical care to unaffected carriers were commonly cited as solutions to these difficulties. A comparison of the willingness to disclose SFs between overseas and in Japan showed more reluctance in Japan (86% vs. 65% for actionable SFs and 62% vs. 16% for non-actionable SFs). The group with difficulty in determining disclosure targets was significantly more likely to discuss this at conferences with other facilities and to refer guidelines. This suggests that the group with difficulties was unable to make decisions solely at their own facility and sought collaboration with other facilities. These findings suggest the necessity for a system that allows consultation with experts across facilities and guidelines that set forth policies for determining SFs.
• 腫瘍組織検査とリキッドバイオプシーにおける生殖細胞系列バリアントの検証シーケンス

  山本 佳宏, 福山 啓太, 金井 雅史, 近藤 知大, 吉岡 正博, 高 忠之, グェン・クィーファム, 木村 礼子, 山田 崇弘, 松本 繁巳, 小杉 眞司, 武藤 学

  日本癌治療学会学術集会抄録集 60回 O56 - 6 2022年10月
• 新生児マススクリーニングで子の遺伝性疾患が見つかった親が次子を検討する際に求める支援 認定遺伝カウンセラーとしてできること

  洪本 加奈, 山田 崇弘, 西垣 昌和, 小杉 眞司

  周産期医学 52 9 1307 - 1312 (株)東京医学社 2022年09月 

  新生児スクリーニングで子の遺伝性疾患が見つかった両親が次子を検討する際にどのような支援を求めているか調査した。5種類の常染色体潜性(劣性)遺伝疾患をもつ子の親である12名を対象に、疾患への認識、疾患告知の際の感情、再発率告知の際の感情、次子の挙児の際に検討した内容などについて半構造化インタビューを行った。内容分析の結果、20のカテゴリーと7の大カテゴリー(自己効力感の向上、肯定感の向上、経験の共有、情報提供、つながりづくり、仕組みづくり、疾患の周知)が生成された。参加者が次子を検討する際には、必ずしも生殖行動に直結するような直接的な支援だけではなく、実際に次子をもつことができる社会環境の整備などの社会を通じた間接的な支援も求められていた。具体的には、現在の罹患児の養育や生活環境を安定させるための支援の要素が抽出された。
• Prevalence of pathogenic germline variants in the circulating tumor DNA testing.

  Yoshihiro Yamamoto, Keita Fukuyama, Masashi Kanai, Tomohiro Kondo, Masahiro Yoshioka, Tadayuki Kou, Pham Nguyen Quy, Reiko Kimura-Tsuchiya, Takahiro Yamada, Shigemi Matsumoto, Shinji Kosugi, Manabu Muto

  International journal of clinical oncology 27 10 1554 - 1561 2022年07月23日 

  BACKGROUND: Somatic and germline variants are not distinguishable by circulating tumor DNA (ctDNA) testing without analyzing non-tumor samples. Although confirmatory germline testing is clinically relevant, the criteria for selecting presumed germline variants have not been established in ctDNA testing. In the present study, we aimed to evaluate the prevalence of pathogenic germline variants in clinical ctDNA testing through their variant allele fractions (VAFs). METHODS: A total of consecutive 106 patients with advanced solid tumors who underwent ctDNA testing (Guardant360®) between January 2018 and March 2020 were eligible for this study. To verify the origin of pathogenic variants reported in ctDNA testing, germline sequencing was performed using peripheral blood DNA samples archived in the Clinical Bioresource Center in Kyoto University Hospital (Kyoto, Japan) under clinical research settings. RESULTS: Among 223 pathogenic variants reported in ctDNA testing, the median VAF was 0.9% (0.02-81.8%), and 88 variants with ≥ 1% VAFs were analyzed in germline sequencing. Among 25 variants with ≥ 30% VAFs, seven were found in peripheral blood DNA (BRCA2: n = 6, JAK2: n = 1). In contrast, among the 63 variants with VAFs ranging from 1 to < 30%, only one variant was found in peripheral blood DNA (TP53: n = 1). Eventually, this variant with 15.6% VAF was defined to be an acquired variant, because its allelic distribution did not completely link to those of neighboring germline polymorphisms. CONCLUSION: Our current study demonstrated that VAFs values are helpful for selecting presumed germline variants in clinical ctDNA testing.
• Mortality and morbidity of infants with trisomy 21, weighing 1500 grams or less, in Japan.

  Hidenori Kawasaki, Takahiro Yamada, Yoshimitsu Takahashi, Takeo Nakayama, Takahito Wada, Shinji Kosugi

  Journal of human genetics 67 11 623 - 628 2022年07月05日 

  Although very low birth weight (VLBW) is well studied in neonatology and the perinatal prognosis of VLBW infants has improved over time, little is known about the prognosis of VLBW infants with trisomy 21 (T21). We aimed to investigate the mortality and morbidity of VLBW infants with T21 during NICU admission in Japan, in comparison to those of infants without birth defects (BD-). Maternal and neonatal data of infants weighing 1500 grams or less admitted to the centers of the Neonatal Research Network of Japan from 2003 to 2016 were collected prospectively. Of 60,136 infants, 328 (0.55%) had T21. Although maternal age in the case of T21 infants was higher, maternal complications tended to be less frequent than in those with BD-. Multivariable analysis revealed that morbidities were higher in infants with T21 than in those with BD- but respiratory distress syndrome and retinopathy of prematurity were less frequent in those with T21 (p < 0.001, and p = 0.014, respectively), and no significant difference was observed between the two groups in the proportion of late-onset circulatory collapse of prematurity as well as cystic periventricular leukomalacia (p = 0.739 and p = 0.733, respectively). The survival rate at discharge from the NICU was 77% and 94% for T21 and BD-, respectively. This was the first nationwide survey of VLBW infants with T21 in Japan. Although there were no data regarding the timing of diagnosis, these data will aid prenatal genetic counseling and perinatal management of T21 infants.
• AYA世代の血友病推定保因者女性に対する遺伝カウンセリングの重要性

  神谷 亮雄, 吉田 彩, 佐藤 智佳, 島田 咲, 山田 崇弘, 岡田 英孝, 野村 昌作

  日本遺伝カウンセリング学会誌 43 2 103 - 103 (一社)日本遺伝カウンセリング学会 2022年06月
• ドイツの妊娠葛藤相談法を参考にした出生前遺伝学的検査に関連した支援体制

  森本 佳奈, 山田 崇弘, 佐野 敦子, 菅野 摂子, 池袋 真, 坂本 美和, 廣瀬 達子, 関沢 明彦, 小杉 眞司, 白土 なほ子

  日本遺伝カウンセリング学会誌 43 2 79 - 79 (一社)日本遺伝カウンセリング学会 2022年06月
• 遺伝性乳癌卵巣癌患者の血縁者を遺伝カウンセリングに導くために克服すべき課題

  大高 理生, 中島 健, 山田 崇弘, 川崎 秀徳, 吉田 晶子, 鳥嶋 雅子, 小杉 眞司

  日本遺伝カウンセリング学会誌 43 2 103 - 103 (一社)日本遺伝カウンセリング学会 2022年06月
• 高-中等度リスク乳癌関連遺伝子GPVの保有とその臨床情報の特性について

  仙田 典子, 山田 崇弘, 川口 展子, 村上 裕美, 戸井 雅和, 小杉 眞司

  日本遺伝カウンセリング学会誌 43 2 115 - 115 (一社)日本遺伝カウンセリング学会 2022年06月
• 婦人科検診時に家族歴から遺伝性腫瘍のリスクを示唆されたクライエントにおける遠隔遺伝カウンセリングの後方視的研究

  吉田 晶子, 鳥嶋 雅子, 川崎 秀徳, 中島 健, 高谷 明秀, 乾 智恵, 飯尾 智美, 山口 園美, 入駒 麻希, 山田 崇弘, 稲葉 慧, 村上 裕美, 本田 明夏, 和田 敬仁, 大内 憲明, 小杉 眞司

  日本遺伝カウンセリング学会誌 43 2 116 - 116 (一社)日本遺伝カウンセリング学会 2022年06月
• ゲノム医療に必要な専門的人材養成のための教材開発 認定遺伝カウンセラー養成課程の学生を対象とした学習支援教材

  乾 智恵, 和田 敬仁, 川崎 秀徳, 吉田 晶子, 鳥嶋 雅子, 高谷 明秀, 中島 健, 山田 崇弘, 稲葉 慧, 本田 明夏, 村上 裕美, 小杉 眞司

  日本遺伝カウンセリング学会誌 43 2 147 - 147 (一社)日本遺伝カウンセリング学会 2022年06月
• 1995例の乳癌症例の生殖細胞系列の解析においてCHEK2またはATMに病的バリアントを認めた6例の臨床像

  服部 響子, 川口 展子, 仙田 典子, 稲垣 有希子, 岩野 由季, 高田 正泰, 鳥井 雅恵, 川島 雅央, 河口 浩介, 松本 純明, 山口 絢音, 村上 裕美, 本田 明夏, 山田 崇弘, 高原 祥子, 鈴木 栄治, 小杉 眞司, 小川 誠司, 戸井 雅和

  日本乳癌学会総会プログラム抄録集 30回 PD4 - 1 (一社)日本乳癌学会 2022年06月
• 遺伝性乳癌卵巣癌患者の血縁者を遺伝カウンセリングに導くために克服すべき課題

  大高 理生, 中島 健, 山田 崇弘, 川崎 秀徳, 吉田 晶子, 鳥嶋 雅子, 小杉 眞司

  日本遺伝カウンセリング学会誌 43 2 103 - 103 (一社)日本遺伝カウンセリング学会 2022年06月
• 婦人科検診時に家族歴から遺伝性腫瘍のリスクを示唆されたクライエントにおける遠隔遺伝カウンセリングの後方視的研究

  吉田 晶子, 鳥嶋 雅子, 川崎 秀徳, 中島 健, 高谷 明秀, 乾 智恵, 飯尾 智美, 山口 園美, 入駒 麻希, 山田 崇弘, 稲葉 慧, 村上 裕美, 本田 明夏, 和田 敬仁, 大内 憲明, 小杉 眞司

  日本遺伝カウンセリング学会誌 43 2 116 - 116 (一社)日本遺伝カウンセリング学会 2022年06月
• ゲノム医療に必要な専門的人材養成のための教材開発 認定遺伝カウンセラー養成課程の学生を対象とした学習支援教材

  乾 智恵, 和田 敬仁, 川崎 秀徳, 吉田 晶子, 鳥嶋 雅子, 高谷 明秀, 中島 健, 山田 崇弘, 稲葉 慧, 本田 明夏, 村上 裕美, 小杉 眞司

  日本遺伝カウンセリング学会誌 43 2 147 - 147 (一社)日本遺伝カウンセリング学会 2022年06月
• AYA世代の血友病推定保因者女性に対する遺伝カウンセリングの重要性

  神谷 亮雄, 吉田 彩, 佐藤 智佳, 島田 咲, 山田 崇弘, 岡田 英孝, 野村 昌作

  日本遺伝カウンセリング学会誌 43 2 103 - 103 (一社)日本遺伝カウンセリング学会 2022年06月
• 34歳以下妊婦における出生前遺伝学的検査の受検動向調査 単一三次施設における後方視的検討

  島田 咲, 佐藤 智佳, 吉田 彩, 神谷 亮雄, 黒田 優美, 矢内 洋次, 山田 崇弘, 岡田 英孝

  日本遺伝カウンセリング学会誌 43 2 125 - 125 (一社)日本遺伝カウンセリング学会 2022年06月
• がんゲノム医療に対する一般市民のリテラシー向上を目的とした教材の開発と評価

  十川 麗美, 和田 敬仁, 榎 朗兆, 岩本 結香子, 黒飛 恵子, 金井 雅史, 近藤 知大, 本田 明夏, 山田 崇弘, 平沢 晃, 武藤 学, 小杉 眞司

  日本遺伝カウンセリング学会誌 43 1 15 - 27 (一社)日本遺伝カウンセリング学会 2022年05月 

  がんゲノム医療の重要性が加速する今日、一般市民が遺伝医療に対するリテラシーを持つことが急務である。本研究では、一般市民のがんゲノム医療啓発を目的として、「遺伝子とがん」をテーマにしたまんが教材を開発した。そして、教材の有用性を評価するため、高校生124名を対象に、教材介入前後の質問紙調査を行った。開発した教材に対し理解のしやすさや有用性の項目で約9割が肯定的回答を示し、がんの原因や遺伝性のがんに関する知識向上が確認された。教材介入による不安感は遺伝性のがんの割合の質問正答率と関連が見られ、正確な知識を持つことが不安感の軽減に繋がると示唆された。遺伝カウンセラーの認知や理解に対しても肯定的評価を得た。本調査から、高校生が遺伝やがんの早期教育の重要性を認識し、知識習得の機会を期待していたことも明らかとなった。教材の開発がリテラシー向上に有用であり、個々の健康管理に繋がることが期待される。(著者抄録)
• がんゲノム医療に対する一般市民のリテラシー向上を目的とした教材の開発と評価

  十川 麗美, 和田 敬仁, 榎 朗兆, 岩本 結香子, 黒飛 恵子, 金井 雅史, 近藤 知大, 本田 明夏, 山田 崇弘, 平沢 晃, 武藤 学, 小杉 眞司

  日本遺伝カウンセリング学会誌 43 1 15 - 27 (一社)日本遺伝カウンセリング学会 2022年05月 

  がんゲノム医療の重要性が加速する今日、一般市民が遺伝医療に対するリテラシーを持つことが急務である。本研究では、一般市民のがんゲノム医療啓発を目的として、「遺伝子とがん」をテーマにしたまんが教材を開発した。そして、教材の有用性を評価するため、高校生124名を対象に、教材介入前後の質問紙調査を行った。開発した教材に対し理解のしやすさや有用性の項目で約9割が肯定的回答を示し、がんの原因や遺伝性のがんに関する知識向上が確認された。教材介入による不安感は遺伝性のがんの割合の質問正答率と関連が見られ、正確な知識を持つことが不安感の軽減に繋がると示唆された。遺伝カウンセラーの認知や理解に対しても肯定的評価を得た。本調査から、高校生が遺伝やがんの早期教育の重要性を認識し、知識習得の機会を期待していたことも明らかとなった。教材の開発がリテラシー向上に有用であり、個々の健康管理に繋がることが期待される。(著者抄録)
• Current status and issues related to secondary findings in the first public insurance covered tumor genomic profiling in Japan: multi-site questionnaire survey.

  Akari Minamoto, Takahiro Yamada, Saki Shimada, Ichiro Kinoshita, Yoko Aoki, Katsutoshi Oda, Arisa Ueki, Satomi Higashigawa, Maki Morikawa, Yuki Sato, Akira Hirasawa, Masanobu Ogawa, Tomohiro Kondo, Masahiro Yoshioka, Masashi Kanai, Manabu Muto, Shinji Kosugi

  Journal of human genetics 67 10 557 - 563 2022年03月23日 

  In June 2019, the Japanese National Health Insurance (NHI) system introduced coverage for two types of tumor genomic profiling (TGP): FoundationOneⓇ CDx (F1) and OncoGuide™ NCC OncoPanel System (NCCOP). TGP sometimes reveals germline variants that are potentially pathogenic as secondary findings (SFs). We conducted a questionnaire-based survey to find out the operational statuses of F1 and NCCOP at institutions where TGP was performed to elucidate issues related to SFs. Responses were received from 97 of 112 institutions (86.6%). As of May 31, 2020, 88 (90.7%) and 78 (80.4%) institutions started performing F1 and NCCOP, respectively. Since F1 only examines tumor samples, germline confirmatory testing is necessary to determine whether they are actually germline pathogenic variants (GPVs). When physicians are obtaining informed consent all but 2.3% of the patients requested SF disclosure. Conversely, when presumed germline pathogenic variants (PGPVs) were detected, 46.2% were not willing to receive confirmatory tests as they wanted to prioritize cancer treatment over SFs investigation, while only 23.3% underwent confirmatory tests. Problems in cancer genomic medicine reported by clinical genetics departments included short-staffing (n = 10), insufficient interdepartmental cooperation (n = 9), inconsistent understanding of genetics among healthcare professionals (n = 8), and low utilization rate of SFs due to lack of insurance coverage for confirmatory tests and post-test health checkups (n = 8). Solutions include; determining the appropriate timing to confirm patient intent on SF disclosure, covering confirmatory tests for PGPVs by the NHI, and establishing cooperation between the oncology and clinical genetics departments.
• 一般集団における出生前検査について知識についての調査研究

  池本 舞, 白土 なほ子, 宮上 景子, 坂本 美和, 和泉 美希子, 廣瀬 達子, 水谷 あかね, 池袋 真, 佐村 修, 山田 崇弘, 清野 仁美, 吉橋 博史, 鈴森 伸宏, 山田 重人, 奥山 虎之, 澤井 英明, 左合 治彦, 関沢 明彦, 成育疾患克服等次世代育成基盤研究事業白土班

  日本産科婦人科学会雑誌 74 臨増 S - 368 (公社)日本産科婦人科学会 2022年02月
• 一般集団における高度生殖補助医療治療歴の有無による出生前検査に対する意識についての検討

  坂本 美和, 白土 なほ子, 宮上 景子, 池本 舞, 和泉 美希子, 廣瀬 達子, 水谷 あかね, 池袋 真, 佐村 修, 山田 崇弘, 清野 仁美, 吉橋 博史, 鈴森 伸宏, 山田 重人, 奥山 虎之, 澤井 英明, 左合 治彦, 関沢 明彦, 成育疾患克服等次世代育成基盤研究事業白土班疾患克服白土班

  日本産科婦人科学会雑誌 74 臨増 S - 630 (公社)日本産科婦人科学会 2022年02月
• 確定的な出生前遺伝学的検査の具体的な解析方法と結果の解釈

  佐藤智佳, 島田咲, 山田崇弘

  臨床婦人科産科 76 69 - 75 2022年 [招待有り]
  
• がん遺伝子パネル検査における二次的所見疑い症例に対する生殖細胞系列確認検査の適応

  近藤 知大, 金井 雅史, 山本 佳宏, 福山 啓太, 松原 淳一, ファムグェン・クィー, 吉岡 正博, 山田 崇弘, 小杉 眞司, 武藤 学

  日本癌治療学会学術集会抄録集 59回 O6 - 2 2021年10月
• がん遺伝子パネル検査における二次的所見疑い症例に対する生殖細胞系列確認検査の適応

  近藤 知大, 金井 雅史, 山本 佳宏, 福山 啓太, 松原 淳一, ファムグェン・クィー, 吉岡 正博, 山田 崇弘, 小杉 眞司, 武藤 学

  日本癌治療学会学術集会抄録集 59回 O6 - 2 2021年10月
• Physicians' perceptions of the factors influencing disclosure of secondary findings in tumour genomic profiling in Japan: a qualitative study.

  Saki Shimada, Takahiro Yamada, Miho Iwakuma, Shinji Kosugi

  European journal of human genetics : EJHG 30 1 88 - 94 2021年08月16日 

  Tumour genomic profiling (TGP), conducted in search of therapeutics, sometimes reveals potentially pathogenic germline variants as secondary findings (SFs). Physicians involved in TGP are often specialised in oncology and not in clinical genetics. To better utilise SFs, we explored issues physicians have during disclosure and the potential for collaborations with clinical genetics professionals. Semi-structured interviews were conducted with 14 physicians who had experience in handling outpatient TGP at designated core hospitals for cancer genomic medicine in Japan. The data were analysed thematically. The difficulties physicians experienced during informed consent (IC) included educating patients about SFs, providing detailed information on SFs, and explaining the impact of SFs on patients' family members. When SFs were detected, physicians had reservations regarding the relevance of the disclosure criteria. Confirmatory germline tests were performed using peripheral blood when tumour-only tests detected suspected SFs. Some physicians had reservations about the necessity of confirmatory tests when they did not affect the patients' treatment options. To encourage patients to receive confirmatory tests, improvements are necessary in the healthcare system, such as insurance reimbursements, education for physicians so that they can provide a better explanation to their patients, and genetic literacy of physicians and patients. The physicians offered insights into the challenges they experienced related to IC, disclosure of SFs, and expectations for active collaborations with clinical genetics professionals. Wider healthcare insurance coverage and better genetic literacy of the population may lead to more patients taking confirmatory tests when SFs are suspected.
• Evaluation of the clinical performance of noninvasive prenatal testing at a Japanese laboratory.

  Yuna Sasaki, Takahiro Yamada, Shiro Tanaka, Akihiko Sekizawa, Tatsuko Hirose, Nobuhiro Suzumori, Takashi Kaji, Satoshi Kawaguchi, Yasuyuki Hasuo, Haruki Nishizawa, Keiichi Matsubara, Haruka Hamanoue, Akimune Fukushima, Masayuki Endo, Masayuki Yamaguchi, Yoshimasa Kamei, Hideaki Sawai, Kiyonori Miura, Masaki Ogawa, Shinya Tairaku, Hiroaki Nakamura, Ayako Sanui, Masahito Mizuuchi, Yoko Okamoto, Michihiro Kitagawa, Yukie Kawano, Hisashi Masuyama, Jun Murotsuki, Hisao Osada, Ryuhei Kurashina, Osamu Samura, Mayuko Ichikawa, Rumi Sasaki, Kazuhisa Maeda, Yasuyo Kasai, Tomomi Yamazaki, Reiko Neki, Naoki Hamajima, Yukiko Katagiri, Shunichiro Izumi, Setsuko Nakayama, Norio Miharu, Yuko Yokohama, Masaya Hirose, Kosuke Kawakami, Kiyotake Ichizuka, Masakatsu Sase, Kohei Sugimoto, Takeshi Nagamatsu, Tomomi Shiga, Lena Tashima, Takeshi Taketani, Mariko Matsumoto, Hironori Hamada, Takafumi Watanabe, Tetsuya Okazaki, Sadahiko Iwamoto, Daisuke Katsura, Nobuo Ikenoue, Toshiyuki Kakinuma, Hiromi Hamada, Makiko Egawa, Atsushi Kasamatsu, Akinori Ida, Naohiko Kuno, Naoaki Kuji, Mika Ito, Hiroko Morisaki, Shinji Tanigaki, Hiromi Hayakawa, Akinori Miki, Shoko Sasaki, Makoto Saito, Naoki Yamada, Toshiyuki Sasagawa, Toshitaka Tanaka, Fumiki Hirahara, Shinji Kosugi, Haruhiko Sago

  The journal of obstetrics and gynaecology research 47 10 3437 - 3446 2021年08月05日 

  AIM: We aimed to evaluate the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of noninvasive prenatal testing (NIPT) in high-risk pregnant women. METHODS: Pregnant women who underwent GeneTech NIPT, the most commonly used NIPT in Japan, between January 2015 and March 2019, at Japan NIPT Consortium medical sites were recruited for this study. The exclusion criteria were as follows: pregnant women with missing survey items, multiple pregnancy/vanishing twins, chromosomal abnormalities in the fetus other than the NIPT target disease, and nonreportable NIPT results. Sensitivity and specificity were calculated from the obtained data, and maternal age-specific PPV and NPV were estimated. RESULTS: Of the 45 504 cases, 44 263 cases fulfilling the study criteria were included. The mean maternal age and gestational weeks at the time of procedure were 38.5 years and 13.1 weeks, respectively. Sensitivities were 99.78% (95% confidence interval [95% CI]: 98.78-99.96), 99.12% (95% CI: 96.83-99.76), and 100% (95% CI: 88.30-100) for trisomies 21, 18, and 13, respectively. Specificities were more than 99.9% for trisomies 21, 18, and 13, respectively. Maternal age-specific PPVs were more than 93%, 77%, and 43% at the age of 35 years for trisomies 21, 18, and 13, respectively. CONCLUSION: The GeneTech NIPT data showed high sensitivity and specificity in the detection of fetal trisomies 21, 18, and 13 in high-risk pregnant women, and maternal age-specific PPVs were obtained. These results could provide more accurate and improved information regarding NIPT for genetic counseling in Japan.
• 日本人のPALB2遺伝子変異による遺伝性乳癌における検討

  樋上 明音, 川口 展子, 仙田 典子, 稲垣 有希子, 本田 明夏, 山田 崇弘, 吉田 健一, 橘 強, 山神 和彦, 露木 茂, 岡村 隆仁, 小杉 眞司, 小川 誠司, 戸井 雅和

  日本乳癌学会総会プログラム抄録集 29回 21 - 21 (一社)日本乳癌学会 2021年07月
• 1995例の乳癌症例の生殖細胞系列の解析においてPTENの病的バリアントを認めた4例

  岩野 由季, 川口 展子, 仙田 典子, 稲垣 有希子, 高田 正泰, 鳥井 雅恵, 川島 雅央, 河口 浩介, 鈴木 栄治, 村上 裕美, 本田 明夏, 山田 崇弘, 吉田 健一, 高原 祥子, 岡村 隆仁, 小杉 眞司, 小川 誠司, 戸井 雅和, 京都癌研究ネットワーク

  日本乳癌学会総会プログラム抄録集 29回 21 - 21 (一社)日本乳癌学会 2021年07月
• BRCA2遺伝性乳癌における病的バリアントによる臨床的特徴の違い

  藤野 麻琴, 川口 展子, 仙田 典子, 稲垣 有希子, 何 佳曦, 樋上 明音, 中川 梨恵, 中村 有輝, 河口 浩介, 高田 正泰, 川島 雅央, 鈴木 栄治, 山田 崇弘, 小杉 眞司, 小川 誠司, 山神 和彦, 露木 茂, 岡村 隆仁, 戸井 雅和

  日本乳癌学会総会プログラム抄録集 29回 54 - 54 (一社)日本乳癌学会 2021年07月
• 日本人のPALB2遺伝子変異による遺伝性乳癌における検討

  樋上 明音, 川口 展子, 仙田 典子, 稲垣 有希子, 本田 明夏, 山田 崇弘, 吉田 健一, 橘 強, 山神 和彦, 露木 茂, 岡村 隆仁, 小杉 眞司, 小川 誠司, 戸井 雅和

  日本乳癌学会総会プログラム抄録集 29回 21 - 21 (一社)日本乳癌学会 2021年07月
• 1995例の乳癌症例の生殖細胞系列の解析においてPTENの病的バリアントを認めた4例

  岩野 由季, 川口 展子, 仙田 典子, 稲垣 有希子, 高田 正泰, 鳥井 雅恵, 川島 雅央, 河口 浩介, 鈴木 栄治, 村上 裕美, 本田 明夏, 山田 崇弘, 吉田 健一, 高原 祥子, 岡村 隆仁, 小杉 眞司, 小川 誠司, 戸井 雅和, 京都癌研究ネットワーク

  日本乳癌学会総会プログラム抄録集 29回 21 - 21 (一社)日本乳癌学会 2021年07月
• BRCA2遺伝性乳癌における病的バリアントによる臨床的特徴の違い

  藤野 麻琴, 川口 展子, 仙田 典子, 稲垣 有希子, 何 佳曦, 樋上 明音, 中川 梨恵, 中村 有輝, 河口 浩介, 高田 正泰, 川島 雅央, 鈴木 栄治, 山田 崇弘, 小杉 眞司, 小川 誠司, 山神 和彦, 露木 茂, 岡村 隆仁, 戸井 雅和

  日本乳癌学会総会プログラム抄録集 29回 54 - 54 (一社)日本乳癌学会 2021年07月
• 本邦での妊娠中のトリプタン製剤の使用についての検討

  山口 裕子, 山田 崇弘, 川崎 秀徳, 後藤 美希, 後藤 美賀子, 村島 温子

  日本周産期・新生児医学会雑誌 57 Suppl. P229 - P229 (一社)日本周産期・新生児医学会 2021年06月
• 胎児胸腔内に脱落した胎児治療カテーテルによる緊張性気胸の周産期管理

  神谷 亮雄, 奥 楓, 副島 周子, 黒田 優美, 吉田 彩, 山田 崇弘, 岡田 英孝

  日本周産期・新生児医学会雑誌 57 Suppl. P176 - P176 (一社)日本周産期・新生児医学会 2021年06月
• 遺伝学的に確認されていない神経変性疾患の発症前診断に関する遺伝カウンセリング:2症例の報告

  山口 裕子, 和田 敬仁, 鳥嶋 雅子, 村上 裕美, 川崎 秀徳, 山田 崇弘, 小杉 眞司

  日本遺伝カウンセリング学会誌 42 2 114 - 114 (一社)日本遺伝カウンセリング学会 2021年06月
• がん遺伝子パネル検査における二次的所見開示に影響する要素 医師を対象とした質的探索的研究

  島田 咲, 山田 崇弘, 岩隈 美穂, 小杉 眞司

  日本遺伝カウンセリング学会誌 42 2 122 - 122 (一社)日本遺伝カウンセリング学会 2021年06月
• 妊娠中に筋強直性ジストロフィーの診断に至り遺伝カウンセリングを行った1例

  森内 芳, 山田 崇弘, 鳥嶋 雅子, 山口 裕子, 友滝 清一, 奥宮 明日香, 山口 綾香, 滝 真奈, 川崎 薫, 千草 義継, 最上 晴太, 山口 建, 濱西 潤三, 近藤 英治, 万代 昌紀

  日本遺伝カウンセリング学会誌 42 2 87 - 87 (一社)日本遺伝カウンセリング学会 2021年06月
• 【これからの出生前遺伝学的検査を考える】確定的な遺伝子解析法とその活用 出生前検査におけるマイクロアレイ(chromosomal micro array:CMA)の活用

  洪本 加奈, 西山 深雪, 山田 崇弘

  周産期医学 51 5 723 - 726 (株)東京医学社 2021年05月
• 診療 出生前診断の一次対応に向けたロールプレイ実習プログラムの開発

  三宅 秀彦, 久具 宏司, 池田 真理子, 左合 治彦, 佐々木 愛子, 佐々木 規子, 鈴森 伸宏, 福島 明宗, 福嶋 義光, 蒔田 芳男, 山田 重人, 山田 崇弘, 西垣 昌和, 伊尾 紳吾, 小西 郁生

  産婦人科の実際 70 3 345 - 352 金原出版(株) 2021年03月 

  ＜文献概要＞出生前遺伝学的検査(出生前診断)の実施においては,状況に応じて様々な段階の遺伝カウンセリングが必要となる。いわゆる一次対応については,通常の産科診療での対応が現実的である。しかしながら,従来の医学教育の枠組みではカリキュラム化されておらず,相談に十分な対応が行われているとはいいがたい。遺伝カウンセリングにおける態度面や行動面の修得にはロールプレイ実習が広く利用されており,本研究では,出生前診断に関する一次対応に当たる産科医療従事者を対象としたロールプレイ実習プログラムの開発を行った。アンケート調査による評価からは,本研修プログラムは有効である可能性が示された。今後,研修指導方法の開発を含めて改善を進めていきたい。
• The short-term mortality and morbidity of very low birth weight infants with trisomy 18 or trisomy 13 in Japan.

  Hidenori Kawasaki, Takahiro Yamada, Yoshimitsu Takahashi, Takeo Nakayama, Takahito Wada, Shinji Kosugi

  Journal of human genetics 66 3 273 - 285 2021年03月 

  Trisomy 18 (T18) and trisomy 13 (T13) are major concerns in prenatal genetic testing due to their poor prognosis; very low birth weight (VLBW) is also a concern in neonatology. The aim of this study was to investigate the mortality and morbidity of VLBW infants diagnosed with T18/T13 in Japan, compared with those with no birth defects (BD-). Maternal and neonatal data were collected prospectively from infants weighing <1501 g and were admitted to centers of the Neonatal Research Network of Japan during 2003 to 2016. Among 60,136 infants, 563 and 60 was diagnosed with T18 and T13, respectively. Although the age of mothers of infants with T18/T13 was higher, the frequency of maternal complications was lower than those with BD-. With maternal and neonatal characteristic adjustments, T18/T13 had a higher incidence of each morbidity when compared with BD-. Mortality rates in the NICU were 70, 77, and 5.8% for T18, T13, and BD-, respectively, while the survival discharge rates of T18 and T13 were 29.5 and 23.3%, respectively, which was significantly higher than previous reports. This was the first nationwide survey for VLBW infants with T18/T13 in Japan; this novel data will be relevant and useful for prenatal genetic counseling and perinatal management. Although T18/T13 were considered to be fatal in the past, with proper epidemiological information, discussions with affected families, and compassionate patient care, the mortality rate of T18/T13 can be improved.
• 【新型コロナウイルス関連特集】診療面(実践報告5) 各遺伝子医療部門の取り組み 遠隔診療に取り組んでいる施設 京都大学医学部附属病院遺伝子診療部におけるCOVID-19流行下における遠隔遺伝カウンセリング体制

  山田 崇弘, 川崎 秀徳, 全 理耶, 山口 裕子, 本田 明夏, 鳥嶋 雅子, 村上 裕美, 岡野 高之, 和田 敬仁, 小杉 眞司

  日本遺伝カウンセリング学会誌 41 4 287 - 291 日本遺伝カウンセリング学会 2021年02月 

  世界的に流行が広がったCOVID-19によって我々も、それ以前とは異なった診療体制を余儀なくされた。当施設において実践したオンラインシステムを用いた遠隔遺伝カウンセリングの体制について報告する。2020年2月〜9月の間に257セッションのオンラインあるいはオンサイトの遺伝カウンセリングが行われた。そのうち19セッション(7.4%)ではCL側が病院を訪れない形であり、124セッション(48.2%)は完全オンサイトであり、残りの114セッション(44.4%)は両者のハイブリッドであった。すなわち全ての遺伝カウンセリングのうち半数以上が何らかの形で遠隔診療として行われた。オンサイトとオンラインの遺伝カウンセリングにはそれぞれメリット・デメリットがあったが、十分遺伝カウンセリングとして成立しており、今後は感染防止だけでなくCOVID-19の収束後も医療資源の不十分な地域における遺伝カウンセリングを始め多くの場面で遠隔遺伝カウンセリングは重要となると考えられた。(著者抄録)
• Analysis of triptan use during pregnancy in Japan: A case series.

  Yamaguchi Y, Yamada T, Goto M, Kawasaki H, Wada T, Ikeda-Sakai Y, Saito Y, Hayashi M, Tanaka S, Takahashi R, Nakayama T, Murashima A, Kosugi S

  Congenit Anom (Kyoto) 2021年
• Real-world outcome of universal screening for Lynch syndrome in Japanese patients with colorectal cancer highlights the importance of targeting patients with young-onset disease.

  Yamada A, Matsuoka Y, Minamiguchi S, Yamamoto Y, Kondo T, Sunami T, Horimatsu T, Kawada K, Seno H, Torishima M, Murakami H, Yamada T, Kosugi S, Sugano K, Muto M

  Mol Clin Oncol 15 6 247 - 247 2021年 [査読有り]
   

  Despite the recommendations of the latest guidelines, the practical efficacy of universal screening for identifying Lynch syndrome (LS) among patients with colorectal cancer (CRC) may be limited in the real world due to infrequent referrals and the difficulties of genetic testing. Thus, the present study aimed to retrospectively analyze the results of universal screening of patients with CRC at a referral hospital in Japan. Immunohistochemistry was performed for mismatch repair proteins [including DNA mismatch repair protein MSH6 (MSH6), mismatch repair endonuclease PMS2 (PMS2), DNA mismatch repair protein Msh2 (MSH2) and DNA mismatch repair protein Mlh1 (MLH1)] and BRAF V600E mutation. Tumors that showed the following were considered to indicate LS and patients with such tumors were designated as genetic testing candidates (GTCs): i) Loss of MSH6/MSH2; ii) loss of MSH6 alone; iii) loss of PMS2 alone; and iv) loss of PMS2/MLH1 with negative BRAF V600E. MLH1 methylation and BRAF V600E mutation were analyzed in deficient mismatch repair (dMMR) tumors retrospectively. The frequency of dMMR and GTCs in an independent cohort of patients with young-onset CRC were also investigated. Universal screening revealed dMMR tumors, GTCs and LS probands in 7.3, 3.9 and 0.4%, respectively, of 463 patients with CRC. Although dMMR tumors were observed in both younger (<50 years) and older (≥60 years) patients, the GTCs were enriched in younger individuals. Evaluation of mismatch repair status in an independent cohort confirmed the high rate of GTCs in patients with young-onset CRC. The low detection rate of LS demonstrated in this study questions the implementation of routine universal screening in regions with low prevalence of LS. Considering the enrichment of GTCs in young-onset CRCs, age-restricted strategies may be simple and efficient practical alternatives to universal screening in the real world.
• Optimization of prediction methods for risk assessment of pathogenic germline variants in the Japanese population.

  Senda N, Kawaguchi-Sakita N, Kawashima M, Inagaki-Kawata Y, Yoshida K, Takada M, Kataoka M, Torii M, Nishimura T, Kawaguchi K, Suzuki E, Kataoka Y, Matsumoto Y, Yoshibayashi H, Yamagami K, Tsuyuki S, Takahara S, Yamauchi A, Shinkura N, Kato H, Moriguchi Y, Okamura R, Kan N, Suwa H, Sakata S, Mashima S, Yotsumoto F, Tachibana T, Tanaka M, Togashi K, Haga H, Yamada T, Kosugi S, Inamoto T, Sugimoto M, Ogawa S, Toi M

  Cancer Sci 2021年
• ゲノム解析における二次的所見の開示に影響する要素の探索：文献の内容分析による質的研究

  島田咲, 山田崇弘, 小杉眞司

  癌と化学療法 48 667 - 671 2021年 [査読有り]
  
• ビスホスホネート製剤導入が骨形成不全症罹患児の両親に与えた影響の調査：質的研究の統合

  佐々木佑菜, 山田崇弘, 小杉眞司

  周産期医学 51 7 1067 - 1072 (株)東京医学社 2021年 [査読有り]
   

  PubMedと医学中央雑誌Webのデータベースを使用して文献検索をした。その結果、骨形成不全症の患児に対するビスホスホネート製剤の導入前後の年代の文献がそれぞれ5件ずつ計10件得られ、対象者は母親:父親が2:1であった。分析により33コードからなる12サブカテゴリーと6カテゴリーが抽出された。6つのカテゴリーは導入前後で共通していたが、それぞれに着目した場合、カテゴリー別のコード出現頻度が異なっていた。導入前では頻度の高い順に、「親の心理へマイナスの影響」、「疾患の無理解」、「生活環境への影響」、「親の健康への影響」、「社会への要望」、「親の心理へプラスの影響」であった。それに対し導入後は、「親の心理へマイナスの影響」、「親の心理へプラスの影響」、「生活環境への影響」、「社会への要望」、「疾患の無理解」、「親の健康への影響」であった。両親の状況を認識し、支援を提供する必要があると考えられた。
• 新生児マススクリーニングと遺伝カウンセリング

  洪本加奈, 森貞直哉, 山田崇弘

  遺伝子医学 11 88 - 92 2021年
• Retrospective details of false-positive and false-negative results in non-invasive prenatal testing for fetal trisomies 21, 18 and 13.

  Nobuhiro Suzumori, Akihiko Sekizawa, Eri Takeda, Osamu Samura, Aiko Sasaki, Rina Akaishi, Seiji Wada, Haruka Hamanoue, Fumiki Hirahara, Hideaki Sawai, Hiroaki Nakamura, Takahiro Yamada, Kiyonori Miura, Hideaki Masuzaki, Setsuko Nakayama, Yoshimasa Kamei, Akira Namba, Jun Murotsuki, Masayuki Yamaguchi, Shinya Tairaku, Kazuhisa Maeda, Takashi Kaji, Yoko Okamoto, Masayuki Endo, Masaki Ogawa, Yasuyo Kasai, Kiyotake Ichizuka, Naoki Yamada, Akinori Ida, Norio Miharu, Satoshi Kawaguchi, Yasuyuki Hasuo, Tetsuya Okazaki, Mayuko Ichikawa, Shunichiro Izumi, Naohiko Kuno, Junko Yotsumoto, Miyuki Nishiyama, Nahoko Shirato, Tatsuko Hirose, Haruhiko Sago

  European journal of obstetrics, gynecology, and reproductive biology 256 75 - 81 2021年01月 

  OBJECTIVE: Maternal characteristics and neonatal outcomes associated with cell-free DNA (cfDNA) results were analysed retrospectively to assess the details of false-positive and false-negative results after initial blood sampling in non-invasive prenatal testing (NIPT). STUDY DESIGN: A multicentre retrospective study was performed for women undergoing NIPT who received discordant cfDNA results between April 2013 and March 2018. The NIPT data obtained using massive parallel sequencing were studied in terms of maternal background, fetal fraction, z-scores, invasive procedure results and neonatal outcomes after birth. RESULTS: Of the 56,545 women who participated in this study, 54 false-positive (0.095 %) and three false-negative (0.006 %) cases were found. Seven of the 54 false-positive cases (13.0 %) had vanishing twin on ultrasonography. Among the 18 false-positive cases of trisomy 18, confined placental mosaicism (CPM) was confirmed in three cases (16.7 %), while CPM was present in one of the three false-negative cases of trisomy 21. CONCLUSION: These data suggest that the incidence of women with false-positive or false-negative results is relatively low, that such false results can often be explained, and that vanishing twin and CPM are potential causes of NIPT failure. Genetic counselling with regard to false results is important for clients prior to undergoing NIPT.
• Morphofunctional cardiac changes in singleton and twin pregnancies: a longitudinal cohort study.

  Takeshi Umazume, Takahiro Yamada, Itsuko Furuta, Hiroyuki Iwano, Mamoru Morikawa, Hidemichi Watari, Hisanori Minakami

  BMC pregnancy and childbirth 20 1 750 - 750 2020年12月02日 

  BACKGROUND: This study aimed to compare the echocardiographic changes and cardiac biomarkers between women with singleton and twin pregnancies. METHODS: From April 2014 to March 2016, this longitudinal cohort study invited pregnant women who were scheduled to give birth at Hokkaido University Hospital. We analyzed prospectively collected data on simultaneously determined echocardiographic parameters and blood cardiac markers of 44 women with singleton and 22 women with twin pregnancies. Furthermore, we tested the mixed-effect models for echocardiographic parameters and cardiac biomarkers. RESULTS: During the third trimester and immediately postpartum (within 1 week after childbirth), the mean left atrial volume index and brain natriuretic peptide (BNP) level were significantly higher in women with twin pregnancies than in those with singleton pregnancies. Women with twin pregnancies also had significantly smaller second-trimester inferior vena cava diameters and significantly higher third-trimester creatinine levels than those with singleton pregnancies. BNP positively correlated with the left atrial volume index (β = 0.49, p < 0.01) and the ratio of early diastolic transmitral to mitral annular velocity (E/e') (β = 0.41, p < 0.01). At 1 month after childbirth in women with singleton pregnancies, BNP and N-terminal precursor protein BNP (NT-proBNP) fragments immediately postpartum negatively correlated with the later E/e' (r = - 0.33, p = 0.02 and r = - 0.36, p < 0.01, respectively). CONCLUSIONS: The intravascular cardiac load reached maximum within 1 week after childbirth and was greater in women with twin pregnancies than in those with singleton pregnancies. BNP/NT-proBNP significantly positively correlated with LA volume index and E/e'. In women with singleton pregnancies, BNP secreted immediately after childbirth might improve the diastolic functions 1 month after childbirth.
• Epidemiology of Birth Defects in Very Low Birth Weight Infants in Japan

  Kawasaki H, Yamada T, Takahashi Y, Nakayama T, Wada T, Kosugi S

  J Pediatr 226 106 - 111 2020年11月 [査読有り]
   

  OBJECTIVE: To evaluate the mortality and morbidity of very low birth weight (VLBW) preterm infants with birth defects in Japan. STUDY DESIGN: Data were collected prospectively for infants weighing <1501 g and born at <37 weeks of gestation admitted to centers of the Neonatal Research Network of Japan during 2003-2016. We compared outcomes of infants with and without birth defects using Pearson χ2 test, Wilcoxon rank-sum test, log-rank test, nominal logistic regression analysis, and stratified analysis by birth defect subgroups. This study was approved by the Ethics Committee of Kyoto University Graduate School and Faculty of Medicine. RESULTS: Among 57 730 VLBW preterm infants, 3557 infants (6.2%) were born with birth defects. Chromosomal abnormalities, congenital heart defects, and congenital malformation of the digestive system were the most common categories. Among diseases, Trisomy 18, Down syndrome, and cleft palate were the most prevalent. There were significant differences between perinatal characteristics of infants with and without birth defects. Most categories of morbidity occurred more frequently in infants with birth defects compared with those without birth defects. The aOR for mortality during the neonatal intensive care unit admission was 10.6 (95% CI 9.5-11.7) for infants with birth defects. A stratified analysis identified birth defect categories with good, moderate, and poor prognoses. CONCLUSIONS: This detailed information about mortality and morbidity of preterm VLBW infants with birth defects should be useful for genetic counseling as well as prenatal and neonatal care, with the limitation that we lacked information about the timing of diagnosis, abortion, or stillbirth.
• 出生前遺伝学的検査と遺伝カウンセリング体制の構築 超音波検査の活用について

  山田 崇弘, 市塚 清健, 関沢 明彦, 伊尾 紳吾, 三宅 秀彦, 山田 重人, 小西 郁生

  超音波医学 47 Suppl. S381 - S381 (公社)日本超音波医学会 2020年11月
• 1995例の乳癌症例の生殖細胞系列の解析で診断されたTP53病的変異4例の臨床像

  松平 彩芳, 川口 展子, 仙田 典子, 川田 有希子, 高田 正泰, 鳥井 雅恵, 川島 雅央, 村上 裕美, 本田 明夏, 山田 崇弘, 吉田 健一, 諏訪 裕文, 小杉 眞司, 小川 誠司, 戸井 雅和

  日本癌治療学会学術集会抄録集 58回 O10 - 3 (一社)日本癌治療学会 2020年10月
• 遺伝性乳がん卵巣がん症候群に対するリスク低減卵管卵巣摘出術の後方視的検討

  山村 幸, 山口 建, 本田 明夏, 堀江 昭史, 山田 崇弘, 濱西 潤三, 小杉 眞司, 万代 昌紀

  産婦人科の進歩 72 3 230 - 236 「産婦人科の進歩」編集室 2020年08月 [査読有り]
  
• Attitudes toward and current status of disclosure of secondary findings from next-generation sequencing: a nation-wide survey of clinical genetics professionals in Japan.

  Mio Tsuchiya, Takahiro Yamada, Rina Akaishi, Haruka Hamanoue, Akira Hirasawa, Maki Hyodo, Issei Imoto, Tomoki Kosho, Kenji Kurosawa, Hiromi Murakami, Kaname Nakatani, Fumio Nomura, Aiko Sasaki, Kenji Shimizu, Mariko Tamai, Hiroshi Umemura, Atsushi Watanabe, Akiko Yoshida, Hiroshi Yoshihashi, Junko Yotsumoto, Shinji Kosugi

  Journal of human genetics 2020年07月13日 [査読有り][通常論文]
   

  The management of secondary findings (SFs), which are beyond the intended purpose of the analysis, from clinical comprehensive genomic analysis using next generation sequencing (NGS) presents challenges. Policy statements regarding their clinical management have been announced in Japan and other countries. In Japan, however, the current status of and attitudes of clinical genetics professionals toward reporting them are unclear. We conducted a questionnaire survey of clinical genetics professionals at two time points (2013 and 2019) to determine the enforcement of the SF management policy in cases of comprehensive genetic analysis of intractable diseases and clinical cancer genome profiling testing. According to the survey findings, 40% and 70% of the respondents stated in the 2013 and 2019 surveys, respectively, that they had an SF policy in the field of intractable diseases, indicating that SF policy awareness in Japan has changed significantly in recent years. Furthermore, a total of 80% of respondents stated that their facility had established a policy for clinical cancer genome profiling testing in the 2019 survey. In both surveys, the policies included the selection criteria for genes to be disclosed and the procedure to return SFs, followed by recommendations and proposals regarding SFs in Japan and other countries. To create a better list of the genes to be disclosed, further examination is needed considering the characteristics of each analysis.
• Current status and legal/ethical problems in the research use of the tissues of aborted human fetuses in Japan.

  Hidenori Kawasaki, Takahiro Yamada, Takahito Wada, Shinji Kosugi

  Congenital anomalies 2020年06月23日 [査読有り][通常論文]
   

  BACKGROUND: To date there is no law regulating the research use of human aborted fetuses in Japan. OBJECTIVE: The aim was to review the current status with historical background and legal/ethical problems limiting the research use of the tissues of aborted human fetuses. METHOD: We reviewed literature via PubMed, Web of Science, Scopus, Japana Centra Revuo Medicina and CiNii, reports from various committees and research groups from Ministry of Health, Labour and Welfare (MHLW), and domestic books. RESULTS: Aborted human fetal tissues used for research purposes were first documented in the 1920s. The first guideline, the Peel Code was released in 1972. Since then, in Western countries, the research use of aborted fetuses has been less restricted compared with that of embryos, due to the following guidelines outlined by expert groups. Currently, aborted fetal tissues are commercially available for research purposes in the US. In Japan, only four indications are presented in "a public statement permitting research use of deceased fetuses' and 'neonates' organs etc." (1987). In the 2000s, expert committees of the MHLW concluded that research use of human aborted fetuses should be discontinued, and that comprehensive rules and independent regulations should be implemented. This issue has not been discussed in the Japanese legislature since 2003. DISCUSSION: Establishment of laws and guidelines for this issue is insufficient not only in Japan but also in other countries. It is important to secure transparency for making laws and guidelines and in obtaining public understanding. This article is protected by copyright. All rights reserved.
• がん遺伝子パネル検査の二次的所見の開示希望に関わる因子の検討 北海道大学での症例をもとに

  吉岡 正博, 山田 崇弘, 柴田 有香, 近藤 知大, 林 秀幸, 西原 広史, 矢部 一郎, 秋田 弘俊, 武藤 学, 木下 一郎, 小杉 真司

  日本遺伝カウンセリング学会誌 41 2 75 - 75 日本遺伝カウンセリング学会 2020年06月
• ビスホスホネート製剤導入が骨形成不全症罹患児の両親に与えた影響 文献調査

  佐々木 佑菜, 山田 崇弘, 小杉 眞司

  日本遺伝カウンセリング学会誌 41 2 60 - 60 (一社)日本遺伝カウンセリング学会 2020年06月
• 先天性難聴の一例 遺伝学的検査結果開示時の印象的な語りの紹介

  吉岡 正博, 村上 裕美, 谷口 美玲, 岡野 高之, 山田 崇弘, 小杉 眞司

  日本遺伝カウンセリング学会誌 41 2 68 - 68 (一社)日本遺伝カウンセリング学会 2020年06月
• ゲノム解析における二次的所見の開示に影響する要素の文献調査

  島田 咲, 山田 崇弘, 小杉 眞司

  日本遺伝カウンセリング学会誌 41 2 140 - 140 (一社)日本遺伝カウンセリング学会 2020年06月
• 日本における出生前遺伝学的検査の現状 2019

  佐々木 愛子, 左合 治彦, 三宅 秀彦, 山田 崇弘, 山田 重人, 小西 郁生

  日本遺伝カウンセリング学会誌 41 2 103 - 103 日本遺伝カウンセリング学会 2020年06月
• 羊水染色体G分染法で不均衡型と診断されていた均衡型転座の1例

  山内 建, 川崎 秀徳, 山田 崇弘, 洪本 加奈, 鳥嶋 雅子, 友滝 清一, 谷 洋彦, 近藤 英治, 河井 昌彦, 小杉 眞司

  日本遺伝カウンセリング学会誌 41 2 88 - 88 日本遺伝カウンセリング学会 2020年06月
• 新生児マススクリーニングで見つかった遺伝性疾患をもつ子の親が次の挙児検討時に考える要素の質的探索的研究

  洪本 加奈, 山田 崇弘, 小杉 眞司

  日本遺伝カウンセリング学会誌 41 2 105 - 105 日本遺伝カウンセリング学会 2020年06月
• がん遺伝子パネル検査実施後、二次的所見について遺伝カウンセリングを行った7家系9症例

  小林 明理, 山田 崇弘, 本田 明夏, 鳥嶋 雅子, 村上 裕美, 西垣 昌和, 近藤 知大, 吉岡 正博, 金井 雅史, 武藤 学, 小杉 眞司

  日本遺伝カウンセリング学会誌 41 2 86 - 86 日本遺伝カウンセリング学会 2020年06月
• Perinatal benign hypophosphatasia antenatally diagnosed through measurements of parental serum alkaline phosphatase and ultrasonography

  Shingo Io, Atsushi Watanabe, Shigehito Yamada, Masaki Mandai, Takahiro Yamada

  Congenital Anomalies 2020年05月11日 [査読有り][通常論文]
  
• 出生前診断の一次対応に向けたロールプレイ研修の開発

  三宅 秀彦, 山田 重人, 山田 崇弘, 伊尾 紳吾, 佐々木 愛子, 鈴森 伸宏, 左合 治彦, 福島 明宗, 久具 宏司, 小西 郁生

  日本産科婦人科学会雑誌 72 臨増 S - 324 (公社)日本産科婦人科学会 2020年03月 [査読有り][通常論文]
  
• Association of ALPL variants with serum alkaline phosphatase and bone traits in the general Japanese population: The Nagahama Study.

  Miho Nagata, Kazuya Setoh, Meiko Takahashi, Koichiro Higasa, Takahisa Kawaguchi, Hidenori Kawasaki, Takahito Wada, Atsushi Watanabe, Hideaki Sawai, Yasuharu Tabara, Takahiro Yamada, Fumihiko Matsuda, Shinji Kosugi

  Journal of human genetics 65 3 337 - 343 2020年03月 [査読有り][通常論文]
   

  Although alkaline phosphatase (ALP) activity is relatively low in carriers of recessive type hypophosphatasia (HPP), most are asymptomatic and therefore do not undergo medical evaluations. We analyzed the association of ALP-encoding ALPL variants with serum ALP and bone traits in the general Japanese population. Study participants (n = 9671) were from the Nagahama Study, which was a longitudinal cohort study of an apparently healthy general Japanese population. ALPL variants were analyzed by whole-genome sequencing or TaqMan probe assays using DNA extracted from peripheral blood samples. The speed of sound in calcaneal bone was assessed by quantitative ultrasound (QUS) and used as surrogate measures of bone mineral density. We identified 13 ALPL variants. Minor allele frequencies of three variants were higher than expected. Variant c.529G > A has been reported as a possible pathogenic variant for adult type HPP. Variants c.979C > T and c.1559delT are reported as pathogenic variants for perinatal severe HPP or infantile HPP. The allele frequencies of c.529G > A, c.979C > T, and c.1559delT were 0.0107, 0.0040, and 0.0014, respectively. Serum ALP activity was significantly lower and differed among the three variants (P < 0.001), as well as between individuals with and without any of the three variants (P < 0.001). Serum ALP activity was inversely associated with QUS values, although no direct association was observed between the ALPL variants and QUS values. An association between serum ALP activity and QUS was confirmed; however, we failed to detect an association between ALPL variants and bone traits in the general Japanese population.
• Qualitative investigation of the factors that generate ambivalent feelings in women who give birth after receiving negative results from non-invasive prenatal testing.

  Junko Yotsumoto, Akihiko Sekizawa, Satomi Inoue, Nobuhiro Suzumori, Osamu Samura, Takahiro Yamada, Kiyonori Miura, Hideaki Masuzaki, Hideaki Sawai, Jun Murotsuki, Haruka Hamanoue, Yoshimasa Kamei, Toshiaki Endo, Akimune Fukushima, Yukiko Katagiri, Naoki Takeshita, Masaki Ogawa, Haruki Nishizawa, Yoko Okamoto, Shinya Tairaku, Takashi Kaji, Kazuhisa Maeda, Keiichi Matsubara, Masanobu Ogawa, Hisao Osada, Takashi Ohba, Yukie Kawano, Aiko Sasaki, Haruhiko Sago

  BMC pregnancy and childbirth 20 1 112 - 112 2020年02月17日 [査読有り][通常論文]
   

  BACKGROUND: Women who receive negative results from non-invasive prenatal genetic testing (NIPT) may find that they later have mixed or ambivalent feelings, for example, feelings of accepting NIPT and regretting undergoing the test. This study aimed to investigate the factors generating ambivalent feelings among women who gave birth after having received negative results from NIPT. METHODS: A questionnaire was sent to women who received a negative NIPT result, and a contents analysis was conducted focusing on ambivalent expressions for those 1562 women who responded the questionnaire. The qualitative data gathered from the questionnaire were analyzed using the N-Vivo software package. RESULTS: Environmental factors, genetic counseling-related factors, and increased anticipatory anxiety, affected the feeling of ambivalence among pregnant women. Furthermore, pregnant women desired more information regarding the detailed prognosis for individuals with Down syndrome and living with them and/or termination, assuming the possibility that they were positive. CONCLUSIONS: Three major interrelated factors affected the feeling of ambivalence in women. Highlighting and discussing such factors during genetic counseling may resolve some of these ambivalences, thereby enhancing the quality of decisions made by pregnant women.
• A familial case of alveolar capillary dysplasia with misalignment of the pulmonary veins: The clinicopathological features and unusual glomeruloid endothelial proliferation.

  Kitano A, Nakaguro M, Tomotaki S, Hanaoka S, Kawai M, Saito A, Hayakawa M, Takahashi Y, Kawasaki H, Yamada T, Ikeda M, Onda T, Cho K, Haga H, Nakazawa A, Minamiguchi S

  Diagn Pathol 15 48 - 54 2020年 [査読有り]
  
• Comprehensive genomic profiling for patients with chemotherapy-naïve advanced cancer

  Kondo T, Matsubara J, Pham Nguyen, Quy PN, Fukuyama K, Nomura M, Funakoshi T, Doi K, Sakamori Y, Yoshioka M, Yokoyama A, Tamaoki M, Kou T, Hirohashi K, Yamada A, Yamamoto Y, Minamiguchi S, Nishigaki M, Yamada T, Kanai M, Matsumoto S, Muto M

  Cancer Sci 2020年
• 遺伝性疾患の当事者またはキャリアの挙児検討に関わる要素の抽出：文献の内容分析による質的研究．

  洪本加奈, 山田崇弘, 小杉眞司

  周産期医学 50 2056 - 2062 2020年 [査読有り][通常論文]
  
• インフルエンザ．産科編 III.疾患に対する薬剤の選び方・使い方・注意点＜合併症妊娠＞感染症

  川崎秀徳, 山田崇弘

  周産期医学 50 112 - 115 2020年 [招待有り]
  
• 実践編 出生前診断 妊娠初期における出生前染色体検査時の対応

  加藤ももこ, 柴田有花, 山田崇弘

  ペリネイタルケア 39 32 - 35 2020年 [招待有り]
  
• Two unrelated pedigrees with achondrogenesis type 1b carrying a Japan-specific pathogenic variant in SLC26A2.

  Sato T, Kojima T, Samura O, Kawaguchi S, Nakamura A, Nakajima M, Tanuma-Takahashi A, Nakabayashi K, Hata K, Ikegawa S, Nishimura G, Okamoto A, Yamada T

  American journal of medical genetics. Part A 182 4 735 - 739 2019年12月 [査読有り][通常論文]
   

  We present two unrelated Japanese pedigrees with achondrogenesis type 1b (ACG1B), characterized by prenatally lethal fetal hydrops and severe micromelia. The affected members in these pedigrees carried a common homozygous missense point mutation in solute carrier family 26 member 2 (SLC26A2), a gene associated with ACG1B (NM_000112:c.1987G>A). This loss-of-function point mutation causes substitution of glycine 663 with arginine in a highly conserved loop domain of SLC26A2. Interestingly, only a few cases of this mutation have been registered in Japanese genomic databases, and there are no reports of this mutation in any major genomic databases outside Japan. Furthermore, we confirmed the presence of a homozygous stretch of approximately 75 kb surrounding the pathogenic variant. Our findings suggest that this missense point mutation in SLC26A2, which is likely the cause of the ACG1B phenotypes in these unrelated fetuses, is distributed exclusively in Japan.
• 【最新遺伝医学研究と遺伝カウンセリング シリーズ4 最新小児・周産期遺伝医学研究と遺伝カウンセリング】(第2章)小児・周産期遺伝医学研究・診療各論 周産期編 出生前遺伝学的検査で認められる染色体異常

  川崎 秀徳, 山田 崇弘

  遺伝子医学MOOK 別冊 最新小児・周産期遺伝医学研究と遺伝カウンセリング 114 - 119 (株)メディカルドゥ 2019年11月 

  高年妊娠において頻度が増加する染色体異数性や構造異常は種類が非常に多岐にわたるだけでなく,表現型の幅も非常に広い。構造異常が認められても表現型の異常に直結しないことや正常変異も存在することから,その解釈には慎重を要する。また,出生前診断においては時間的な制約に常に注意する必要があり,限られた時間,そして限られた材料の中で,両親が意思決定できるよう支援を行うことが医療者として何よりも大切である。(著者抄録)
• Perlecan分子からみたSchwartz-Jampel syndromeとDyssegmental dysplasia分類の検討

  山下 由莉, 山田 崇弘, 右田 王介, 大西 聡, 大橋 博文, 野中 里紗, 大野 欽司, 西村 玄, 池川 志郎, 服部 信孝, 平澤 恵理

  臨床神経学 59 Suppl. S234 - S234 (一社)日本神経学会 2019年11月
• Perlecan分子からみたSchwartz-Jampel syndromeとDyssegmental dysplasia分類の検討

  山下 由莉, 山田 崇弘, 右田 王介, 大西 聡, 大橋 博文, 野中 里紗, 大野 欽司, 西村 玄, 池川 志郎, 服部 信孝, 平澤 恵理

  臨床神経学 59 Suppl. S234 - S234 (一社)日本神経学会 2019年11月
• Clinical significance of TP53 variants as possible secondary findings in tumor-only next-generation sequencing.

  Yamamoto Y, Kanai M, Kou T, Sugiyama A, Nakamura E, Miyake H, Yamada T, Nishigaki M, Kondo T, Murakami H, Torishima M, Matsumoto S, Kosugi S, Muto M

  Journal of human genetics 65 2 125 - 132 2019年10月 [査読有り][通常論文]
   

  In tumor-only next-generation sequencing (NGS), identified variants have the potential to be secondary findings (SFs), but they require verification through additional germline testing. In the present study, 194 patients with advanced cancer who underwent tumor-only NGS between April 2015 and March 2018 were enrolled, and the incidences of possible and true SFs were evaluated. Among them, 120 patients (61.9%) harbored at least one possible SF. TP53 was the most frequent gene in which 97 variants were found in 91 patients (49.5%). Nine patients provided informed consent to undergo additional germline testing, and a total of 14 variants (BRCA1, n = 1; BRCA2, n = 2; PTEN, n = 2; RB1, n = 1; SMAD4, n = 1; STK11, n = 1; TP53, n = 6) were analyzed. Three variants (BRCA1, n = 1; BRCA2, n = 2) were confirmed to be SFs, whereas TP53 variants were confirmed to be somatic variants. To confirm the low prevalence of SFs in TP53, we analyzed 24 patients with TP53 variants who underwent a paired tumor–normal NGS assay. As expected, all TP53 variants were confirmed to be somatic variants. A total of 30 patients were tested for germline variants in TP53, but none of them resulted in true SFs, suggesting the low prevalence of SFs in this gene. Therefore, the significance of additional germline testing for TP53 variants appears to be relatively low in daily clinical practice using a tumor-only NGS assay, unless patients have any relevant medical or family history.
• リンチ症候群の免疫染色スクリーニング(Immunostaining screening for Lynch syndrome)

  松岡 由, 南口 早智子, 山田 敦, 山田 崇弘, 住吉 真治, 片岡 竜貴, 吉澤 明彦, 羽賀 博典

  日本病理学会会誌 108 2 98 - 98 2019年09月
• Attitudes of clinical geneticists and certified genetic counselors to genome editing and its clinical applications: A nation-wide questionnaire survey in Japan.

  Iku Taguchi, Takahiro Yamada, Rina Akaishi, Issei Imoto, Kenji Kurosawa, Kaname Nakatani, Fumio Nomura, Haruka Hamanoue, Maki Hyodo, Hiromi Murakami, Hiroshi Yoshihashi, Junko Yotsumoto, Shinji Kosugi

  Journal of human genetics 64 9 945 - 954 2019年09月 [査読有り][通常論文]
   

  Genome editing of the human embryo using CRISPR/Cas9 has the potential to prevent hereditary diseases from being transmitted to the next generation. However, attitudes to this technology have not been examined sufficiently among the genetic professionals who will use it in the near future. We conducted a questionnaire survey of Japanese clinical geneticists and certified genetic counselors. Differences were observed between them in their recognition of this technology and impressions on its difficulty and cost. Both groups worried about misuse of it, with insufficient information and rules. As key elements for such rules, they considered ethics, safety, and purpose. Most disapproved of modifying physical traits as an enhancement, though they hoped for the treatment of severe diseases. At current clinical sites, they tended to adopt a prudent attitude by mentioning only the possibility of genome editing in the future. Academic policies and legislation are required, especially for application in human embryos, through a consensus of professionals and general citizens. Furthermore, professionals should maintain awareness of new developments and regularly reexamine attitudes for the ongoing development of more suitable rules, education systems, and clinical protocols. As preparation for changes, opportunities to address ethical issues and initiate discussions are also required.
• Fetal middle cerebral artery peak systolic velocity as a predictor of fetal anemia in unselected women giving birth at or near term.

  Kosuke Kawabata, Mamoru Morikawa, Satoshi Ishikawa, Kinuko Nakagawa, Kentaro Chiba, Takahiro Yamada, Yoshihiro Saito, Takuma Akimoto, Kazutoshi Cho, Hisanori Minakami

  Taiwanese journal of obstetrics & gynecology 58 2 212 - 217 2019年03月 [査読有り][通常論文]
   

  OBJECTIVE: This study was performed to evaluate the application of fetal middle cerebral artery peak systolic velocity (MCA-PSV) for prediction of newborn anemia with umbilical cord blood hemoglobin concentration at birth (UCB-Hb) < 10.0 g/dL among infants born at gestational week (GW) ≥ 36 to unselected women. MATERIALS AND METHODS: We reviewed the medical charts of 699 women giving birth to singleton infants at GW ≥ 36 with available data on MCA-PSV measured at GW ≥ 25 at the discretion of the attending physician. Multiple of the median (MoM) MCA-PSV (MCA-PSV MoM) > 1.5 was defined as a positive MCA-PSV test result. RESULTS: The MCA-PSV test was applied 2309 times (313 and 1996 times during second and third trimesters, respectively) in 699 women. The results were positive in 4.4% (102/2309) of tests and at least once in 9.9% (69/699) of women. Anemic infants were born to one (1.4%) and six (1.0%) of 69 and 630 women with and without at least one positive test result, respectively. MoM determined 4, 3, and 2 weeks before birth showed significant weak negative correlations with UCB-Hb at birth (correlation coefficient: 0.298-0.325). CONCLUSIONS: Among unselected women giving birth at or near term, the MCA-PSV test was unsatisfactory for prediction of newborn anemia in this retrospective observational study.
• Investigating the role of genetic counseling in neuromuscular disease considering life events.

  Shibata Y, Yabe I, Matsushima M, Hashimoto M, Yamada T, Sasaki H

  J Hum Genet 2019年03月 [査読有り][通常論文]
  
• FOCUS 母体血を用いた胎児の遺伝子診断

  山田崇弘

  臨床婦人科産科 73 494 - 497 2019年 [招待有り]
  
• Lecture 臨床遺伝学・人類遺伝学誌上講義 メンデル遺伝

  山田崇弘

  遺伝子医学 9 18 - 23 2019年 [招待有り]
  
• 文献紹介：低ホスファターゼ症の原因となるALPL遺伝子のレアバリアントは卵巣および子宮疾患と強く関連する

  山田崇弘

  HPP Frontier 2 328 - 329 2019年 [査読有り][通常論文]
  
• がんクリニカルシークエンスにおける遺伝カウンセリング

  近藤知大, 山田崇弘

  産婦人科の実際 68 207 - 213 2019年 [査読無し][招待有り]
  
• NIPTの対象として母体年齢による制限は必要か？

  山田崇弘

  臨床婦人科産科 73 237 - 242 2019年 [査読無し][招待有り]
  
• 母体年齢の高年化が先天異常の発症頻度に及ぼす影響

  柴田有花, 山田崇弘

  遺伝子医学 9 18 - 23 2019年 [査読無し][招待有り]
  
• 「遺伝医療・ゲノム医療」生殖医療と周産期医療の最前線

  山田崇弘

  北海道医報 1209 18 - 20 2019年 [査読有り][通常論文]
  
• Classification of factors involved in nonreportable results of noninvasive prenatal testing (NIPT) and prediction of success rate of second NIPT.

  Nobuhiro Suzumori, Akihiko Sekizawa, Eri Takeda, Osamu Samura, Aiko Sasaki, Rina Akaishi, Seiji Wada, Haruka Hamanoue, Fumiki Hirahara, Hiroko Kuriki, Hideaki Sawai, Hiroaki Nakamura, Takahiro Yamada, Kiyonori Miura, Hideaki Masuzaki, Takahiro Yamashita, Yoshimasa Kamei, Akira Namba, Jun Murotsuki, Tomohiro Tanemoto, Akimune Fukushima, Kazufumi Haino, Shinya Tairaku, Keiichi Matsubara, Kazutoshi Maeda, Takashi Kaji, Masanobu Ogawa, Hisao Osada, Haruki Nishizawa, Yoko Okamoto, Takeshi Kanagawa, Aiko Kakigano, Masayuki Endo, Michihiro Kitagawa, Masaki Ogawa, Shunichiro Izumi, Yukiko Katagiri, Naoki Takeshita, Yasuyo Kasai, Katsuhiko Naruse, Reiko Neki, Hisashi Masuyama, Maki Hyodo, Yukie Kawano, Takashi Ohba, Kiyotake Ichizuka, Takeshi Nagamatsu, Atsushi Watanabe, Naomi Nishikawa, Naoki Hamajima, Nahoko Shirato, Junko Yotsumoto, Miyuki Nishiyama, Keiko Koide, Tatsuko Hirose, Haruhiko Sago

  Prenatal diagnosis 39 2 100 - 106 2019年01月 [査読有り][通常論文]
   

  OBJECTIVE: To evaluate the reasons for nonreportable cell-free DNA (cfDNA) results in noninvasive prenatal testing (NIPT), we retrospectively studied maternal characteristics and other details associated with the results. METHODS: A multicenter retrospective cohort study in pregnant women undergoing NIPT by massively parallel sequencing (MPS) with failed cfDNA tests was performed between April 2013 and March 2017. The women's data and MPS results were analyzed in terms of maternal characteristics, test performance, fetal fraction (FF), z scores, anticoagulation therapy, and other details of the nonreportable cases. RESULTS: Overall, 110 (0.32%) of 34 626 pregnant women had nonreportable cfDNA test results after an initial blood sampling; 22 (20.0%) cases had a low FF (<4%), and 18 (16.4%) cases including those with a maternal malignancy, were found to have altered genomic profile. Approximately half of the cases with nonreportable results had borderline z score. Among the women with nonreportable results because of altered genomic profile, the success rate of retesting using a second blood sampling was relatively low (25.0%-33.3%). Thirteen (11.8%) of the women with nonreportable results had required hypodermic heparin injection. CONCLUSIONS: The classification of nonreportable results using cfDNA analysis is important to provide women with precise information and to reduce anxiety during pregnancy.
• Secondary findings in clinical cancer genome sequencing

  Takahiro Yamada, Shinji Kosugi

  CANCER SCIENCE 109 616 - 616 2018年12月 [査読有り][通常論文]
  
• Patients with SATB2-associated syndrome exhibiting multiple odontomas

  Takashi Kikuiri, Hiroyuki Mishima, Hideto Imura, Satoshi Suzuki, Yusuke Matsuzawa, Takashi Nakamura, Satoshi Fukumoto, Yoshitaka Yoshimura, Satoshi Watanabe, Akira Kinoshita, Takahiro Yamada, Masanobu Shindoh, Yoshihiko Sugita, Hatsuhiko Maeda, Yasutaka Yawaka, Tadashi Mikoya, Nagato Natsume, Koh ichiro Yoshiura

  American Journal of Medical Genetics, Part A 176 12 2614 - 2622 2018年12月 [査読有り][通常論文]
   

  © 2018 Wiley Periodicals, Inc. Special AT-rich sequence-binding protein 2 (SATB2)-associated syndrome (SAS) is characterized by alterations of SATB2. Its clinical features include intellectual disability and craniofacial abnormalities, such as cleft palate, dysmorphic features, and dental abnormalities. Here, we describe three previously undiagnosed, unrelated patients with SAS who exhibited dental abnormalities, including multiple odontomas. Although isolated odontomas are common, multiple odontomas are rare. Individuals in families 1 and 3 underwent whole-exome sequencing. Patient 2 and parents underwent targeted amplicon sequencing. On the basis of the hg19/GRCh37 reference and the RefSeq mRNA NM_001172517, respective heterozygous mutations were found and validated in Patients 1, 2, and 3: a splice-site mutation (chr2:g.200137396C > T, c.1741-1G > A), a nonsense mutation (chr2:g.200213750G > A, c.847C > T, p.R283*), and a frame-shift mutations (chr2:g.200188589_200188590del, c.1478_1479del, p.Q493Rfs*19). All mutations occurred de novo. The mutations in Patients 1 and 3 were novel; the mutation in Patient 2 has been described previously. Tooth mesenchymal cells derived from Patient 2 showed diminished SATB2 expression. Multiple odontomas were evident in the patients in this report; however, this has not been recognized previously as a SAS-associated phenotype. We propose that multiple odontomas be considered as an occasional manifestation of SAS.
• Correction: Maternal age-specific risk for trisomy 21 based on the clinical performance of NIPT and empirically derived NIPT age-specific positive and negative predictive values in Japan.

  Takahiro Yamada, Akihiko Sekizawa, Yosuke Fujii, Tatsuko Hirose, Osamu Samura, Nobuhiro Suzumori, Kiyonori Miura, Hideaki Sawai, Fumiki Hirahara, Jun Murotsuki, Yoshimasa Kamei, Haruhiko Sago

  Journal of human genetics 63 10 1097 - 1098 2018年10月 [査読有り][通常論文]
   

  Since the advance online publication of this article, the authors of the above paper have noticed errors in the list of authors and affiliations. The article with correct author information now appears in this issue.
• Maternal age-specific risk for trisomy 21 based on the clinical performance of NIPT and empirically derived NIPT age-specific positive and negative predictive values in Japan.

  Takahiro Yamada, Akihiko Sekizawa, Yosuke Fujii, Tatsuko Hirose, Osamu Samura, Nobuhiro Suzumori, Kiyonori Miura, Hideaki Sawai, Fumiki Hirahara, Jun Murotsuki, Yoshimasa Kamei, Haruhiko Sago

  Journal of human genetics 63 10 1035 - 1040 2018年10月 [査読有り][通常論文]
   

  The data collected by nation-wide study of noninvasive prenatal genetic testing (NIPT) for trisomy 21 from 21,610 pregnant women with advanced maternal age in Japan were reported. Among 188 NIPT-positive cases, 180 cases were true positive. The incidence of aneuploidy according to maternal age was estimated using a state-space model. Although, the frequency of trisomy increased exponentially with maternal age as previously reported, the maternal age-specific risk for trisomy 21 that was based on the clinical performance of NIPT was lower than the predicted risk in previous Western cohorts based on the data from invasive prenatal testing (Bayesian two-sided tail-area probability P = 0.0156). The empirical positive predictive value (PPV) of NIPT is likely to turn out higher than that of the theoretical PPV calculated from the sensitivity/specificity of the test and the incidence of trisomy 21 from this study.
• 産科一次施設において出生前診断の相談を受ける際の問題点

  山田 崇弘, 関沢 明彦, 金井 誠, 佐村 修, 澤井 英明, 高田 史男, 吉橋 博史, 伊尾 紳吾, 三宅 秀彦, 山田 重人, 小西 郁生, 厚労科研出生前診断実施時の遺伝カウンセリング体制の構築に関する研究班

  日本周産期・新生児医学会雑誌 54 2 542 - 542 (一社)日本周産期・新生児医学会 2018年06月 [査読有り][通常論文]
  
• BRCA1/2変異予測モデルの日本人への適応について

  仙田 典子, 川口 展子, 川田 有希子, 川島 雅央, 村上 弘美, 山田 崇弘, 戸井 雅和

  日本乳癌学会総会プログラム抄録集 26回 351 - 351 (一社)日本乳癌学会 2018年05月
• Fetal cell-free DNA fraction in maternal plasma for the prediction of hypertensive disorders of pregnancy.

  Nobuhiro Suzumori, Akihiko Sekizawa, Takeshi Ebara, Osamu Samura, Aiko Sasaki, Rina Akaishi, Seiji Wada, Haruka Hamanoue, Fumiki Hirahara, Haruna Izumi, Hideaki Sawai, Hiroaki Nakamura, Takahiro Yamada, Kiyonori Miura, Hideaki Masuzaki, Takahiro Yamashita, Takashi Okai, Yoshimasa Kamei, Akira Namba, Jun Murotsuki, Tomohiro Tanemoto, Akimune Fukushima, Kazufumi Haino, Shinya Tairaku, Keiichi Matsubara, Kazutoshi Maeda, Takashi Kaji, Masanobu Ogawa, Hisao Osada, Haruki Nishizawa, Yoko Okamoto, Takeshi Kanagawa, Aiko Kakigano, Michihiro Kitagawa, Masaki Ogawa, Shunichiro Izumi, Yukiko Katagiri, Naoki Takeshita, Yasuyo Kasai, Katsuhiko Naruse, Reiko Neki, Hisashi Masuyama, Maki Hyodo, Yukie Kawano, Takashi Ohba, Kiyotake Ichizuka, Takeshi Nagamatsu, Atsushi Watanabe, Nahoko Shirato, Junko Yotsumoto, Miyuki Nishiyama, Tatsuko Hirose, Haruhiko Sago

  European journal of obstetrics, gynecology, and reproductive biology 224 165 - 169 2018年05月 [査読有り][通常論文]
   

  OBJECTIVE: The purpose of this study is to compare the fetal fractions during non-invasive prenatal testing (NIPT) in singleton pregnancies according to gestational age and maternal characteristics to evaluate the utility of this parameter for the prediction of pregnancy complications including gestational diabetes mellitus (GDM) and hypertensive disorders of pregnancy (HDP). STUDY DESIGN: This study was a multicenter prospective cohort study. The present data were collected from women whose NIPT results were negative. The relationships between the fetal fractions and the gestational age, maternal weight and height, and incidences of miscarriage, preterm delivery, and pregnancy complications including GDM, HDP and placental abruption were assessed. RESULTS: A total of 5582 pregnant women with verified NIPT negative results were registered in the study. The demographic characteristics of the study populations were statistically analyzed, and the women with HDP tended to have a low fetal fraction in samples taken during early gestation. The area under the curve (AUC) in a receiver operating characteristic curve (ROC) analysis was 0.608 for women with HDP. CONCLUSION: A low fetal fraction on NIPT might be correlated with future HDP. However, predicting HDP during early pregnancy in women with a low fetal fraction might be difficult.
• A novel heterozygous ITGB3 p.T720del inducing spontaneous activation of integrin αIIbβ3 in autosomal dominant macrothrombocytopenia with aggregation dysfunction.

  Naohiro Miyashita, Masahiro Onozawa, Koji Hayasaka, Takahiro Yamada, Ohsuke Migita, Kenichiro Hata, Kohei Okada, Hideki Goto, Masao Nakagawa, Daigo Hashimoto, Kaoru Kahata, Takeshi Kondo, Shinji Kunishima, Takanori Teshima

  Annals of Hematology 97 4 629 - 640 2018年04月01日 [査読有り][通常論文]
   

  We identified a novel heterozygous ITGB3 p.T720del mutation in a pedigree with macrothrombocytopenia exhibiting aggregation dysfunction. Platelet aggregation induced by ADP and collagen was significantly reduced, while ristocetin aggregation was normal. Integrin αIIbβ3 was partially activated in a resting status, but platelet expression of αIIbβ3 was downregulated. Functional analysis using a cell line showed spontaneous phosphorylation of FAK in αIIb/β3 (p.T720del)-transfected 293T cells in suspension conditions. Abnormal cytoplasmic protrusions, membrane ruffling, and cytoplasmic localization of αIIbβ3 were observed in αIIb/β3 (p.T720del)-transfected CHO cells. Such morphological changes were reversed by treatment with an FAK inhibitor. These findings imply spontaneous, but partial, activation of αIIbβ3 followed by phosphorylation of FAK as the initial mechanism of abnormal thrombopoiesis. Internalization and decreased surface expression of αIIbβ3 would contribute to aggregation dysfunction. We reviewed the literature of congenital macrothrombocytopenia associated with heterozygous ITGA2B or ITGB3 mutations. Reported mutations were highly clustered at the membrane proximal region of αIIbβ3, which affected the critical interaction between αIIb R995 and β3 D723, resulting in a constitutionally active form of the αIIbβ3 complex. Macrothrombocytopenia caused by a heterozygous activating mutation of ITGA2B or ITGB3 at the membrane proximal region forms a distinct entity of rare congenital thrombocytopenia.
• 各種の治療で対応したvon Willebrand病合併妊娠の3例

  赤羽 慧一郎, 馬詰 武, 山田 崇弘, 金川 明功, 細川 亜美, 中川 絹子, 荒木 直人, 千葉 健太郎, 小島 崇史, 石川 聡司, 森川 守, 水上 尚典

  北海道産科婦人科学会会誌 62 1 179 - 180 北海道産科婦人科学会 2018年03月
• 分娩前後での母体の心形態及び血行動態変化の検討 帝王切開と経腟分娩の比較

  細川 亜美, 馬詰 武, 山田 崇弘, 金川 明功, 中川 絹子, 荒木 直人, 千葉 健太郎, 小島 崇史, 石川 聡司, 森川 守, 水上 尚典

  北海道産科婦人科学会会誌 62 1 202 - 202 北海道産科婦人科学会 2018年03月
• 多職種で連携して診療にあたったHIV合併妊娠管理についての検討

  金川 明功, 小島 崇史, 山田 崇弘, 長 和俊, 遠藤 知之, 西村 あや子, 石川 聡司, 森川 守, 山田 俊, 近藤 健, 水上 尚典

  北海道産科婦人科学会会誌 62 1 219 - 220 北海道産科婦人科学会 2018年03月
• NIPTから推定した本邦におけるトリソミー頻度とNIPTの経験的陽性的中率及び陰性的中率

  山田 崇弘, 関沢 明彦, 廣瀬 達子, 佐村 修, 鈴森 伸宏, 三浦 清徳, 澤井 英明, 平原 史樹, 左合 治彦

  日本産科婦人科学会雑誌 70 2 723 - 723 (公社)日本産科婦人科学会 2018年02月
• 出生前遺伝学的検査の進歩．出生前診断の進歩と遺伝カウンセリングの役割．

  山田崇弘

  日本遺伝カウンセリング学会誌 39 9 - 14 2018年 [査読有り][招待有り]
  
• 無侵襲的出生前遺伝学的検査（NIPT）の導入により遺伝カウンセリングに来談するクライエントの特徴は変化した

  柴田有花, 山田崇弘, 小島崇史, 河口哲, 赤石理奈, 矢部一郎

  日本遺伝カウンセリング学会誌 39 61 - 72 2018年 [査読有り][通常論文]
  
• Association of peripartum troponin I levels with left ventricular relaxation in women with hypertensive disorders of pregnancy.

  Takeshi Umazume, Satoshi Yamada, Takahiro Yamada, Satoshi Ishikawa, Itsuko Furuta, Hiroyuki Iwano, Daisuke Murai, Taichi Hayashi, Kazunori Okada, Mamoru Morikawa, Hiroyuki Tsutsui, Hisanori Minakami

  Open heart 5 2 e000829  2018年 [査読有り][通常論文]
   

  Objective: Women with hypertensive disorders of pregnancy (HDP) show elevated risk of heart failure despite decreased circulating plasma volume compared with those with normotensive control pregnancies (NCP). This study was performed to better characterise the heart in women with HDP and determine whether high-sensitivity troponin I (hs-TnI) around childbirth predicts reduced left ventricular (LV) relaxation at 1 month postpartum. Methods: Echocardiography was performed longitudinally during the first, second and third trimesters and immediately postpartum within 1 week and 1 month postpartum in 24 women with HDP, with simultaneous determination of blood variables in comparison with 51 women with NCP. Results: Compared with NCP, HDP showed greater antepartum left atrial (LA) volume, LV mass and inferior vena cava (IVC) diameter, higher peripartum brain natriuretic peptide/N-terminal pro-B-type natriuretic peptide and hs-TnI with the highest value immediately postpartum, and lower early diastolic mitral annular velocity (e') during pregnancy/postpartum. In analyses of data on HDP and NCP, hs-TnI at the third trimester as well as that immediately postpartum was negatively correlated with later e' at 1 month postpartum. The areas under the receiver operating characteristic curves were 0.82 and 0.81 for hs-TnI at the third trimester and immediately postpartum, respectively, in the prediction of reduced LV relaxation at 1 month postpartum. Conclusion: Reduced LV diastolic function and decreased splanchnic blood reservoir may contribute to the increased third trimester IVC diameter and LA volume in women with HDP. The rise in hs-TnI around childbirth was associated with poor LV relaxation ability at 1 month postpartum.
• Morphofunctional cardiac changes in pregnant women: associations with biomarkers.

  Takeshi Umazume, Takahiro Yamada, Satoshi Yamada, Satoshi Ishikawa, Itsuko Furuta, Hiroyuki Iwano, Daisuke Murai, Taichi Hayashi, Kazunori Okada, Mamoru Morikawa, Takashi Yamada, Kota Ono, Hiroyuki Tsutsui, Hisanori Minakami

  Open heart 5 2 e000850  2018年 [査読有り][通常論文]
   

  Objective: This longitudinal study was performed to determine changes in echocardiography parameters in association with various biomarker levels in pregnancy/postpartum. Methods: Fifty-one healthy pregnant women underwent echocardiography with simultaneous determination of blood levels of five biomarkers at each of the first, second and third trimesters of pregnancy, immediately postpartum within 1 week after childbirth and approximately 1 month postpartum. Data on 255 echocardiography scans (five times per woman) and biomarkers were analysed. Results: Left ventricular end-diastolic dimension, left atrial (LA) volume index and left ventricular (LV) mass index increased with advancing gestation and reached the maximum immediately postpartum concomitant with the highest brain natriuretic peptide (BNP), N-terminal pro B-type natriuretic peptide (NT-proBNP), high-sensitivity troponin I (hs-TnI) and creatine kinase MB levels. The inferior vena cava diameter was significantly reduced in the third trimester compared with that in the first trimester and the peak occurred immediately after childbirth. In 255 paired measurements, hs-TnI level was significantly positively correlated with LA volume index and LV mass index; BNP and NT-proBNP were significantly positively correlated with LA volume index and estimated glomerular filtration rate (eGFR) was significantly positively correlated with the average of early diastolic septal and lateral mitral annular velocity (e'). Conclusions: Maximal cardiac changes in morphology occurred postpartum within 1 week after childbirth, not during pregnancy. BNP/NT-proBNP, hs-TnI and eGFR reflected cardiac changes in pregnancy.
• フローサイトメトリーを用いた胎児赤血球計量系の構築

  政氏 伸夫, 馬詰 武, 山田 崇弘, 長 和俊, 岡田 一範, 加賀 早苗, 森川 守

  臨床血液 58 12 2464 - 2464 (一社)日本血液学会-東京事務局 2017年12月
• 胎児期に臍帯嚢胞を認め、胎児MRIで尿膜管遺残と診断した1例

  兼次 洋介, 丸尾 優爾, 鈴木 諒太, 高橋 美智, 加藤 晶, 鳴神 雅史, 寺下 友佳代, 鈴木 靖人, 仲西 正憲, 米原 利栄, 山田 崇弘, 森川 守, 本多 昌平, 守屋 仁彦

  日本小児科学会雑誌 121 11 1893 - 1893 (公社)日本小児科学会 2017年11月
• Everolimus in pregnancy: Case report and literature review

  Mie Yamamura, Takashi Kojima, Masayuki Koyama, Ataru Sazawa, Takahiro Yamada, Hisanori Minakami

  JOURNAL OF OBSTETRICS AND GYNAECOLOGY RESEARCH 43 8 1350 - 1352 2017年08月 [査読有り][通常論文]
   

  There have been few reports on the effects of everolimus on the fetus, but none of six infants with documented everolimus exposure in utero had congenital malformations. A 32-year-old nulliparous woman on everolimus (5.0mg/day) for renal angiomyolipoma (AML) due to tuberous sclerosis complex (TSC) was found to be pregnant at gestational week (GW) 7-5/7, at which time everolimus was withheld. To control AML in this patient, transarterial embolization was performed in the right and left kidneys at GW 21 and 24, respectively, and everolimus was reinitiated at GW 25. The patient gave birth at GW 37 to a normally formed infant weighing 3057g, but who had cardiac tumors thought to be rhabdomyomas due to inherited TSC. Thus, although data are still limited, everolimus may be promising with respect to teratogenicity. Everolimus concentration in the maternal and umbilical cord blood at birth was 1.1ng/mL and 1.0ng/mL, respectively.
• Current status of non-invasive prenatal testing in Japan

  Osamu Samura, Akihiko Sekizawa, Nobuhiro Suzumori, Aiko Sasaki, Seiji Wada, Haruka Hamanoue, Fumiki Hirahara, Hideaki Sawai, Hiroaki Nakamura, Takahiro Yamada, Kiyonori Miura, Hideaki Masuzaki, Setsuko Nakayama, Takashi Okai, Yoshimasa Kamei, Akira Namba, Jun Murotsuki, Tomohiro Tanemoto, Akimune Fukushima, Kazufumi Haino, Shinya Tairaku, Keiichi Matsubara, Kazuhisa Maeda, Takashi Kaji, Masanobu Ogawa, Hisao Osada, Haruki Nishizawa, Yoko Okamoto, Takeshi Kanagawa, Aiko Kakigano, Michihiro Kitagawa, Masaki Ogawa, Shunichiro Izumi, Yukiko Katagiri, Naoki Takeshita, Yasuyo Kasai, Katsuhiko Naruse, Reiko Neki, Hisashi Masuyama, Maki Hyodo, Yukie Kawano, Takashi Ohba, Kiyotake Ichizuka, Yasuhiro Kido, Toshiyuki Fukao, Norio Miharu, Takeshi Nagamatsu, Atsushi Watanabe, Naoki Hamajima, Masaya Hirose, Ayako Sanui, Nahoko Shirato, Junko Yotsumoto, Miyuki Nishiyama, Tatsuko Hirose, Haruhiko Sago

  JOURNAL OF OBSTETRICS AND GYNAECOLOGY RESEARCH 43 8 1245 - 1255 2017年08月 [査読有り][通常論文]
   

  AimThe purpose of this study was to report the 3-year experience of a nationwide demonstration project to introduce non-invasive prenatal testing (NIPT) of maternal plasma for aneuploidy, and review the current status of NIPT in Japan. MethodsTests were conducted to detect aneuploidy in high-risk pregnant women, and adequate genetic counseling was provided. The clinical data, test results, and pregnancy outcomes were recorded. We discuss the problems of NIPT on the basis of published reports and meta-analyses. ResultsFrom April 2013 to March 2016, 30613 tests were conducted at 55 medical sites participating in a multicenter clinical study. Among the 30613 women tested, 554 were positive (1.81%) and 30021 were negative (98.1%) for aneuploidy. Of the 289, 128, and 44 women who tested positive for trisomies 21, 18, and 13, respectively, and underwent definitive testing, 279 (96.5%), 106 (82.8%), and 28 (63.6%) were determined to have a true-positive result. For the 13481 women with negative result and whose progress could be traced, two had a false-negative result (0.02%). The tests were performed on the condition that a standard level of genetic counseling be provided at hospitals. ConclusionHere, we report on the 3-year nationwide experience with NIPT in Japan. It is important to establish a genetic counseling system to enable women to make informed decisions regarding prenatal testing. Moreover, a welfare system is warranted to support women who decide to give birth to and raise children with chromosomal diseases.
• Serum placental growth factor and soluble fms-like tyrosine kinase 1 at mid-gestation in healthy women: Association with small-for-gestational-age neonates

  Itsuko Furuta, Takeshi Umazume, Takashi Kojima, Kentaro Chiba, Kinuko Nakagawa, Ami Hosokawa, Satoshi Ishikawa, Takahiro Yamada, Mamoru Morikawa, Hisanori Minakami

  JOURNAL OF OBSTETRICS AND GYNAECOLOGY RESEARCH 43 7 1152 - 1158 2017年07月 [査読有り][通常論文]
   

  Aim This study was performed to determine the associations between serum placental growth factor (PlGF) and soluble fms-like tyrosine kinase 1 (sFlt-1) levels at mid-gestation with the risk of small-for-gestational-age (SGA) neonates born at gestational week (GW) 36 in healthy women. Methods PlGF and sFlt-1 concentrations were determined at GW 24-27 in 183 women with births at GW36, but without gestational diabetes mellitus and hypertension. Results Thirteen (7.1%) SGA neonates were born. Median (range) GW at blood sampling was similar between women with and without SGA (25 [24-25] and 24 [24-27], respectively, P = 0.671). Pre-pregnancy body mass index (BMI) and PlGF levels were significantly lower in women with than without SGA, while sFlt-1 levels and sFlt-1:PlGF ratio (sFlt-1/PlGF) did not differ significantly between the two groups. PlGF and sFlt-1/PlGF, but not BMI or sFlt-1, showed significant correlations with birthweight z-score; the correlation was positive for PlGF and negative for sFlt-1/PlGF. Women with PlGF level< 10th percentile and those with sFlt-1/PlGF level> 90th percentile showed significantly increased risk of SGA compared to those with respective counterpart characteristics; relative risk was 3.8 (95% confidence interval, 1.3-11.3; 21% [4/19] vs 5.5% [9/164]) for PlGF and 7.9 (95% confidence interval, 3.0-20.8, 33.3% [6/18] vs 4.2% [7/165]) for sFlt-1/PlGF. Conclusion Maternal PlGF and sFlt-1/PlGF determined during GW 24-27 were associated with the risk of SGA neonates born at GW >= 36, even in women with uncomplicated pregnancies.
• Effects of childbirth on podocyturia in women with normotensive, uncomplicated pregnancies

  Itsuko Furuta, Tianyue Zhai, Takeshi Umazume, Satoshi Ishikawa, Kinuko Nakagawa, Takashi Kojima, Takahiro Yamada, Mamoru Morikawa, Hisanori Minakami

  American Journal of Physiology - Renal Physiology 312 6 F1112 - F1119 2017年06月04日 [査読有り][通常論文]
   

  Changes in hemodynamics and blood pressure occur shortly before and after childbirth regardless of the mode of delivery. This study aimed to test the hypothesis that parturition induces a temporal increase in podocyturia monitored by podocyte-specific protein podocin mRNA expression levels (Pod-mRNA). A total of 105 urine specimens, consisting of 43 and 62 from 18 and 20 otherwise healthy women with vaginal delivery (VD) and elective cesarean delivery (ECS), respectively, were studied. Determination of urine protein and creatinine (Cr) concentrations and quantitative analyses of Pod-mRNA, nephrin mRNA (Nep-mRNA), synaptopodin mRNA (Syn-mRNA), and aquaporin 2 mRNA expression were performed using RT-PCR in pelleted urine samples. Levels of mRNA expression were corrected by urine Cr concentration. Podocyturia increased significantly, concomitant with a significantly decreased Nep:Pod-mRNA ratio (NPR) in the urine, collected immediately before or after childbirth regardless of the delivery mode compared with urine collected before commencement of labor or on postpartum day 3 or later. Podocyturia was significantly negatively correlated with NPR [correlation coefficient (r) =-0.614/-0.750 for VD/ECS women, respectively], as well as the Syn:Pod-mRNA ratio. Systolic blood pressure exceeded 140 mmHg during labor in 50% of VD women, and mean arterial pressure was significantly positively correlated with podocyturia during labor in VD women (r = 0.733). Thus parturition induces a transient increase in urine podocytes with reduced Nep- and Syn-mRNA expressions. Glomerular podocytes with reduced Nep- and Syn-mRNA levels were suggested to be likely to detach from the glomerular basement membrane around childbirth.
• 分娩を繰り返すと、妊婦は妊娠糖尿病(GDM)になりやすくなるか?

  森川 守, 山田 崇弘, 長 和俊, 水上 尚典

  日本周産期・新生児医学会雑誌 53 2 605 - 605 (一社)日本周産期・新生児医学会 2017年06月
• 妊娠高血圧腎症の急性増悪に先行し、母体の徐脈が出現した1例

  細川 亜美, 馬詰 武, 山田 崇弘, 中川 絹子, 小島 崇史, 千葉 健太郎, 石川 聡司, 森川 守, 水上 尚典

  日本周産期・新生児医学会雑誌 53 2 613 - 613 (一社)日本周産期・新生児医学会 2017年06月
• Cystic hygromaを契機に発見された軟骨無発生症IB型の一例

  小島 崇史, 山田 崇弘, 細川 亜美, 中川 絹子, 馬詰 武, 千葉 健太郎, 石川 聡司, 森川 守, 水上 尚典

  日本周産期・新生児医学会雑誌 53 2 661 - 661 (一社)日本周産期・新生児医学会 2017年06月
• Moebius症候群の一例

  池田 雅彦, 長 和俊, 早坂 格, 夘月 ゆたか, 秋元 琢真, 石川 聡司, 山田 崇弘, 森川 守, 水上 尚典

  日本周産期・新生児医学会雑誌 53 2 753 - 753 (一社)日本周産期・新生児医学会 2017年06月
• Post-partum podocyturia following pre-eclamptic pregnancy

  Furuta I, Zhai T, Umazume T, Ishikawa S, Hosokawa A, Kojima T, Chiba K, Yamada T, Morikawa M, Minakami H

  J Obstet Gynaecol Res 43 6 1008 - 1013 2017年06月 [査読有り][通常論文]
   

  Aim: Urine podocin mRNA expression and urine podocin : nephrin mRNA expression ratio (PNR) increase with increasing proteinuria during pregnancy complicated with pre-eclampsia (PE). This suggests that urine podocytes with reduced nephrin mRNA expression are abundant in pathological podocyturia. The aim of this study was therefore to determine post-partum changes in podocyturia and PNR in relation to proteinuria after pre-eclampsia (PE). Methods: A total of 137 peripartum urine specimens, consisting of 72 and 65 from 24 and 30 women with PE and normotensive control pregnancies (NCP), respectively, were studied. Determination of urine protein and creatinine concentration and quantitative analysis of podocyte-specific podocin and nephrin mRNA expression were carried out using reverse transcription-polymerase chain reaction in pelleted urine samples. Podocyturia was monitored via urine podocin mRNA expression. Podocyturia and proteinuria were normalized by urine creatinine concentration. Results: Podocyturia and urine PNR decreased with decreasing proteinuria as well as with increasing time after delivery in the urine from PE women. In physiological proteinuria (i.e. protein : creatinine ratio [P/Cr] 0.005-0.1 mg/mg), however, both podocyturia and PNR were significantly greater in the urine from PE women compared with NPC women, although P/Cr was similar between the groups (median, 0.037 mg/mg for PE vs 0.029 mg/mg for NCP). Conclusions: Podocyturia decreases with decreasing proteinuria in PE women after childbirth. In PE women, however, pathological podocyturia consisting of podocytes with decreased nephrin mRNA expression persisted even after proteinuria decreased to a level similar to that in NCP women.
• Effects of childbirth on podocyturia in women with normotensive, uncomplicated pregnancies

  Itsuko Furuta, Tianyue Zhai, Takeshi Umazume, Satoshi Ishikawa, Kinuko Nakagawa, Takashi Kojima, Takahiro Yamada, Mamoru Morikawa, Hisanori Minakami

  AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY 312 6 F1112 - F1119 2017年06月 [査読有り][通常論文]
   

  Changes in hemodynamics and blood pressure occur shortly before and after childbirth regardless of the mode of delivery. This study aimed to test the hypothesis that parturition induces a temporal increase in podocyturia monitored by podocyte-specific protein podocin mRNA expression levels (Pod-mRNA). A total of 105 urine specimens, consisting of 43 and 62 from 18 and 20 otherwise healthy women with vaginal delivery (VD) and elective cesarean delivery (ECS), respectively, were studied. Determination of urine protein and creatinine (Cr) concentrations and quantitative analyses of Pod-mRNA, nephrin mRNA (Nep-mRNA), synaptopodin mRNA (Syn-mRNA), and aquaporin 2 mRNA expression were performed using RT-PCR in pelleted urine samples. Levels of mRNA expression were corrected by urine Cr concentration. Podocyturia increased significantly, concomitant with a significantly decreased Nep:Pod-mRNA ratio (NPR) in the urine, collected immediately before or after childbirth regardless of the delivery mode compared with urine collected before commencement of labor or on postpartum day 3 or later. Podocyturia was significantly negatively correlated with NPR [correlation coefficient (r) = -0.614/-0.750 for VD/ECS women, respectively], as well as the Syn:Pod-mRNA ratio. Systolic blood pressure exceeded 140 mmHg during labor in 50% of VD women, and mean arterial pressure was significantly positively correlated with podocyturia during labor in VD women (r = 0.733). Thus parturition induces a transient increase in urine podocytes with reduced Nep- and Syn-mRNA expressions. Glomerular podocytes with reduced Nep- and Syn-mRNA levels were suggested to be likely to detach from the glomerular basement membrane around childbirth.
• Effect of urine creatinine level during pregnancy on dipstick test

  Yosuke Baba, Itsuko Furuta, Tianyue Zhai, Akihide Ohkuchi, Takahiro Yamada, Kayo Takahashi, Shigeki Matsubara, Hisanori Minakami

  JOURNAL OF OBSTETRICS AND GYNAECOLOGY RESEARCH 43 6 967 - 973 2017年06月 [査読有り][通常論文]
   

  Aim: Dipstick results for proteinuria are affected by urine concentration, and thus urine creatinine concentration ([Cr]). This study was performed to determine whether spot urine [Cr] changes significantly during pregnancy, leading to a significantly different false-negative rate (FNR) on dipstick test between trimester. Methods: The [Cr] and protein concentrations ([P]) were analyzed in 631 spot urine samples with negative/equivocal dipstick from 425 pregnant women. False-negative dipstick was defined as [P] : [Cr] ratio (P/Cr) > 0.27 mg/mg. Results: Median [Cr] was 117 mg/dL (range, 6.5-326 mg/dL), 72 mg/dL (range, 4.3-477 mg/dL), and 73 mg/dL (range, 8.4-396 mg/dL) in the first (n = 96), second (n = 344), and third (n = 191) trimester urine samples, respectively (P = 0.000, Kruskal-Wallis). Both [P] and P/Cr increased significantly with advancing gestation. FNR 9.4% (18/191) in the third trimester was significantly higher than that of 0.0% (0/96) in the second trimester and that of 0.5% (2/344) in the third trimester. In the 20 urine samples with false-negative dipstick, median [Cr] was 47.0 mg/dL (range, 11.0-358 mg/dL) and the proportion of samples with dilute urine, that is, [Cr] <47 mg/dL, was significantly higher than in the remaining 611 urine samples (50%, 10/20 vs 28%, 174/611, respectively, P = 0.046). Conclusions: Urine samples in the second and third trimesters were more likely to be diluted compared with the first trimester. This was associated with high FNR in third trimester urine samples.
• Maternal bradycardia occurring prior to onset of HELLP syndrome in a woman with pre-eclampsia.

  Ami Hosokawa, Takeshi Umazume, Takahiro Yamada, Hisanori Minakami

  BMJ case reports 2017 2017年05月13日 [査読有り][通常論文]
   

  A 36-year-old nulliparous woman developed pre-eclampsia at gestational week (GW) 28-6/7 Cardiac status was checked regularly. Heart rate of 93 beats per minute (bpm) with left atrial diameter (LAD) of 35 mm, left ventricular hypertrophy and inferior vena cava diameter (IVCD) of 8 mm at GW 32-0/7 decreased to 48 bpm with an expanded IVCD to 25 mm, dilated left atrium (LAD to 39 mm), increased pulmonary arterial pressure, increased systemic vascular resistance (approximate 3000  dyn s/cm5) and biphasic intrarenal venous flow pattern 3.5 hours prior to childbirth at GW 32-3/7 Epigastralgia, tachycardia (160 bpm) and marked hypertension (201/111 mm Hg) occurring 2 hours after echocardiography necessitated caesarean section, with subsequent development of HELLP syndrome. Acute fluid shift from the splanchnic vasculature to central vasculature may have occurred causing HELLP syndrome as a result from vasospasm associated with sympathetic hyperactivity. The cause of bradycardia prior to tachycardia remains unclear.
• NIPTから推定した本邦におけるトリソミー頻度とNIPTの経験的陽性的中率及び陰性的中率

  山田 崇弘, 関沢 明彦, 廣瀬 達子, 佐村 修, 鈴森 伸宏, 三浦 清徳, 澤井 英明, 平原 史樹, 左合 治彦

  日本遺伝カウンセリング学会誌 38 2 83 - 83 日本遺伝カウンセリング学会 2017年05月
• Risk factors for central serous chorioretinopathy in pregnant Japanese women

  Mamoru Morikawa, Kazutoshi Cho, Takashi Kojima, Kentaro Chiba, Satoshi Ishikawa, Takeshi Umazume, Kinuko Nakagawa, Takashi Yamada, Takahiro Yamada, Hisanori Minakami

  JOURNAL OF OBSTETRICS AND GYNAECOLOGY RESEARCH 43 5 866 - 872 2017年05月 [査読有り][通常論文]
   

  Aim: This study was performed to determine risk factors for central serous chorioretinopathy (CSC) in pregnant women. Methods: This retrospective observational study was performed in a cohort of all 1881 women giving birth at a single center. The hospital database was searched to abstract all women diagnosed with pre-eclampsia (PE) as well as those visiting the eye clinic during the current pregnancy. Medical chart review was performed in all women diagnosed with CSC and PE. Results: PE developed in 73 (3.9%) women, six (8.2%) of whom visited the eye clinic for problems occurring in the current pregnancy; 47 of 1808 (2.6%) women without PE visited the eye clinic (P = 0.015). Four women were identified as having developed CSC after onset of PE, and none of those without PE developed CSC (5.5% [4/73] vs 0.0% [0/1808], respectively, P < 0.0001). Stepwise regression analysis selected four risk factors for CSC: hematocrit value > 38.0% (odds ratio [OR], 22.9; 95% confidence interval [CI], 2.12-247), serum creatinine > 0.7 mg/dL (OR, 21.7; 95% CI, 1.12-422), time interval from diagnosis of PE until delivery > 14 days (OR, 20.0; 95% CI, 1.87-214), and urine protein : creatinine ratio (mg/mg) > 4.5 (OR, 15.7; 95% CI, 0.81-304). Hematocrit value-38.0% was finally identified as the only independent risk factor (OR, 22.9; 95% CI, 2.12-1716) for CSC in PE women. Conclusion: CSC was likely to occur in PE women, especially in those with hemoconcentration as a result of plasma leakage from the circulating blood due to increased vascular permeability.
• Increased podocyturia in pregnant women compared to non-pregnant women

  Itsuko Furuta, Tianyue Zhai, Takeshi Umazume, Satoshi Ishikawa, Kinuko Nakagawa, Rina Akaishi, Takahiro Yamada, Mamoru Morikawa, Hisanori Minakami

  JOURNAL OF OBSTETRICS AND GYNAECOLOGY RESEARCH 43 5 873 - 879 2017年05月 [査読有り][通常論文]
   

  Aim: Hyperfiltration is a cause of podocyturia and occurs physiologically in the kidney of pregnant women. Podocyturia is increased in preeclamptic pregnancies, but it is unclear whether there is also any increase in uncomplicated pregnancies. This study was performed to examine whether podocyturia and urine aquaporin 2 mRNA expression are increased in healthy pregnant women (PW) compared to healthy non-pregnant women (NPW). Methods: Eleven urines obtained from 11 NPW and longitudinal 76 urines from 40 PW with uncomplicated pregnancies (median number [range] of urine samples/person, 2 [1 - 3]) were studied. Determination of protein and creatinine concentrations and number of cells in urine other than blood cells, and quantitative analyses of the mRNA expression of aquaporin 2 (AQP2-mRNA), podocin (Pod-mRNA), and nephrin (Nep-mRNA) were performed using RT-PCR in pelleted urine samples. Podocyturia was monitored with urine Pod- and Nep-mRNA expression levels normalized relative to creatinine. Results: Urine cell density and urine AQP2-, Pod-, and Nep-mRNA expression normalized relative to creatinine were significantly higher in PW than NPW. The number of cells per milligram of creatinine was significantly positively correlated with expression of all three mRNAs with correlation coefficients (R-value) of 0.442, 0.481, and 0.561 for Pod-, Nep-, and AQP2-mRNA, respectively. AQP2-mRNA expression was strongly (R > 0.8) positively correlated with both Pod- and Nep-mRNA expression. Conclusion: Podocyturia monitored by Pod- and Nep-mRNA expression and urine cells expressing AQP2-mRNA were increased in uncomplicated pregnancies compared to healthy non-pregnant women. Urine cells expressing AQP2-mRNA increased with increasing podocyturia in healthy women.
• Parental serum alkaline phosphatase activity as an auxiliary tool for prenatal diagnosis of hypophosphatasia

  Yuichiro Takahashi, Hideaki Sawai, Jun Murotsuki, Shuhei Satoh, Takahiro Yamada, Hiromi Hayakawa, Yutaka Kouduma, Masakatsu Sase, Atsushi Watanabe, Osamau Miyazaki, Gen Nishimura

  PRENATAL DIAGNOSIS 37 5 491 - 496 2017年05月 [査読有り][通常論文]
   

  ObjectiveThe objective of this study is to clarify the usefulness of parental alkaline phosphatase (ALP) for prenatal diagnosis of hypophosphatasia (HPP). MethodsMaternal (m) and paternal (p) ALP values were measured in 77 cases from a multicenter cohort (fetal skeletal dysplasia forum in Japan) of cases with short limbs on ultrasonography during pregnancy. After birth, X-rays, cord blood ALP, and gene analysis were evaluated to achieve an exact diagnosis. The screening usefulness of ALP was examined retrospectively. ResultsSeventeen cases were eventually diagnosed as HPP and 60 as not HPP; the overall mean m-ALP and p-ALP (standard deviation) values were 133.4 (53) versus 197 (69) IU/L and 149.6 (71.8) versus 231 (61.4) IU/L (p<0.001). Receiver operating characteristic curve analysis showed that the optimal m-ALP and p-ALP cutoff values were 123 and 165IU/L, respectively. Presence of at least one of the m-ALP or p-ALP values abnormally low had a sensitivity, specificity, and positive predictive values of 82% (14/17), 93%, and 78%, respectively, for the diagnosis of HPP. ConclusionParental ALP measurement might be an auxiliary tool to hone in the prenatal diagnosis of fetal HPP. (c) 2017 John Wiley & Sons, Ltd.
• 日本超音波医学会としての胎児形態観察項目を考える 日本産科婦人科学会推奨項目との関係 本邦における超音波検査による胎児診断の現状に関する調査

  三浦 清徳, 山田 崇弘, 澤井 英明, 信実 孝洋, 田中 教文, 室月 淳, 工藤 美樹, 増崎 英明

  超音波医学 44 Suppl. S315 - S315 (公社)日本超音波医学会 2017年04月
• Follow-up study on fetal CT radiation dose in Japan: Validating the decrease in radiation dose

  Osamu Miyazaki, Hideaki Sawai, Takahiro Yamada, Jun Murotsuki, Gen Nishimura

  American Journal of Roentgenology 208 4 862 - 867 2017年04月01日 [査読有り][通常論文]
   

  OBJECTIVE. In 2011, we collected data on fetal CT radiation dose to determine the diagnostic reference level (DRL) however, continuous evaluation of the DRL is necessary. The hypothesis of this study is that the fetal CT radiation dose has decreased, and we predict a widespread use of iterative reconstruction (IR). We also predict that the national decrease in exposure is because of the DRL reported as a result of the previous national study. MATERIALS AND METHODS. Various testing protocols from each site were summarized as part of the study results. The minimum, one-fourth (25th percentile), median, three-fourths (75th percentile), and maximum values were obtained for volume CT dose index (CTDIvol), dose-length product (DLP), and scan length of 120 fetal CT examinations. The trends for IR usage and tube voltage were also investigated. RESULTS. Compared to the results of the 2011 study (n = 119), the minimum, 25th percentile, median, and 75th percentile values for CTDIvol and DLP have decreased for the tabulated results in 2015 (n = 120). The 75th percentile value for CTDIvol was 4.9 mGy, which is 43% of the previous value. IR was used in 70% of the sites. The radiation dose was significantly lower among groups that used IR. CONCLUSION. Four years passed between our initial survey on DRL and the present follow-up survey, and it appears that the previous report sufficiently fulfilled its objective and role in contributing to the decrease in DRL observed in this follow-up study.
• 妊婦血液の血小板自然凝集塊形成についての検討

  馬詰 武, 山田 崇弘, 古田 伊都子, 千葉 健太郎, 石川 聡司, 小山 貴弘, 赤石 理奈, 森川 守, 松野 一彦, 水上 尚典

  北海道産科婦人科学会会誌 61 1 53 - 54 北海道産科婦人科学会 2017年03月
• 北海道大学病院における胎児鏡下胎盤吻合血管レーザー凝固術の成績

  森川 守, 山田 俊, 馬詰 武, 木村 敬子, 川端 公輔, 中川 絹子, 千葉 健太郎, 小島 崇史, 荒木 直人, 小山 貴弘, 石川 聡司, 山田 崇弘, 長 和俊, 水上 尚典

  北海道産科婦人科学会会誌 61 1 54 - 55 北海道産科婦人科学会 2017年03月
• 試験紙法で蛋白尿が診断できず妊娠高血圧腎症の診断ができないまま子癇を発症した1例

  木村 敬子, 山田 崇弘, 川端 公輔, 中川 絹子, 馬詰 武, 荒木 直人, 千葉 健太郎, 小島 崇史, 石川 聡司, 小山 貴弘, 森川 守, 水上 尚典

  北海道産科婦人科学会会誌 61 1 59 - 60 北海道産科婦人科学会 2017年03月
• Frequency of malformed infants in a tertiary center in Hokkaido, Japan over a period of 10 years

  Itaru Hayasaka, Kazutoshi Cho, Yutaka Uzuki, Keita Morioka, Takuma Akimoto, Satoshi Ishikawa, Kohta Takei, Takahiro Yamada, Mamoru Morikawa, Takashi Yamada, Tadashi Ariga, Hisanori Minakami

  JOURNAL OF OBSTETRICS AND GYNAECOLOGY RESEARCH 43 3 505 - 510 2017年03月 [査読有り][通常論文]
   

  AimThis retrospective study was performed to determine the frequency of malformed infants born at a tertiary center in Hokkaido, Japan. The accuracy of prenatal diagnosis rates was also investigated. MethodsAn observational study was performed using data of 1509 and 1743 newborn infants at a single center during two study periods, 2005-2009 (first) and 2010-2014 (second), respectively. Cases including minor anomalies (accessory auricle, nevus and fistula auris congenita) were not included. ResultsIn total, 274 and 569 malformations were identified in 191 and 337 newborn infants in the first and second study periods, respectively. The number of malformed infants increased significantly over time (13% [191/1509] vs 19% [337/1743], respectively; P < 0.001), mainly as a result of an increase in cases of congenital heart disease (CHD), from 59 to 141 (31% [59/191] vs 42% [141/337] of all malformed infants in the first and second periods, respectively). The overall accurate prenatal diagnosis rate improved over time from 47% (128/274) to 58% (329/569) because of significant improvements in accurate prenatal diagnosis of CHD subtypes (23% [16/70] vs 65% [151/232] in the first and second periods, respectively, P < 0.0001). ConclusionsThe frequency of malformed newborns was higher in the tertiary center than in the general population. The increased number of cases with prenatal suspicion and diagnosis of CHD contributed to the increased frequency of malformed infants during the study period.
• 妊娠・分娩に伴う尿中podocyte排泄量の変化

  古田 伊都子, 馬詰 武, 中川 絹子, 山田 崇弘, 森川 守, 水上 尚典

  日本産科婦人科学会雑誌 69 2 655 - 655 (公社)日本産科婦人科学会 2017年02月
• EZH2 inhibition suppresses endometrial cancer progression via miR-361/Twist axis

  Kei Ihira, Peixin Dong, Ying Xiong, Hidemichi Watari, Yosuke Konno, Sharon J. B. Hanley, Masayuki Noguchi, Noriyuki Hirata, Futoshi Suizu, Takahiro Yamada, Masataka Kudo, Noriaki Sakuragi

  ONCOTARGET 8 8 13509 - 13520 2017年02月 [査読有り][通常論文]
   

  EZH2 inhibition and reactivation of tumor suppressor microRNAs (miRNAs) represent attractive anti-cancer therapeutic strategies. We found that EZH2-suppressed let 7b and miR-361, two likely tumor suppressors, inhibited endometrial cancer (EC) cell proliferation and invasion, and abrogated cancer stem cell-like properties. In EC cells, EZH2 induced and functioned together with YY1 to epigenetically suppress miR-361, which upregulated Twist, a direct target of miR361. Treating EC cells with GSK343, a specific EZH2 inhibitor, mimicked the effects of siRNA-mediated EZH2 knockdown, upregulating miR-361 and downregulating Twist expression. Combining GSK343 with 5 AZA-2'-deoxycytidine synergistically suppressed cell proliferation and invasion in vitro, and decreased tumor size and weight in EC cell xenografted mice. Quantitative real-time PCR analysis of 24 primary EC tissues showed that lower let-7b and miR-361 levels were associated with worse patient outcomes. These results were validated in a larger EC patient dataset from The Cancer Genome Atlas. Our findings suggest that EZH2 drives EC progression by regulating miR-361/Twist signaling, and support EZH2 inhibition as a promising anti-EC therapeutic strategy.
• Liver dysfunction in women with pregnancy-induced antithrombin deficiency

  Morikawa M, Kawabata K, Kato-Hirayama E, Oda Y, Ueda H, Kataoka S, Yamada T, Okuyama K, Sengoku K, Minakami H

  J Obstet Gynaecol Res 43 257 - 264 2017年 [査読有り]
  
• Association between nephrinuria, podocyturia, and proteinuria in women with pre-eclampsia

  Itsuko Furuta, Tianyue Zhai, Satoshi Ishikawa, Takeshi Umazume, Kinuko Nakagawa, Takahiro Yamada, Mamoru Morikawa, Hisanori Minakami

  JOURNAL OF OBSTETRICS AND GYNAECOLOGY RESEARCH 43 1 34 - 41 2017年01月 [査読有り][通常論文]
   

  AimPodocyte depletion in the kidney is associated with end-stage kidney disease (ESKD). Pre-eclampsia (PE) increases the risk of ESKD in later life. This study was performed to determine whether nephrinuria (soluble nephrin in the urine) is correlated with proteinuria and/or podocyturia (podocytes in the urine) in PE women. MethodsEighty-three urine samples, consisting of 45 and 38 samples from 27 normotensive and nine PE women, respectively, underwent simultaneous determination of nephrin, protein, and creatinine concentrations in the urine supernatant and quantitative analysis of podocyte-specific protein mRNA expression. This included podocin (Pod-mRNA) and nephrin (Nep-mRNA), using real-time polymerase chain reaction in the pelleted urine. Nephrinuria and proteinuria were corrected by creatinine concentration. Pod- and Nep-mRNA expression levels were corrected by GAPDH. ResultsNephrinuria, proteinuria, Pod-mRNA expression, and Nep-mRNA expression all increased with advancing gestation in PE women, while not in normotensive women. The nephrinuria was strongly correlated with proteinuria (R= 0.901, P < 0.001), Pod-mRNA expression level (R=0.824, P<0.001), and Nep-mRNA expression level (R = 0.724, P < 0.001) in urine samples from PE women, while the nephrinuria was significantly correlated with proteinuria alone (R = 0.419, P < 0.005) in urine samples from normotensive women. ConclusionNephrinuria reflected well the degrees of proteinuria and podocyturia in PE women. This suggested that increased nephrinuria/proteinuria was associated with podocyte loss in the kidneys of PE women.
• 【周産期のウイルス感染症】 妊娠・分娩・産褥時の対応 C型肝炎

  細川 亜美, 山田 崇弘

  周産期医学 47 240 - 242 2017年 [査読無し][招待有り]
  
• 【母と子の診断羅針盤】 【産科編】出血 妊娠中期・後期の性器出血

  中川 絹子, 山田 崇弘

  周産期医学 47 9 - 17 2017年 [査読無し][招待有り]
  
• 3分でわかる 周産期医療キーワード2017(第16回) NIPT(解説)

  小島 崇史, 赤石 理奈, 山田 崇弘

  ペリネイタルケア 36 6 610 - 612 メディカ出版 2017年 [査読無し][招待有り]
  
• NIPTにおける遺伝カウンセリング

  小島 崇史, 赤石 理奈, 山田 崇弘

  産婦人科の実際 66 439 - 446 2017年 [査読無し][招待有り]
  
• A survey on awareness of genetic counseling for non-invasive prenatal testing: the first year experience in Japan.

  Junko Yotsumoto, Akihiko Sekizawa, Nobuhiro Suzumori, Takahiro Yamada, Osamu Samura, Miyuki Nishiyama, Kiyonori Miura, Hideaki Sawai, Jun Murotsuki, Michihiro Kitagawa, Yoshimasa Kamei, Hideaki Masuzaki, Fumiki Hirahara, Toshiaki Endo, Akimune Fukushima, Akira Namba, Hisao Osada, Yasuyo Kasai, Atsushi Watanabe, Yukiko Katagiri, Naoki Takeshita, Masaki Ogawa, Takashi Okai, Shunichiro Izumi, Haruka Hamanoue, Mayuko Inuzuka, Kazufumi Haino, Naoki Hamajima, Haruki Nishizawa, Yoko Okamoto, Hiroaki Nakamura, Takeshi Kanegawa, Jun Yoshimatsu, Shinya Tairaku, Katsuhiko Naruse, Hisashi Masuyama, Maki Hyodo, Takashi Kaji, Kazuhisa Maeda, Keiichi Matsubara, Masanobu Ogawa, Toshiyuki Yoshizato, Takashi Ohba, Yukie Kawano, Haruhiko Sago

  Journal of human genetics 61 12 995 - 1001 2016年12月 [査読有り][通常論文]
   

  The purpose of this study is to summarize the results from a survey on awareness of genetic counseling for pregnant women who wish to receive non-invasive prenatal testing (NIPT) in Japan. As a component of a clinical study by the Japan NIPT Consortium, genetic counseling was conducted for women who wished to receive NIPT, and a questionnaire concerning both NIPT and genetic counseling was given twice: once after pre-test counseling and again when test results were reported. The responses of 7292 women were analyzed. They expressed high satisfaction with the genetic counseling system of the NIPT Consortium (94%). The number of respondents who indicated that genetic counseling is necessary for NIPT increased over time. Furthermore, they highly valued genetic counseling provided by skilled clinicians, such as clinical geneticists or genetic counselors. The vast majority (90%) responded that there was sufficient opportunity to consider the test ahead of time. Meanwhile, women who received positive test results had a poor opinion and expressed a low-degree satisfaction. We confirmed that the pre-test genetic counseling that we conducted creates an opportunity for pregnant women to sufficiently consider prenatal testing, promotes its understanding and has possibilities to effectively facilitate informed decision making after adequate consideration. A more careful and thorough approach is considered to be necessary for women who received positive test results.
• Factors affecting parental decisions to terminate pregnancy in the presence of chromosome abnormalities: a Japanese multicenter study

  Miyuki Nishiyama, Akihiko Sekizawa, Kohei Ogawa, Hideaki Sawai, Hiroaki Nakamura, Osamu Samura, Nobuhiro Suzumori, Setsuko Nakayama, Takahiro Yamada, Masaki Ogawa, Yukiko Katagiri, Jun Murotsuki, Yoko Okamoto, Akira Namba, Haruka Hamanoue, Masanobu Ogawa, Kiyonori Miura, Shunichiro Izumi, Yoshimasa Kamei, Haruhiko Sago

  PRENATAL DIAGNOSIS 36 12 1121 - 1126 2016年12月 [査読有り][通常論文]
   

  Objective To investigate the rates of termination of pregnancy ( TOP) for fetal chromosomal abnormalities and factors related to such parental decision in Japan. Methods A multicenter retrospective cohort study of chromosomal abnormalities diagnosed before 22 weeks of gestation between April 2008 and March 2015. The pregnancy outcomes and parental decisions were investigated. Results Among 931 fetuses with chromosome abnormalities, the total TOP rate was 75.1% (699/931). TOP rates were 89.3% (585/655) in autosomal aneuploidies and 40.8% (51/125) in sex chromosome aneuploidies. Trisomy 21 showed the highest TOP rate (93.8% [390/416]) followed by trisomy 18 (84.5% [163/193]) and trisomy 13 (71.9% [23/32]). Indications for karyotyping were related to a parental decision for TOP (P < 0.01): in cases of autosomal aneuploidy, with fetal abnormal ultrasound findings as the reference value, diagnoses made following positive results at non-invasive prenatal testing (adjusted odds ratio [OR]: 13.7, 95% confidence interval [CI] 4.07-45.9) and those because of advanced maternal age (adj. OR 2.91, 95% CI 1.15-7.35) were significantly more frequent. Conclusions In Japan, pregnancies with fetal trisomy 21 are more likely to result in TOP when diagnosed in utero than any other chromosome anomaly. The indications for prenatal karyotyping strongly affect the decision to TOP. (C) 2016 John Wiley & Sons, Ltd.
• Second-trimester urine nephrin: creatinine ratio versus soluble fms-like tyrosine kinase-1: placental growth factor ratio for prediction of preeclampsia among asymptomatic women

  Tianyue Zhai, Itsuko Furuta, Kinuko Nakagawa, Takashi Kojima, Takeshi Umazume, Satoshi Ishikawa, Takahiro Yamada, Mamoru Morikawa, Hisanori Minakami

  SCIENTIFIC REPORTS 6 37442 - 37442 2016年11月 [査読有り][通常論文]
   

  This prospective observational study compare urine nephrin: creatinine ratio (NCR, ng/mg) with serum soluble fms-like tyrosine kinase-1: placental growth factor ratio (FPR, pg/pg) for preeclampsia (PE) prediction among unselected asymptomatic pregnant women in 2nd trimester. NCR and FPR were determined in 254 paired urine/blood samples collected simultaneously from 254 women at median gestational week (GW) 24 (range, 22-27) without hypertension or significant proteinuria in pregnancy (SPIP). Fifteen (5.9%) developed SPIP and hypertension at GW 34.0 (26.0-38.6) and 35.3 (27.6-38.6), respectively, and were diagnosed with PE at GW 35.7 (27.6-38.6). The 90th percentile level determined in 239 women normotensive throughout pregnancy gave NCR (139) sensitivity and positive predictive values (PPV) of 60% (9/15) and 27% (9/33), while those for serum FPR (4.85) were 40% (6/15) and 20% (6/30), respectively. Relative risks (95% CI) of later PE were 10.0 (3.82-26.4; 27% [9/33] vs. 2.7% [6/221]) and 4.98 (1.91-13.0; 20% [6/30] vs. 4.0% [9/224]) for NCR-positive and FPR-positive women, respectively. Cut-offs suggested by ROC gave NCR (86.6) sensitivity and PPV of 87% (13/15) and 17% (13/79), and FPR (8.8) values of 40% (6/15) and 40% (6/15), respectively. Thus, 2nd trimester NCR was superior to FPR for PE prediction.
• Suppression of iASPP-dependent aggressiveness in cervical cancer through reversal of methylation silencing of microRNA-124

  Peixin Dong, Ying Xiong, Hidemichi Watari, Sharon J. B. Hanley, Yosuke Konno, Kei Ihira, Fumihiko Suzuki, Takahiro Yamada, Masataka Kudo, Junming Yue, Noriaki Sakuragi

  SCIENTIFIC REPORTS 6 35480 - 35480 2016年10月 [査読有り][通常論文]
   

  Derepression of wild-type p53 by suppressing its negative inhibitor iASPP (Inhibitor of apoptosis-stimulating protein of p53) represents a potential therapeutic option for cervical cancer (CC). Here, we reported a novel functional significance of iASPP upregulation in cervical tumorigenesis: iASPP acts as a key promoter of CC cell proliferation, epithelial-mesenchymal transition, invasion and cancer stemness, by interacting with p53 to suppress p53-mediated transcription of target genes and reducing p53-responsive microRNA-34a levels. Moreover, we demonstrate that miR-124, directly targeting iASPP, reduces expression of iASPP and attenuates CC cell growth and invasiveness. Low miR-124 expression is inversely correlated with increased expression of iASPP mRNA in CC tissues. In a cohort of 40 patients with CC, the low miR-124 expression was correlated with poor 5-year overall survival (P = 0.0002) and shorter disease-free survival 5-year (P = 0006). Treatment with the DNA methyltransferase inhibitor Zebularine increases miR-124 expression and retards CC cell growth and invasion with minimal toxicity to normal cells. Even at a non-toxic concentration, Zebularine was effective in suppressing CC cell invasion and migration. Altogether, the restoration of miR-124 reduces iASPP expression and leads to p53-dependent tumor suppression, suggesting a therapeutic strategy to treat iASPP-associated CC.
• 妊娠高血圧腎症妊婦における尿中ポドサイトの量的ならびに質的変化

  てき 天げつ, 古田 伊都子, 赤石 理奈, 石川 聡司, 森川 守, 山田 崇弘, 小山 貴弘, 水上 尚典

  日本妊娠高血圧学会雑誌 23 40 - 40 (一社)日本妊娠高血圧学会 2016年09月
• 中心性漿液性脈絡網膜症と妊娠高血圧腎症

  森川 守, 山田 崇弘, 長 和俊, 水上 尚典

  日本妊娠高血圧学会雑誌 23 74 - 74 (一社)日本妊娠高血圧学会 2016年09月
• 各種の治療で対応したvon Willebrand病合併妊娠の三例

  赤羽 慧一郎, 馬詰 武, 山田 崇弘, 金川 明功, 細川 亜美, 中川 絹子, 荒木 直人, 千葉 健太郎, 小島 崇史, 石川 聡司, 森川 守, 水上 尚典

  北日本産科婦人科学会総会・学術講演会プログラム・抄録集 64回 98 - 98 東北連合産科婦人科学会・北日本産科婦人科学会 2016年09月
• 分娩前後での母体の心形態及び血行動態変化の検討 帝王切開と経腟分娩の比較

  細川 亜美, 馬詰 武, 山田 崇弘, 金川 明功, 中川 絹子, 荒木 直人, 千葉 健太郎, 小島 崇史, 石川 聡司, 森川 守, 水上 尚典

  北日本産科婦人科学会総会・学術講演会プログラム・抄録集 64回 126 - 126 東北連合産科婦人科学会・北日本産科婦人科学会 2016年09月
• 多職種で連携して診療にあたったHIV合併妊娠管理についての検討

  金川 明功, 小島 崇史, 山田 崇弘, 長 和俊, 遠藤 知之, 西村 あや子, 石川 聡司, 森川 守, 山田 俊, 近藤 健, 水上 尚典

  北日本産科婦人科学会総会・学術講演会プログラム・抄録集 64回 145 - 145 東北連合産科婦人科学会・北日本産科婦人科学会 2016年09月
• MiR-137 and miR-34a directly target Snail and inhibit EMT, invasion and sphere-forming ability of ovarian cancer cells

  Peixin Dong, Ying Xiong, Hidemichi Watari, Sharon J. B. Hanley, Yosuke Konno, Kei Ihira, Takahiro Yamada, Masataka Kudo, Junming Yue, Noriaki Sakuragi

  JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH 35 132 - 132 2016年09月 [査読有り][通常論文]
   

  Background: In ovarian cancer (OC) cells, Snail was reported to induce the epithelial-to-mesenchymal transition (EMT), which is a critical step in OC metastasis. At present little is known about controlling Snail expression in OC cells by using specific microRNAs (miRNAs). Methods: We first used a computational target prediction analysis to identify 6 candidate miRNAs that bind to the 3'-untranslated region (3'-UTR) region of the Snail mRNA. Among these miRNAs, two miRNAs (miR-137 and miR-34a) with a potential to regulate Snail were validated by quantitative real-time PCR, Western blot analysis, and Snail 3'- UTR reporter assays. We assessed the effects of miR-137 and miR-34a on EMT, invasion and sphere formation in OC cells. We also evaluated the expression of miR-137 and miR-34a in OC tissues and adjacent normal tissues and analyzed the relationship between their expression and patient survival. Results: We report that OC tissues possess significantly decreased levels of miR-137 and miR-34a and increased expression of Snail when compared to their adjacent normal tissues, and lower miR-137 and miR-34a expression correlates with worse patient survival. Using luciferase constructs containing the 3'- UTR region of Snail mRNA combined with miRNA overexpression and mutagenesis, we identified miR-137 and miR-34a as direct suppressors of Snail in OC cells. The introduction of miR-137 and miR-34a resulted in the suppression of Snail at both the transcript and protein levels, and effectively suppressed the EMT phenotype and sphere formation of OC cells. However, the inhibition of miR-137 and miR-34a with antisense oligonucleotides promoted EMT and OC cell invasion. Moreover, ectopic expression of Snail significantly reversed the inhibitory effects of miR-137 and miR-34a on OC cell invasion and sphere formation. Conclusions: These findings suggest that both miR-137 and miR-34a act as Snail suppressors to negatively regulate EMT, invasive and sphere-forming properties of OC cells.
• Isolated gestational proteinuria preceding the diagnosis of preeclampsia - an observational study

  Takahiro Yamada, Mana Obata-Yasuoka, Hiromi Hamada, Yosuke Baba, Akihide Ohkuchi, Shun Yasuda, Kosuke Kawabata, Shiori Minakawa, Chihiro Hirai, Hideto Kusaka, Nao Murabayashi, Yusuke Inde, Michikazu Nagura, Takeshi Umazume, Atsuo Itakura, Makoto Maeda, Norimasa Sagawa, Yasumasa Ohno, Soromon Kataoka, Keiya Fujimori, Yoshiki Kudo, Tomoaki Ikeda, Akihito Nakai, Hisanori Minakami

  ACTA OBSTETRICIA ET GYNECOLOGICA SCANDINAVICA 95 9 1048 - 1054 2016年09月 [査読有り][通常論文]
   

  Introduction. Some pregnant women develop significant proteinuria in the absence of hypertension. However, clinical significance of isolated gestational proteinuria (IGP) is not well understood. This study aimed to determine the prevalence of IGP in singleton pregnancies and the proportion of women with IGP who subsequently developed preeclampsia (IGP-PE) among all PE cases. Material and methods. This was an observational study of 6819 women with singleton pregnancies at 12 centers, including 938 women with at least once determination of protein-to-creatinine ratio (P/Cr). Significant proteinuria in pregnancy (SPIP) was defined as P/Cr (mg/mg) level >0.27. IGP was defined as SPIP in the absence of hypertension. Gestational hypertension (GH) preceding preeclampsia (GH-PE) was defined as preeclampsia (PE) in which GH preceded SPIP. Simultaneous PE (S-PE) was defined as PE in which both SPIP and hypertension occurred simultaneously. Results. IGP and PE were diagnosed in 130 (1.9%) and 158 (2.3%) of 6819 women, respectively. Of 130 women with IGP, 32 (25%) progressed to PE and accounted for 20% of all women with PE. Hence, women with IGP had a relative risk of 13.1 (95% CI; 9.2-18.5) for developing PE compared with those without IGP [25% (32/130) vs. 1.9% (126/6689)]. At diagnosis of SPIP, P/Cr levels already exceeded 1.0 more often in women with S-PE than in those with IGP-PE [67% (33/49) vs. 44% (14/32), respectively, p = 0.031]. Conclusions. IGP is a risk factor for PE, and IGP-PE accounts for a considerable proportion (20%) of all PE.
• Fetal cell-free DNA fraction in maternal plasma is affected by fetal trisomy

  Nobuhiro Suzumori, Takeshi Ebara, Takahiro Yamada, Osamu Samura, Junko Yotsumoto, Miyuki Nishiyama, Kiyonori Miura, Hideaki Sawai, Jun Murotsuki, Michihiro Kitagawa, Yoshimasa Kamei, Hideaki Masuzaki, Fumiki Hirahara, Juan-Sebastian Saldivar, Nilesh Dharajiya, Haruhiko Sago, Akihiko Sekizawa

  JOURNAL OF HUMAN GENETICS 61 7 647 - 652 2016年07月 [査読有り][通常論文]
   

  The purpose of this noninvasive prenatal testing (NIPT) study was to compare the fetal fraction of singleton gestations by gestational age, maternal characteristics and chromosome-specific aneuploidies as indicated by z-scores. This study was a multicenter prospective cohort study. Test data were collected from women who underwent NIPT by the massively parallel sequencing method. We used sequencing-based fetal fraction calculations in which we estimated fetal DNA fraction by simply counting the number of reads aligned within specific autosomal regions and applying a weighting scheme derived from a multivariate model. Relationships between fetal fractions and gestational age, maternal weight and height, and z-scores for chromosomes 21, 18 and 13 were assessed. A total of 7740 pregnant women enrolled in the study, of which 6993 met the study criteria. As expected, fetal fraction was inversely correlated with maternal weight (P<0.001). The median fetal fraction of samples with euploid result (n=6850) and trisomy 21 (n=70) were 13.7% and 13.6%, respectively. In contrast, the median fetal fraction values for samples with trisomies 18 (n=35) and 13 (n=9) were 11.0% and 8.0%, respectively. The fetal fraction of samples with trisomy 21 NIPT result is comparable to that of samples with euploid result. However, the fetal fractions of samples with trisomies 13 and 18 are significantly lower compared with that of euploid result. We conclude that it may make detecting these two trisomies more challenging.
• 妊婦における「抗リン脂質抗体症候群」と「抗リン脂質抗体陽性」の周産期予後の違い

  森川 守, 山田 崇弘, 長 和俊, 水上 尚典

  日本産婦人科・新生児血液学会誌 26 1 S - 26 日本産婦人科・新生児血液学会 2016年06月
• 周産期心筋症の早期発見を目指したバイオマーカーの検討

  馬詰 武, 山田 崇弘, 中川 絹子, 坂本 綾子, 川端 公輔, 齊藤 良玄, 小島 崇史, 石川 聡司, 小山 貴弘, 森川 守, 水上 尚典

  日本周産期・新生児医学会雑誌 52 2 498 - 498 (一社)日本周産期・新生児医学会 2016年06月
• ループス腎炎合併妊娠の周産期予後に関する後方視的検討

  森川 守, 平山 恵美, 馬詰 武, 中川 絹子, 小島 崇史, 千葉 健太郎, 石川 聡司, 山田 崇弘, 長 和俊, 奥山 和彦, 水上 尚典

  日本周産期・新生児医学会雑誌 52 2 499 - 499 (一社)日本周産期・新生児医学会 2016年06月
• 正常妊娠における妊娠中から分娩後の心形態と機能の変化

  中川 絹子, 馬詰 武, 山田 崇弘, 川端 公輔, 坂本 綾子, 齊藤 良玄, 小島 崇史, 石川 聡司, 小山 貴弘, 森川 守, 水上 尚典

  日本周産期・新生児医学会雑誌 52 2 756 - 756 (一社)日本周産期・新生児医学会 2016年06月
• 広汎子宮頸部全摘後、妊娠初期に腹腔鏡下頸管縫縮術を施行した1例

  齊藤 良玄, 森川 守, 川端 公輔, 坂本 綾子, 中川 絹子, 馬詰 武, 小島 崇史, 千葉 健太郎, 小山 貴弘, 石川 聡司, 山田 崇弘, 水上 尚典

  日本周産期・新生児医学会雑誌 52 2 780 - 780 (一社)日本周産期・新生児医学会 2016年06月
• Isolated pregnancy-induced anti-thrombin deficiency in a woman with twin pregnancy

  Kosuke Kawabata, Mamoru Morikawa, Takahiro Yamada, Hisanori Minakami

  JOURNAL OF OBSTETRICS AND GYNAECOLOGY RESEARCH 42 6 719 - 721 2016年06月 [査読有り][通常論文]
   

  A woman with twin pregnancy had a gradual decline in anti-thrombin (AT) activity from 72% at gestational week (GW) 29(-3/7), to 53% at GW31(-2/7), and to 41% at GW32(-2/7), at which time hypertension (148/90 mmHg) and proteinuria (protein-to-creatinine ratio [P/Cr], 0.79 mg/mg) developed in the presence of normal platelet count (159 x 10(9)/L) and serum aspartate aminotransferase/lactate dehydrogenase (22/164 IU/L). AT product was given three times to maintain AT activity >50% and blood pressure was maintained below 155/95 mmHg with no treatment, but generalized edema with a weekly weight gain of 4.9 kg and increased proteinuria (to P/Cr, 7.6 mg/mg) required cesarean section at GW33(-3/7). This case highlights the occurrence of pregnancy-induced AT deficiency alone in the absence of any other abnormality, including hypertension, proteinuria, or thrombocytopenia. Measurement of AT activity was considered helpful for determination of the appropriate time for delivery in this patient.
• Occult fetomaternal hemorrhage in women with pathological placenta with respect to permeability

  T. Umazume, T. Yamada, M. Morikawa, S. Ishikawa, T. Kojima, K. Cho, N. Masauzi, H. Minakami

  JOURNAL OF OBSTETRICS AND GYNAECOLOGY RESEARCH 42 6 632 - 639 2016年06月 [査読有り][通常論文]
   

  Aim: Women with pre-eclampsia (PE), placenta previa (PP), placental abruption (PA), and placental mesenchymal dysplasia (PMD) have been described as having placental permeability dysfunction. This study was performed to determine whether occult fetomaternal hemorrhage (FMH) is common in women with such complications and in women with non-reassuring fetal status. Methods: Forty-one antenatal and 39 postnatal blood samples were obtained from 46 women, including 11 with placental permeability dysfunction (5, 3, 2, and 1 with PE, PP, PA, and PMD, respectively) and 35 controls without such complications. To estimate the amount of fetal red blood cells, flow cytometry was performed using the fetal cell count system with two antibodies against fetal hemoglobin and carbonic anhydrase and the beta-gamma system with two monoclonal antibodies against hemoglobin beta-chain and hemoglobin gamma-chain. A diagnosis of FMH was made when the fraction size of the isolated cell population on scatter plots expressing fetal hemoglobin alone or hemoglobin gamma-chain alone accounted for >= 0.02% of the total cell population on scatter plots. Results: FMH was identified in five women, including one each with PE, PA, PP, PMD, and no complications. Thus, the prevalence rate of FMH was significantly higher in women with complications than in controls (36% [4/11] vs 2.9% [1/35], respectively, P = 0.009). The FMH occurrence rate did not differ between women with and without non-reassuring fetal status (7.7% [1/13] vs 12% [4/33], respectively, P = 1.000). Conclusion: The risk of fetal red blood cells trafficking into the maternal circulation may be increased in women complicated with PE, PA, PP, and PMD.
• 妊娠初期の血小板凝集塊形成についての検討

  馬詰 武, 松野 一彦, 山田 崇弘, 古田 伊都子, 千葉 健太郎, 石川 聡司, 小山 貴弘, 赤石 理奈, 森川 守, 水上 尚典

  日本血栓止血学会誌 27 2 237 - 237 (一社)日本血栓止血学会 2016年05月
• 単胎妊娠と双胎妊娠の血小板凝集塊形成の比較

  馬詰 武, 松野 一彦, 山田 崇弘, 古田 伊都子, 千葉 健太郎, 石川 聡司, 小山 貴弘, 赤石 理奈, 森川 守, 水上 尚典

  日本血栓止血学会誌 27 2 238 - 238 (一社)日本血栓止血学会 2016年05月
• Anemia in a neonate with placental mesenchymal dysplasia.

  Satoshi Ishikawa, Mamoru Morikawa, Takeshi Umazume, Takahiro Yamada, Hiromi Kanno, Emi Takakuwa, Hisanori Minakami

  Clinical case reports 4 5 463 - 5 2016年05月 [査読有り][通常論文]
   

  Causes of intrauterine fetal death (IUFD) are uncertain in most placental mesenchymal dysplasia (PMD) cases. Our case showed high α-fetoprotein levels in the maternal circulation, markedly dilated subchorionic vessels, and neonatal hemoglobin concentration of 8.4 g/dL, suggesting that fetal anemia may explain some adverse outcomes in PMD pregnancies.
• 妊娠28週で子宮内胎児死亡となった胎児上顎体の一例

  川端 公輔, 中川 絹子, 馬詰 武, 千葉 健太郎, 小島 崇史, 小山 貴弘, 石川 聡司, 山田 崇弘, 森川 守, 水上 尚典

  超音波医学 43 Suppl. S847 - S847 (公社)日本超音波医学会 2016年04月
• Reactivation of epigenetically silenced miR-124 reverses the epithelial-to-mesenchymal transition and inhibits invasion in endometrial cancer cells via the direct repression of IQGAP1 expression

  Peixin Dong, Kei Ihira, Ying Xiong, Hidemichi Watari, Sharon J. B. Hanley, Takahiro Yamada, Masayoshi Hosaka, Masataka Kudo, Junming Yue, Noriaki Sakuragi

  ONCOTARGET 7 15 20260 - 20270 2016年04月 [査読有り][通常論文]
   

  Overexpression of IQGAP1 and microRNA (miRNA) dysregulation are frequent in human tumors, but little is known about the role of IQGAP1 and its relationship to miRNA in endometrial carcinogenesis. We demonstrate that IQGAP1 activates the epithelial-mesenchymal transition (EMT) program and that miR-124 directly represses IQGAP1 expression in endometrial cancer (EC) cells. The overexpression of IQGAP1 stimulates EMT features and enhances migration, invasion and proliferation of EC cells, whereas knocking down IQGAP1 expression reverses EMT and inhibits these malignant properties. Using miRNA microarray profiling, we identified 29 miRNAs (let-7b, let-7f, miR-10b, miR-15b, miR-23a, miR-24, miR-25, miR-27a, miR-29b, miR-30a-5p, miR-34a, miR-124, miR-127, miR-130b, miR-148a, miR-155, miR-191*, miR-194, miR-224, miR-362, miR-409-3p, miR-422b, miR-424, miR-453, miR-497, miR-518d, miR-518f*, miR-526a and miR-656) that are significantly down-regulated in an in vitro-selected highly invasive derivative cell line (HEC-50-HI) relative to the parental HEC-50 cells. We further identified miR-124 as a direct regulator of IQGAP1 in EC cells. Enforced expression of miR-124 suppresses EC cell invasion and proliferation. The expression of IQGAP1 mRNA was significantly elevated in EC tissues, while the expression of miR-124 was decreased. The downregulation of miR-124 correlates with a poor survival outcome for patients with EC. Treating EC cells with the demethylating agent 5-aza-2'-deoxycytidine increased miR-124 expression and down-regulated IQGAP1 levels. Our data suggest that IQGAP1 promotes EMT, migration and invasion of EC cells. MiR-124, a novel tumor suppressor miRNA that is epigenetically silenced in EC, can reverse EMT and the invasive properties, by attenuating the expression of the IQGAP1 oncogene.
• Alteration of podocyte phenotype in the urine of women with preeclampsia

  Tianyue Zhai, Itsuko Furuta, Rina Akaishi, Satoshi Ishikawa, Mamoru Morikawa, Takahiro Yamada, Takahiro Koyama, Hisanori Minakami

  SCIENTIFIC REPORTS 6 24258 - 24258 2016年04月 [査読有り][通常論文]
   

  Podocyte injury has been suggested to induce phenotypic alteration of glomerular podocytes and accelerate the detachment of podocytes from the glomeruli resulting in podocyturia. However, it is not clear whether podocyte phenotypic alteration occurs in the urine of women with preeclampsia (PE). Seventy-seven and 116 pelleted urine samples from 38 and 18 women at various stages of normal and PE pregnancies, respectively underwent quantitative analysis of podocyte-specific or associated protein mRNA expression, including podocin, nephrin, and synaptopodin using RT-PCR. Significant proteinuria in pregnancy (SPIP) is defined as protein: creatinine ratio (P/Cr, mg/mg) >= 0.27 in the urine supernatant. All three urine-pellet mRNAs expression levels were significantly positively correlated with P/Cr levels, suggesting that podocyturia increased with proteinuria. The podocin: nephrin mRNA ratio (PNR) and synaptopodin: nephrin mRNA ratio (SNR) increased significantly with increasing P/Cr, while the podocin: synaptopodin mRNA ratio (PSR) did not change significantly according to P/Cr, resulting in significantly higher PNR and SNR, but not PSR levels, in urine from PE women with than without SPIP. The PNR, SNR, and PSR in urine from PE women before onset of SPIP were comparable to those from controls. Thus, nephrin mRNA expression was reduced in the podocytes recovered from PE women.
• Survey of prenatal testing for genetic disorders in Japan: Recent report

  Takahiro Nobuzane, Takahiro Yamada, Kiyonori Miura, Hideaki Sawai, Hideaki Masuzaki, Yoshiki Kudo

  JOURNAL OF OBSTETRICS AND GYNAECOLOGY RESEARCH 42 4 375 - 379 2016年04月 [査読有り][通常論文]
   

  AimIn order to investigate the current status of prenatal testing for genetic disorders, we conducted a multicenter retrospective questionnaire survey. MethodsThe questionnaire was sent to 105 facilities with genetic counseling systems. The questionnaire consisted of two parts: (i) the number of prenatal tests conducted for genetic disorders from January 2010 to December 2012, whether the laboratory was combined with the counseling facility or separate, the sampling procedure method, the testing results, and the outcomes of the affected fetus in addition to treatment; and (ii) a survey of personal comments regarding prenatal testing for genetic disorders. ResultsWe received responses from 69 of the 105 facilities (65.7%), and genetic testing was performed at 26 of these facilities. Nucleic acid sequential testing was performed on 45 disorders and 252 cases during a three-year period. There were 67 cases of affected fetuses. Six cases continued pregnancy and were treated. The comment survey highlighted difficulties in locating a laboratory to assess prenatal samples, as well as inadequate counseling and preparation for genetic disorders. ConclusionsOur study revealed that a number of prenatal testing for genetic disorders are conducted in Japan; however, it is difficult for counselors to locate a laboratory capable of testing for specific genetic disorders. Inadequate counseling and healthcare providers' lack of knowledge is a current problem. A well-established system of prenatal testing for genetic disorders and the further education of general physicians is required.
• Criteria for radiologic diagnosis of hypochondroplasia in neonates

  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 - 518 2016年04月 [査読有り][通常論文]
   

  A radiologic diagnosis of hypochondroplasia is hampered by the absence of age-dependent radiologic criteria, particularly in the neonatal period. To establish radiologic criteria and scoring system for identifying neonates with fibroblast growth factor receptor 3 (FGFR3)-associated hypochondroplasia. 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. 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 a parts per thousand yen6. Our set of diagnostic radiologic criteria might be useful for early identification of hypochondroplastic neonates.
• Influenza 2014-2015 among pregnant Japanese women: primiparous vs multiparous women

  T. Yamada, S. Kawakami, Y. Yoshida, H. Kawamura, S. Ohta, K. Abe, H. Hamada, S. Dohi, K. Ichizuka, H. Takita, Y. Baba, S. Matsubara, J. Mochizuki, N. Unno, Y. Maegawa, M. Maeda, E. Inubashiri, N. Akutagawa, T. Kubo, T. Shirota, Y. Oda, T. Yamada, E. Yamagishi, A. Nakai, N. Fuchi, H. Masuzaki, S. Urabe, Y. Kudo, M. Nomizo, N. Sagawa, T. Maeda, M. Kamitomo, K. Kawabata, S. Kataoka, A. Shiozaki, S. Saito, A. Sekizawa, H. Minakami

  EUROPEAN JOURNAL OF CLINICAL MICROBIOLOGY & INFECTIOUS DISEASES 35 4 665 - 671 2016年04月 [査読有り][通常論文]
   

  This study was performed to determine whether multiparous pregnant women are prone to influenza. A questionnaire survey was conducted at 19 centres located throughout Japan, targeting all 6,694 postpartum women within 7 days after birth before leaving the hospital. All women gave birth during the study period between March 1, 2015, and July 31, 2015. Data regarding vaccination and influenza infection in or after October 2014, age, previous experience of childbirth, and number and ages of cohabitants were collected. Seventy-eight percent (n = 51,97) of women given questionnaires responded. Of these, 2,661 (51 %) and 364 (7.0 %) women reported having been vaccinated and having contracted influenza respectively. Multiparous women had a higher risk of influenza regardless of vaccination status (8.9 % [121/1362] vs 5.7 % [74/1299], relative risk [95 % confidence interval], 1.80 [1.36 to 2.38] for vaccinated and 9.3 % [112/1198] vs 4.3 % [57/1328], 2.18 [1.60 to 2.97] for unvaccinated women) compared to primiparous women. The risk of influenza increased with increasing number of cohabitants: 4.8 % (100/2089), 7.5 %, (121/1618), 9.0 %, (71/785), and 10.4 % (58/557) for women with 1, 2, 3, and a parts per thousand yen4 cohabitants respectively. Family size is a risk factor for influenza infection in pregnancy.
• Platelet reactivity in twin pregnancies

  Takeshi Umazume, Takahiro Yamada, Mamoru Morikawa, Satoshi Ishikawa, Itsuko Furuta, Takahiro Koyama, Kazuhiko Matsuno, Hisanori Minakami

  THROMBOSIS RESEARCH 138 43 - 48 2016年02月 [査読有り][通常論文]
   

  Background: Gestational thrombocytopenia is more likely to occur in twin than singleton pregnancies. However, it is unclear whether platelets are more reactive in twin than singleton pregnancies. Methods: Changes in spontaneous platelet aggregation and concomitant fall in platelet count were examined over 90 min after blood sampling in 171 and 52 citrated whole blood (CWB) samples from 59 and 17 women with singleton and twin pregnancies, respectively. Soluble P-selectin (sP-selectin) levels in the plasma were also determined. Results: CWB 60 min after blood sampling during 2nd trimester exhibited significantly larger numbers of platelet aggregates (1297 +/- 1600 vs. 497 +/- 432/mu l, P = 0.040) concomitant with significantly greater net decrease in platelet count (152 +/- 55 vs. 115 +/- 45 x 10(9)/mu l, P = 0.036) in twin than singleton pregnancies, respectively. This was followed by significantly lower 3rd trimester platelet count (181 +/- 43 vs. 229 +/- 62 x 10(9)/l, P = 0.009) with significantly greater mean platelet volume (8.0 +/- 1.2 vs. 7.1 +/- 1.1 fl, P = 0.021) in twin than singleton pregnancies, respectively. The 3rd trimester sP-selectin per platelet was significantly higher in twin than singleton pregnancies. Conclusions: Platelets were more reactive in the 2nd trimester of twin than singleton pregnancies. This enhanced platelet reactivity may explain the decreased platelet count in the 3rd trimester of twin pregnancy. (C) 2016 Elsevier Ltd. All rights reserved.
• Clinical significance of second-trimester 50-g glucose challenge test among Japanese women diagnosed as normoglycemic after first-trimester 75-g glucose tolerance test

  Mamoru Morikawa, Takahiro Yamada, Takashi Yamada, Takashi Kojima, Ryutaro Nishida, Kazutoshi Cho, Hisanori Minakami

  TAIWANESE JOURNAL OF OBSTETRICS & GYNECOLOGY 55 1 16 - 19 2016年02月 [査読有り][通常論文]
   

  Objective: This study was performed to determine how often Japanese women diagnosed as normoglycemic on first-trimester 75-g glucose tolerance test (75gGTT) later develop gestational diabetes mellitus (GDM). Material and methods: Sixty-two women with random plasma glucose (PG) level >= 105 mg/dL during the first trimester and subsequent first-trimester diagnosis of normoglycemia with 75gGTT underwent 50-g glucose challenge test (50gGCT) during the second trimester. Twenty-one with a positive 50gGCT result (60-m PG >= 140 mg/dL) underwent second-trimester 75gGTT. First-trimester random PG levels and 75gGTT results were compared between 21 and 41 women with positive and negative 50gGCT results, respectively. Changes in immunoreactive insulin (IRI) associated with 75gGTT were determined simultaneously. Results: All 21 women with a positive 50gGCT result showed normoglycemia on second-trimester 75gGTT. Thus, none of the 62 women developed GDM. Insulin resistance increased significantly in the 21 women with 75gGTT during the first and second trimesters, as indicated by increases in homeostasis model assessment for insulin resistance (HOMA-IR) and homeostasis model assessment for beta-cell function (HOMA-beta) with no significant changes in preload or afterload PG levels. Neither random PG levels (116 +/- 12 vs. 116 +/- 12 mg/dL, respectively) nor 75gGTT results (86 +/- 6 vs. 84 +/- 5 mg/dL for 0-minute [0-m] PG level, 130 +/- 28 vs. 131 +/- 25 mg/dL for 60-m PG, and 111 +/- 19 vs. 118 +/- 18 mg/dL for 120-m PG, respectively) during the first trimester differed significantly between the 41 and 21 women with negative and positive second-trimester 50gGCT results, respectively. Conclusion: Although insulin resistance increased in the second trimester, risk of developing GDM was < 1/62 among Japanese women in whom hyperglycemia was excluded with first-trimester GTT. Copyright (C) 2016, Taiwan Association of Obstetrics & Gynecology. Published by Elsevier Taiwan LLC.
• Seatbelt use and seat preference among pregnant women in Sapporo, Japan, in 2013.

  Morikawa M, Yamada T, Kato-Hirayama E, Nishikawa A, Watari M, Maeda N, Kogo H, Minakami H

  J Obstet Gynaecol Res 42 810 - 815 2016年 [査読有り]
  
• 検査と私 出生前遺伝学的検査

  山田 崇弘

  アニムス 21 48 - 51 2016年
• Changes in echocardiography and blood variables during and after development of Ballantyne syndrome

  Takeshi Umazume, Mamoru Morikawa, Takahiro Yamada, Hisanori Minakami

  BMJ Case Reports 2016 2016年 [査読有り][通常論文]
   

  We report a pregnant woman who was monitored by echocardiography and determination of blood variables, including components of the renin-angiotensin- aldosterone system (RAAS), cardiac biomarkers and soluble fms-like tyrosine kinase-1 (sFlt-1), during and after the development of Ballantyne syndrome. Generalised maternal oedema with dyspnoea following fetal and placental hydrops necessitated a caesarean section at 33 weeks of gestation. Changes in blood variables and simultaneous echocardiography changes indicated acutely enhanced RAAS and hyperdynamic left ventricular function in response to excessive volume overload (as evidenced by brain-type natriuretic peptide level of 523 pg/mL) in the absence of increased systemic vascular resistance. Elevated sFlt-1 (15 600 pg/mL) and human chorionic gonadotrophin (404 000 IU/L) levels were also noted. The increased plasma aldosterone concentration (2070 pg/mL) may have been responsible for the increase in circulating plasma volume, and the increased sFlt-1 level was responsible for generalised maternal oedema. It remains unclear which factor(s) triggered RAAS activation.
• Feasibility of nephrinuria as a screening tool for the risk of pre-eclampsia: prospective observational study

  Tianyue Zhai, Itsuko Furuta, Rina Akaishi, Kosuke Kawabata, Kentaro Chiba, Takeshi Umazume, Satoshi Ishikawa, Takahiro Yamada, Mamoru Morikawa, Hisanori Minakami

  BMJ OPEN 6 8 e011229 - e011229 2016年 [査読有り][通常論文]
   

  Objectives: To investigate the possibility of nephrinuria as a screening tool for the risk of pre-eclampsia (PE). Design: Prospective observational study. Setting: A single university hospital. Changes in urinary nephrin: creatinine ratio (NCR, ng/mg) and protein: creatinine ratio (PCR, mg/mg) in pregnancy were determined. Significant proteinuria in pregnancy (SPIP) was defined as PCR> 0.27. PE was diagnosed in women with both SPIP and hypertension. Participants: 89 pregnant women in whom neither hypertension nor SPIP was present at enrolment, providing 31, 125 and 93 random urine samples during first, second and third trimesters, respectively. Results: PE developed in 14 of the 89 women. NCR increased with increasing PCR in 14 women with PE (correlation coefficient, 0.862; p<0.0001). In contrast, NCR did not change significantly despite significant increases in PCR in 75 women with normotensive pregnancies defined as neither SPIP nor hypertension, indicating that there was little increase in nephrinuria over the physiological range of proteinuria in pregnancy. Relative risk of later development of PE among asymptomatic second and third trimester women with NCR (ng/mg) > 122 (95th centile value for 75 women with normotensive pregnancies) was 5.93 (95% CI 2.59 to 13.6; 60% (6/10) vs 10% (8/79)) and 13.5 (95% CI 3.31 to 55.0; 75% (6/8) vs 5.5% (2/36)), respectively, compared with women with NCR <= 122 at that time. Conclusions: Nephrinuria was unlikely to increase in normal pregnancy. A certain NCR cut-off may efficiently differentiate women at higher risk of PE.
• 日本遺伝カウンセリング学会, 出生前遺伝カウンセリング検討委員会．出生前遺伝カウンセリングに関する提言(解説)

  斎藤 加代子, 平原 史樹, 金井 誠, 浦野 真理, 川目 裕, 黒澤 健司, 左合 治彦, 鈴木 由美, 堤 正好, 三宅 秀彦, 武藤 香織, 山田 崇弘, 吉田 邦広, 四元 淳子, 涌井 敬子, 佐々木 愛子, 中込 さと子

  日本遺伝カウンセリング学会誌 37 58 - 61 2016年 [査読有り][通常論文]
  
• 胎児3DCTにより分節異常骨異形成症(dyssegmental dysplasia)の出生前診断が可能であった一例

  中澤 悠, 田村 みどり, 名古 崇史, 飯田 智博, 山田 崇弘, 室月 淳, 中川 侑子, 安藤 歩, 西島 千絵, 鈴木 季美枝, 水主川 純, 鈴木 直

  関東連合産科婦人科学会誌 53 647 - 653 2016年 [査読有り][通常論文]
  
• 正常・異常の見極めポイント 妊娠初期(妊娠11～13週)，【週数別 エコーのみかたコツとワザ いつ診る?どこ診る?どう伝える?】

  小島崇史, 山田崇弘

  ペリネイタルケア 35 1 40 - 47 メディカ出版 2016年 [査読無し][招待有り]
  
• いま、性分化とその異常を考える】 二卵性一絨毛膜双胎の問題(解説/特集)

  長 和俊, 山田 崇弘, 水上 尚典

  産婦人科の実際 64 1295 - 1299 2016年 [査読無し][招待有り]
  
• 【周産期医学必修知識第8版】 産科編 インフルエンザ(解説/特集)

  山田 崇弘, 水上 尚典

  周産期医学 46 142 - 144 2016年 [査読無し][招待有り]
  
• 【周産期医学必修知識第8版】 産科編 B群溶血性レンサ球菌感染症

  馬詰 武, 山田 崇弘, 水上 尚典

  周産期医学 46 155 - 157 2016年 [査読無し][招待有り]
  
• Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition).

  Daniel J Klionsky, Kotb Abdelmohsen, Akihisa Abe, Md Joynal Abedin, Hagai Abeliovich, Abraham Acevedo Arozena, Hiroaki Adachi, Christopher M Adams, Peter D Adams, Khosrow Adeli, Peter J Adhihetty, Sharon G Adler, Galila Agam, Rajesh Agarwal, Manish K Aghi, Maria Agnello, Patrizia Agostinis, Patricia V Aguilar, Julio Aguirre-Ghiso, Edoardo M Airoldi, Slimane Ait-Si-Ali, Takahiko Akematsu, Emmanuel T Akporiaye, Mohamed Al-Rubeai, Guillermo M Albaiceta, Chris Albanese, Diego Albani, Matthew L Albert, Jesus Aldudo, Hana Algül, Mehrdad Alirezaei, Iraide Alloza, Alexandru Almasan, Maylin Almonte-Beceril, Emad S Alnemri, Covadonga Alonso, Nihal Altan-Bonnet, Dario C Altieri, Silvia Alvarez, Lydia Alvarez-Erviti, Sandro Alves, Giuseppina Amadoro, Atsuo Amano, Consuelo Amantini, Santiago Ambrosio, Ivano Amelio, Amal O Amer, Mohamed Amessou, Angelika Amon, Zhenyi An, Frank A Anania, Stig U Andersen, Usha P Andley, Catherine K Andreadi, Nathalie Andrieu-Abadie, Alberto Anel, David K Ann, Shailendra Anoopkumar-Dukie, Manuela Antonioli, Hiroshi Aoki, Nadezda Apostolova, Saveria Aquila, Katia Aquilano, Koichi Araki, Eli Arama, Agustin Aranda, Jun Araya, Alexandre Arcaro, Esperanza Arias, Hirokazu Arimoto, Aileen R Ariosa, Jane L Armstrong, Thierry Arnould, Ivica Arsov, Katsuhiko Asanuma, Valerie Askanas, Eric Asselin, Ryuichiro Atarashi, Sally S Atherton, Julie D Atkin, Laura D Attardi, Patrick Auberger, Georg Auburger, Laure Aurelian, Riccardo Autelli, Laura Avagliano, Maria Laura Avantaggiati, Limor Avrahami, Suresh Awale, Neelam Azad, Tiziana Bachetti, Jonathan M Backer, Dong-Hun Bae, Jae-Sung Bae, Ok-Nam Bae, Soo Han Bae, Eric H Baehrecke, Seung-Hoon Baek, Stephen Baghdiguian, Agnieszka Bagniewska-Zadworna, Hua Bai, Jie Bai, Xue-Yuan Bai, Yannick Bailly, Kithiganahalli Narayanaswamy Balaji, Walter Balduini, Andrea Ballabio, Rena Balzan, Rajkumar Banerjee, Gábor Bánhegyi, Haijun Bao, Benoit Barbeau, Maria D Barrachina, Esther Barreiro, Bonnie Bartel, Alberto Bartolomé, Diane C Bassham, Maria Teresa Bassi, Robert C Bast Jr, Alakananda Basu, Maria Teresa Batista, Henri Batoko, Maurizio Battino, Kyle Bauckman, Bradley L Baumgarner, K Ulrich Bayer, Rupert Beale, Jean-François Beaulieu, George R Beck Jr, Christoph Becker, J David Beckham, Pierre-André Bédard, Patrick J Bednarski, Thomas J Begley, Christian Behl, Christian Behrends, Georg Mn Behrens, Kevin E Behrns, Eloy Bejarano, Amine Belaid, Francesca Belleudi, Giovanni Bénard, Guy Berchem, Daniele Bergamaschi, Matteo Bergami, Ben Berkhout, Laura Berliocchi, Amélie Bernard, Monique Bernard, Francesca Bernassola, Anne Bertolotti, Amanda S Bess, Sébastien Besteiro, Saverio Bettuzzi, Savita Bhalla, Shalmoli Bhattacharyya, Sujit K Bhutia, Caroline Biagosch, Michele Wolfe Bianchi, Martine Biard-Piechaczyk, Viktor Billes, Claudia Bincoletto, Baris Bingol, Sara W Bird, Marc Bitoun, Ivana Bjedov, Craig Blackstone, Lionel Blanc, Guillermo A Blanco, Heidi Kiil Blomhoff, Emilio Boada-Romero, Stefan Böckler, Marianne Boes, Kathleen Boesze-Battaglia, Lawrence H Boise, Alessandra Bolino, Andrea Boman, Paolo Bonaldo, Matteo Bordi, Jürgen Bosch, Luis M Botana, Joelle Botti, German Bou, Marina Bouché, Marion Bouchecareilh, Marie-Josée Boucher, Michael E Boulton, Sebastien G Bouret, Patricia Boya, Michaël Boyer-Guittaut, Peter V Bozhkov, Nathan Brady, Vania Mm Braga, Claudio Brancolini, Gerhard H Braus, José M Bravo-San Pedro, Lisa A Brennan, Emery H Bresnick, Patrick Brest, Dave Bridges, Marie-Agnès Bringer, Marisa Brini, Glauber C Brito, Bertha Brodin, Paul S Brookes, Eric J Brown, Karen Brown, Hal E Broxmeyer, Alain Bruhat, Patricia Chakur Brum, John H Brumell, Nicola Brunetti-Pierri, Robert J Bryson-Richardson, Shilpa Buch, Alastair M Buchan, Hikmet Budak, Dmitry V Bulavin, Scott J Bultman, Geert Bultynck, Vladimir Bumbasirevic, Yan Burelle, Robert E Burke, Margit Burmeister, Peter Bütikofer, Laura Caberlotto, Ken Cadwell, Monika Cahova, Dongsheng Cai, Jingjing Cai, Qian Cai, Sara Calatayud, Nadine Camougrand, Michelangelo Campanella, Grant R Campbell, Matthew Campbell, Silvia Campello, Robin Candau, Isabella Caniggia, Lavinia Cantoni, Lizhi Cao, Allan B Caplan, Michele Caraglia, Claudio Cardinali, Sandra Morais Cardoso, Jennifer S Carew, Laura A Carleton, Cathleen R Carlin, Silvia Carloni, Sven R Carlsson, Didac Carmona-Gutierrez, Leticia Am Carneiro, Oliana Carnevali, Serena Carra, Alice Carrier, Bernadette Carroll, Caty Casas, Josefina Casas, Giuliana Cassinelli, Perrine Castets, Susana Castro-Obregon, Gabriella Cavallini, Isabella Ceccherini, Francesco Cecconi, Arthur I Cederbaum, Valentín Ceña, Simone Cenci, Claudia Cerella, Davide Cervia, Silvia Cetrullo, Hassan Chaachouay, Han-Jung Chae, Andrei S Chagin, Chee-Yin Chai, Gopal Chakrabarti, Georgios Chamilos, Edmond Yw Chan, Matthew Tv Chan, Dhyan Chandra, Pallavi Chandra, Chih-Peng Chang, Raymond Chuen-Chung Chang, Ta Yuan Chang, John C Chatham, Saurabh Chatterjee, Santosh Chauhan, Yongsheng Che, Michael E Cheetham, Rajkumar Cheluvappa, Chun-Jung Chen, Gang Chen, Guang-Chao Chen, Guoqiang Chen, Hongzhuan Chen, Jeff W Chen, Jian-Kang Chen, Min Chen, Mingzhou Chen, Peiwen Chen, Qi Chen, Quan Chen, Shang-Der Chen, Si Chen, Steve S-L Chen, Wei Chen, Wei-Jung Chen, Wen Qiang Chen, Wenli Chen, Xiangmei Chen, Yau-Hung Chen, Ye-Guang Chen, Yin Chen, Yingyu Chen, Yongshun Chen, Yu-Jen Chen, Yue-Qin Chen, Yujie Chen, Zhen Chen, Zhong Chen, Alan Cheng, Christopher Hk Cheng, Hua Cheng, Heesun Cheong, Sara Cherry, Jason Chesney, Chun Hei Antonio Cheung, Eric Chevet, Hsiang Cheng Chi, Sung-Gil Chi, Fulvio Chiacchiera, Hui-Ling Chiang, Roberto Chiarelli, Mario Chiariello, Marcello Chieppa, Lih-Shen Chin, Mario Chiong, Gigi Nc Chiu, Dong-Hyung Cho, Ssang-Goo Cho, William C Cho, Yong-Yeon Cho, Young-Seok Cho, Augustine Mk Choi, Eui-Ju Choi, Eun-Kyoung Choi, Jayoung Choi, Mary E Choi, Seung-Il Choi, Tsui-Fen Chou, Salem Chouaib, Divaker Choubey, Vinay Choubey, Kuan-Chih Chow, Kamal Chowdhury, Charleen T Chu, Tsung-Hsien Chuang, Taehoon Chun, Hyewon Chung, Taijoon Chung, Yuen-Li Chung, Yong-Joon Chwae, Valentina Cianfanelli, Roberto Ciarcia, Iwona A Ciechomska, Maria Rosa Ciriolo, Mara Cirone, Sofie Claerhout, Michael J Clague, Joan Clària, Peter Gh Clarke, Robert Clarke, Emilio Clementi, Cédric Cleyrat, Miriam Cnop, Eliana M Coccia, Tiziana Cocco, Patrice Codogno, Jörn Coers, Ezra Ew Cohen, David Colecchia, Luisa Coletto, Núria S Coll, Emma Colucci-Guyon, Sergio Comincini, Maria Condello, Katherine L Cook, Graham H Coombs, Cynthia D Cooper, J Mark Cooper, Isabelle Coppens, Maria Tiziana Corasaniti, Marco Corazzari, Ramon Corbalan, Elisabeth Corcelle-Termeau, Mario D Cordero, Cristina Corral-Ramos, Olga Corti, Andrea Cossarizza, Paola Costelli, Safia Costes, Susan L Cotman, Ana Coto-Montes, Sandra Cottet, Eduardo Couve, Lori R Covey, L Ashley Cowart, Jeffery S Cox, Fraser P Coxon, Carolyn B Coyne, Mark S Cragg, Rolf J Craven, Tiziana Crepaldi, Jose L Crespo, Alfredo Criollo, Valeria Crippa, Maria Teresa Cruz, Ana Maria Cuervo, Jose M Cuezva, Taixing Cui, Pedro R Cutillas, Mark J Czaja, Maria F Czyzyk-Krzeska, Ruben K Dagda, Uta Dahmen, Chunsun Dai, Wenjie Dai, Yun Dai, Kevin N Dalby, Luisa Dalla Valle, Guillaume Dalmasso, Marcello D'Amelio, Markus Damme, Arlette Darfeuille-Michaud, Catherine Dargemont, Victor M Darley-Usmar, Srinivasan Dasarathy, Biplab Dasgupta, Srikanta Dash, Crispin R Dass, Hazel Marie Davey, Lester M Davids, David Dávila, Roger J Davis, Ted M Dawson, Valina L Dawson, Paula Daza, Jackie de Belleroche, Paul de Figueiredo, Regina Celia Bressan Queiroz de Figueiredo, José de la Fuente, Luisa De Martino, Antonella De Matteis, Guido Ry De Meyer, Angelo De Milito, Mauro De Santi, Wanderley de Souza, Vincenzo De Tata, Daniela De Zio, Jayanta Debnath, Reinhard Dechant, Jean-Paul Decuypere, Shane Deegan, Benjamin Dehay, Barbara Del Bello, Dominic P Del Re, Régis Delage-Mourroux, Lea Md Delbridge, Louise Deldicque, Elizabeth Delorme-Axford, Yizhen Deng, Joern Dengjel, Melanie Denizot, Paul Dent, Channing J Der, Vojo Deretic, Benoît Derrien, Eric Deutsch, Timothy P Devarenne, Rodney J Devenish, Sabrina Di Bartolomeo, Nicola Di Daniele, Fabio Di Domenico, Alessia Di Nardo, Simone Di Paola, Antonio Di Pietro, Livia Di Renzo, Aaron DiAntonio, Guillermo Díaz-Araya, Ines Díaz-Laviada, Maria T Diaz-Meco, Javier Diaz-Nido, Chad A Dickey, Robert C Dickson, Marc Diederich, Paul Digard, Ivan Dikic, Savithrama P Dinesh-Kumar, Chan Ding, Wen-Xing Ding, Zufeng Ding, Luciana Dini, Jörg Hw Distler, Abhinav Diwan, Mojgan Djavaheri-Mergny, Kostyantyn Dmytruk, Renwick Cj Dobson, Volker Doetsch, Karol Dokladny, Svetlana Dokudovskaya, Massimo Donadelli, X Charlie Dong, Xiaonan Dong, Zheng Dong, Terrence M Donohue Jr, Kelly S Doran, Gabriella D'Orazi, Gerald W Dorn 2nd, Victor Dosenko, Sami Dridi, Liat Drucker, Jie Du, Li-Lin Du, Lihuan Du, André du Toit, Priyamvada Dua, Lei Duan, Pu Duann, Vikash Kumar Dubey, Michael R Duchen, Michel A Duchosal, Helene Duez, Isabelle Dugail, Verónica I Dumit, Mara C Duncan, Elaine A Dunlop, William A Dunn Jr, Nicolas Dupont, Luc Dupuis, Raúl V Durán, Thomas M Durcan, Stéphane Duvezin-Caubet, Umamaheswar Duvvuri, Vinay Eapen, Darius Ebrahimi-Fakhari, Arnaud Echard, Leopold Eckhart, Charles L Edelstein, Aimee L Edinger, Ludwig Eichinger, Tobias Eisenberg, Avital Eisenberg-Lerner, N Tony Eissa, Wafik S El-Deiry, Victoria El-Khoury, Zvulun Elazar, Hagit Eldar-Finkelman, Chris Jh Elliott, Enzo Emanuele, Urban Emmenegger, Nikolai Engedal, Anna-Mart Engelbrecht, Simone Engelender, Jorrit M Enserink, Ralf Erdmann, Jekaterina Erenpreisa, Rajaraman Eri, Jason L Eriksen, Andreja Erman, Ricardo Escalante, Eeva-Liisa Eskelinen, Lucile Espert, Lorena Esteban-Martínez, Thomas J Evans, Mario Fabri, Gemma Fabrias, Cinzia Fabrizi, Antonio Facchiano, Nils J Færgeman, Alberto Faggioni, W Douglas Fairlie, Chunhai Fan, Daping Fan, Jie Fan, Shengyun Fang, Manolis Fanto, Alessandro Fanzani, Thomas Farkas, Mathias Faure, Francois B Favier, Howard Fearnhead, Massimo Federici, Erkang Fei, Tania C Felizardo, Hua Feng, Yibin Feng, Yuchen Feng, Thomas A Ferguson, Álvaro F Fernández, Maite G Fernandez-Barrena, Jose C Fernandez-Checa, Arsenio Fernández-López, Martin E Fernandez-Zapico, Olivier Feron, Elisabetta Ferraro, Carmen Veríssima Ferreira-Halder, Laszlo Fesus, Ralph Feuer, Fabienne C Fiesel, Eduardo C Filippi-Chiela, Giuseppe Filomeni, Gian Maria Fimia, John H Fingert, Steven Finkbeiner, Toren Finkel, Filomena Fiorito, Paul B Fisher, Marc Flajolet, Flavio Flamigni, Oliver Florey, Salvatore Florio, R Andres Floto, Marco Folini, Carlo Follo, Edward A Fon, Francesco Fornai, Franco Fortunato, Alessandro Fraldi, Rodrigo Franco, Arnaud Francois, Aurélie François, Lisa B Frankel, Iain Dc Fraser, Norbert Frey, Damien G Freyssenet, Christian Frezza, Scott L Friedman, Daniel E Frigo, Dongxu Fu, José M Fuentes, Juan Fueyo, Yoshio Fujitani, Yuuki Fujiwara, Mikihiro Fujiya, Mitsunori Fukuda, Simone Fulda, Carmela Fusco, Bozena Gabryel, Matthias Gaestel, Philippe Gailly, Malgorzata Gajewska, Sehamuddin Galadari, Gad Galili, Inmaculada Galindo, Maria F Galindo, Giovanna Galliciotti, Lorenzo Galluzzi, Luca Galluzzi, Vincent Galy, Noor Gammoh, Sam Gandy, Anand K Ganesan, Swamynathan Ganesan, Ian G Ganley, Monique Gannagé, Fen-Biao Gao, Feng Gao, Jian-Xin Gao, Lorena García Nannig, Eleonora García Véscovi, Marina Garcia-Macía, Carmen Garcia-Ruiz, Abhishek D Garg, Pramod Kumar Garg, Ricardo Gargini, Nils Christian Gassen, Damián Gatica, Evelina Gatti, Julie Gavard, Evripidis Gavathiotis, Liang Ge, Pengfei Ge, Shengfang Ge, Po-Wu Gean, Vania Gelmetti, Armando A Genazzani, Jiefei Geng, Pascal Genschik, Lisa Gerner, Jason E Gestwicki, David A Gewirtz, Saeid Ghavami, Eric Ghigo, Debabrata Ghosh, Anna Maria Giammarioli, Francesca Giampieri, Claudia Giampietri, Alexandra Giatromanolaki, Derrick J Gibbings, Lara Gibellini, Spencer B Gibson, Vanessa Ginet, Antonio Giordano, Flaviano Giorgini, Elisa Giovannetti, Stephen E Girardin, Suzana Gispert, Sandy Giuliano, Candece L Gladson, Alvaro Glavic, Martin Gleave, Nelly Godefroy, Robert M Gogal Jr, Kuppan Gokulan, Gustavo H Goldman, Delia Goletti, Michael S Goligorsky, Aldrin V Gomes, Ligia C Gomes, Hernando Gomez, Candelaria Gomez-Manzano, Rubén Gómez-Sánchez, Dawit Ap Gonçalves, Ebru Goncu, Qingqiu Gong, Céline Gongora, Carlos B Gonzalez, Pedro Gonzalez-Alegre, Pilar Gonzalez-Cabo, Rosa Ana González-Polo, Ing Swie Goping, Carlos Gorbea, Nikolai V Gorbunov, Daphne R Goring, Adrienne M Gorman, Sharon M Gorski, Sandro Goruppi, Shino Goto-Yamada, Cecilia Gotor, Roberta A Gottlieb, Illana Gozes, Devrim Gozuacik, Yacine Graba, Martin Graef, Giovanna E Granato, Gary Dean Grant, Steven Grant, Giovanni Luca Gravina, Douglas R Green, Alexander Greenhough, Michael T Greenwood, Benedetto Grimaldi, Frédéric Gros, Charles Grose, Jean-Francois Groulx, Florian Gruber, Paolo Grumati, Tilman Grune, Jun-Lin Guan, Kun-Liang Guan, Barbara Guerra, Carlos Guillen, Kailash Gulshan, Jan Gunst, Chuanyong Guo, Lei Guo, Ming Guo, Wenjie Guo, Xu-Guang Guo, Andrea A Gust, Åsa B Gustafsson, Elaine Gutierrez, Maximiliano G Gutierrez, Ho-Shin Gwak, Albert Haas, James E Haber, Shinji Hadano, Monica Hagedorn, David R Hahn, Andrew J Halayko, Anne Hamacher-Brady, Kozo Hamada, Ahmed Hamai, Andrea Hamann, Maho Hamasaki, Isabelle Hamer, Qutayba Hamid, Ester M Hammond, Feng Han, Weidong Han, James T Handa, John A Hanover, Malene Hansen, Masaru Harada, Ljubica Harhaji-Trajkovic, J Wade Harper, Abdel Halim Harrath, Adrian L Harris, James Harris, Udo Hasler, Peter Hasselblatt, Kazuhisa Hasui, Robert G Hawley, Teresa S Hawley, Congcong He, Cynthia Y He, Fengtian He, Gu He, Rong-Rong He, Xian-Hui He, You-Wen He, Yu-Ying He, Joan K Heath, Marie-Josée Hébert, Robert A Heinzen, Gudmundur Vignir Helgason, Michael Hensel, Elizabeth P Henske, Chengtao Her, Paul K Herman, Agustín Hernández, Carlos Hernandez, Sonia Hernández-Tiedra, Claudio Hetz, P Robin Hiesinger, Katsumi Higaki, Sabine Hilfiker, Bradford G Hill, Joseph A Hill, William D Hill, Keisuke Hino, Daniel Hofius, Paul Hofman, Günter U Höglinger, Jörg Höhfeld, Marina K Holz, Yonggeun Hong, David A Hood, Jeroen Jm Hoozemans, Thorsten Hoppe, Chin Hsu, Chin-Yuan Hsu, Li-Chung Hsu, Dong Hu, Guochang Hu, Hong-Ming Hu, Hongbo Hu, Ming Chang Hu, Yu-Chen Hu, Zhuo-Wei Hu, Fang Hua, Ya Hua, Canhua Huang, Huey-Lan Huang, Kuo-How Huang, Kuo-Yang Huang, Shile Huang, Shiqian Huang, Wei-Pang Huang, Yi-Ran Huang, Yong Huang, Yunfei Huang, Tobias B Huber, Patricia Huebbe, Won-Ki Huh, Juha J Hulmi, Gang Min Hur, James H Hurley, Zvenyslava Husak, Sabah Na Hussain, Salik Hussain, Jung Jin Hwang, Seungmin Hwang, Thomas Is Hwang, Atsuhiro Ichihara, Yuzuru Imai, Carol Imbriano, Megumi Inomata, Takeshi Into, Valentina Iovane, Juan L Iovanna, Renato V Iozzo, Nancy Y Ip, Javier E Irazoqui, Pablo Iribarren, Yoshitaka Isaka, Aleksandra J Isakovic, Harry Ischiropoulos, Jeffrey S Isenberg, Mohammad Ishaq, Hiroyuki Ishida, Isao Ishii, Jane E Ishmael, Ciro Isidoro, Ken-Ichi Isobe, Erika Isono, Shohreh Issazadeh-Navikas, Koji Itahana, Eisuke Itakura, Andrei I Ivanov, Anand Krishnan V Iyer, José M Izquierdo, Yotaro Izumi, Valentina Izzo, Marja Jäättelä, Nadia Jaber, Daniel John Jackson, William T Jackson, Tony George Jacob, Thomas S Jacques, Chinnaswamy Jagannath, Ashish Jain, Nihar Ranjan Jana, Byoung Kuk Jang, Alkesh Jani, Bassam Janji, Paulo Roberto Jannig, Patric J Jansson, Steve Jean, Marina Jendrach, Ju-Hong Jeon, Niels Jessen, Eui-Bae Jeung, Kailiang Jia, Lijun Jia, Hong Jiang, Hongchi Jiang, Liwen Jiang, Teng Jiang, Xiaoyan Jiang, Xuejun Jiang, Xuejun Jiang, Ying Jiang, Yongjun Jiang, Alberto Jiménez, Cheng Jin, Hongchuan Jin, Lei Jin, Meiyan Jin, Shengkan Jin, Umesh Kumar Jinwal, Eun-Kyeong Jo, Terje Johansen, Daniel E Johnson, Gail Vw Johnson, James D Johnson, Eric Jonasch, Chris Jones, Leo Ab Joosten, Joaquin Jordan, Anna-Maria Joseph, Bertrand Joseph, Annie M Joubert, Dianwen Ju, Jingfang Ju, Hsueh-Fen Juan, Katrin Juenemann, Gábor Juhász, Hye Seung Jung, Jae U Jung, Yong-Keun Jung, Heinz Jungbluth, Matthew J Justice, Barry Jutten, Nadeem O Kaakoush, Kai Kaarniranta, Allen Kaasik, Tomohiro Kabuta, Bertrand Kaeffer, Katarina Kågedal, Alon Kahana, Shingo Kajimura, Or Kakhlon, Manjula Kalia, Dhan V Kalvakolanu, Yoshiaki Kamada, Konstantinos Kambas, Vitaliy O Kaminskyy, Harm H Kampinga, Mustapha Kandouz, Chanhee Kang, Rui Kang, Tae-Cheon Kang, Tomotake Kanki, Thirumala-Devi Kanneganti, Haruo Kanno, Anumantha G Kanthasamy, Marc Kantorow, Maria Kaparakis-Liaskos, Orsolya Kapuy, Vassiliki Karantza, Md Razaul Karim, Parimal Karmakar, Arthur Kaser, Susmita Kaushik, Thomas Kawula, A Murat Kaynar, Po-Yuan Ke, Zun-Ji Ke, John H Kehrl, Kate E Keller, Jongsook Kim Kemper, Anne K Kenworthy, Oliver Kepp, Andreas Kern, Santosh Kesari, David Kessel, Robin Ketteler, Isis do Carmo Kettelhut, Bilon Khambu, Muzamil Majid Khan, Vinoth Km Khandelwal, Sangeeta Khare, Juliann G Kiang, Amy A Kiger, Akio Kihara, Arianna L Kim, Cheol Hyeon Kim, Deok Ryong Kim, Do-Hyung Kim, Eung Kweon Kim, Hye Young Kim, Hyung-Ryong Kim, Jae-Sung Kim, Jeong Hun Kim, Jin Cheon Kim, Jin Hyoung Kim, Kwang Woon Kim, Michael D Kim, Moon-Moo Kim, Peter K Kim, Seong Who Kim, Soo-Youl Kim, Yong-Sun Kim, Yonghyun Kim, Adi Kimchi, Alec C Kimmelman, Tomonori Kimura, Jason S King, Karla Kirkegaard, Vladimir Kirkin, Lorrie A Kirshenbaum, Shuji Kishi, Yasuo Kitajima, Katsuhiko Kitamoto, Yasushi Kitaoka, Kaio Kitazato, Rudolf A Kley, Walter T Klimecki, Michael Klinkenberg, Jochen Klucken, Helene Knævelsrud, Erwin Knecht, Laura Knuppertz, Jiunn-Liang Ko, Satoru Kobayashi, Jan C Koch, Christelle Koechlin-Ramonatxo, Ulrich Koenig, Young Ho Koh, Katja Köhler, Sepp D Kohlwein, Masato Koike, Masaaki Komatsu, Eiki Kominami, Dexin Kong, Hee Jeong Kong, Eumorphia G Konstantakou, Benjamin T Kopp, Tamas Korcsmaros, Laura Korhonen, Viktor I Korolchuk, Nadya V Koshkina, Yanjun Kou, Michael I Koukourakis, Constantinos Koumenis, Attila L Kovács, Tibor Kovács, Werner J Kovacs, Daisuke Koya, Claudine Kraft, Dimitri Krainc, Helmut Kramer, Tamara Kravic-Stevovic, Wilhelm Krek, Carole Kretz-Remy, Roswitha Krick, Malathi Krishnamurthy, Janos Kriston-Vizi, Guido Kroemer, Michael C Kruer, Rejko Kruger, Nicholas T Ktistakis, Kazuyuki Kuchitsu, Christian Kuhn, Addanki Pratap Kumar, Anuj Kumar, Ashok Kumar, Deepak Kumar, Dhiraj Kumar, Rakesh Kumar, Sharad Kumar, Mondira Kundu, Hsing-Jien Kung, Atsushi Kuno, Sheng-Han Kuo, Jeff Kuret, Tino Kurz, Terry Kwok, Taeg Kyu Kwon, Yong Tae Kwon, Irene Kyrmizi, Albert R La Spada, Frank Lafont, Tim Lahm, Aparna Lakkaraju, Truong Lam, Trond Lamark, Steve Lancel, Terry H Landowski, Darius J R Lane, Jon D Lane, Cinzia Lanzi, Pierre Lapaquette, Louis R Lapierre, Jocelyn Laporte, Johanna Laukkarinen, Gordon W Laurie, Sergio Lavandero, Lena Lavie, Matthew J LaVoie, Betty Yuen Kwan Law, Helen Ka-Wai Law, Kelsey B Law, Robert Layfield, Pedro A Lazo, Laurent Le Cam, Karine G Le Roch, Hervé Le Stunff, Vijittra Leardkamolkarn, Marc Lecuit, Byung-Hoon Lee, Che-Hsin Lee, Erinna F Lee, Gyun Min Lee, He-Jin Lee, Hsinyu Lee, Jae Keun Lee, Jongdae Lee, Ju-Hyun Lee, Jun Hee Lee, Michael Lee, Myung-Shik Lee, Patty J Lee, Sam W Lee, Seung-Jae Lee, Shiow-Ju Lee, Stella Y Lee, Sug Hyung Lee, Sung Sik Lee, Sung-Joon Lee, Sunhee Lee, Ying-Ray Lee, Yong J Lee, Young H Lee, Christiaan Leeuwenburgh, Sylvain Lefort, Renaud Legouis, Jinzhi Lei, Qun-Ying Lei, David A Leib, Gil Leibowitz, Istvan Lekli, Stéphane D Lemaire, John J Lemasters, Marius K Lemberg, Antoinette Lemoine, Shuilong Leng, Guido Lenz, Paola Lenzi, Lilach O Lerman, Daniele Lettieri Barbato, Julia I-Ju Leu, Hing Y Leung, Beth Levine, Patrick A Lewis, Frank Lezoualc'h, Chi Li, Faqiang Li, Feng-Jun Li, Jun Li, Ke Li, Lian Li, Min Li, Min Li, Qiang Li, Rui Li, Sheng Li, Wei Li, Wei Li, Xiaotao Li, Yumin Li, Jiqin Lian, Chengyu Liang, Qiangrong Liang, Yulin Liao, Joana Liberal, Pawel P Liberski, Pearl Lie, Andrew P Lieberman, Hyunjung Jade Lim, Kah-Leong Lim, Kyu Lim, Raquel T Lima, Chang-Shen Lin, Chiou-Feng Lin, Fang Lin, Fangming Lin, Fu-Cheng Lin, Kui Lin, Kwang-Huei Lin, Pei-Hui Lin, Tianwei Lin, Wan-Wan Lin, Yee-Shin Lin, Yong Lin, Rafael Linden, Dan Lindholm, Lisa M Lindqvist, Paul Lingor, Andreas Linkermann, Lance A Liotta, Marta M Lipinski, Vitor A Lira, Michael P Lisanti, Paloma B Liton, Bo Liu, Chong Liu, Chun-Feng Liu, Fei Liu, Hung-Jen Liu, Jianxun Liu, Jing-Jing Liu, Jing-Lan Liu, Ke Liu, Leyuan Liu, Liang Liu, Quentin Liu, Rong-Yu Liu, Shiming Liu, Shuwen Liu, Wei Liu, Xian-De Liu, Xiangguo Liu, Xiao-Hong Liu, Xinfeng Liu, Xu Liu, Xueqin Liu, Yang Liu, Yule Liu, Zexian Liu, Zhe Liu, Juan P Liuzzi, Gérard Lizard, Mila Ljujic, Irfan J Lodhi, Susan E Logue, Bal L Lokeshwar, Yun Chau Long, Sagar Lonial, Benjamin Loos, Carlos López-Otín, Cristina López-Vicario, Mar Lorente, Philip L Lorenzi, Péter Lõrincz, Marek Los, Michael T Lotze, Penny E Lovat, Binfeng Lu, Bo Lu, Jiahong Lu, Qing Lu, She-Min Lu, Shuyan Lu, Yingying Lu, Frédéric Luciano, Shirley Luckhart, John Milton Lucocq, Paula Ludovico, Aurelia Lugea, Nicholas W Lukacs, Julian J Lum, Anders H Lund, Honglin Luo, Jia Luo, Shouqing Luo, Claudio Luparello, Timothy Lyons, Jianjie Ma, Yi Ma, Yong Ma, Zhenyi Ma, Juliano Machado, Glaucia M Machado-Santelli, Fernando Macian, Gustavo C MacIntosh, Jeffrey P MacKeigan, Kay F Macleod, John D MacMicking, Lee Ann MacMillan-Crow, Frank Madeo, Muniswamy Madesh, Julio Madrigal-Matute, Akiko Maeda, Tatsuya Maeda, Gustavo Maegawa, Emilia Maellaro, Hannelore Maes, Marta Magariños, Kenneth Maiese, Tapas K Maiti, Luigi Maiuri, Maria Chiara Maiuri, Carl G Maki, Roland Malli, Walter Malorni, Alina Maloyan, Fathia Mami-Chouaib, Na Man, Joseph D Mancias, Eva-Maria Mandelkow, Michael A Mandell, Angelo A Manfredi, Serge N Manié, Claudia Manzoni, Kai Mao, Zixu Mao, Zong-Wan Mao, Philippe Marambaud, Anna Maria Marconi, Zvonimir Marelja, Gabriella Marfe, Marta Margeta, Eva Margittai, Muriel Mari, Francesca V Mariani, Concepcio Marin, Sara Marinelli, Guillermo Mariño, Ivanka Markovic, Rebecca Marquez, Alberto M Martelli, Sascha Martens, Katie R Martin, Seamus J Martin, Shaun Martin, Miguel A Martin-Acebes, Paloma Martín-Sanz, Camille Martinand-Mari, Wim Martinet, Jennifer Martinez, Nuria Martinez-Lopez, Ubaldo Martinez-Outschoorn, Moisés Martínez-Velázquez, Marta Martinez-Vicente, Waleska Kerllen Martins, Hirosato Mashima, James A Mastrianni, Giuseppe Matarese, Paola Matarrese, Roberto Mateo, Satoaki Matoba, Naomichi Matsumoto, Takehiko Matsushita, Akira Matsuura, Takeshi Matsuzawa, Mark P Mattson, Soledad Matus, Norma Maugeri, Caroline Mauvezin, Andreas Mayer, Dusica Maysinger, Guillermo D Mazzolini, Mary Kate McBrayer, Kimberly McCall, Craig McCormick, Gerald M McInerney, Skye C McIver, Sharon McKenna, John J McMahon, Iain A McNeish, Fatima Mechta-Grigoriou, Jan Paul Medema, Diego L Medina, Klara Megyeri, Maryam Mehrpour, Jawahar L Mehta, Yide Mei, Ute-Christiane Meier, Alfred J Meijer, Alicia Meléndez, Gerry Melino, Sonia Melino, Edesio Jose Tenorio de Melo, Maria A Mena, Marc D Meneghini, Javier A Menendez, Regina Menezes, Liesu Meng, Ling-Hua Meng, Songshu Meng, Rossella Menghini, A Sue Menko, Rubem Fs Menna-Barreto, Manoj B Menon, Marco A Meraz-Ríos, Giuseppe Merla, Luciano Merlini, Angelica M Merlot, Andreas Meryk, Stefania Meschini, Joel N Meyer, Man-Tian Mi, Chao-Yu Miao, Lucia Micale, Simon Michaeli, Carine Michiels, Anna Rita Migliaccio, Anastasia Susie Mihailidou, Dalibor Mijaljica, Katsuhiko Mikoshiba, Enrico Milan, Leonor Miller-Fleming, Gordon B Mills, Ian G Mills, Georgia Minakaki, Berge A Minassian, Xiu-Fen Ming, Farida Minibayeva, Elena A Minina, Justine D Mintern, Saverio Minucci, Antonio Miranda-Vizuete, Claire H Mitchell, Shigeki Miyamoto, Keisuke Miyazawa, Noboru Mizushima, Katarzyna Mnich, Baharia Mograbi, Simin Mohseni, Luis Ferreira Moita, Marco Molinari, Maurizio Molinari, Andreas Buch Møller, Bertrand Mollereau, Faustino Mollinedo, Marco Mongillo, Martha M Monick, Serena Montagnaro, Craig Montell, Darren J Moore, Michael N Moore, Rodrigo Mora-Rodriguez, Paula I Moreira, Etienne Morel, Maria Beatrice Morelli, Sandra Moreno, Michael J Morgan, Arnaud Moris, Yuji Moriyasu, Janna L Morrison, Lynda A Morrison, Eugenia Morselli, Jorge Moscat, Pope L Moseley, Serge Mostowy, Elisa Motori, Denis Mottet, Jeremy C Mottram, Charbel E-H Moussa, Vassiliki E Mpakou, Hasan Mukhtar, Jean M Mulcahy Levy, Sylviane Muller, Raquel Muñoz-Moreno, Cristina Muñoz-Pinedo, Christian Münz, Maureen E Murphy, James T Murray, Aditya Murthy, Indira U Mysorekar, Ivan R Nabi, Massimo Nabissi, Gustavo A Nader, Yukitoshi Nagahara, Yoshitaka Nagai, Kazuhiro Nagata, Anika Nagelkerke, Péter Nagy, Samisubbu R Naidu, Sreejayan Nair, Hiroyasu Nakano, Hitoshi Nakatogawa, Meera Nanjundan, Gennaro Napolitano, Naweed I Naqvi, Roberta Nardacci, Derek P Narendra, Masashi Narita, Anna Chiara Nascimbeni, Ramesh Natarajan, Luiz C Navegantes, Steffan T Nawrocki, Taras Y Nazarko, Volodymyr Y Nazarko, Thomas Neill, Luca M Neri, Mihai G Netea, Romana T Netea-Maier, Bruno M Neves, Paul A Ney, Ioannis P Nezis, Hang Tt Nguyen, Huu Phuc Nguyen, Anne-Sophie Nicot, Hilde Nilsen, Per Nilsson, Mikio Nishimura, Ichizo Nishino, Mireia Niso-Santano, Hua Niu, Ralph A Nixon, Vincent Co Njar, Takeshi Noda, Angelika A Noegel, Elsie Magdalena Nolte, Erik Norberg, Koenraad K Norga, Sakineh Kazemi Noureini, Shoji Notomi, Lucia Notterpek, Karin Nowikovsky, Nobuyuki Nukina, Thorsten Nürnberger, Valerie B O'Donnell, Tracey O'Donovan, Peter J O'Dwyer, Ina Oehme, Clara L Oeste, Michinaga Ogawa, Besim Ogretmen, Yuji Ogura, Young J Oh, Masaki Ohmuraya, Takayuki Ohshima, Rani Ojha, Koji Okamoto, Toshiro Okazaki, F Javier Oliver, Karin Ollinger, Stefan Olsson, Daniel P Orban, Paulina Ordonez, Idil Orhon, Laszlo Orosz, Eyleen J O'Rourke, Helena Orozco, Angel L Ortega, Elena Ortona, Laura D Osellame, Junko Oshima, Shigeru Oshima, Heinz D Osiewacz, Takanobu Otomo, Kinya Otsu, Jing-Hsiung James Ou, Tiago F Outeiro, Dong-Yun Ouyang, Hongjiao Ouyang, Michael Overholtzer, Michelle A Ozbun, P Hande Ozdinler, Bulent Ozpolat, Consiglia Pacelli, Paolo Paganetti, Guylène Page, Gilles Pages, Ugo Pagnini, Beata Pajak, Stephen C Pak, Karolina Pakos-Zebrucka, Nazzy Pakpour, Zdena Palková, Francesca Palladino, Kathrin Pallauf, Nicolas Pallet, Marta Palmieri, Søren R Paludan, Camilla Palumbo, Silvia Palumbo, Olatz Pampliega, Hongming Pan, Wei Pan, Theocharis Panaretakis, Aseem Pandey, Areti Pantazopoulou, Zuzana Papackova, Daniela L Papademetrio, Issidora Papassideri, Alessio Papini, Nirmala Parajuli, Julian Pardo, Vrajesh V Parekh, Giancarlo Parenti, Jong-In Park, Junsoo Park, Ohkmae K Park, Roy Parker, Rosanna Parlato, Jan B Parys, Katherine R Parzych, Jean-Max Pasquet, Benoit Pasquier, Kishore Bs Pasumarthi, Daniel Patschan, Cam Patterson, Sophie Pattingre, Scott Pattison, Arnim Pause, Hermann Pavenstädt, Flaminia Pavone, Zully Pedrozo, Fernando J Peña, Miguel A Peñalva, Mario Pende, Jianxin Peng, Fabio Penna, Josef M Penninger, Anna Pensalfini, Salvatore Pepe, Gustavo Js Pereira, Paulo C Pereira, Verónica Pérez-de la Cruz, María Esther Pérez-Pérez, Diego Pérez-Rodríguez, Dolores Pérez-Sala, Celine Perier, Andras Perl, David H Perlmutter, Ida Perrotta, Shazib Pervaiz, Maija Pesonen, Jeffrey E Pessin, Godefridus J Peters, Morten Petersen, Irina Petrache, Basil J Petrof, Goran Petrovski, James M Phang, Mauro Piacentini, Marina Pierdominici, Philippe Pierre, Valérie Pierrefite-Carle, Federico Pietrocola, Felipe X Pimentel-Muiños, Mario Pinar, Benjamin Pineda, Ronit Pinkas-Kramarski, Marcello Pinti, Paolo Pinton, Bilal Piperdi, James M Piret, Leonidas C Platanias, Harald W Platta, Edward D Plowey, Stefanie Pöggeler, Marc Poirot, Peter Polčic, Angelo Poletti, Audrey H Poon, Hana Popelka, Blagovesta Popova, Izabela Poprawa, Shibu M Poulose, Joanna Poulton, Scott K Powers, Ted Powers, Mercedes Pozuelo-Rubio, Krisna Prak, Reinhild Prange, Mark Prescott, Muriel Priault, Sharon Prince, Richard L Proia, Tassula Proikas-Cezanne, Holger Prokisch, Vasilis J Promponas, Karin Przyklenk, Rosa Puertollano, Subbiah Pugazhenthi, Luigi Puglielli, Aurora Pujol, Julien Puyal, Dohun Pyeon, Xin Qi, Wen-Bin Qian, Zheng-Hong Qin, Yu Qiu, Ziwei Qu, Joe Quadrilatero, Frederick Quinn, Nina Raben, Hannah Rabinowich, Flavia Radogna, Michael J Ragusa, Mohamed Rahmani, Komal Raina, Sasanka Ramanadham, Rajagopal Ramesh, Abdelhaq Rami, Sarron Randall-Demllo, Felix Randow, Hai Rao, V Ashutosh Rao, Blake B Rasmussen, Tobias M Rasse, Edward A Ratovitski, Pierre-Emmanuel Rautou, Swapan K Ray, Babak Razani, Bruce H Reed, Fulvio Reggiori, Markus Rehm, Andreas S Reichert, Theo Rein, David J Reiner, Eric Reits, Jun Ren, Xingcong Ren, Maurizio Renna, Jane Eb Reusch, Jose L Revuelta, Leticia Reyes, Alireza R Rezaie, Robert I Richards, Des R Richardson, Clémence Richetta, Michael A Riehle, Bertrand H Rihn, Yasuko Rikihisa, Brigit E Riley, Gerald Rimbach, Maria Rita Rippo, Konstantinos Ritis, Federica Rizzi, Elizete Rizzo, Peter J Roach, Jeffrey Robbins, Michel Roberge, Gabriela Roca, Maria Carmela Roccheri, Sonia Rocha, Cecilia Mp Rodrigues, Clara I Rodríguez, Santiago Rodriguez de Cordoba, Natalia Rodriguez-Muela, Jeroen Roelofs, Vladimir V Rogov, Troy T Rohn, Bärbel Rohrer, Davide Romanelli, Luigina Romani, Patricia Silvia Romano, M Isabel G Roncero, Jose Luis Rosa, Alicia Rosello, Kirill V Rosen, Philip Rosenstiel, Magdalena Rost-Roszkowska, Kevin A Roth, Gael Roué, Mustapha Rouis, Kasper M Rouschop, Daniel T Ruan, Diego Ruano, David C Rubinsztein, Edmund B Rucker 3rd, Assaf Rudich, Emil Rudolf, Ruediger Rudolf, Markus A Ruegg, Carmen Ruiz-Roldan, Avnika Ashok Ruparelia, Paola Rusmini, David W Russ, Gian Luigi Russo, Giuseppe Russo, Rossella Russo, Tor Erik Rusten, Victoria Ryabovol, Kevin M Ryan, Stefan W Ryter, David M Sabatini, Michael Sacher, Carsten Sachse, Michael N Sack, Junichi Sadoshima, Paul Saftig, Ronit Sagi-Eisenberg, Sumit Sahni, Pothana Saikumar, Tsunenori Saito, Tatsuya Saitoh, Koichi Sakakura, Machiko Sakoh-Nakatogawa, Yasuhito Sakuraba, María Salazar-Roa, Paolo Salomoni, Ashok K Saluja, Paul M Salvaterra, Rosa Salvioli, Afshin Samali, Anthony Mj Sanchez, José A Sánchez-Alcázar, Ricardo Sanchez-Prieto, Marco Sandri, Miguel A Sanjuan, Stefano Santaguida, Laura Santambrogio, Giorgio Santoni, Claudia Nunes Dos Santos, Shweta Saran, Marco Sardiello, Graeme Sargent, Pallabi Sarkar, Sovan Sarkar, Maria Rosa Sarrias, Minnie M Sarwal, Chihiro Sasakawa, Motoko Sasaki, Miklos Sass, Ken Sato, Miyuki Sato, Joseph Satriano, Niramol Savaraj, Svetlana Saveljeva, Liliana Schaefer, Ulrich E Schaible, Michael Scharl, Hermann M Schatzl, Randy Schekman, Wiep Scheper, Alfonso Schiavi, Hyman M Schipper, Hana Schmeisser, Jens Schmidt, Ingo Schmitz, Bianca E Schneider, E Marion Schneider, Jaime L Schneider, Eric A Schon, Miriam J Schönenberger, Axel H Schönthal, Daniel F Schorderet, Bernd Schröder, Sebastian Schuck, Ryan J Schulze, Melanie Schwarten, Thomas L Schwarz, Sebastiano Sciarretta, Kathleen Scotto, A Ivana Scovassi, Robert A Screaton, Mark Screen, Hugo Seca, Simon Sedej, Laura Segatori, Nava Segev, Per O Seglen, Jose M Seguí-Simarro, Juan Segura-Aguilar, Ekihiro Seki, Christian Sell, Iban Seiliez, Clay F Semenkovich, Gregg L Semenza, Utpal Sen, Andreas L Serra, Ana Serrano-Puebla, Hiromi Sesaki, Takao Setoguchi, Carmine Settembre, John J Shacka, Ayesha N Shajahan-Haq, Irving M Shapiro, Shweta Sharma, Hua She, C-K James Shen, Chiung-Chyi Shen, Han-Ming Shen, Sanbing Shen, Weili Shen, Rui Sheng, Xianyong Sheng, Zu-Hang Sheng, Trevor G Shepherd, Junyan Shi, Qiang Shi, Qinghua Shi, Yuguang Shi, Shusaku Shibutani, Kenichi Shibuya, Yoshihiro Shidoji, Jeng-Jer Shieh, Chwen-Ming Shih, Yohta Shimada, Shigeomi Shimizu, Dong Wook Shin, Mari L Shinohara, Michiko Shintani, Takahiro Shintani, Tetsuo Shioi, Ken Shirabe, Ronit Shiri-Sverdlov, Orian Shirihai, Gordon C Shore, Chih-Wen Shu, Deepak Shukla, Andriy A Sibirny, Valentina Sica, Christina J Sigurdson, Einar M Sigurdsson, Puran Singh Sijwali, Beata Sikorska, Wilian A Silveira, Sandrine Silvente-Poirot, Gary A Silverman, Jan Simak, Thomas Simmet, Anna Katharina Simon, Hans-Uwe Simon, Cristiano Simone, Matias Simons, Anne Simonsen, Rajat Singh, Shivendra V Singh, Shrawan K Singh, Debasish Sinha, Sangita Sinha, Frank A Sinicrope, Agnieszka Sirko, Kapil Sirohi, Balindiwe Jn Sishi, Annie Sittler, Parco M Siu, Efthimios Sivridis, Anna Skwarska, Ruth Slack, Iva Slaninová, Nikolai Slavov, Soraya S Smaili, Keiran Sm Smalley, Duncan R Smith, Stefaan J Soenen, Scott A Soleimanpour, Anita Solhaug, Kumaravel Somasundaram, Jin H Son, Avinash Sonawane, Chunjuan Song, Fuyong Song, Hyun Kyu Song, Ju-Xian Song, Wei Song, Kai Y Soo, Anil K Sood, Tuck Wah Soong, Virawudh Soontornniyomkij, Maurizio Sorice, Federica Sotgia, David R Soto-Pantoja, Areechun Sotthibundhu, Maria João Sousa, Herman P Spaink, Paul N Span, Anne Spang, Janet D Sparks, Peter G Speck, Stephen A Spector, Claudia D Spies, Wolfdieter Springer, Daret St Clair, Alessandra Stacchiotti, Bart Staels, Michael T Stang, Daniel T Starczynowski, Petro Starokadomskyy, Clemens Steegborn, John W Steele, Leonidas Stefanis, Joan Steffan, Christine M Stellrecht, Harald Stenmark, Tomasz M Stepkowski, Stęphan T Stern, Craig Stevens, Brent R Stockwell, Veronika Stoka, Zuzana Storchova, Björn Stork, Vassilis Stratoulias, Dimitrios J Stravopodis, Pavel Strnad, Anne Marie Strohecker, Anna-Lena Ström, Per Stromhaug, Jiri Stulik, Yu-Xiong Su, Zhaoliang Su, Carlos S Subauste, Srinivasa Subramaniam, Carolyn M Sue, Sang Won Suh, Xinbing Sui, Supawadee Sukseree, David Sulzer, Fang-Lin Sun, Jiaren Sun, Jun Sun, Shi-Yong Sun, Yang Sun, Yi Sun, Yingjie Sun, Vinod Sundaramoorthy, Joseph Sung, Hidekazu Suzuki, Kuninori Suzuki, Naoki Suzuki, Tadashi Suzuki, Yuichiro J Suzuki, Michele S Swanson, Charles Swanton, Karl Swärd, Ghanshyam Swarup, Sean T Sweeney, Paul W Sylvester, Zsuzsanna Szatmari, Eva Szegezdi, Peter W Szlosarek, Heinrich Taegtmeyer, Marco Tafani, Emmanuel Taillebourg, Stephen Wg Tait, Krisztina Takacs-Vellai, Yoshinori Takahashi, Szabolcs Takáts, Genzou Takemura, Nagio Takigawa, Nicholas J Talbot, Elena Tamagno, Jerome Tamburini, Cai-Ping Tan, Lan Tan, Mei Lan Tan, Ming Tan, Yee-Joo Tan, Keiji Tanaka, Masaki Tanaka, Daolin Tang, Dingzhong Tang, Guomei Tang, Isei Tanida, Kunikazu Tanji, Bakhos A Tannous, Jose A Tapia, Inmaculada Tasset-Cuevas, Marc Tatar, Iman Tavassoly, Nektarios Tavernarakis, Allen Taylor, Graham S Taylor, Gregory A Taylor, J Paul Taylor, Mark J Taylor, Elena V Tchetina, Andrew R Tee, Fatima Teixeira-Clerc, Sucheta Telang, Tewin Tencomnao, Ba-Bie Teng, Ru-Jeng Teng, Faraj Terro, Gianluca Tettamanti, Arianne L Theiss, Anne E Theron, Kelly Jean Thomas, Marcos P Thomé, Paul G Thomes, Andrew Thorburn, Jeremy Thorner, Thomas Thum, Michael Thumm, Teresa Lm Thurston, Ling Tian, Andreas Till, Jenny Pan-Yun Ting, Vladimir I Titorenko, Lilach Toker, Stefano Toldo, Sharon A Tooze, Ivan Topisirovic, Maria Lyngaas Torgersen, Liliana Torosantucci, Alicia Torriglia, Maria Rosaria Torrisi, Cathy Tournier, Roberto Towns, Vladimir Trajkovic, Leonardo H Travassos, Gemma Triola, Durga Nand Tripathi, Daniela Trisciuoglio, Rodrigo Troncoso, Ioannis P Trougakos, Anita C Truttmann, Kuen-Jer Tsai, Mario P Tschan, Yi-Hsin Tseng, Takayuki Tsukuba, Allan Tsung, Andrey S Tsvetkov, Shuiping Tu, Hsing-Yu Tuan, Marco Tucci, David A Tumbarello, Boris Turk, Vito Turk, Robin Fb Turner, Anders A Tveita, Suresh C Tyagi, Makoto Ubukata, Yasuo Uchiyama, Andrej Udelnow, Takashi Ueno, Midori Umekawa, Rika Umemiya-Shirafuji, Benjamin R Underwood, Christian Ungermann, Rodrigo P Ureshino, Ryo Ushioda, Vladimir N Uversky, Néstor L Uzcátegui, Thomas Vaccari, Maria I Vaccaro, Libuše Váchová, Helin Vakifahmetoglu-Norberg, Rut Valdor, Enza Maria Valente, Francois Vallette, Angela M Valverde, Greet Van den Berghe, Ludo Van Den Bosch, Gijs R van den Brink, F Gisou van der Goot, Ida J van der Klei, Luc Jw van der Laan, Wouter G van Doorn, Marjolein van Egmond, Kenneth L van Golen, Luc Van Kaer, Menno van Lookeren Campagne, Peter Vandenabeele, Wim Vandenberghe, Ilse Vanhorebeek, Isabel Varela-Nieto, M Helena Vasconcelos, Radovan Vasko, Demetrios G Vavvas, Ignacio Vega-Naredo, Guillermo Velasco, Athanassios D Velentzas, Panagiotis D Velentzas, Tibor Vellai, Edo Vellenga, Mikkel Holm Vendelbo, Kartik Venkatachalam, Natascia Ventura, Salvador Ventura, Patrícia St Veras, Mireille Verdier, Beata G Vertessy, Andrea Viale, Michel Vidal, Helena L A Vieira, Richard D Vierstra, Nadarajah Vigneswaran, Neeraj Vij, Miquel Vila, Margarita Villar, Victor H Villar, Joan Villarroya, Cécile Vindis, Giampietro Viola, Maria Teresa Viscomi, Giovanni Vitale, Dan T Vogl, Olga V Voitsekhovskaja, Clarissa von Haefen, Karin von Schwarzenberg, Daniel E Voth, Valérie Vouret-Craviari, Kristina Vuori, Jatin M Vyas, Christian Waeber, Cheryl Lyn Walker, Mark J Walker, Jochen Walter, Lei Wan, Xiangbo Wan, Bo Wang, Caihong Wang, Chao-Yung Wang, Chengshu Wang, Chenran Wang, Chuangui Wang, Dong Wang, Fen Wang, Fuxin Wang, Guanghui Wang, Hai-Jie Wang, Haichao Wang, Hong-Gang Wang, Hongmin Wang, Horng-Dar Wang, Jing Wang, Junjun Wang, Mei Wang, Mei-Qing Wang, Pei-Yu Wang, Peng Wang, Richard C Wang, Shuo Wang, Ting-Fang Wang, Xian Wang, Xiao-Jia Wang, Xiao-Wei Wang, Xin Wang, Xuejun Wang, Yan Wang, Yanming Wang, Ying Wang, Ying-Jan Wang, Yipeng Wang, Yu Wang, Yu Tian Wang, Yuqing Wang, Zhi-Nong Wang, Pablo Wappner, Carl Ward, Diane McVey Ward, Gary Warnes, Hirotaka Watada, Yoshihisa Watanabe, Kei Watase, Timothy E Weaver, Colin D Weekes, Jiwu Wei, Thomas Weide, Conrad C Weihl, Günther Weindl, Simone Nardin Weis, Longping Wen, Xin Wen, Yunfei Wen, Benedikt Westermann, Cornelia M Weyand, Anthony R White, Eileen White, J Lindsay Whitton, Alexander J Whitworth, Joëlle Wiels, Franziska Wild, Manon E Wildenberg, Tom Wileman, Deepti Srinivas Wilkinson, Simon Wilkinson, Dieter Willbold, Chris Williams, Katherine Williams, Peter R Williamson, Konstanze F Winklhofer, Steven S Witkin, Stephanie E Wohlgemuth, Thomas Wollert, Ernst J Wolvetang, Esther Wong, G William Wong, Richard W Wong, Vincent Kam Wai Wong, Elizabeth A Woodcock, Karen L Wright, Chunlai Wu, Defeng Wu, Gen Sheng Wu, Jian Wu, Junfang Wu, Mian Wu, Min Wu, Shengzhou Wu, William Kk Wu, Yaohua Wu, Zhenlong Wu, Cristina Pr Xavier, Ramnik J Xavier, Gui-Xian Xia, Tian Xia, Weiliang Xia, Yong Xia, Hengyi Xiao, Jian Xiao, Shi Xiao, Wuhan Xiao, Chuan-Ming Xie, Zhiping Xie, Zhonglin Xie, Maria Xilouri, Yuyan Xiong, Chuanshan Xu, Congfeng Xu, Feng Xu, Haoxing Xu, Hongwei Xu, Jian Xu, Jianzhen Xu, Jinxian Xu, Liang Xu, Xiaolei Xu, Yangqing Xu, Ye Xu, Zhi-Xiang Xu, Ziheng Xu, Yu Xue, Takahiro Yamada, Ai Yamamoto, Koji Yamanaka, Shunhei Yamashina, Shigeko Yamashiro, Bing Yan, Bo Yan, Xianghua Yan, Zhen Yan, Yasuo Yanagi, Dun-Sheng Yang, Jin-Ming Yang, Liu Yang, Minghua Yang, Pei-Ming Yang, Peixin Yang, Qian Yang, Wannian Yang, Wei Yuan Yang, Xuesong Yang, Yi Yang, Ying Yang, Zhifen Yang, Zhihong Yang, Meng-Chao Yao, Pamela J Yao, Xiaofeng Yao, Zhenyu Yao, Zhiyuan Yao, Linda S Yasui, Mingxiang Ye, Barry Yedvobnick, Behzad Yeganeh, Elizabeth S Yeh, Patricia L Yeyati, Fan Yi, Long Yi, Xiao-Ming Yin, Calvin K Yip, Yeong-Min Yoo, Young Hyun Yoo, Seung-Yong Yoon, Ken-Ichi Yoshida, Tamotsu Yoshimori, Ken H Young, Huixin Yu, Jane J Yu, Jin-Tai Yu, Jun Yu, Li Yu, W Haung Yu, Xiao-Fang Yu, Zhengping Yu, Junying Yuan, Zhi-Min Yuan, Beatrice Yjt Yue, Jianbo Yue, Zhenyu Yue, David N Zacks, Eldad Zacksenhaus, Nadia Zaffaroni, Tania Zaglia, Zahra Zakeri, Vincent Zecchini, Jinsheng Zeng, Min Zeng, Qi Zeng, Antonis S Zervos, Donna D Zhang, Fan Zhang, Guo Zhang, Guo-Chang Zhang, Hao Zhang, Hong Zhang, Hong Zhang, Hongbing Zhang, Jian Zhang, Jian Zhang, Jiangwei Zhang, Jianhua Zhang, Jing-Pu Zhang, Li Zhang, Lin Zhang, Lin Zhang, Long Zhang, Ming-Yong Zhang, Xiangnan Zhang, Xu Dong Zhang, Yan Zhang, Yang Zhang, Yanjin Zhang, Yingmei Zhang, Yunjiao Zhang, Mei Zhao, Wei-Li Zhao, Xiaonan Zhao, Yan G Zhao, Ying Zhao, Yongchao Zhao, Yu-Xia Zhao, Zhendong Zhao, Zhizhuang J Zhao, Dexian Zheng, Xi-Long Zheng, Xiaoxiang Zheng, Boris Zhivotovsky, Qing Zhong, Guang-Zhou Zhou, Guofei Zhou, Huiping Zhou, Shu-Feng Zhou, Xu-Jie Zhou, Hongxin Zhu, Hua Zhu, Wei-Guo Zhu, Wenhua Zhu, Xiao-Feng Zhu, Yuhua Zhu, Shi-Mei Zhuang, Xiaohong Zhuang, Elio Ziparo, Christos E Zois, Teresa Zoladek, Wei-Xing Zong, Antonio Zorzano, Susu M Zughaier

  Autophagy 12 1 1 - 222 2016年 [査読有り][通常論文]
  
• Non-invasive prenatal genetic testingの遺伝カウンセリング担当者に対する質問紙調査

  西山 深雪, 左合 治彦, 鈴森 伸宏, 山田 崇弘, 佐村 修, 澤井 英明, 室月 淳, 亀井 良政, 増崎 英明, 平原 史樹, 北川 道弘, 関沢 明彦

  日本遺伝カウンセリング学会誌 37 2 11 - 20 日本遺伝カウンセリング学会 2016年 [査読有り][通常論文]
   

  2014年3月時点で、日本医学会の認可を得ていた非侵襲的出生前遺伝学的検査(NIPT)コンソーシアム参加38施設の施設責任者および遺伝カウンセリング担当者を対象に、現場の遺伝カウンセリングの状況について質問紙調査を実施した。31施設の施設責任者と115名の遺伝カウンセリング担当者より回答が得られた。受診希望者数に対して十分に対応できていないと、9施設(30%)が回答した。NIPT希望者の特徴として、「遺伝に関する基礎知識が十分ではない」(64%)、「検査を受けると決めている」(23%)、「気軽に受検している」(19%)などがあげられた。双胎妊娠の検査適応や、性染色体や染色体微細欠損症候群への対象疾患の拡大については、慎重な意見が多く見られた。侵襲的確定検査、母体血清マーカー検査の実態把握システムが必要との回答が7割近くであった。遺伝学教育や出生前遺伝学的検査に関する知識普及、出生前遺伝学的検査の体制整備が必要であると考えられた。
• Urinary protein-to-creatinine ratio in pregnant women after dipstick testing: prospective observational study

  Yosuke Baba, Takahiro Yamada, Mana Obata-Yasuoka, Shun Yasuda, Yasumasa Ohno, Kosuke Kawabata, Shiori Minakawa, Chihiro Hirai, Hideto Kusaka, Nao Murabayashi, Yusuke Inde, Michikazu Nagura, Hiromi Hamada, Atsuo Itakura, Akihide Ohkuchi, Makoto Maeda, Norimasa Sagawa, Akihito Nakai, Soromon Kataoka, Keiya Fujimori, Yoshiki Kudo, Tomoaki Ikeda, Hisanori Minakami

  BMC PREGNANCY AND CHILDBIRTH 15 331 - 331 2015年12月 [査読有り][通常論文]
   

  Background: The dipstick test is widely used as a primary screening test for detection of significant proteinuria in pregnancy (SPIP). However, it often shows a false positive test result. This study was performed to determine which pregnant women should be recommended to undergo determination of urinary protein-to-creatinine ratio (mg/mg, P/Cr test) after dipstick test for confirmation of SPIP. Methods: This was a multicenter, prospective, and observational study of 2212 urine specimens from 1033 pregnant women who underwent simultaneous dipstick and P/Cr tests in the same spot urine samples at least once. SPIP was defined as P/Cr > 0.27. Preeclampsia was diagnosed in women with both hypertension and SPIP. Results: Preeclampsia, hypertension alone, and SPIP alone developed in 202 (20 %), 73 (7.1 %), and 120 (12 %) women, respectively. Creatinine concentration [Cr] varied greatly, ranging from 8.1 to 831 mg/dL in the 2212 urine samples. Rate of positive dipstick test results increased with increasing [Cr], while SPIP prevalence rate was lower in urine samples with higher [Cr], yielding higher false positive rates in samples with higher [Cr]. Postpartum urine samples had significantly lower [Cr] compared to those obtained antepartum (60 [8.7-297] vs. 100 [10-401] mg/dL, respectively). At the first P/Cr test among women with similar dipstick test results, the risk of having SPIP was consistently and significantly higher for hypertensive women than for normotensive women at any dipstick test result: 18 % (14/77) vs. 3.2 % (8/251), 47 % (26/55) vs. 8.7 % (37/425), 91 % (82/90) vs. 59 % (44/75) for negative/equivocal, 1+, and >= 2+ test results, respectively. The risk of SPIP was 16 % (9/55) for normotensive women when two successive antenatal urine samples showed a dipstick test result of 1 +. Conclusions: For prediction of SPIP, the dipstick test was more likely to show a false positive result in concentrated urine samples with higher [Cr]. Hypertensive women with >= 1+ as well as normotensive women with >= 2+ on dipstick test should be advised to undergo the P/Cr test.
• Long-term persistent fetomaternal hemorrhage.

  Takeshi Umazume, Mamoru Morikawa, Takahiro Yamada, Kazutoshi Cho, Nobuo Masauzi, Hisanori Minakami

  Clinical case reports 3 11 916 - 9 2015年11月 [査読有り][通常論文]
   

  It is not clear that how long the affected fetuses can tolerate fetomaternal hemorrhage (FMH). Incidental serial measurements of the fetal peak systolic velocity of the middle cerebral artery and the retrospective analysis of stocked blood available incidentally indicated that our patient had suffered from FMH for at least 2 weeks prior to delivery.
• A novel mutation Ser344Cys in FGFR3 causes achondroplasia with severe platyspondyly

  Masaki Takagi, Masanori Kouwaki, Koya Kawase, Hiroyuki Shinohara, Yukihiro Hasegawa, Takahiro Yamada, Ikuma Fujiwara, Hideaki Sawai, Gen Nishimura, Tomonobu Hasegawa

  AMERICAN JOURNAL OF MEDICAL GENETICS PART A 167 11 2851 - 2854 2015年11月 [査読有り][通常論文]
  
• Intrapartum risk factors for neonatal encephalopathy leading to cerebral palsy in women without apparent sentinel events

  Takahiro Yamada, Kazutoshi Cho, Mamoru Morikawa, Takashi Yamada, Hisanori Minakami

  JOURNAL OF OBSTETRICS AND GYNAECOLOGY RESEARCH 41 10 1520 - 1525 2015年10月 [査読有り][通常論文]
   

  AimTo determine intrapartum factors associated with neonatal encephalopathy leading to cerebral palsy (NE-CP). MethodsA total of 70 NE-CP patients who fulfilled study criteria (cephalic singleton pregnancy with attempted vaginal delivery [AVD] at gestational week [GW] 36; intrapartum occurrence of non-reassuring fetal status without apparent cause following reassuring fetal status on admission; and development of NE-CP) were compared with 210 AVD controls who had 1- and 5-min Apgar score 8 matched for GW, maternal parity, and use of uterotonics. Suboptimal care was defined as delayed reaction due to misinterpretation of fetal heart rate (FHR) tracing, or inappropriate trial of instrumental delivery (TOID). Successful and failed TOID were defined as vaginal and cesarean delivery after TOID, respectively. The 210 controls were assumed not to have had suboptimal care. ResultsThe rates of successful (34% vs 12%) and failed TOID (11% vs 0.0%), cesarean section (34% vs 14%), suboptimal care (57% vs 0.0%), pregnancy-induced hypertension (11% vs 2.4%), birthweight 3800 g (8.6% vs 1.9%), subgaleal hemorrhage (16% vs 0.0%) were significantly higher in NE-CP patients than in controls. Selection with the stepwise method and logistic regression analysis identified four independent risk factors for NE-CP: suboptimal intrapartum care (OR, 2.21; 95%CI: 1.99-2.47), cesarean section (OR, 1.19; 95%CI: 1.08-1.31), successful TOID (OR, 1.14; 95%CI: 1.03-1.25), and hypertension (OR, 1.20; 95%CI: 1.01-1.42). ConclusionsTraining programs for improved interpretation of FHR tracing and appropriate TOID are required to prevent NE-CP among healthy and mature fetuses in Japan.
• Prospective risk of stillbirth in women with placental mesenchymal dysplasia

  Satoshi Ishikawa, Mamoru Morikawa, Takahiro Yamada, Rina Akaishi, Masanori Kaneuchi, Hisanori Minakami

  JOURNAL OF OBSTETRICS AND GYNAECOLOGY RESEARCH 41 10 1562 - 1568 2015年10月 [査読有り][通常論文]
   

  AimThe aim of this study was to provide better counsel to pregnant women with suspected placental mesenchymal dysplasia (PMD) regarding the risks of preterm birth and intrauterine fetal death. Material and MethodsWe reviewed the outcomes of 109 PMD pregnancies with gestational week (GW)24 abstracted from 63 reports in the English-language published reports, including two cases that we encountered recently. The prospective risk of stillbirth at GW N was defined as the number of women with stillbirth at GWN divided by the number of women giving birth at GWN. ResultsA total of 32 (29.4%) women experienced stillbirth at a median GW of 31 (range, 24-38). Preterm birth (GW <37) occurred in 52 (67.5%) of the 77 live-born infants. Only 25 (22.9%) women had full-term (GW37) live-born infants. The prospective risks of stillbirth were 29.4% (32/109), 27.5% (25/91), 20.9% (14/67) and 13.0% (6/46) for women who reached GW 24(+0), 28(+0), 32(+0) and 36(+0) respectively. ConclusionAs women with PMD are at markedly elevated risk of intrauterine fetal death, early admission to the hospital and intensive monitoring of fetal status should be considered, although whether this policy improves outcome has not been validated.
• 36週で陣痛発来し、緊急血小板輸血後に分娩となったITP合併妊娠の一例

  中川 絹子, 山田 崇弘, 千葉 健太郎, 小島 崇史, 石川 聡司, 小山 貴弘, 森川 守, 水上 尚典

  北日本産科婦人科学会総会・学術講演会プログラム・抄録集 63回 71 - 71 東北連合産科婦人科学会・北日本産科婦人科学会 2015年09月
• Prospective study on changes in blood variables in pregnant women at higher risk of peripartum cardiomyopathy.

  Umazume T, Yamada T, Ishikawa S, Yamada T, Koyama T, Furuta I, Morikawa M, Yamada S, Minakami H

  ESC heart failure 2 3 208 - 215 2015年09月 [査読有り][通常論文]
  
• Increased epigenetic alterations at the promoters of transcriptional regulators following inadequate maternal gestational weight gain

  Tomoko Kawai, Takahiro Yamada, Kosei Abe, Kohji Okamura, Hiromi Kamura, Rina Akaishi, Hisanori Minakami, Kazuhiko Nakabayashi, Kenichiro Hata

  SCIENTIFIC REPORTS 5 14224 - 14224 2015年09月 [査読有り][通常論文]
   

  Epigenetic modifications are thought to serve as a memory of exposure to in utero environments. However, few human studies have investigated the associations between maternal nutritional conditions during pregnancy and epigenetic alterations in offspring. In this study, we report genome-wide methylation profiles for 33 postpartum placentas from pregnancies of normal and foetal growth restriction with various extents of maternal gestational weight gain. Epigenetic alterations accumulate in the placenta under adverse in utero environments, as shown by application of Smirnov-Grubbs' outlier test. Moreover, hypermethylation occurs frequently at the promoter regions of transcriptional regulator genes, including polycomb targets and zinc-finger genes, as shown by annotations of the genomic and functional features of loci with altered DNA methylation. Aberrant epigenetic modifications at such developmental regulator loci, if occurring in foetuses as well, will elevate the risk of developing various diseases, including metabolic and mental disorders, later in life.
• Role of the Atg9a gene in intrauterine growth and survival of fetal mice

  Takashi Kojima, Takahiro Yamada, Rina Akaishi, Itsuko Furuta, Tatsuya Saitoh, Kazuhiko Nakabayashi, Keiichi I. Nakayama, Keiko Nakayama, Shizuo Akira, Hisanori Minakami

  REPRODUCTIVE BIOLOGY 15 3 131 - 138 2015年09月 [査読有り][通常論文]
   

  Autophagy is activated by environment unfavorable for survival and requires Atg9a protein. Mice heterozygous for p57(KiP2), devoid of the imprinted paternal allele (p57(KiP2+/-)), are known to develop hypertension during pregnancy. To determine whether fetal Atg9a is involved in the intrauterine survival and growth of fetal mice, this study was performed on Atg9a heterozygous (Atg9a(+/-)) pregnant mice with and without p57(KiP2+/-). The pregnant mice heterozygous for both knockout alleles of Atg9a and p57(KiP2) (Atg9a(+/-)/p57(KiP2+/-)), but not those heterozygous for Atg9a alone, developed hypertension during pregnancy. Placental expression of Atg9a mRNA was significantly decreased in the Atg9a(-/-) mice compared to Atg9a(+/-) or Atg9a(+/+) mice. The Atg9a(-/-) fetal mice exhibited significantly retarded growth and were more likely to die in utero compared to Atg9a(+/+) and Atg9a(+/-) fetal mice. Growth retardation was observed in the presence of maternal hypertension in Atg9a(-/-) fetal mice. These results suggest that Atg9a(-/-) fetal mice from pregnant dams heterozygous for both knockout alleles of Atg9a and p57(KiP2) are more susceptible to hypertensive stress than fetuses with intact autophagic machinery. (C) 2015 Society for Biology of Reproduction & the Institute of Animal Reproduction and Food Research of Polish Academy of Sciences in Olsztyn. Published by Elsevier Sp. z.o.o. All rights reserved.
• 妊娠糖尿病の血糖管理と血糖自己測定法(SMBG) 血糖自己測定法(SMBG)は全ての妊娠糖尿病(GDM)妊婦に必要か?

  森川 守, 山田 竜太郎, 馬詰 武, 小島 崇史, 小山 貴弘, 石川 聡司, 赤石 理奈, 西田 竜太郎, 荒木 直人, 山田 崇弘, 水上 尚典

  糖尿病と妊娠 15 1 82 - 82 (一社)日本糖尿病・妊娠学会 2015年08月
• 妊娠高血圧腎症、HELLP症候群(疑い)、子癇・PRES(疑い)の管理〜娩出時期はどのようにして決定するか? 娩出時期はどのようにして決定するか? 妊娠蛋白尿と妊娠高血圧腎症

  森川 守, 赤石 理奈, 山田 崇弘, 山田 俊, 長 和俊, 水上 尚典

  日本妊娠高血圧学会雑誌 22 39 - 39 (一社)日本妊娠高血圧学会 2015年08月
• 妊娠高血圧腎症 尿中ポドサイト検出の臨床的意義の解析

  てき 天げつ, 赤石 理奈, 古田 伊都子, 森川 守, 山田 崇弘, 石川 聡司, 小山 貴弘, 水上 尚典

  日本妊娠高血圧学会雑誌 22 51 - 51 (一社)日本妊娠高血圧学会 2015年08月
• Reactivating p53 functions by suppressing its novel inhibitor iASPP: a potential therapeutic opportunity in p53 wild-type tumors

  Peixin Dong, Kei Ihira, Junichi Hamada, Hidemichi Watari, Takahiro Yamada, Masayoshi Hosaka, Sharon J. B. Hanley, Masataka Kudo, Noriaki Sakuragi

  ONCOTARGET 6 24 19968 - 19975 2015年08月 [査読有り][通常論文]
   

  Although mutational inactivation of p53 is found in 50% of all human tumors, a subset of tumors display defective p53 function, but retain wild-type (WT) p53. Here, direct and indirect mechanisms leading to the loss of WT p53 activities are discussed. We summarize the oncogenic roles of iASPP, an inhibitor of WT p53, in promoting proliferation, invasion, drug or radiation-resistance and metastasis. From the therapeutic view, we highlight promising perspectives of microRNA-124, peptide and small molecules that reduce or block iASPP for the treatment of cancer. High iASPP expression enhances proliferation, aggressive behavior, the resistance to radiation/chemotherapy and correlates with poor prognosis in a range of human tumors. Overexpression of iASPP accelerates tumorigenesis and invasion through p53-dependent and p53-independent mechanisms. MicroRNA-124 directly targets iASPP and represses the growth and invasiveness of cancer cells. The disruption of iASPP-p53 interaction by a p53-derived peptide A34 restores p53 function in cancer cells. The inhibition of iASPP phosphorylation with small molecules induces p53-dependent apoptosis and growth suppression. The mechanisms underlying aberrant expression of iASPP in human tumors should be further investigated. Reactivating WT p53 functions by targeting its novel inhibitor iASPP holds promise for potential therapeutic interventions in the treatment of WT p53-containing tumors.
• Platelet aggregation in citrated whole blood of the first trimester of pregnancy

  Takeshi Umazume, Takahiro Yamada, Mamoru Morikawa, Satoshi Ishikawa, Itsuko Furuta, Takahiro Koyama, Kazuhiko Matsuno, Hisanori Minakami

  CLINICA CHIMICA ACTA 448 448 60 - 64 2015年08月 [査読有り][通常論文]
   

  Background: It was recently suggested that platelet reactivity is reduced in early pregnancy. This study was performed to determine whether the citrated whole blood from 33 pregnant women in their first trimester showed spontaneous platelet aggregation and whether it differed in extent from that of 11 non-pregnant women. Methods: The platelet count and number of platelet aggregates (PA) were serially determined in the same citrated whole blood specimens at 15, 30, 45, 60, 75, and 90 min after blood sampling using a hematology analyzer. Results: The number of PA increased significantly at 30 min and thereafter in both groups, but was consistently lower for pregnant than non-pregnant women over the 90-min observation period. The platelet count decreased significantly in a time-dependent manner in both groups, but was significantly lower at 30 and 90 min for nonpregnant than pregnant women. The number of PA showed a significant positive correlation with net decrease in platelet count for both pregnant and non-pregnant women. PA counts were also significantly positively correlated with the mean platelet volume. Conclusion: Platelet reactivity monitored by the increase in number of PA and the fall in platelet count was reduced in early pregnancy compared with non-pregnant healthy controls. (C) 2015 Elsevier B.V. All rights reserved.
• 妊娠高血圧症候群 最近の話題 妊娠蛋白尿とアンチトロンビン活性低下

  森川 守, 山田 崇弘, 長 和俊, 水上 尚典

  日本周産期・新生児医学会雑誌 51 2 631 - 631 (一社)日本周産期・新生児医学会 2015年06月
• 出生当日に手術を行った胎児重複大動脈弓の1例

  塩野 展子, 武井 黄太, 塩野 直子, 三宅 敏一, 山田 崇弘, 森川 守, 長 和俊, 水上 尚典

  日本周産期・新生児医学会雑誌 51 2 655 - 655 (一社)日本周産期・新生児医学会 2015年06月
• 異常胎児心拍パターンと胎児母体間輸血症候群の有無について フローサイトメトリーを用いた検討

  馬詰 武, 山田 崇弘, 山田 竜太郎, 小島 崇史, 赤石 理奈, 石川 聡司, 小山 貴弘, 西田 竜太郎, 森川 守, 水上 尚典

  日本周産期・新生児医学会雑誌 51 2 676 - 676 (一社)日本周産期・新生児医学会 2015年06月
• Atg9aノックアウトマウス胎盤におけるオートファジー活性化の検討

  小島 崇史, 山田 崇弘, 赤石 理奈, 森川 守, 山田 俊, 水上 尚典

  日本周産期・新生児医学会雑誌 51 2 677 - 677 (一社)日本周産期・新生児医学会 2015年06月
• 妊婦血液の血小板自然凝集塊形成についての検討

  馬詰 武, 山田 崇弘, 山田 竜太郎, 小島 崇史, 赤石 理奈, 石川 聡司, 小山 貴弘, 西田 竜太郎, 森川 守, 水上 尚典

  日本周産期・新生児医学会雑誌 51 2 716 - 716 (一社)日本周産期・新生児医学会 2015年06月
• 双胎妊婦では単胎妊婦に比し産後睡眠障害を有す

  森川 守, 山田 崇弘, 長 和俊, 水上 尚典

  日本周産期・新生児医学会雑誌 51 2 738 - 738 (一社)日本周産期・新生児医学会 2015年06月
• 結節性硬化症に合併した胎児心臓腫瘍により血行動態に異常を来した3例

  武井 黄太, 山田 崇弘, 森川 守, 長 和俊, 水上 尚典

  日本周産期・新生児医学会雑誌 51 2 851 - 851 (一社)日本周産期・新生児医学会 2015年06月
• L1CAMに複数の変異を認めたX連鎖性遺伝性水頭症の1例

  夘月 ゆたか, 長 和俊, 兼次 洋介, 森岡 圭太, 早坂 格, 水上 尚典, 森川 守, 山田 崇弘, 山崎 麻美

  日本周産期・新生児医学会雑誌 51 2 933 - 933 (一社)日本周産期・新生児医学会 2015年06月
• 分娩前血漿フィブリノーゲン濃度と分娩時出血

  山田 俊, 赤石 理奈, 山田 崇弘, 森川 守, 水上 尚典

  日本産婦人科・新生児血液学会誌 25 1 S - 86 日本産婦人科・新生児血液学会 2015年05月
• Outcomes of 83 fetuses exposed to angiotensin receptor blockers during the second or third trimesters: a literature review

  Chisa Shimada, Rina Akaishi, Kazutoshi Cho, Mamoru Morikawa, Yosuke Kaneshi, Takahiro Yamda, Hisanori Minakami

  HYPERTENSION RESEARCH 38 5 308 - 313 2015年05月 [査読有り][通常論文]
   

  This literature review was conducted to provide better counsel to pregnant women who erroneously took angiotensin receptor blockers (ARBs) during the second and/or third trimesters regarding infant outcomes. Information was available on 83 fetuses in 34 literature reports, including one that we encountered recently. Fourteen pregnancies were terminated, and six were unknown regarding status of amniotic fluid volume (AFV). Fifty-eight and five fetuses did and did not show oligohydramnios, respectively, after being exposed to ARBs. Of the 58 fetuses that presented with oligohydramnios, 57 were exposed to ARBs at gestational week (GW). 20, and 19 exhibited resolution of oligohydramnios 1-6 weeks after cessation of ARBs. The 24 mothers without oligohydramnios at delivery ceased taking ARBs earlier (GW of 26.8 +/- 5.1 vs. 31.8 +/- 4.0, respectively, P=0.000) and had longer duration of gestation after cessation of ARBs (8.4 +/- 5.2 vs. 0.7 +/- 2.3 weeks, respectively, P=0.000). The mothers without oligohydramnios also had better outcomes in terms of favorable infant outcomes (63% (15/24) vs. 15% (6/39), respectively, P=0.000) and infant mortality rates (13% (3/24) vs. 56% (22/39), respectively, P=0.001) than the 39 with oligohydramnios. Thus, a favorable outcome may be feasible if the fetuses are not indicated for prompt delivery at presentation and exhibit normal AFV or resolution of oligohydramnios after cessation of ARBs. Although the prevalence rate of oligohydramnios was high in this study, it may have been due to publication bias. A prospective study suggested a lower prevalence rate than that reported in the present study.
• Protein S deficiency present in a pregnant woman with dyspnea, abdominal pains, restlessness, agitation and hypofibrinogenemia.

  Takeshi Umazume, Mamoru Morikawa, Takahiro Yamada, Rina Akaishi, Takahiro Koyama, Hisanori Minakami

  Clinical case reports 3 4 213 - 6 2015年04月 [査読有り][通常論文]
   

  Hypofibrinogenemia is rare in pulmonary thromboembolism. A pregnant woman with dyspnea, abdominal pain, restlessness, agitation and protein S deficiency exhibited normal blood oxygenation and high D-dimer (370 μg/mL) and undetectable fibrinogen levels in the blood. The pathogenesis responsible for present findings may have some features similar to amniotic fluid embolism.
• 多量の胸腹水に対して行った胎児胸腔羊水腔シャントが有効であった一例

  荒木 直人, 赤石 理奈, 河口 哲, 西田 竜太郎, 山田 崇弘, 森川 守, 長 和俊, 水上 尚典

  北海道産科婦人科学会会誌 59 1 200 - 200 北海道産科婦人科学会 2015年03月
• Vaccination during the 2013-2014 influenza season in pregnant Japanese women

  T. Yamada, K. Abe, Y. Baba, E. Inubashiri, K. Kawabata, T. Kubo, Y. Maegawa, N. Fuchi, M. Nomizo, M. Shimada, A. Shiozaki, H. Hamada, S. Matsubara, N. Akutagawa, S. Kataoka, M. Maeda, H. Masuzaki, N. Sagawa, A. Nakai, S. Saito, H. Minakami

  EUROPEAN JOURNAL OF CLINICAL MICROBIOLOGY & INFECTIOUS DISEASES 34 3 543 - 548 2015年03月 [査読有り][通常論文]
   

  This questionnaire survey was conducted at 11 hospitals in Japan to determine vaccination coverage against seasonal influenza and the prevalence rate of influenza among pregnant Japanese women. Of 2,808 postpartum women who gave birth at the 11 hospitals during the study period from March 1, 2014, to July 31, 2014, 1,713 (61 %) participated in this study and 876 (51 %) reported having received vaccination against influenza in or after October 2013. Women aged < 25 years had a significantly lower vaccination rate than those aged a parts per thousand yen25 years (31 % vs. 53 %, respectively; p = 0.0000). Eighty-seven (5.1 %) and 1,626 (94.9 %) women did and did not contract influenza, respectively. Although prior birth did not affect overall vaccination coverage (50 % for primiparous vs. 53 % for multiparous), multiparous women had a significantly higher rate of contracting influenza than primiparous women, irrespective of vaccination status (5.6 % vs. 2.2 % [p = 0.0216] and 9.7 % vs. 3.5 % [p = 0.0003] for women with and without vaccination, respectively). The 2013-2014 vaccination program significantly reduced the influenza infection rate by 35 % (3.9 % vs. 6.3 % for women with and without vaccination, respectively; p = 0.0272). Seventy-two (83 %) of the 87 women took antiviral agents for the treatment of influenza and two (2.3 %) required hospitalization. These results suggested that pregnant Japanese women had a high level of concern regarding seasonal influenza. However, campaigns targeting young pregnant Japanese women, as well as multiparous women, for vaccination are needed in order to further reduce the incidence of influenza among pregnant Japanese women.
• Fibrinogen levels in the late stage of twin pregnancy.

  Yamada T, Morikawa M, Yamada T, Akaishi R, Kojima T, Minakami H

  Thrombosis research 135 2 318 - 321 2015年02月 [査読有り][通常論文]
  
• Prevalence of hyperglycaemia in singleton versus twin pregnancy

  Mamoru Morikawa, Takahiro Yamada, Rina Akaishi, Takashi Kojima, Ryutaro Nishida, Takahiro Koyama, Kazutoshi Cho, Hisanori Minakami

  DIABETES-METABOLISM RESEARCH AND REVIEWS 31 2 198 - 203 2015年02月 [査読有り][通常論文]
   

  BackgroundThere is conflicting information regarding the risk of gestational diabetes mellitus in twin pregnancies. This study was conducted to determine whether the risk of gestational diabetes mellitus is higher in pregnant Japanese women with twin versus singleton pregnancy. MethodsThe prevalence of gestational diabetes mellitus was studied in two different populations: 144589 women registered with the Japan Society of Obstetrics and Gynecology (JSOG cohort) over 3years between 2007 and 2009 in which patient selection bias was unavoidable; and 430 Japanese women who gave birth at a single centre over 5years between 2008 and 2012 (single-centre cohort), consisting of 86 women with twins and 344 women with singletons matched for maternal age and prepregnancy body mass index. The gestational diabetes mellitus was diagnosed on the basis of the previous criteria in the JSOG cohort. The gestational diabetes mellitus was screened in a stepwise method and diagnosed on the basis of the new criteria in the single-centre cohort. ResultsIn the single-centre cohort, neither frequency of random glucose level 105mg/dL in the first trimester [9.0% (31/344) vs 5.8% (5/86)], positive result (140mg/dL) on 50g glucose challenge test in the second trimester [26.5% (90/339) vs 26.7% (23/86)], nor women diagnosed with GDM [8.4% (29/344) vs 9.3% (8/86)] differed between the two groups. The prevalence of hyperglycaemia was higher in singleton than in twin pregnancies in the JSOG cohort (2.6% vs 1.8%, p<0.001). ConclusionsThe risk of gestational diabetes mellitus may be similar between Japanese women with singleton and twin pregnancies. Difference in the risk of hyperglycaemia in the JSOG cohort may have been due to selection bias. Copyright (c) 2014 John Wiley & Sons, Ltd.
• Nationwide demonstration project of next-generation sequencing of cell-free DNA in maternal plasma in Japan: 1-year experience

  Haruhiko Sago, Haruhiko Sago, Akihiko Sekizawa, Akihiko Sekizawa, Takahiro Yamada, Toshiaki Endo, Akimune Hukushima, Jun Murotsuki, Kamei Yoshimasa, Satoshi Nanba, Junko Yotsumoto, Hisao Osada, Yasuyo Kasai, Atsushi Watanabe, Yukiko Katagiri, Naoki Takesita, Masaki Ogawa, Tomohiro Tanemoto, Osamu Samura, Michihiro Kitagawa, Takashi Okai, Shun Ichiro Izumi, Haruka Hamanoue, Fumiki Hirahara, Kazufumi Haino, Nobuhiro Suzumori, Naoki Hamajima, Naoki Hamajima, Yoko Okamoto, Hiroaki Nakamura, Takeshi Kanekawa, Jun Yoshimatsu, Hideaki Sawai, Shinya Tairaku, Katsuhiko Naruse, Hisashi Masuyama, Maki Hyodo, Takashi Kaji, Kazutoshi Maeda, Keiichi Matsubara, Masanobu Ogawa, Toshiyuki Yoshizato, Kiyonori Miura, Hideaki Masuzaki, Takashi Ohba, Yukie Kawano, Miyuki Nishiyama

  Prenatal Diagnosis 35 331 - 336 2015年01月01日 [査読無し][通常論文]
   

  © 2014 John Wiley & Sons, Ltd. Objective: To report the 1-year experience of a nationwide demonstration project to introduce noninvasive prenatal testing of aneuploidy from maternal plasma and discuss how to implement this program in Japan. Methods: The test was conducted to detect aneuploidy in high-risk pregnant women with adequate genetic counseling. The clinical data, test results, and pregnancy outcomes were recorded. Results: Of the 7740 women tested, 142 (1.8%) had positive results, 7594 (98.1%) had negative results, and four (0.1%) had results that were not reportable. Of the 142 women who tested positive, 13 cases resulted in intrauterine fetal death, and three cases refused to undergo the invasive procedure. Of the 126 positive cases confirmed on karyotyping, a normal karyotype was observed for trisomy 21 in three cases, trisomy 18 in eight cases, and trisomy 13 in two cases. In the follow-up study of the negative cases (n=1638), only one false-negative case of trisomy 18 was detected. Conclusions: We described our nationwide 1-year experience with noninvasive prenatal genetic testing. It is expected that the present data will stimulate a debate regarding prenatal genetic testing and hopefully lead to improvements in the perinatal care system with respect to genetic counseling in Japan.
• A Case of Prenatal Presentation with Double Aortic Arch.

  Shiono N, Takei K, Yamada T, Tachibana T, Cho K, Minakami H

  J Neonatal Biol 4 3 - 3 2015年 [査読有り][通常論文]
  
• Uptake of non-invasive prenatal testing by Japanese women

  R. Akaishi, T. Yamada, S. Kawaguchi, T. Kojima, T. Koyama, T. Umazume, M. Morikawa, K. Cho, H. Minakami

  ULTRASOUND IN OBSTETRICS & GYNECOLOGY 45 1 113 - 114 2015年01月 [査読有り][通常論文]
  
• 出血性びらん・子宮頸管ポリープ Ⅰ．妊娠週数ごとの健診の実際【妊娠11週まで】 ≪診断と外来対応≫ 妊婦健診のすべて――週数別・大事なことを見逃さないためのチェックポイント

  小島崇史, 山田崇弘

  臨床婦人科産科 69 78 - 81 2015年 [査読無し][招待有り]
  
• 骨系統疾患と遺伝 特集 産婦人科医必修！臨床遺伝学の最新知識

  山田崇弘, 澤井英明, 室月淳

  産婦人科の実際 64 345 - 348 2015年 [査読無し][招待有り]
  
• 出生前診断と生命倫理

  山田崇弘, 柴田有花, 矢部一郎

  小児内科 47 10 - 13 2015年 [査読無し][招待有り]
  
• 常位胎盤早期剥離の初期症状についての情報を妊娠30週までに全妊婦に提供することを忘れるべからず 妊娠中・後期[産科合併症] 【母体・胎児編】周産期診療べからず集

  山田崇弘

  「周産期医学」増刊号 45 189 - 190 2015年 [査読無し][招待有り]
  
• 陣痛発来入院時のアンチトロンビン(AT)活性値定期測定で偶然発見されたAT欠損症

  森川 守, 山田 竜太郎, 馬詰 武, 小島 崇史, 赤石 理奈, 小山 貴弘, 石川 聡司, 荒木 直人, 山田 崇弘, 長 和俊, 水上 尚典

  日本産婦人科・新生児血液学会誌 25 1 24 - 25 日本産婦人科・新生児血液学会 2015年 [査読有り][通常論文]
   

  27歳(初産婦)。妊娠40週4日に陣痛発来のため当科入院となった。入院時のAT活性値が異常低値を示したため、分娩直前にAT製剤を補充し、3150gの女児を無事に経腟分娩することができた。分娩後もAT製剤を補充し、その後の精査で先天性AT欠損症と診断され、半年毎の経過観察となった。2年後に再度妊娠したが、初期より未分化ヘパリン自己注射を開始し、分娩時は前回同様にAT製剤補充を行い経腟分娩した。
• 妊娠高血圧腎症の病態

  水上 尚典, 山田 崇弘, 森川 守, 山田 俊

  分娩と麻酔 96 20 - 24 (一社)日本産科麻酔学会 2014年12月
• Liver dysfunction in triplet pregnancies: Relation to antenatal changes in antithrombin activity and platelet count

  Ryutaro Nishida, Mamoru Morikawa, Takahiro Yamada, Rina Akaishi, Takashi Yamada, Hisanori Minakami

  JOURNAL OF OBSTETRICS AND GYNAECOLOGY RESEARCH 40 12 2177 - 2183 2014年12月 [査読有り][通常論文]
   

  AimThe aim of this study was to determine whether antenatal decline in antithrombin (AT) activity occurs frequently and precedes the development of perinatal liver dysfunction in women with triplet pregnancies. Material and MethodsA retrospective observational study was conducted on all women who gave birth to triplets at gestational week 22 at a single centre during a study period from January 2001 to March 2013. The following eight blood parameters were monitored weekly during the last 5 weeks of pregnancy and postpartum: AT activity, platelet count, fibrinogen, D-dimer, aspartate aminotransferase (AST), lactate dehydrogenase (LDH), uric acid and creatinine. Pregnancy-induced AT deficiency (PIATD) and gestational thrombocytopenia were defined as antenatal AT activity <70% of normal level and antenatal platelet count <150x10(9)/L, respectively. Liver dysfunction was defined as AST >40 IU/L. LDH elevation was defined as LDH >450 IU/L. ResultsSixteen women were eligible for this study. All variables except LDH exhibited significant changes antenatally: AT activity, platelet count and fibrinogen decreased, while D-dimer, AST, urate and creatinine increased. LDH increased significantly postpartum. PIATD, gestational thrombocytopenia, perinatal liver dysfunction, and LDH elevation occurred in eight, seven, six, and eight women, respectively. Liver dysfunction was preceded by PIATD alone in three, by both PIATD and gestational thrombocytopenia in one and by gestational thrombocytopenia alone in none of the subjects. After delivery, laboratory abnormalities similar to HELLP syndrome were seen in three women exclusively in the presence of PIATD. ConclusionsReduced AT activity was likely to precede perinatal liver dysfunction in women with triplets.
• Autophagy in the placenta of women with hypertensive disorders in pregnancy

  R. Akaishi, T. Yamada, K. Nakabayashi, H. Nishihara, I. Furuta, T. Kojima, M. Morikawa, T. Yamada, N. Fujita, H. Minakami

  PLACENTA 35 12 974 - 980 2014年12月 [査読有り][通常論文]
   

  Introduction: Autophagy has not been studied extensively in the human placenta. This study was performed to determine whether autophagy is increased in the placentas of women with hypertensive disorders in pregnancy compared to normotensive pregnancies. Methods: LC3-II and p62 protein expression were examined by quantitative Western blotting analysis in 40 placentas from women not experiencing labor pains. The 40 placentas were from 13, 8, and 19 women with preeclampsia, gestational hypertension, and normal pregnancy, respectively. Hypertensive disorders in pregnancy included preeclampsia and gestational hypertension. Results: LC3-II expression was significantly increased, while that of p62 was significantly reduced in 21 placentas of women with hypertensive disorders compared to those with normal blood pressure irrespective of the presence or absence of fetal growth restriction (FGR). LC3-II expression was also significantly increased in 13 placentas of women with preeclampsia irrespective of the presence or absence of FGR. Discussion: The results of this study suggested that autophagy is active in the placenta of hypertensive disorders even in the absence of FGR. (C) 2014 Elsevier Ltd. All rights reserved.
• Peripartum cardiomyopathy in a woman with preeclampsia with twin pregnancy.

  Umazume T, Yamada T, Yamada S, Minakami H

  BMJ Case Rep 2014 2014年11月20日 [査読有り][通常論文]
   

  A 27-year-old nulliparous Japanese woman with twin pregnancy developed preeclampsia at gestational week (GW) 26. Cardiac function was checked regularly as women carrying twins with preeclampsia are expected to have increased risk of peripartum cardiomyopathy (PPCM). Although conventional parameters including blood pressure, proteinuria, platelet count and liver function did not indicate early delivery, gradual worsening of left ventricular ejection fraction (LVEF) to 44% and plasma brain-type natriuretic peptide level of 254 pg/mL suggested impending PPCM and a need for early delivery at GW 32. A nadir LVEF value of 35% on postpartum day (PPD) 3 followed by a value of 49% on PPD 32 was seen in this patient with PPCM. This case highlights the risk of PPCM among women with preeclampsia carrying twins and the role of pregnancy termination in the clinical course of PPCM.
• Antenatal fibrinogen concentrations and postpartum haemorrhage

  T. Yamada, R. Akaishi, Y. Oda, R. Nishida, T. Yamada, S. Ishikawa, M. Morikawa, T. Kojima, H. Minakami

  INTERNATIONAL JOURNAL OF OBSTETRIC ANESTHESIA 23 4 365 - 370 2014年11月 [査読有り][通常論文]
   

  Background: It is unclear whether antenatal fibrinogen concentrations are associated with postpartum haemorrhage. Methods: This retrospective study included 871 women with a singleton pregnancy but no known risk factors for postpartum haemorrhage, in whom fibrinogen concentration was measured within the 21 days before delivery. Correlation between antenatal fibrinogen concentrations and estimated blood loss was analysed. We tested the hypothesis that the risk of postpartum haemorrhage was higher in women with antenatal fibrinogen concentrations of <3.3 g/L. Postpartum haemorrhage was defined as an estimated blood loss >= 700 mL following vaginal delivery and >= 1000 mL following caesarean delivery. Results: In women delivering vaginally (n = 337), estimated blood loss tended to increase with decreasing antenatal fibrinogen concentration (R = -0.107, P = 0.05), median fibrinogen concentration was significantly lower in 69 women with postpartum haemorrhage than in 268 women without postpartum haemorrhage (3.93 vs. 4.18 g/L, P = 0.025), and postpartum haemorrhage occurred significantly more often in women with fibrinogen concentrations <3.3 g/L than in those with concentrations >= 3.3 g/L (38% [11/29] vs. 19% [58/308], P = 0.018). In women undergoing caesarean delivery (n = 534), median fibrinogen concentration did not differ between those who experienced postpartum haemorrhage (n = 128) and those who did not (n = 406) (4.18 g/L vs. 4.07 g/L, P = 0.43). Antenatal fibrinogen concentrations of <3.3 g/L were not associated with higher rates of postpartum haemorrhage (26% [11/43] vs. 24% [117/491], P = 0.80). Conclusions: Antenatal fibrinogen concentration <3.3 g/L may be a risk factor for postpartum haemorrhage among women following vaginal delivery. (C) 2014 Elsevier Ltd. All rights reserved.
• 妊娠糖尿病の血糖管理と血糖自己測定法(SMBG) 血糖自己測定法(SMBG)は全ての妊娠糖尿病(GDM)妊婦に必要か?

  森川 守, 山田 竜太郎, 馬詰 武, 小島 崇史, 小山 貴弘, 石川 聡司, 赤石 理奈, 西田 竜太郎, 荒木 直人, 山田 崇弘, 水上 尚典

  糖尿病と妊娠 14 2 S - 74 (一社)日本糖尿病・妊娠学会 2014年10月
• Prevalence of human T-lymphotropic virus type 1 carriers among pregnant women in Hokkaido, Japan

  Takahiro Yamada, Takehiro Togashi, Hiroyuki Tsutsumi, Masahiro Imamura, Hitoshi Okubo, Mihiro Okabe, Noriko Takamuro, Kunio Tashiro, Koichi Yano, Nagafumi Yamamoto, Yukiko Hirakawa, Hisanori Minakami

  MICROBIOLOGY AND IMMUNOLOGY 58 8 427 - 431 2014年08月 [査読有り][通常論文]
   

  As there is a risk of MTCT of HTLV-1, the HSGP HTLV-1 MTCT was organized in 2011. To determine how many pregnant women are infected with HTLV-1 in Hokkaido, which is the northernmost and the second largest island in Japan with a population of 5 467 000 and 39 392 newborns in 2011, the HSGP HTLV-1 MTCT asked all facilities that may care for pregnant women in Hokkaido in July 2013 to provide information on the number of pregnant women who underwent screening for anti-HTLV-1 antibody using particle agglutination or chemiluminescent enzyme immunoassay, and the numbers of those with positive, equivocal, and negative test results in the screening and confirmation tests using western blotting or PCR methods in 2012, respectively. A total of 111 facilities participated in this study and provided information on 33 617 pregnant women who underwent screening in 2012, corresponding to approximately 85% of all pregnant women who gave birth in Hokkaido in 2012. Of 81 candidates for a confirmation test because of positive (n = 77) or equivocal (n = 4) results on screening, 63 (78%) underwent the confirmation test and, finally, 34 (0.1%) and 33 563 (99.8%) women were judged to be HTLV-1 carriers and non-carriers, respectively. It was concluded that the prevalence rate of HTLV-1 carriers was low, one per 1000 pregnant women in Hokkaido. Approximately 40 infants are born yearly to mothers infected with HTLV-1 in Hokkaido.
• 品胎妊娠における周産期肝機能障害についての検討 妊娠中のアンチトロンビン活性と血小板数との関連

  西田 竜太郎, 嶋田 知紗, 馬詰 武, 小島 崇史, 小山 貴弘, 赤石 理奈, 山田 崇弘, 森川 守, 山田 俊, 長 和俊, 水上 尚典

  日本周産期・新生児医学会雑誌 50 2 717 - 717 (一社)日本周産期・新生児医学会 2014年06月
• 妊婦交通事故に関する後方視的検討 妊婦交通事故搬送時の救急隊員の精神的負担について意識調査

  森川 守, 山田 崇弘, 長 和俊, 水上 尚典

  日本周産期・新生児医学会雑誌 50 2 756 - 756 (一社)日本周産期・新生児医学会 2014年06月
• 妊婦交通事故に関する後方視的検討 運転・同乗・シートベルト着用について妊婦への意識調査(多施設研究)

  森川 守, 山田 崇弘, 長 和俊, 水上 尚典, 山田 俊, 西川 鑑, 平山 恵美, 渡利 道子, 渡邊 行朗, 高後 裕匡

  日本周産期・新生児医学会雑誌 50 2 756 - 756 (一社)日本周産期・新生児医学会 2014年06月
• Spatio-Temporal Image Correlation(STIC)法を用いた遠隔胎児心臓スクリーニングの試み

  武井 黄太, 山田 崇弘, 塩野 展子, 山田 俊, 渡邊 行朗, 菅原 正樹, 三宅 敏一, 出口 圭三, 赤石 理奈, 森川 守, 水上 尚典

  日本周産期・新生児医学会雑誌 50 2 776 - 776 (一社)日本周産期・新生児医学会 2014年06月
• 先天性アンチトロンビン欠損症と先天性プロテインS欠損症を合併し健児を得た一例

  馬詰 武, 山田 崇弘, 嶋田 知紗, 小島 崇史, 小山 貴弘, 赤石 理奈, 西田 竜太郎, 森川 守, 水上 尚典

  日本周産期・新生児医学会雑誌 50 2 858 - 858 (一社)日本周産期・新生児医学会 2014年06月
• Risk of cerebral palsy associated with neonatal encephalopathy in macrosomic neonates

  Takahiro Yamada, Rina Akaishi, Takashi Yamada, Mamoru Morikawa, Masanori Kaneuchi, Hisanori Minakami

  JOURNAL OF OBSTETRICS AND GYNAECOLOGY RESEARCH 40 6 1611 - 1617 2014年06月 [査読有り][通常論文]
   

  Aim To determine whether macrosomic infants with a birthweight of 4.0kg or more have increased risk of cerebral palsy associated with neonatal encephalopathy (Enc-CP). Methods A retrospective review of 132 singleton infants with Enc-CP fulfilling all of the following criteria: born at gestational week (GW) 37 or more (n=126) or weighing 2.5kg or more at birth (n=116) in or after January 2009 in Japan; no identifiable causes of cerebral palsy other than antenatal or intrapartum hypoxia; and exhibition of neonatal encephalopathy. National statistics of Japan were used to determine the numbers of infants according to birthweight categories. Results Of the 116 infants with a birthweight of 2.5kg or more, 46 (39.7%), 49 (42.2%), 17 (14.7%) and four (3.4%) infants had birthweights of 2.5-2.99, 3.0-3.49, 3.5-3.99 and 4.0kg or more, respectively. Corresponding figures among Japanese infants born in 2009-2011 were 42.8%, 45.4%, 10.9% and 0.90%, respectively. Infants with a birthweight of 4.0kg or more had a relative risk (95% confidence interval) of Enc-CP of 3.89 (1.52-9.95) compared to those with a birthweight of 2.5-2.99kg. Conclusion Japanese infants with a birthweight of 4.0kg or more have increased risk of Enc-CP.
• 子宮温存困難な癒着胎盤における子宮摘出術は1期的と2期的のどちらが適当か?

  森川 守, 馬詰 武, 小島 崇史, 小山 貴弘, 赤石 理奈, 西田 竜太郎, 荒木 直人, 山田 崇弘, 長 和俊, 水上 尚典

  日本産婦人科・新生児血液学会誌 24 1 S - 82 日本産婦人科・新生児血液学会 2014年05月
• Successful pregnancy in a woman with uterine scarring by transverse fundal cesarean section

  Ryutaro Nishida, Mamoru Morikawa, Takahiro Yamada, Masamitsu Takeda, Rina Akaishi, Kazutoshi Cho, Hisanori Minakami

  JOURNAL OF OBSTETRICS AND GYNAECOLOGY RESEARCH 40 5 1420 - 1422 2014年05月 [査読有り][通常論文]
   

  There has been only one case to date of pregnancy outcome after fundal transverse cesarean section (FTC). We report a pregnancy established after FTC. The FTC was performed at gestational week (GW) 24 in this patient's first pregnancy, but the uterus was preserved. Magnetic resonance imaging studies performed four times in her second pregnancy consistently showed part of the uterine fundus in which the muscle layer was interrupted. Concern regarding spontaneous uterine rupture in the absence of labor pains prompted us to interrupt her pregnancy at GW 31(+5), delivering a premature, but otherwise healthy female infant, weighing 1832g. The infant required transient intratracheal intubation for respiratory distress syndrome (for less than 1h), but had an otherwise uneventful clinical course. Two cases, including ours, suggest that successful pregnancy outcome is feasible at least in some women with uterine scarring due to FTC.
• Do uterotonic drugs increase risk of abruptio placentae and eclampsia?

  Mamoru Morikawa, Kazutoshi Cho, Takahiro Yamada, Takashi Yamada, Shoji Sato, Hisanori Minakami

  ARCHIVES OF GYNECOLOGY AND OBSTETRICS 289 5 987 - 991 2014年05月 [査読有り][通常論文]
   

  To determine whether the use of uterotonics, including oxytocin and prostaglandins, increases the risk of abruptio placentae and eclampsia. A retrospective analysis was conducted among 260,174 Japanese women at term. Demographic characteristics were studied as possible candidates for risk factors of abruptio placentae and eclampsia using multivariate logistic regression analyses. A total of 1,058 (0.41 %) and 147 (0.06 %) women developed abruptio placentae and eclampsia, respectively. Abruptio placentae and eclampsia occurred in 177 (0.29 %) and 42 (0.07 %) of the 61,857 women treated with uterotonics, respectively. Multivariate regression analyses indicated that uterotonics did not increase risk of developing either abruptio placentae or eclampsia. Primiparity [odds ratio (95 % confidence interval) 1.41 (1.24-1.60)], age a parts per thousand yen35 years [1.17 (1.03-1.33)], and presence of hypertension [2.42 (1.93-3.03)] were significant independent risk factors for abruptio placentae, while advancing gestation [0.67 (0.63-0.71)] decreased risk of abruptio placentae. Primiparity [odds ratio (95 % confidence interval) 4.06 (2.49-6.63)], age < 20 years [2.44 (1.07-5.58)], presence of hypertension [28.7 (20.5-40.1)], and advancing gestation [1.28 (1.11-1.47)] were significant independent risk factors for eclampsia. The use of uterotonics did not increase the risk of abruptio placentae and eclampsia.
• Seasonal variation in the prevalence of pregnancy-induced hypertension in Japanese women

  Mamoru Morikawa, Takashi Yamada, Takahiro Yamada, Kazutoshi Cho, Shoji Sato, Hisanori Minakami

  JOURNAL OF OBSTETRICS AND GYNAECOLOGY RESEARCH 40 4 926 - 931 2014年04月 [査読有り][通常論文]
   

  AimWhether prevalence rate of pregnancy-induced hypertension (PIH), including gestational hypertension and pre-eclampsia, is lower for summer delivery than for winter delivery remains to be studied in Japanese women. MethodsThe prevalence rate of PIH was retrospectively determined according to month of year at delivery and at conception in 301510 Japanese women who gave birth to singleton infants on or after gestational week 22 between 2005 and 2009. ResultsThe overall prevalence of PIH was 4.6% (13848/301510). The prevalence rate of PIH, ranging 3.6-4.6% for women with deliveries in July-August was consistently lowest during the 5-year study period. The meanstandard deviation prevalence rate of 4.2 +/- 0.3% for delivery in July-August was significantly lower than those for any other month (January-February, 4.7 +/- 0.4%; March-April, 4.9 +/- 0.4%; May-June, 4.6 +/- 0.2%; September-October, 4.6 +/- 0.1%; and November-December, 4.6 +/- 0.2%). The prevalence rate of PIH was highest (4.9%) for women with conception in March and April and lowest (2.9%) for those with conception in November and December. ConclusionThe prevalence rate of PIH was higher for delivery in winter and early spring and lowest for summer delivery among Japanese women.
• 1絨毛膜2羊膜双胎における1児胎児発育不全に関する後方視的検討

  遠藤 大介, 森川 守, 千葉 健太郎, 荒木 直人, 小島 崇史, 河口 哲, 武田 真光, 西田 竜太郎, 山田 崇弘, 山田 俊, 櫻木 範明, 水上 尚典

  北海道産科婦人科学会会誌 58 1 123 - 124 北海道産科婦人科学会 2014年03月
• 妊娠初期に静脈血栓症をきたした2例

  細川 亜美, 武田 真光, 遠藤 大介, 千葉 健太郎, 小島 崇史, 河口 哲, 荒木 直人, 西田 竜太郎, 山田 崇弘, 森川 守, 家子 正裕, 山田 俊, 櫻木 範明, 水上 尚典

  北海道産科婦人科学会会誌 58 1 124 - 124 北海道産科婦人科学会 2014年03月
• 妊娠中の出血傾向で発見された後天性第XI因子欠乏症合併妊娠の1例

  小島 崇史, 山田 崇弘, 安本 篤史, 森下 英理子, 西田 竜太郎, 小山 貴弘, 石川 聡司, 武田 真光, 森川 守, 山田 俊, 松野 一彦, 家子 正裕, 櫻木 範明, 水上 尚典

  北海道産科婦人科学会会誌 58 1 120 - 120 北海道産科婦人科学会 2014年03月
• Effects of campaign for postpartum vaccination on seronegative rate against rubella among Japanese women

  Takahiro Yamada, Junko Mochizuki, Masachi Hanaoka, Eriko Hashimoto, Akihide Ohkuchi, Mika Ito, Takahiko Kubo, Akihito Nakai, Shigeru Saito, Nobuya Unno, Shigeki Matsubara, Hisanori Minakami

  BMC INFECTIOUS DISEASES 14 152  2014年03月 [査読有り][通常論文]
   

  Background: Japan experienced two rubella outbreaks in the past decade (2004 and 2012 - 2013), resulting in 10 and 20 infants with congenital rubella syndrome (CRS), respectively. This study was performed to determine whether the seronegative rate was lower in multiparous women than in primiparous women in Japan. Methods: Hemagglutination inhibition (HI) test results during pregnancy were analyzed retrospectively in 11048 primiparous and 9315 multiparous women who gave birth at six hospitals in northern Japan in the 5-year study period (January 2008 through December 2012). Women with HI titer < 1: 8 were defined as susceptible to rubella. Results: The seronegative rate was significantly lower in multiparous than primiparous women aged 30 - 31 years (2.3% [22/967] vs. 4.5% [66/1454], P = 0.0036), 36 - 37 years (3.4% [55/1601] vs. 5.7% [79/1389], P = 0.0030), and overall women (3.8% [350/9315] aged 34.7 +/- 5.2 vs. 5.4% [597/11048] for 33.2 +/- 5.9, P < 0.001). The susceptible fraction size did not differ largely according to hospital, ranging from 3.5% to 6.3%. Those for each year did not change markedly; 4.5% [150/3369], 5.2% [221/4268], 4.4% [195/4412], 4.6% [186/4056], and 4.6% [195/4258] for 2008, 2009, 2010, 2011, and 2012, respectively. Those for teenagers were consistently high: 22.7% [5/22], 20.7% [6/29], 20.6% [7/34], 13.0% [3/23], and 23.5% [4/17] for 2008, 2009, 2010, 2011, and 2012, respectively. Conclusions: The seronegative rate was significantly lower in multiparous than primiparous women. However, Japanese rubella vaccination programs were insufficient to eliminate CRS.
• Immune status among Japanese during nationwide rubella outbreak in Japan 2012-2013

  Takahiro Yamada, Takahiko Kubo, Junko Mochizuki, Eriko Hashimoto, Akihide Ohkuchi, Mika Ito, Masachi Hanaoka, Akihito Nakai, Shigeru Saito, Nobuya Unno, Shigeki Matsubara, Hisanori Minakami

  JOURNAL OF INFECTION 68 3 300 - 302 2014年03月 [査読有り][通常論文]
  
• Differentiation of acute fatty liver of pregnancy from syndrome of hemolysis, elevated liver enzymes and low platelet counts

  Hisanori Minakami, Mamoru Morikawa, Takahiro Yamada, Takashi Yamada, Rina Akaishi, Ryutaro Nishida

  JOURNAL OF OBSTETRICS AND GYNAECOLOGY RESEARCH 40 3 641 - 649 2014年03月 [査読有り][通常論文]
   

  As proposed criteria (Swansea criteria) for the diagnosis of acute fatty liver of pregnancy (AFLP) do not include antithrombin (AT) activity, diagnosis of AFLP may be delayed. The aim of this review is to underscore problems in the differential diagnosis of AFLP and the syndrome of hemolysis, elevated liver enzymes and low platelet counts (HELLP syndrome) and to facilitate prompt diagnosis of AFLP. Published works dealing with liver dysfunction in pregnancy, HELLP syndrome and AFLP were reviewed. AFLP and HELLP syndrome shared common clinical, laboratory, histological and genetic features, and differential diagnosis between them was often difficult. However, HELLP syndrome was likely to occur in patients with hypertension, but AFLP occurred often in the absence of hypertension. In addition, AFLP was exclusively associated with pregnancy-induced antithrombin deficiency (PIATD). Approximately 50% of patients with AFLP did not have thrombocytopenia at presentation. As the Swansea criteria for AFLP did not include PIATD, diagnosis of AFLP was delayed until manifestation of life-threatening complications; 60% of women were admitted to intensive care and 15% to a specialist liver unit. In conclusion, incorporation of AT activity of less than 65% into the diagnostic criteria for AFLP may facilitate suspicion and prompt diagnosis of AFLP, decrease uncertainty regarding the diagnosis of AFLP, and contribute to better investigation and understanding of the process leading to the development of liver dysfunction.
• 胎児の循環機能評価 胎児心拍数波形5段階レベル分類におけるコンピューター判定システム(TRIUM)と医師のレベル判定一致率とそれに及ぼす要因(心拍数基線、基線細変動、一過性徐脈)の検証

  三宅 菜月, 横井 暁, 宮崎 顕, 南 宏次郎, 前田 眞, 堀部 暢人, 馬場 真澄, 亀井 良政, 村林 奈緒, 山田 崇弘, 多田 和美, 紀平 正道

  日本産科婦人科学会雑誌 66 2 452 - 452 (公社)日本産科婦人科学会 2014年02月 [査読有り][通常論文]
  
• Prospective risk of abruptio placentae

  Mamoru Morikawa, Takahiro Yamada, Kazutoshi Cho, Takashi Yamada, Shoji Sato, Hisanori Minakami

  JOURNAL OF OBSTETRICS AND GYNAECOLOGY RESEARCH 40 2 369 - 374 2014年02月 [査読有り][通常論文]
   

  AimThe aim of this study was to better characterize the nature of abruptio placentae (AP) with regard to the timing of onset. Material and MethodsPrevalence and prospective risk of AP according to gestational week (GW) were determined among 293899 women who gave birth to singleton infants at and after GW 30. The prospective risk of AP at gestational week N was defined as the number of all women who experienced an AP at GW N divided by the number of all women who gave birth at GW N. ResultsAP developed in 2649 (0.90%) women. The prevalence of AP (6.7% among women who gave birth at GW 30-33) sharply decreased with advancing GW at delivery to 0.9% for GW 37 and 0.1% for GW 42. The highest prospective risk of AP, 9 per 1000 women at GW 30, decreased linearly with advancing gestation to 1 per 1000 women at GW 42. AP accounted for 4.7% (1591/33725) of all preterm births at GW <37, while prevalence of AP was 0.41% (1058/260174) among term births. Preterm AP accounted for 60.1% (1591/2649) of all AP. ConclusionOur figures indicate that AP is more common in preterm births than in term birth and may be helpful for better understanding the epidemiology of this condition.
• Essential thrombocythemia as a risk factor for stillbirth

  Takeshi Umazume, Takahiro Yamada, Rina Akaishi, Naoto Araki, Ryutaro Nishida, Mamoru Morikawa, Hisanori Minakami

  THROMBOSIS RESEARCH 133 2 158 - 161 2014年02月 [査読有り][通常論文]
   

  Introduction: The risk of abortion is known to be high in women with essential thrombocythemia (ET). However, a few studies have focused on the risk of stillbirth among fetuses reaching gestational age compatible with life. Methods: Review of medical charts of pregnant women with ET who received cares at a single center between January 2003 and June 2013 and the English literature in which more than 20 pregnancies with ET were dealt with regarding outcomes. Outcomes were classified into three categories: spontaneous abortion or preterm delivery before GW 24, stillbirth at and after GW 24, and live birth (LB). Japan national statistics was used to estimate the risk of stillbirth among women with GW 22 or more. Results: In all nine pregnancies in four women with ET at our hospital, two miscarriages, one stillbirth (intrauterine death at GW 35), and six LBs occurred. There were six reports in the English literature in which a total of 374 pregnancy outcomes were described: 110 miscarriages (29%), 14 stillbirths (3.7% of all 374 pregnancies and 5.3% of 264 pregnancies with GW >= 24), and 250 LBs (67%) occurred. Japan national statistics between 1995 and 2011 indicated that the risk of stillbirth was less than 0.50% among women with GW >= 22. Conclusions: The risk of still birth was extremely high among women with ET. More intensified monitoring of fetal wellbeing may be required to improve outcome of pregnancy complicated with ET. (C) 2013 Elsevier Ltd. All rights reserved.
• Electronic fetal heart rate monitoring in five fetuses with Ebstein’s anomaly.

  Morikawa M, Endo D, Yamada T, Cho K, Yamada T, Minakami H

  J Obstet Gynecol Res 40 2 424 - 428 2014年02月 [査読有り][通常論文]
   

  AimIt is not clear whether fetuses with Ebstein's anomaly are likely to show abnormalities on electronic fetal heart rate (FHR) monitoring during labor. MethodsWe performed retrospective analysis of FHR monitoring results obtained between 2.5 and 0.5h prior to delivery in all of five fetuses prenatally diagnosed as having Ebstein's anomaly and born at our institution during the period between March 2005 and July 2011. All five mothers attempted to give birth vaginally. The results of FHR monitoring in 100 consecutive women with otherwise healthy singletons who attempted vaginal delivery were included as controls. ResultsThe absence of FHR acceleration (4/5 [80%]), decreased baseline FHR variability (3/5 [60%]) and late deceleration (4/5 [80%]) were seen significantly more often in the five fetuses with Ebstein's anomaly than the 100 fetuses born to control women (6.0%, 6.0%, and 10%, respectively). ConclusionFetuses with Ebstein's anomaly during labor were likely to exhibit absent acceleration, decreased baseline FHR variability and late deceleration compared to infants without cardiac structural anomalies.
• Impact of planning of pregnancy in women with epilepsy on seizure control during pregnancy and on maternal and neonatal outcomes

  Kanako Abe, Hiromi Hamada, Takahiro Yamada, Mana Obata-Yasuoka, Hisanori Minakami, Hiroyuki Yoshikawa

  SEIZURE-EUROPEAN JOURNAL OF EPILEPSY 23 2 112 - 116 2014年02月 [査読有り][通常論文]
   

  Purpose: To investigate whether planning of pregnancy in women with epilepsy affects seizure control during pregnancy and to compare the maternal and neonatal outcomes in planned and unplanned pregnancies. Methods: This was a retrospective cohort study of 153 pregnant women with epilepsy who were treated at the University of Tsukuba Hospital and Hokkaido University Hospital between 2003 and 2011. Twenty-one pregnancies were excluded due to insufficient data. Data of patients followed by neurologists during their planned pregnancies (planned-pregnancy group, n = 51) were compared to those of patients referred to neurologists after conception for managing epilepsy during pregnancy (unplanned-pregnancy group, n = 81). The treatment profile for epilepsy, seizure control, and maternal and neonatal outcomes in both groups were compared using Chi-square test or Fisher's exact test and Mann-Whitney U test. Results: Compared to the unplanned-pregnancy group, the planned-pregnancy group showed a significantly greater proportion of patients receiving monotherapy with antiepileptic drugs (80% vs. 61%: planned vs. unplanned, P = 0.049) and those not requiring valproic acid (77% vs. 56%, P = 0.031). Furthermore, the frequency of epileptic seizures (16% vs. 35%, P = 0.018) and changes in antiepileptic drugs (24% vs. 41%, P = 0.042) were significantly lower in the planned-pregnancy group than in the unplanned-pregnancy group. No significant intergroup differences were noted in the obstetric complications and neonatal outcomes, including congenital malformations. Conclusion: For women with epilepsy, planning of pregnancy is associated with good seizure control during pregnancy and less fetal exposure to antiepileptic drugs. (C) 2013 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.
• Association of NT-proBNP with plasma renin activity and plasma aldosterone concentration in women with singleton pregnancy

  Takashi Yamada, Takahiro Koyama, Itsuko Furuta, Masamitsu Takeda, Ryutaro Nishida, Takahiro Yamada, Mamoru Morikawa, Hisanori Minakami

  PREGNANCY HYPERTENSION-AN INTERNATIONAL JOURNAL OF WOMENS CARDIOVASCULAR HEALTH 4 1 23 - 28 2014年01月 [査読有り][通常論文]
   

  Objective: To determine the association of the N-terminal fragment of precursor protein brain-type natriuretic peptide (NT-proBNP) levels with plasma renin activity (PRA) and plasma aldosterone concentration (PAC) in singleton pregnancies. Design: Serum NT-proBNP levels, PRA and PAC were determined in 215 blood specimens from 139 women with singleton pregnancies, including 34 and 105 women who did and did not develop hypertensive disorders in pregnancy, respectively. Twenty-five blood specimens were obtained from 25 women who later developed hypertension (systolic BP >= 140 mmHg and/or diastolic BP >= 90 mmHg), but were normotensive at the time of blood sampling. Results: The serum NT-proBNP levels [pg/ml, median (range), 32 (5-142)] did not change in normotensive women, but increased significantly to 97 (23-436) after the development of hypertension (D/H). The PRA [ng/ml/h, median (range), 7.1 (1-20)] did not change in normotensive women, but decreased significantly to 1.9 (1-16) after D/H. PAC (pg/ml) increased significantly from 397 (94-1750) to 667 (123-2010) between the 2nd and 3rd trimesters in normotensive women. However, as PAC of hypertensive women did not change significantly before and after D/H, PAC [293 (116-1720)] after D/H was significantly lower than that [667 (123-2010)] of the 3rd trimester in the normotensive women. The serum levels of NT-proBNP were significantly and negatively correlated with both PRA and PAC. Conclusions: The renin-angiotensin-aldosterone system is suppressed in pregnant women with cardiac conditions associated with higher NT-proBNP levels. (C) 2013 International Society for the Study of Hypertension in Pregnancy Published by Elsevier B.V. All rights reserved.
• Extraordinary weight gain: initial finding in a patient with peripartum cardiomyopathy.

  山田崇弘

  Case Reports in Perinatal Medicine, 3 1 45 - 47 Walter de Gruyter 2014年 [査読有り][通常論文]
   

  Extraordinary weight gain may be an initial finding in some patients with peripartum cardiomyopathy (PPCM). This case highlights the need for studies of therelationship between degrees of antenatal weight gain and risk of PPCM. A 33-year-old woman exhibited weight gain of 1.0 kg/week (38.5–60.6 kg) between gestational weeks (GW) 12+2 and 33+2 at which dyspnea appeared. Her body weight further increased to 69.1 kg at GW 34+2 at which echocardiography revealed left ventricular dysfunction (ejection fraction = 27%, fractional shortening = 4.0%). She then lost 24 kg in body weight by 4 weeks postpartum.
• Clinical features of isolated gestational proteinuria progressing to pre-eclampsia: retrospective observational study

  Rina Akaishi, Takahiro Yamada, Mamoru Morikawa, Ryutaro Nishida, Hisanori Minakami

  BMJ OPEN 4 4 e004870  2014年 [査読有り][通常論文]
   

  Objectives Some women with isolated gestational proteinuria (IGP) later develop hypertension and are diagnosed with pre-eclampsia (PE). This study was performed to determine whether clinical features of such proteinuria preceding PE (P-PE) differ from those of other PE (O-PE). Design Retrospective observational study after approval of the institutional review board of ethics. Setting A single university hospital. Proteinuria was defined as a protein-to-creatinine ratio (mg/mg; P/Cr) of 0.27 in the spot urine specimen. IGP was defined as proteinuria in the absence of hypertension. P-PE was defined as PE in which proteinuria preceded hypertension by more than 2days. Participants All of 10 and 18 consecutive women with P-PE and O-PE, respectively, who gave birth between January 2008 and August 2013. Results Proteinuria appeared earlier (at 30.23.0 vs 35.3 +/- 4.3weeks, p=0.001), the P/Cr level was greater at birth (7.28 +/- 2.14 vs 3.19 +/- 2.49, p<0.001), net maternal weight gain during the last antenatal 1week was greater (3.1 +/- 1.8 vs 1.3 +/- 1.7kg, p=0.023) and length of pregnancy was shorter (32.5 +/- 1.9 vs 36.1 +/- 3.6weeks, p=0.001) in women with P-PE than in O-PE. The duration of IGP was 10.0 +/- 5.9days (range 3-20), and the time interval until delivery after diagnosis of PE was 6.1 +/- 8.2days (range 0-23) in 10 women with P-PE. The P/Cr levels at birth were significantly inversely correlated with the antenatal lowest antithrombin activity and fibrinogen levels among the 28 women with PE. Conclusions Women with P-PE were likely to exhibit greater proteinuria in the urine, greater water retention in the interstitial space and more enhanced coagulation-fibrinolysis, thus suggesting that they may constitute a more severe form of PE than women with O-PE do.
• Problems in methods for the detection of significant proteinuria in pregnancy

  Takahiro Yamada, Takashi Kojima, Rina Akaishi, Satoshi Ishikawa, Masamitsu Takeda, Satoshi Kawaguchi, Ryutaro Nishida, Mamoru Morikawa, Takashi Yamada, Hisanori Minakami

  JOURNAL OF OBSTETRICS AND GYNAECOLOGY RESEARCH 40 1 161 - 166 2014年01月 [査読有り][通常論文]
   

  AimThe aim of this study was to underscore problems associated with the dipstick test and determination of protein concentration alone in spot-urine (P-test) compared with spot-urine protein-to-creatinine ratio (P/Cr test) and to determine whether urine collection for 24-h test was complete. Material and MethodsDipstick and P/Cr tests were performed simultaneously in 357 random spot-urine specimens from 145 pregnant women, including 35 with pre-eclampsia. Positive results were defined as 1+ on dipstick test, protein concentration 30mg/dL on P-test, and P/Cr ratio0.27 (mg/mg) on P/Cr test. Sixty-four 24-h urine tests (quantification of protein in urine collected during 24h) were performed in 27 of the 145 women. We assumed that P/Cr ratio0.27 predicted significant proteinuria (urinary protein0.3g/day). The 24-h urine collection was considered incomplete when urinary creatinine excretion was<11.0mg/kg/day or >25.0mg/kg/day. ResultsForty-four percent (69/156) of specimens with a positive test result on dipstick test contained protein<30mg/dL. Dipstick test was positive for 25.7% (69/269) of specimens with protein<30mg/dL and for 28.8% (79/274) of specimens with P/Cr ratio<0.27. P-test results were positive for 7.3% (20/274) and negative for 18.1% (15/83) of specimens with P/Cr ratio<0.27 and 0.27, respectively. Incomplete 24-h urine collection occurred in 15.6% (10/64) of 24-h urine tests. Daily urinary creatinine excretion was 702-1397mg, while creatinine concentration varied from 16mg/dL to 475mg/dL in spot-urine specimens. ConclusionDipstick test and P-test were likely to over- and underestimate risks of significant proteinuria, respectively. The 24-h urine collection was often incomplete.
• 産科ショックへの対応．研修コーナー

  山田崇弘, 水上尚典

  日産婦誌 2014年 [査読無し][招待有り]
  
• 染色体異常スクリーニング：血清マーカー検査・胎児後頸部浮腫. 特集：遺伝子検査による早期診断

  赤石理奈, 山田崇弘

  周産期医学 44 2 189 - 192 東京医学社 2014年 [査読無し][招待有り]
  
• 胎児染色体検査とマイクロアレイ．特集「出生前遺伝学的検査」

  山田崇弘

  日産婦誌 66 982 - 988 2014年 [査読有り][招待有り]
  
• 妊婦のB群溶連菌感染症 II.産科から見た周産期感染症 特集：周産期感染症

  山田崇弘, 水上尚典

  周産期医学 44 127 - 129 2014年 [査読無し][招待有り]
  
• 出生前診断（NIPTを除く） 遺伝子医療の現状遺伝子医療の現状とゲノム医療の近未来

  山田崇弘

  医学のあゆみ 250 378 - 382 2014年 [査読無し][招待有り]
  
• HELLP症候群・臨床的急性妊娠脂肪肝の早期発見法 今月の臨床 診療ガイドライン産科編2014 改訂と追加のポイント

  山田崇弘, 水上尚典

  臨床婦人科産科 68 779 - 783 2014年 [査読無し][招待有り]
  
• 子宮収縮薬の使用指針 今月の臨床 診療ガイドライン産科編2014 改訂と追加のポイント

  山田崇弘, 水上尚典

  臨床婦人科産科 68 795 - 798 2014年 [査読無し][招待有り]
  
• Number of women requiring care at a tertiary hospital equipped with a neonatal intensive care unit at night in an area with a population of 2 million

  Takahiro Yamada, Kazutoshi Cho, Mamoru Morikawa, Takashi Yamada, Rina Akaishi, Satoshi Ishikawa, Hisanori Minakami

  JOURNAL OF OBSTETRICS AND GYNAECOLOGY RESEARCH 39 12 1592 - 1595 2013年12月 [査読有り][通常論文]
   

  AimWomen with imminent premature labor (IPL) are transported to a tertiary hospital equipped with neonatal intensive care unit (NICU) even during the night. However, there have been no extensive studies of the occurrence rate of night IPL. The aim of this study was to determine the occurrence rate of night IPL in an area with a population of 2 million. Materials and MethodsA retrospective analysis was conducted using data collected by the Sapporo Obstetric System for Emergency Patients launched in October 2008, in which women, physicians, and ambulance staff who sought appropriate obstetric/gynecological facilities available in the night (19.00-06.00hours) were informed of candidate hospitals by coordinators through telephone consultation. This system covered the Sapporo area, which has a population of 2000000 and 17000 births annually. Approximately 14% and 86% of women received antenatal care at six and 35 obstetric facilities with and without NICU, respectively, in this area. Night IPL was defined as a threatened premature labor and transport to one of six tertiary hospitals with NICU between 19.00 and 06.00hours the next morning. ResultsDuring a 4-year period from 1 October 2008 to 30 September 2012, the Sapporo Obstetric System for Emergency Patients received 15823 (mean +/- standard deviation) monthly telephone consultations (range 114-218 per month). The monthly number of patients with night IPL was 3.0 +/- 2.2 (range 0-9 per month). ConclusionsThe monthly number of cases of night IPL was around three among women who received antenatal care at obstetrics facilities without NICU in an area with a population of 2000000.
• Unusual clinical course of preeclampsia heralded by generalized edema

  Takashi Kojima, Takahiro Yamada, Takashi Yamada, Mamoru Morikawa, Kazutoshi Cho, Hisanori Minakami

  JOURNAL OF OBSTETRICS AND GYNAECOLOGY RESEARCH 39 11 1538 - 1540 2013年11月 [査読有り][通常論文]
   

  Preeclampsia monitored by the amount of proteinuria usually does not show amelioration during pregnancy. A 37-year-old nulliparous woman was admitted to our hospital at gestational week (GW) 24(-1/7) due to rapid weight gain (6.2kg/4 weeks) and oligohydramnios. Hypertension (151/91mmHg) appeared at GW 25(-0/7) and proteinuria not detected at GW 24(-0/7) became significant (0.55g/day) at GW 25(-2/7). During the 2 successive weeks after administration of betamethasone at 12mg twice and transabdominal amnioinfusion with 250mL of Ringer's acetate solution at GW 25(-3/7), generalized edema, proteinuria and thrombocytopenia markedly improved: bodyweight, 78.0 to 69.0kg; proteinuria, from 7.1 to 1.3g/day; and platelet count, from 111 to 230 x 10(9)/L. However, intrauterine infection accompanied by non-reassuring fetal status necessitated emergency cesarean section at GW 28(-3/7). Extraordinary bodyweight gain can herald the occurrence of preeclampsia and this weight gain together with signs of preeclampsia can ameliorate even during pregnancy, although its mechanism is unclear.
• 双胎妊娠では単胎妊娠に比べ妊娠糖尿病が発症しやすいか?

  森川 守, 山田 崇弘, 赤石 理奈, 小山 貴弘, 嶋田 知紗, 小島 崇史, 荒木 直人, 西田 竜太郎, 水上 尚典

  糖尿病と妊娠 13 2 S - 79 (一社)日本糖尿病・妊娠学会 2013年10月
• 多量の胸腹水に対して行った胎児胸腔羊水腔シャントが有効であった一例

  荒木 直人, 赤石 理奈, 河口 哲, 西田 竜太郎, 山田 崇弘, 森川 守, 長和 俊, 水上 尚典

  北日本産科婦人科学会総会・学術講演会プログラム・抄録集 61回 93 - 93 東北連合産科婦人科学会・北日本産科婦人科学会 2013年09月
• Viable delivery after conservative management of a cesarean scar pregnancy.

  Nishida R, Yamada T, Yamada T, Morikawa M, Kawaguchi S, Minakami H

  Journal of ultrasound in medicine : official journal of the American Institute of Ultrasound in Medicine 32 1682 - 1684 9 2013年09月 [査読有り][通常論文]
  
• Clinical significance of proteinuria determined with dipstick test, edema, and weekly weight gain ⩾500g at antenatal visit.

  Chiba K, Yamada T, Kawaguchi S, Takeda M, Nishida R, Yamada T, Morikawa M, Minakami H

  Pregnancy hypertension 3 3 161 - 165 Elsevier 2013年07月 [査読有り][通常論文]
  
• Changes in d-dimer levels in pregnant women according to gestational week.

  Kawaguchi S, Yamada T, Takeda M, Nishida R, Yamada T, Morikawa M, Minakami H

  Pregnancy hypertension 3 3 172 - 177 Elsevier 2013年07月 [査読有り][通常論文]
  
• Labor induction by transcervical balloon catheter and cerebral palsy associated with umbilical cord prolapse

  Takahiro Yamada, Kazutoshi Cho, Takashi Yamada, Mamoru Morikawa, Hisanori Minakami

  JOURNAL OF OBSTETRICS AND GYNAECOLOGY RESEARCH 39 6 1159 - 1164 2013年06月 [査読有り][通常論文]
   

  Aim The aim of this study was to determine whether the use of transcervical balloon catheter (TCBC) for induction of labor (IOL) is a risk factor for cerebral palsy (CP) associated with umbilical cord prolapse (UCP-CP) in singleton pregnancies with cephalic presentation. Material and Methods Among all 102 infants with CP who were preliminarily determined as caused by antenatal and/or intrapartum hypoxemia by the Japan Council for Quality Health Care until April 2012, all 56 infants who met all of the following criteria were studied: cephalic singleton pregnancy, reassuring fetal status on electronic cardiotocogram at time of admission to obstetric facilities for labor pains, ruptured fetal membranes, and/or IOL, and hypoxic-ischemic encephalopathy at birth. Clinical backgrounds were compared between six infants with UCP-CP and the remaining 50 infants with CP not associated with UCP (non-UCP-CP). Results Frequencies of IOL (83% [5/6] vs 32% [16/50], P=0.0236), use of TCBC (67% [4/6] vs 10% [5/50], P=0.0044), and amniotomy (67% [4/6] vs 24% [12/50], P=0.0494) were significantly higher in the UCP-CP than the non-UCP-CP group. Only TCBC was a risk factor significantly associated with UCP-CP after logistic regression analysis, yielding an odds ratio of 18.0 (95% confidence interval, 2.6-124; P=0.003). Saline volumes of 80-150mL were used for TCBC inflation in the four UCP-CP patients. Conclusion Use of TCBC with a saline volume80mL was a significant risk factor for UCP-CP; however, the absolute risk of UCP-CP was estimated to be very low, approximately one in 7875 TCBC users.
• Difference in the D-dimer rise between women with singleton and multifetal pregnancies

  Takashi Yamada, Satoshi Kawaguchi, Naoto Araki, Masamitsu Takeda, Ryutaro Nishida, Takahiro Yamada, Mamoru Morikawa, Hisanori Minakami

  Thrombosis Research 131 6 493 - 496 2013年06月 [査読有り][通常論文]
   

  Introduction The differences in the d-dimer rise between women with singleton and multifetal pregnancies have not been studied extensively. Materials and Methods d-Dimer levels were determined in 1089 blood specimens from 1089 women in various stages of pregnancy, including 977 and 112 women with singleton and multifetal pregnancies, respectively. None of the 1089 women developed hypertension or clinical venous thromboembolism during pregnancy or in the postpartum period. Results The d-dimer levels were significantly and positively correlated with gestational week at examination in women with singleton or multifetal pregnancies. The d-dimer levels (μg/ml, mean ± SD [number of specimens]) determined at the 1st trimester did not differ significantly (0.81 ± 0.82 [102] for singleton vs. 1.20 ± 0.77 [7] for multifetal), but those at the 2nd (1.61 ± 1.45 [216] vs. 2.62 ± 2.26 [59]) and 3rd (2.37 ± 2.22 [659] vs. 4.02 ± 2.14 [46]) trimesters were significantly higher in women with multifetal than singleton pregnancies. The 90th percentile value was 4.31 μg/ml for 1089 specimens. A significantly greater number of women exceeded 4.31 μg/ml during the 2nd (16.9% vs. 5.6%, P = 0.0043) and 3rd (34.8% vs. 10.6%, P < 0.0001) trimesters among those with multifetal than with singleton pregnancies. Conclusions The degree of d-dimer rise in pregnancy was greater in women with multifetal than with singleton pregnancies. © 2013 Elsevier Ltd.
• 本邦における品胎妊娠における臨床的特徴と短期周産期予後

  森川 守, 長 和俊, 山田 俊, 山田 崇弘, 水上 尚典

  日本周産期・新生児医学会雑誌 49 2 646 - 646 (一社)日本周産期・新生児医学会 2013年06月
• 子宮底部横切開による帝王切開術後の妊娠管理の経験

  武田 真光, 山田 崇弘, 山田 俊, 遠藤 大介, 千葉 健太郎, 河口 哲, 森川 守, 水上 尚典

  日本周産期・新生児医学会雑誌 49 2 665 - 665 (一社)日本周産期・新生児医学会 2013年06月
• 妊娠中の抗甲状腺抗体陽性および潜在性甲状腺機能低下症と産後甲状腺機能異常との関連について

  西田 竜太郎, 山田 俊, 小島 崇史, 河口 哲, 山田 崇弘, 森川 守, 長 和俊, 水上 尚典

  日本周産期・新生児医学会雑誌 49 2 694 - 694 (一社)日本周産期・新生児医学会 2013年06月
• 当科で経験した先天性第7因子欠乏症合併妊娠3例の検討

  小島 崇史, 山田 崇弘, 遠藤 大介, 千葉 健太郎, 河口 哲, 武田 真光, 西田 竜太郎, 森川 守, 水上 尚典

  日本周産期・新生児医学会雑誌 49 2 700 - 700 (一社)日本周産期・新生児医学会 2013年06月
• 本邦における妊娠性高血圧症候群の発症率には季節変動がある

  森川 守, 山田 俊, 山田 崇弘, 長 和俊, 水上 尚典

  日本周産期・新生児医学会雑誌 49 2 703 - 703 (一社)日本周産期・新生児医学会 2013年06月
• 妊婦のVTE診断に対するD-dimerの有用性

  河口 哲, 山田 俊, 遠藤 大介, 千葉 健太郎, 小島 崇史, 武田 真光, 西田 竜太郎, 山田 崇弘, 森川 守, 水上 尚典

  日本周産期・新生児医学会雑誌 49 2 892 - 892 (一社)日本周産期・新生児医学会 2013年06月
• Fetal macrosomia in Japanese women

  Mamoru Morikawa, Kazutoshi Cho, Takashi Yamada, Takahiro Yamada, Shoji Sato, Hisanori Minakami

  JOURNAL OF OBSTETRICS AND GYNAECOLOGY RESEARCH 39 5 960 - 965 2013年05月 [査読有り][通常論文]
   

  Aim It is unknown how to reduce the number of macrosomic neonates among women without hyperglycemia. The aim of this study was to determine clinically useful risk factors for macrosomic neonates among women without hyperglycemia. Material and Methods A retrospective observational study was conducted in 117680 Japanese women without hyperglycemia who gave birth to singleton infants at 37 weeks of gestation or later. Maternal age, parity, fetal sex, pregnancy length, and maternal body composition were studied as possible candidates for risk factors of macrosomic neonates using multivariate logistic regression analyses. Outcome measures were clinically available independent risk factors for macrosomic neonates weighing 4000g or more. Results A total of 1037 (0.9%) women gave birth to macrosomic neonates. A male fetus (odds ratio [95% confidence interval]: 1.99 [1.752.27]), multiparity (1.75 [1.531.99]), pregnancy length of 41 weeks or more (4.28 [3.734.91]) and six characteristics at or above the 90th percentile values consisting of body height (1.65m: 1.70 [1.451.99]), pre-pregnancy body weight (65kg: 1.47 [1.121.93]), pre-pregnancy body mass index (BMI) (25kg/m2: 1.49 [1.161.91]), weight gain during pregnancy (15kg: 2.32 [1.783.03]), BMI gain during pregnancy (6.0kg/m2: 1.52 [1.162.00]), and body weight at delivery (75kg: 2.57 [2.083.17]) were identified as independent risk factors for macrosomia. Conclusion Intervention, such as a counseling on dietary habits leading to a lesser net weight gain may be considered among women suspected of having fetal overgrowth.
• 妊娠中のD-dimer 単胎vs多胎

  荒木 直人, 山田 俊, 森川 守, 河口 哲, 西田 竜太郎, 山田 崇弘, 武田 真光, 水上 尚典

  日本産婦人科・新生児血液学会誌 23 1 S - 36 日本産婦人科・新生児血液学会 2013年05月
• 当科における癒着胎盤に対する回収式自己血輸血の経験

  森川 守, 山田 崇弘, 長 和俊, 水上 尚典, 金内 優典, 櫻木 範明, 金山 尚裕

  日本産婦人科・新生児血液学会誌 23 1 6 - 7 日本産婦人科・新生児血液学会 2013年05月
• 当科における貯血式自己血輸血に関する検討

  森川 守, 山田 崇弘, 山田 俊, 長 和俊, 水上 尚典

  日本産婦人科・新生児血液学会誌 23 1 12 - 13 日本産婦人科・新生児血液学会 2013年05月
• Clinical features and short-term outcomes of triplet pregnancies in Japan

  Mamoru Morikawa, Kazutoshi Cho, Takashi Yamada, Takahiro Yamada, Shoji Sato, Hisanori Minakami

  INTERNATIONAL JOURNAL OF GYNECOLOGY & OBSTETRICS 121 1 86 - 90 2013年04月 [査読有り][通常論文]
   

  Objective: To review clinical features and short-term outcomes of triplet pregnancies among Japanese women. Methods: A retrospective analysis was carried out among 320 Japanese women with triplet pregnancies (8 monochorionic, 75 dichorionic, and 150 trichorionic triplets; 87 with unknown placental chorionicity) who delivered at 22 gestational weeks or more between January 2005 and December 2008. Results: Delivery was by cesarean for 315 (98%) women. Gestational age at delivery was 32.3 +/- 2.8 weeks (mean +/- SD) and 33.2 weeks (median), and 97%, 61%, and 14% of women delivered at less than 37, less than 34, and less than 30 gestational weeks, respectively. For live-born infants, mean birth weight was 1762 +/- 437 g, 1608 +/- 396 g, and 1406 +/- 380 g for the heaviest, middle, and lightest triplet, respectively. Eighteen (5.6%) women experienced perinatal mortality (3 triplets for 1 woman, 2, triplets for 4 women, and 1 triplet for 13 women). Perinatal mortality was 25 deaths per 1000 deliveries, and decreased with increasing number of chorionic membranes (125, 44, and 20 per 1000 mono-, di-, and trichorionic triplet deliveries, respectively). Conclusion: Short-term outcomes were good among triplet pregnancies in Japan. The data may be useful for counseling Japanese women with triplet pregnancies. (C) 2012 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd. All rights reserved.
• Effects of caesarean section on serum levels of NT-proBNP

  Takashi Yamada, Takahiro Koyama, Itsuko Furuta, Masamitsu Takeda, Ryutaro Nishida, Takahiro Yamada, Mamoru Morikawa, Hisanori Minakami

  Clinical Endocrinology 78 3 460 - 465 2013年03月 [査読有り][通常論文]
   

  Objective To determine the effects of delivery by caesarean on serum levels of N-terminal fragment of precursor protein brain-type natriuretic peptide (NT-proBNP). Methods Serum NT-proBNP levels were determined longitudinally at 24 and 36 weeks of gestation (GW) and on post-partum day 3 and month 1 (PPD3 and PPM1, respectively) in 78 women with normotensive singleton pregnancies. Thirty-nine women underwent caesarean delivery. Plasma renin activity (PRA) and plasma aldosterone concentration (PAC) were determined on PPD3. Effects of maternal demographic characteristics on NT-proBNP levels were also analysed. Results NT-proBNP levels (pg/ml) either in pregnancy or on PPM1 did not differ between women with vaginal and caesarean deliveries (44 ± 24 vs 41 ± 30, 24 GW 37 ± 22 vs 29 ± 22, 36 GW 43 ± 28 vs 39 ± 24, PPM1, respectively). Levels on PPD3 were significantly higher (94 ± 105 vs 247 ± 186, P < 0·0001) in women with caesarean delivery. Among women with caesarean delivery, a larger rise of NT-proBNP on PPD3 occurred in nulliparous than in multiparous women (319 ± 232 vs 185 ± 107, P = 0·023), while no rise occurred among multiparous women with vaginal delivery (108 ± 115 vs 47 ± 27). NT-proBNP levels on PPD3 were significantly and negatively correlated with PRA, PAC and maternal weight loss after childbirth on PPD3. These 3 variables on PPD3 were significantly lower in women undergoing caesarean than vaginal delivery (0·8 ± 0·4 vs 1·9 ± 1·4 ng/ml/h for PRA 70 ± 38 vs 136 ± 88 pg/ml for PAC 2·7 ± 1·2 vs 4·3 ± 1·1 kg for weight loss, each P < 0·0001). Conclusions The transient post-partum rise in serum NT-proBNP may reflect transient volume overload after parturition and is remarkable in nulliparous women, especially after caesarean section. © 2012 Blackwell Publishing Ltd.
• Umbilical cord presentation after use of a trans-cervical balloon catheter

  Takashi Yamada, Soromon Kataoka, Masamitsu Takeda, Takashi Kojima, Takahiro Yamada, Mamoru Morikawa, Katsuya Tsuda, Kaoru Hanatani, Tatsumi Yamaguchi, Hisanori Minakami

  JOURNAL OF OBSTETRICS AND GYNAECOLOGY RESEARCH 39 3 658 - 662 2013年03月 [査読有り][通常論文]
   

  Aim To examine the incidence of umbilical cord presentation, including cord prolapse (UCP) and cord descent (UCD), after the use of a trans-cervical balloon catheter (TCBC), such as a Foley catheter and a metreurynter, for the induction of labor (IOL). Methods A retrospective medical chart review was conducted, focusing on the occurrence of UCP and UCD in 800 women who underwent IOL with a TCBC at five hospitals during the study period (20082009 for two hospitals and 20062009 for three hospitals). The five hospitals had a total of 8245 deliveries during the study period. UCP and UCD were defined as the descent of the umbilical cord in advance of the presenting fetal part in the presence and absence of rupture of fetal membranes, respectively. Results The frequency of IOL using a TCBC with 70250mL of saline varied among the five hospitals from 4.9% to 18.8% (mean +/- SD, 10.7 +/- 5.0%). UCP and UCD occurred in two and four women, respectively, with the frequency of cord presentation varying among the hospitals from 0.0% to 1.8% (mean +/- SD, 0.9 +/- 0.9%); the cord presentation was significantly more likely to occur when 180250mL of saline was used, compared with when 70150mL of saline was used (8.2% [5/61] vs 0.15% [1/662], P<0.0001). A change in the presenting fetal body part also occurred in 0.5% (4/800) of the women. Conclusion The use of a TCBC with 180250mL of saline increases the risk of cord presentation.
• 経腹的絨毛採取による出生前診断

  山田 崇弘, 赤石 理奈, 小島 崇史, 荒木 直人, 石川 聡司, 武田 真光, 西田 竜太郎, 森川 守, 山田 俊, 長 和俊, 水上 尚典

  北海道産科婦人科学会会誌 57 1 102 - 102 北海道産科婦人科学会 2013年03月
• QT延長症候群合併妊娠において胎児心拍パターンから胎児QT延長症候群が疑われた1例

  石川 聡司, 西尾 佐奈恵, 山田 崇弘, 森川 守, 山田 俊, 武井 黄太, 長 和俊, 水上 尚典

  北海道産科婦人科学会会誌 57 1 108 - 109 北海道産科婦人科学会 2013年03月
• B-type natriuretic peptide levels are correlated with birth-weight discordance in monochorionic-diamniotic twins without twin-twin transfusion syndrome

  A. Moriichi, K. Cho, Y. Furuse, T. Akimoto, Y. Kaneshi, T. Yamada, M. Morikawa, T. Yamada, H. Minakami

  JOURNAL OF PERINATOLOGY 33 3 182 - 187 2013年03月 [査読有り][通常論文]
   

  Objective: To determine whether B-type natriuretic peptide (BNP) levels in umbilical cord blood (UCB) and amniotic fluid (AF) are correlated with birth-weight discordances in monochorionic-diamniotic twins. Study Design: The UCB-BNP and AF-BNP levels were determined at birth in 36 twin-pairs without twin twin transfusion syndrome (TTTS). Result: Both the UCB-BNP and the AF-BNP levels were significantly higher among twins with either a birth-weight discordance >= 20% (141.6 versus 52.9 pg ml(-1) for UCB BNP, 38.0 versus 17.2 pg ml(-1) for AF BNP) or cardiac dysfunction at birth (167.2 versus 56.3 pg ml(-1) for UCB BNP, 34.9 versus 19.0 pg ml(-1) for AF BNP), compared with neonates without the respective characteristics. The UCB BNP and AF BNP levels in both the larger and the smaller twins were significantly correlated with birth-weight discordance. Conclusion: Cardiac dysfunction occurs in both larger and smaller co-twins with increasing birth-weight discordances, even in the absence of TTTS. Journal of Perinatology (2013) 33, 182-187; doi:10.1038/jp.2012.94; published online 12 July 2012
• Usefulness of transverse fundal incision method of cesarean section for women with placentas widely covering the entire anterior uterine wall

  Ryutaro Nishida, Takahiro Yamada, Rina Akaishi, Takashi Kojima, Satoshi Ishikawa, Masamitsu Takeda, Mamoru Morikawa, Takashi Yamada, Hisanori Minakami

  Journal of Obstetrics and Gynaecology Research 39 1 91 - 95 2013年01月 [査読有り][通常論文]
   

  Aim: To assess the usefulness of a new method for cesarean section (CS) that is comprised of a transverse incision into the uterine fundus, developed for women with placentas covering the entire anterior uterine wall, and introduced in September 2006. Material and Methods: Review of medical records of 12 and 29 women who underwent CS by the new and conventional methods, respectively, for placenta previa, placenta accreta (accreta, increta and percreta) or placenta widely covering the entire anterior uterinewall in which placenta accreta cannot be excluded, between June 2003 and March 2011. Results: Placenta accreta (67% [8/12] vs 10% [3/29], P = 0.0006) and cesarean hysterectomy (67% vs 10%) were significantly more frequent in the group with the new compared with the conventional method. There were no significant differences between groups with the new and conventional methods in amount of blood loss (1732 ± 1067 vs 1847 ± 1279 g, respectively), prevalence of blood loss > 3000 g (8.3% vs 17%, respectively) or blood transfusion (92% vs 72%, respectively), time required for cesarean hysterectomy (210 ± 58 vs 195 ± 41 min), or neonatal conditions at birth. The amount of blood loss for cesarean hysterectomy was significantly less for the new than conventional method (1959 ± 1025 g vs 4450 ± 1145 g, P = 0.041). Conclusion: The new method was superior to the conventional method with respect to reduction of blood loss during cesarean hysterectomy. However, careful observations are mandatory in women with preserved uterus with respect to a possible increased risk of uterine rupture in future pregnancies. © 2012 The Authors.
• Fetal presentation of long QT syndrome - Evaluation of prenatal risk factors: A systematic review

  Satoshi Ishikawa, Takashi Yamada, Tomoyuki Kuwata, Mamoru Morikawa, Takahiro Yamada, Shigeki Matsubara, Hisanori Minakami

  Fetal Diagnosis and Therapy 33 1 1 - 7 2013年01月 [査読有り][通常論文]
   

  Objective: This systematic review evaluated the existence of risk factors for the fetal manifestation of long QT syndrome (LQTS). Methods: Prenatal cardiac findings suggestive of fetal LQTS were studied using 30 English literature reports extracted from the Pubmed database (1979 to December 2011) using the search terms 'long QT syndrome', 'fetal arrhythmia' and 'congenital heart disease'. Results: LQTS accounted for 15-17% of fetal bradycardias < 110 bpm among fetuses with a normally structured heart. Of the patients with significant prenatal findings of LQTS, 17-35% exhibited a reduced baseline fetal heart rate (FHR) of 110-120 bpm on electronic cardiotocography. Other prenatal signs were sinus or intermittent bradycardia < 110 bpm arising from atrioventricular block, tachyarrhythmias, pleural effusion and hydrops. More than 30% of Japanese infants with LQTS born at or after the mid-1980s exhibited the above-mentioned in utero signs. Conclusions: Fetal factors including a slightly reduced baseline FHR of 110-120 bpm, bradycardia < 110 bpm, tachyarrhythmias or clinical signs of heart failure, such as pleural effusion and hydrops, were associated with a higher frequency of LQTS. The use of these signs may help to increase the perinatal diagnosis of LQTS. Copyright © 2012 S. Karger AG, Basel.
• First-trimester serum folate levels and subsequent risk of abortion and preterm birth among Japanese women with singleton pregnancies

  Takashi Yamada, Mamoru Morikawa, Takahiro Yamada, Reiko Kishi, Kazuo Sengoku, Toshiaki Endo, Tsuyoshi Saito, Kazutoshi Cho, Hisanori Minakami

  ARCHIVES OF GYNECOLOGY AND OBSTETRICS 287 1 9 - 14 2013年01月 [査読有り][通常論文]
   

  To determine whether a low serum folate level during the first trimester predicts subsequent late abortion, preterm birth, or fetal growth restriction (FGR). A prospective cohort study involving 5,075 women whose serum folate levels were measured during the first trimester. The participants were informed of their serum folate levels. The pregnancy duration, birthweight, rate of late abortion/preterm birth, and the rate of FGR did not differ significantly among the four groups classified according to folate status. The mean serum folate levels did not differ among quartiles classified according to the gestational week at the time of delivery. Nineteen of the 20 women with folate deficiency gave birth at term to infants with a birthweight of 3.132 +/- A 321 g; only one infant had FGR. Low serum folate levels during the first trimester were not associated with the risk of late abortion, preterm birth, or FGR.
• Serum levels of N-terminal fragment of precursor protein brain-type natriuretic peptide (NT-proBNP) in twin pregnancy

  Takashi Yamada, Takahiro Koyama, Itsuko Furuta, Masamitsu Takeda, Ryutaro Nishida, Takahiro Yamada, Mamoru Morikawa, Hisanori Minakami

  CLINICA CHIMICA ACTA 415 41 - 44 2013年01月 [査読有り][通常論文]
   

  Twin pregnancy differs considerably from singleton pregnancy in many aspects and it is unknown how serum NT-proBNP level behaves in women with twin pregnancies. Serum NT-proBNP levels were determined longitudinally at gestational weeks (GW) 24 and 35 in normotensive women with 13 twin and 99 singleton pregnancies. The effects of maternal demographic characteristics on NT-proBNP levels were also analyzed. The serum NT-proBNP levels (pg/ml) in twin pregnancies, which were not different from those in singleton pregnancies at 24 GW (26 +/- 15 vs. 40 +/- 27, respectively, P=0.0718), increased significantly (P=0.0038) and were significantly higher than those in singleton pregnancies at 35 GW (72 +/- 49 vs. 34 +/- 24, P<0.0001). In the analysis including women with singleton pregnancies, the serum levels of NT-proBNP at 35 GW were significantly inversely correlated with pre-pregnancy body mass index (BMI, kg/m(2)) and were significantly higher in nulliparous than multiparous women. Thus, women with twin pregnancy were likely to exhibit an increase in serum NT-proBNP levels in the late stage of pregnancy, especially in lean and nulliparous women. The relative greater blood volume expansion occurring in twin than in singleton pregnancies was considered to be responsible for this phenomenon. (c) 2012 Elsevier B.V. All rights reserved.
• Changes in hemoglobin F levels in pregnant women unaffected by clinical fetomaternal hemorrhage

  Takashi Yamada, Mamoru Morikawa, Takahiro Yamada, Ryutaro Nishida, Masamitsu Takeda, Satoshi Kawaguchi, Hisanori Minakami

  CLINICA CHIMICA ACTA 415 124 - 127 2013年01月 [査読有り][通常論文]
   

  Background: Complete automation of high-performance liquid chromatography (HPLC) for determination of hemoglobin F (%Hb F) and hemoglobin A1c (%Hb A1c) levels has made this procedure available in many clinical laboratories. However, the physiological changes in %Hb F during pregnancy and the effects of physiological and supraphysiological levels of %Hb A1c on measurement of %Hb F have not been studied extensively. Methods: Simultaneous determination of %Hb F and %Hb A1c was conducted in 490 blood samples obtained before (n=21), during the 1st (n=150), 2nd (n=116), and 3rd (n=192) trimesters of pregnancy, and postpartum (n=11) from 357 women, including 60 women with hyperglycemia but unaffected by clinical fetomatemal hemorrhage, by HPLC. Results: Mean (SD) Hb F levels were 0.71% (0.25%) before pregnancy. The value of 0.82% (0.47%) during the 1st trimester decreased significantly to 0.66% (0.35%) during the 2nd trimester and to 0.58% (0.38%) during the 3rd trimester. The level was 0.62% (0.31%) approximately one year after delivery. Thus, %Hb F was highest during the 1st trimester of pregnancy. The effects of varied %Hb A1c levels on %Hb F measurements were clinically negligible. Conclusions: The data presented in this work may be used as reference intervals of %Hb F determined with HPLC during pregnancy. (c) 2012 Elsevier B.V. All rights reserved.
• Association of Antithrombin Activity with Plasma Aldosterone Concentration and Plasma Renin Activity in Pregnant Women

  Takashi Yamada, Takahiro Koyama, Itsuko Furuta, Mamoru Morikawa, Takahiro Yamada, Hisanori Minakami

  HYPERTENSION IN PREGNANCY 32 1 96 - 103 2013年 [査読有り][通常論文]
   

  Objective. To test the hypothesis that the blood antithrombin (AT) activity is correlated with the plasma aldosterone concentration (PAC), the plasma renin activity (PRA), and/or the PAC-to-PRA ratio during the late stage of pregnancy. Methods. The AT activity, PAC, and PRA were determined within 7 days prior to delivery in 47 women, consisting of 30 normotensive and 6 hypertensive women with singleton pregnancies and 11 normotensive women with twin pregnancies. Results. The median values of the 47 women were 86% of the normal activity level for the AT activity, 442 pg/mL for the PAC, 3.7 ng/mL/h for the PRA, and 108 pg/mL per ng/mL/h for the PAC-to-PRA ratio. Women with an AT activity <= 86% had a significantly lower PRA and a higher PAC-to-PRA ratio than women with an AT activity >86% (3.5 +/- 3.0 vs. 6.6 +/- 4.7 ng/mL/h for PRA, p 0.008; 156 +/- 109 vs. 97 +/- 46 pg/mL per ng/h for PAC-to-PRA ratio, p = 0.021). The AT activity was significantly correlated positively with the PRA and negatively with the PAC-to-PRA ratio. Conclusions. The existence of a common pathophysiological background between a reduced AT activity and a reduced PRA during the late stage of pregnancy was suggested.
• Coagulation/Fibrinolysis and laboratory characteristics of pregnant pomen with severely depressed antithrombin activity

  Takashi Yamada, Satoshi Ishikawa, Soromon Kataoka, Tomohiro Uda, Youichiro Iinuma, Rifumi Hattori, Takahiro Yamada, Mamoru Morikawa, Masanori Kaneuchi, Hisanori Minakami

  HYPERTENSION IN PREGNANCY 32 3 235 - 244 2013年 [査読有り][通常論文]
   

  Objective: To examine the pathophysiology of reductions in antithrombin (AT) activity during pregnancy and to better characterize the laboratory features of pregnant women with severely depressed AT activity. Methods: Laboratory variables for blood samples obtained within 5 d prior to delivery were compared among three women groups with severely depressed (<45%, n = 6), modestly depressed (45-69%, n = 10), and normal AT activity levels (>70%, n = 134). Results: Pregnancy-induced hypertension was present in 16.7% (1/6), 30.0% (3/10), and 9.0% (12/134) of the women with the above-mentioned AT activities, respectively. The AT activities were significantly and negatively correlated with the D-dimer, urate, and creatinine levels. The D-dimer level was significantly and negatively correlated with the fibrinogen level. Women with AT activity <45% exhibited markedly elevated levels of hemoglobin and liver enzymes and a significantly lower level of fibrinogen than the other women groups, while the platelet count did not differ among the three groups. Conclusions: Enhanced thrombin generation was involved in the decrease in AT activity. AT activity can decrease in the absence of thrombocytopenia. The liver dysfunction that was seen in cases with severely depressed AT activity may have resulted from impairments in liver perfusion caused by microthromboses generated as a result of the relative lack of AT and/or the shortage of circulating plasma in women with reduced AT activities.
• 胎児消化管奇形の出生前診断における骨盤内MRI T1強調画像の有用性についての検討

  吉井一樹, 山田 俊, 加藤扶美, 尾松徳彦, 小山貴弘, 赤石理奈, 武田真光, 西田竜太郎, 山田崇弘, 森川 守, 長 和俊, 寺江 聡, 水上尚典

  北海道産科婦人科学会会誌 57 1 79 - 85 北海道産科婦人科学会 2013年 [査読有り][通常論文]
   

  胎児MRI検査で胎児骨盤部分のT1強調画像があり、出生後に消化管狭窄・閉鎖の有無が確認できた105例(114検査)を対象に、新生児診断の疾患分類との関連について検討した。胎児MRI検査における骨盤内T1強調画像高信号の索状構造についての判定結果は、索状構造「陽性」は103検査(90.4%)、「境界」は4検査(3.5%)、「陰性」は7検査(6.1%)であった。出生後に消化管狭窄・閉鎖と診断された19検査中17検査(89.5%)が「陽性」、2検査が「境界」で十二指腸閉鎖であった。出生後にMMIHS・高位鎖肛と診断された7検査中1検査(14.3%)が「陽性」、2検査(28.6%)が「境界」、4検査(57.1%)が「陰性」であった。先天性消化管狭窄・閉鎖や骨盤内病変のなかった88検査中85検査(96.5%)が「陽性」であった。膀胱背側に索状構造を明瞭に確認できなかった11検査中8検査(72.7%)に消化管異常があり、明確に確認できた103検査中18検査(17.5%)に比べ相対危険は4.16であった。
• Fetal presentation of Klippel–Trénaunay–Weber syndrome with massive pleural effusion and ascites.

  Araki N, Ymada T*, Morikawa M, Akimoto T, Cho K, Minakami H.

  Case Reports in Perinatal Medicine 3 75 - 77 2013年 [査読有り][通常論文]
  
• Gestational weight gain according to number of fetuses in Japanese women.

  Morikawa M, Yamada T, Akaishi R, Yamada T, Nishida R, Sato S, Kaneuchi M, Minakami H

  J Perinat Med 13 1 - 6 2013年 [査読有り][通常論文]
  
• 早剥の診断 １）臨床所見の特徴． 特集 常位胎盤早期剥離の病態と管理

  山田崇弘, 水上尚典

  周産期医学 43 452 - 455 2013年 [査読無し][招待有り]
  
• Clinical features of abruptio placentae as a prominent cause of cerebral palsy

  Takahiro Yamada, Takashi Yamada, Mamoru Morikawa, Hisanori Minakami

  EARLY HUMAN DEVELOPMENT 88 11 861 - 864 2012年11月 [査読有り][通常論文]
   

  Background: Although abruptio placentae causes hypoxia in the infant and thus leading to cerebral palsy (CP), its incidence and clinical features at a nationwide level have not been demonstrated. Aims: To determine the proportion of abruptio placentae among antenatal and intrapartum causative factors leading to cerebral palsy (CP) and clinical features of such abruptio placentae. Study design: A review was conducted in 107 infants with CP in whom CP was determined to be due to antenatal and or intrapartum hypoxic conditions by the Japan Council for Quality Health Care until April 2012. Results: Abruptio placenta was responsible for 28 (26%) of the 107 CP infants, and was the single leading causative factor of CP. Of these 28 women, 22 (79%) exhibited non-reassuring fetal status on admission to obstetric facilities at 36.2 +/- 2.6 weeks of gestation and had neonates with umbilical cord arterial blood pH (base excess) of 6.728 +/- 0.164 (-25 +/- 5.4 mmol/L). In these 22 women, strong abdominal pain and/or profuse vaginal bleeding occurred 159 +/- 99 min prior to admission to an obstetric facility, and the interval until delivery after admission was 47 +/- 31 min. Hypertension or isolated proteinuria preceded clinical events in one (4.5%) and five (23%) of these 22 women, respectively. Conclusions: Abruptio placentae was responsible for CP in one quarter of all cases determined to be due to antenatal and/or intrapartum hypoxic conditions in Japan. New strategies to shorten the interval until admission to an obstetric facility after onset of symptoms are urgently needed. (C) 2012 Elsevier Ireland Ltd. All rights reserved.
• Recurrence of osteogenesis imperfecta due to maternal mosaicism of a novel COL1A1 mutation

  Takahiro Yamada, Masaki Takagi, Gen Nishimura, Rina Akaishi, Itsuko Furuta, Mamoru Morikawa, Takashi Yamada, Kazutoshi Cho, Hideaki Sawai, Shiro Ikegawa, Tomonobu Hasegawa, Hisanori Minakami

  AMERICAN JOURNAL OF MEDICAL GENETICS PART A 158A 11 2969 - 2971 2012年11月 [査読有り][通常論文]
  
• Prevalence of hyperglycemia during pregnancy according to maternal age and pre-pregnancy body mass index in Japan, 2007-2009

  Mamoru Morikawa, Takashi Yamada, Takahiro Yamada, Shoji Sato, Kazutoshi Cho, Hisanori Minakami

  INTERNATIONAL JOURNAL OF GYNECOLOGY & OBSTETRICS 118 3 198 - 201 2012年09月 [査読有り][通常論文]
   

  Objective: To assess the prevalence of hyperglycemia according to maternal age and pre-pregnancy body mass index (BMI) among Japanese women before introduction of the current diagnostic criteria. Methods: In a retrospective study, data were analyzed from women with singleton pregnancies who were registered with the JSOG Successive Pregnancy Birth Registry System and who gave birth at 22 weeks of gestation or more between January 2007 and December 2009. Results: Among 138 530 women, 3667 (2.6%) were diagnosed with hyperglycemia including gestational diabetes and diabetes mellitus. The prevalence of hyperglycemia increased with advancing maternal age and increasing BMI. Among women aged <= 24, 25-34, 35-39, and >= 40 years, the prevalence was 0.4%, 0.8%, 1.5%, and 4.0%, respectively, in lean women (BMI<18.5); 1.0%, 1.6%, 2.3%, and 3.1%, respectively, in normal weight women (BMI 18.5-24.9); and 5.7%, 9.2%, 12.9%, and 15.2%, respectively, in obese women (BMI >= 25.0). Of the 1181 newborns with a birth weight of 4000 g or more, 1046 (88.6%) were born to women not diagnosed with hyperglycemia. Conclusion: The results may reflect the baseline prevalence of hyperglycemia and macrosomic neonates (birth weight >= 4000 g) during the era of the old diagnostic criteria in Japan. (C) 2012 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd. All rights reserved.
• 北海道における妊娠中の新型インフルエンザ (Pandemic (H1N1) 2009) 感染

  山田 崇弘, 山田 俊, 森川 守, 長 和俊, 遠藤 俊明, 佐藤 佐和子, 斎藤 豪, 千石 一雄, 水上 尚典

  北海道醫學雜誌 = Acta medica Hokkaidonensia 87 4 181 - 181 2012年08月01日 [査読有り][通常論文]
  
• Antithrombin activity, platelet count, hemoglobin concentration and hematocrit value determined immediately before vaginal delivery among healthy women.

  Mamoru Morikawa, Takashi Yamada, Takahiro Yamada, Takahiro Koyama, Rina Akaishi, Satoshi Ishikawa, Masamitsu Takeda, Ryutaro Nishida, Naoto Araki, Hisanori Minakami

  [Hokkaido igaku zasshi] The Hokkaido journal of medical science 87 4-5 141 - 6 2012年08月 [査読有り][通常論文]
   

  AIMS: To determine the normal reference values for antithrombin (AT) activity, platelet count (Plt), hemoglobin concentration (Hb), and hematocrit value (Ht) immediately before vaginal delivery among healthy pregnant women with singleton pregnancies and to determine association of these blood parameters with fetal growth. METHODS: A complete blood count was performed and the AT activity was examined in 300 consecutive women admitted to hospital at > or = gestational week 36 for labor pains and/or the rupture of fetal membranes. All the women were normotensive and had singleton pregnancies, and none of the women had proteinuria, a weekly weight gain > or = 0.5 kg, or other specific complications upon admission. All the women attempted a vaginal delivery. RESULTS: The medians (5th-95th percentile) were 90% (71-110%) for AT activity, 234x10(9)/L (150-337x10(9)/L) for Plt, 11.0 g/dL (9.5-12.8 g/dL) for Hb, and 34.0% (30.4-38.6%) for Ht. Women with an Hb value of > or = the median (11.0 g/dL) gave birth to significantly smaller infants than their counterparts. CONCLUSIONS: A considerable number of healthy women exhibit a reduced AT activity and/or platelet count immediately before delivery. Hemoconcentration evidenced by a raised Hb value adversely effects on infant growth. Our data may be helpful when considering the normal ranges of these blood parameters for healthy parturient women.
• 胎児心拍パターンから胎児QT延長症候群が疑われた1例

  石川 聡司, 山田 俊, 小島 崇史, 小山 貴弘, 武田 真光, 西田 竜太郎, 山田 崇弘, 森川 守, 武井 黄太, 上野 倫彦, 盛一 享徳, 長 和俊, 水上 尚典

  日本周産期・新生児医学会雑誌 = Journal of Japan Society of Perinatal and Neonatal Medicine 48 1 131 - 135 2012年05月20日 [査読無し][通常論文]
  
• Risk factors for eclampsia in Japan between 2005 and 2009

  Mamoru Morikawa, Kazutoshi Cho, Takashi Yamada, Takahiro Yamada, Shoji Sato, Hisanori Minakami

  INTERNATIONAL JOURNAL OF GYNECOLOGY & OBSTETRICS 117 1 66 - 68 2012年04月 [査読有り][通常論文]
   

  Objective: To determine risk factors for eclampsia among Japanese women with singleton pregnancies. Methods: A retrospective observational study was carried out among patients with and those without eclampsia who were registered on the Japan Society of Obstetrics and Gynecology registry system and who gave birth to singleton infants at 22 weeks or more between 2005 and 2009. Multivariate logistic regression analyses were performed to determine independent risk factors for eclampsia. Results: One-third (75/225) of eclampsia patients developed the condition in the absence of hypertension. Maternal age, nulliparity, and pregnancy-induced hypertension (PIH) were all independent risk factors for eclampsia. The risk of eclampsia decreased by 3.0% per 1-year increase in maternal age, and increased 2.6-fold and 35.4-fold in nulliparous women and women with PIH, respectively. Among teenaged girls with hypertension, the prevalence of eclampsia was 1 case per 28 teenagers. Conclusion: Hypertension alone was not a reliable predictor of eclampsia. More intensified monitoring of nulliparous women and teenaged girls with hypertension is needed in order to prevent eclampsia. (C) 2011 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd. All rights reserved.
• Prospective risk of stillbirth: monochorionic diamniotic twins vs. dichorionic twins

  Mamoru Morikawa, Takashi Yamada, Takahiro Yamada, Shoji Sato, Kazutoshi Cho, Hisanori Minakami

  JOURNAL OF PERINATAL MEDICINE 40 3 245 - 249 2012年04月 [査読有り][通常論文]
   

  Aims : To determine reliably the risk of stillbirth among twin pregnancies. Methods : A data analysis of 3241 and 6581 women with monochorionic diamniotic (MD) and dichorionic (DD) twins, respectively, who gave birth at >= 22 weeks of gestation. Results : The prospective risk (per 1000 women) of stillbirth, 25.3 and 11.5 at gestational week 22, decreased to <10.0 at gestational weeks 31 and 28 among the MD and DD twins, respectively. After single intrauterine fetal death, the co-twin died in utero or within 7 days of life more frequently among MD twins than among DD twins [42.7 % (35/82) vs. 2.6 % (2/76); relative risk, 16.2; 95 % confidence interval, 4.0-65.1]. Conclusion : Women with MD twins were 2.2-fold more likely to experience stillbirth than women with DD twins. The prospective risks of stillbirth were <1.0 % for both groups of women at >= 32 weeks of gestation.
• 異常妊娠のエピゲノム解析

  直井 裕子, 鳥巣 弘道, 久須美 真紀, 諸隈 誠一, 山田 崇弘, 水上 尚典, 和氣 徳夫, 左合 治彦, 秦 健一郎

  日本産科婦人科学会雑誌 64 2 412 - 412 (公社)日本産科婦人科学会 2012年02月
• Pandemic (H1N1) 2009 in pregnant Japanese women in Hokkaido

  Takahiro Yamada, Takashi Yamada, Mamoru Morikawa, Kazutoshi Cho, Toshiaki Endo, Sawako Seto Sato, Tsuyoshi Saito, Kazuo Sengoku, Hisanori Minakami

  JOURNAL OF OBSTETRICS AND GYNAECOLOGY RESEARCH 38 1 130 - 136 2012年01月 [査読有り][通常論文]
   

  Aim: No maternal mortality from pandemic (H1N1) 2009 occurred in Japan. However, the reasons for this lack of maternal deaths remain unknown. This study was performed to investigate how many pregnant women were infected, how many women took antiviral drugs for prophylaxis or treatment, and the rate of vaccination effectiveness. Material and Methods: A questionnaire study was given to 20 500 postpartum women before leaving obstetric facilities between December 2009 and May 2010 in Hokkaido, asking about antiviral drugs, vaccination, and infection with pandemic (H1N1) 2009. Results: Approximately one-third (n = 7535) of women given the questionnaires responded. Of these, 268 women (3.5%) indicated that they had contracted influenza. 353 (4.7%) women took antiviral drugs for prophylaxis after close contact with an infected person and 140 (39.7%) of 353 women finally contracted influenza during or after prophylaxis with antiviral drugs, accounting for 52.2% (140/268) of all patients. 229 (85.4%) of 268 patients took antiviral drug for treatment and 6 (2.2%) needed hospitalization, but not mechanical ventilation or intensive care unit. 196 of 268 (73.1%) patients were already infected before the availability of a vaccine. Among 7328 candidates for vaccination, 4921 (67.2%) were vaccinated. Infection occurred in 0.22% (11/4921) and 2.1% (50/2407) of vaccinated and non-vaccinated women, respectively. Conclusion: Frequent use of antiviral drugs for prophylaxis and treatment may partially explain the low infection rate and no maternal mortality from pandemic (H1N1) 2009 in Japan. Vaccination reduced infection by 89% in pregnant Japanese women.
• Risk factors for postpartum hypertension in women with twin pregnancies

  Mamoru Morikawa, Kazutoshi Cho, Takashi Yamada, Takahiro Yamada, Rina Akaishi, Takahiro Koyama, Masamitsu Takeda, Ryutaro Nishida, Hisanori Minakami

  JOURNAL OF PERINATAL MEDICINE 40 2 115 - 120 2012年 [査読有り][通常論文]
   

  Objective: Which physical findings and blood parameters predict postpartum hypertension remain to be studied in women with twin pregnancies. Methods: The antenatal systolic and diastolic blood pressures (SBP and DBP, respectively), and 16 laboratory variables were investigated in 150 normotensive women who gave birth to twins. Results: When the median values of the 18 continuous variables were used as cut-off values, an SBP>120 mm Hg (relative risk [95% confidence interval], 2.81 [1.94-4.08]), a DBP>70 mm Hg (2.42 [1.68-3.49]), an aspartate aminotransferase level>18 U/L (2.22 [1.55-3.19]), and a uric acid level>5.3 mg/dL (1.68 [1.20-2.36]) were independent risk factors for postpartum hypertension. Conclusions: Antenatal blood pressure measurements and a laboratory work-up may be useful clinically for predicting postpartum hypertension in women with twin pregnancies.
• Characteristics of insulin secretion patterns in Japanese women with overt diabetes and gestational diabetes defined according to the International Association of Diabetes and Pregnancy Study Groups criteria

  Mamoru Morikawa, Takashi Yamada, Takahiro Yamada, Rina Akaishi, Takahiro Koyama, Masamitsu Takeda, Ryutaro Nishida, Kazutoshi Cho, Hisanori Minakami

  JOURNAL OF OBSTETRICS AND GYNAECOLOGY RESEARCH 38 1 220 - 225 2012年01月 [査読有り][通常論文]
   

  Aim: To characterize patterns of insulin secretion in women with overt diabetes and gestational diabetes (GDM) defined by the International Association of Diabetes and Pregnancy Study Groups (IADPSG) criteria. Material and Methods: A total of 228 Japanese women were examined retrospectively. All 228 women had a positive 50-g glucose challenge test (GCT) result at 25.2 +/- 1.2 weeks of gestation and underwent a 75-g glucose tolerance test (GTT) at 27.4 +/- 1.8 weeks of gestation. The immunoreactive insulin levels were determined during the GTT in four groups of pregnant women: five with overt diabetes, 20 with GDM according to both the previous Japan Society of Gynecology and Obstetrics (JSOG) and current IADPSG criteria (traditional GDM group), 43 with GDM according to only the IADPSG criteria (new GDM group), and 160 with non-GDM, but with a positive GCT result. Results: Attenuated and slow rise in plasma insulin in concert with prolonged hyperglycemia were characteristic in women with overt diabetes, compared with women with GDM in whom excessive insulin secretion in the presence of hyperglycemia was characteristic. The new GDM group did not differ significantly from the traditional GDM group with respect to scores of such indices as the insulinogenic index, the homeostasis model assessment for insulin resistance, and the quantitative insulin sensitivity check index. Conclusion: Women with overt diabetes have both an impaired capacity for insulin secretion and elevated insulin resistance, while women with GDM exhibit a maintained insulin secretory capacity with an elevated insulin resistance.
• Risk Factors of Eclampsia Other Than Hypertension: Pregnancy-Induced Antithrombin Deficiency and Extraordinary Weight Gain

  Takashi Yamada, Tomoyuki Kuwata, Hideo Matsuda, Keizo Deguchi, Mamoru Morikawa, Takahiro Yamada, Kennichi Furuya, Shigeki Matsubara, Hisanori Minakami

  HYPERTENSION IN PREGNANCY 31 2 268 - 277 2012年 [査読有り][通常論文]
   

  Objective. Recent findings suggest that cerebral edema is a characteristic finding on magnetic resonance imaging in women with eclampsia and that pregnancy-induced antithrombin deficiency (PIATD) may reflect enhanced vascular permeability and may allow the retention of excess water in the interstitial space. Whether PIATD and extraordinary weight gain (EOWG) are risk factors for eclampsia remains to be studied. Methods. The medical records of 11 women with eclampsia among 17,522 deliveries were reviewed retrospectively with respect to changes in the laboratory data and the maternal body weight. PIATD was defined as a perinatal antithrombin activity of <= 65% of the normal activity levels with an antenatal decline and/or a prompt postnatal increase. A large net weight gain during the last two antenatal weeks >97.5th percentile value (>4.01 kg) obtained from 272 control women with neither hypertension nor PIATD was defined as EOWG. Relative risk was obtained on the assumption that the prevalences of PIATD and EOWG were 2.0 and 2.5%, respectively, among 17,511 women who did not develop eclampsia. Results. The duration of hypertension until an eclamptic fit was within 7 days in all 11 cases. PIATD and EOWG were observed in 6 (54.5%) and 2 (18.2%) cases, yielding a relative risk (95% confidential interval) of 57.9 (17.7-188.7) and 8.65 (1.87-39.91) for eclampsia among women with PIATD and EOWG, respectively. Conclusions. PIATD and EOWG may be risk factors for eclampsia.
• Plasma Aldosterone Concentration and Plasma Renin Activity Decrease during the Third Trimester in Women with Twin Pregnancies

  Takahiro Koyama, Takashi Yamada, Itsuko Furuta, Mamoru Morikawa, Takahiro Yamada, Hisanori Minakami

  HYPERTENSION IN PREGNANCY 31 4 419 - 426 2012年 [査読有り][通常論文]
   

  Objective: Changes in the plasma aldosterone concentration (PAC) and the plasma renin activity (PRA) have not been extensively studied in women with twin pregnancies. Methods: The PAC and PRA levels were determined during the second and third trimesters and on postpartum day 3 in 14 normotensive women with twin pregnancies and 80 normotensive and 7 preeclamptic women with singleton pregnancies. Results: In women with twin pregnancies, elevated PAC and PRA levels (598 +/- 248 pg/mL and 10.0 +/- 4.7 ng/mL/h, respectively) in the second trimester decreased significantly during the third trimester (to 396 +/- 210 pg/mL and 3.5 +/- 2.9 ng/mL/h, respectively), whereas the corresponding PAC increased significantly (from 421 +/- 207 to 667 +/- 371 pg/mL) and the PRA did not change significantly (from 7.3 +/- 3.4 to 6.9 +/- 4.2 ng/mL/h) in women with normal singleton pregnancies. These changes in the PAC and PRA levels in women with twin pregnancies resembled those in hypertensive women with singleton pregnancies. Conclusions: In women with twin pregnancies, both the PAC and PRA levels were significantly enhanced during the second trimester, whereas those in the third trimester were significantly reduced compared with those in women with normal singleton pregnancies.
• 周産期医療と胎盤–最近の話題 10. 胎盤と疾患 3) 常位胎盤早期剥離

  山田崇弘, 水上尚典

  周産期医学 40 1101 - 1104 2012年 [査読無し][招待有り]
  
• 前置胎盤と癒着胎盤＜ワンランク上の診断と治療＞II 癒着胎盤 １．癒着胎盤の疫学

  山田崇弘, 水上尚典

  臨床婦人科産科 66 744 - 746 2012年 [査読無し][招待有り]
  
• 研修コーナー(第17回) 代表的異常分娩とその管理 陣痛の異常(解説)

  山田崇弘

  日産婦誌 64 2012年 [査読無し][招待有り]
  
• 研修コーナー(第17回) 代表的異常分娩とその管理 胎児機能不全(解説)

  山田崇弘

  日産婦誌 64 2012年 [査読無し][招待有り]
  
• 重症PIHの対処法．特集 周産期医が習得したい専門的手技—産科編

  山田崇弘, 水上尚典

  周産期医学 42 11 1475 - 1480 東京医学社 2012年 [査読無し][招待有り]
  
• Relationships between fetal growth and maternal body mass indices, plasma glucose level, and plasma insulin level in Japanese women with mildly impaired glucose tolerance

  Mamoru Morikawa, Kazutoshi Cho, Takashi Yamada, Takahiro Yamada, Rina Shono, Takahiro Koyama, Masamitsu Takeda, Ryutaro Nishida, Hisanori Minakami

  JOURNAL OF OBSTETRICS AND GYNAECOLOGY RESEARCH 37 12 1797 - 1801 2011年12月 [査読有り][通常論文]
   

  Aim: To identify variables which are strongly associated with fetal growth. Material and Methods: The study subjects were 203 Japanese women who had a plasma glucose level >= 140 mg/dL (7.8 mmol/L) on a 50-g glucose challenge test but were normoglycemic when challenged with a 75-g oral glucose tolerance test (GTT) according to the criteria previously used in Japan. All the subjects subsequently gave birth to singleton infants. The correlations between the standard deviation for birthweight (birthweight SD) and 15 other variables, including the maternal body mass index (BMI), plasma levels of glucose and insulin on the GTT, and various indices calculated using data from the GTT, were then examined. Univariate and multivariate regression analyses were performed. Results: Univariate analyses revealed significant correlations between the birthweight SD and the fasting plasma glucose level (P = 0.0063), the pre-pregnancy BMI (P = 0.0001), and the BMI at delivery (P < 0.0001). Only the BMI at delivery remained as a significant factor that was independently correlated with the birthweight SD after a multivariate regression analysis. Conclusion: The suppression of maternal weight gain, rather than the suppression of the plasma glucose level, may be effective for avoiding infants with overgrowth among Japanese women with mildly impaired glucose tolerance.
• Maternal weight gain in twin-twin transfusion syndrome

  Mamoru Morikawa, Takashi Yamada, Emi Hirayama-Kato, Takahiro Yamada, Kazuhiko Okuyama, Hisanori Minakami

  ACTA OBSTETRICIA ET GYNECOLOGICA SCANDINAVICA 90 12 1434 - 1439 2011年12月 [査読有り][通常論文]
   

  Objective. To examine the association between maternal weight gain and twintwin transfusion syndrome (TTTS). Design. Retrospective observational study in two tertiary care centers. Population. All 124 women with monochorionic diamniotic twin pregnancies who gave birth at =16 gestational weeks between 2002 and 2010. Methods. Analysis of chronological relation between maternal weight gain per week (weekly gain) and the diagnosis of TTTS. Main outcome measure. Sonographic diagnosis of TTTS. Results. A weekly weight gain =1.4 kg occurred in 45 women, preceded the diagnosis of TTTS in 22 (78.6%) of the 28 women with TTTS, and was associated with TTTS [women with one weekly weight gain =1.4 kg vs. women with no weekly weight gains =1.4 kg who were diagnosed as having TTTS: 48.9% (22/45) vs. 7.6% (6/79); RR, 6.44; 95%CI, 2.8214.69]. At given gestational weeks between 16 and 27, the mean (+/- SD) prospective risk of the development of TTTS within three weeks was 52.0 +/- 33.8% among women who showed a weekly weight gain =1.4 kg for the first time, whereas the risk of the development of TTTS within one week was 1.6 +/- 1.7% among women who never showed a weekly weight gain =1.4 kg. Conclusions. Excessive maternal weight gain =1.4 kg/week is likely to occur during the development of TTTS.
• Changes in D-dimer levels after cesarean section in women with singleton and twin pregnancies

  Mamoru Morikawa, Takashi Yamada, Takahiro Yamada, Rina Akaishi, Takahiro Koyama, Hisanori Minakami

  THROMBOSIS RESEARCH 128 4 E33 - E38 2011年10月 [査読有り][通常論文]
   

  Objective: To determine how the D-dimer level changes after cesarean section, a topic that has not been studied extensively. Methods: The D-dimer level (mu g/mL) was measured in 792 and 119 women with singleton and twin pregnancies, respectively, on the day or one day before cesarean section and on postpartum days 1, 3, and 7. None of the women developed venous thromboembolism with clinical symptoms. The data for other two women who underwent a cesarean section and developed pulmonary thromboembolism on postpartum days 0 to 1 were also presented. Results: The preoperative D-dimer level (median, mu g/mL) of 2.4 increased on postpartum day 1 to 6.0, then decreased to 2.8 on postpartum day 3, and again increased to 4.5 on postpartum day 7 in the singleton pregnancies. A similar pattern, but with slightly higher values, was seen in the twin pregnancies. The 95 percentile value of D-dimer for singleton and twin pregnancies was 6.9 and 10.5 on days -1/0, 19.7 and 25.7 on day 1, 9.7 and 13.5 on day 3, and 15.7 and 17.7 on day 7, respectively. The D-dimer level after pulmonary thromboembolism was greater than the 99 percentile value and the 98 percentile value in the two women, respectively. Conclusion: Our data regarding the D-dimer level may be helpful when considering the normal range of D-dimer for postpartum women with cesarean delivery. (C) 2011 Elsevier Ltd. All rights reserved.
• Prenatal molecular diagnosis of a severe type of L1 syndrome (X-linked hydrocephalus) Clinical article

  Mami Yamasaki, Masahiro Nonaka, Nobuhiro Suzumori, Hiroaki Nakamura, Hiroshi Fujita, Akira Namba, Yoshimasa Kamei, Takahiro Yamada, Ritsuko K. Pooh, Mitsuyo Tanemura, Norihito Sudo, Masato Nagasaka, Ema Yoshioka, Tomoko Shofuda, Yonehiro Kanemura

  JOURNAL OF NEUROSURGERY-PEDIATRICS 8 4 411 - 416 2011年10月 [査読有り][通常論文]
   

  Object. The aim of this study was to evaluate the feasibility of prenatal LICAM gene testing for X-linked hydrocephalus (XLH). Methods. In a nationwide study conducted in Japan between 1999 and 2009, the authors identified 51 different LICAM gene mutations in 56 families with XLH. Of these 56 families, 9 obligate carriers requested prenatal gene mutation analysis for the fetal LICAM gene in 14 pregnancies. Results. In 2004, new clinical guidelines for genetic testing were established by 10 Japanese genetic medicine-related societies. These guidelines stated that the genetic testing of carriers should be done only with their consent and with genetic counseling. Therefore, because females are carriers, since 2004, LICAM gene analysis has not been performed for female fetuses. The authors report on 7 fetal genetic analyses that were performed at the request of families carrying LICAM mutations, involving 3 female (prior to 2004) and 4 male fetuses. Of the 7 fetuses, 3 (1 male and 2 female) carried LICAM mutations. Of these 3, I pregnancy (the male fetus) was terminated; in the other cases, the pregnancies continued, and 3 female and 3 male babies without the XLH phenotype were born. Conclusions. Prenatal LICAM gene testing combined with genetic counseling was beneficial for families carrying LICAM mutations. (DOI: 10.3171/2011.7.PEDS10531)
• Contribution of twin-to-twin transfusion syndrome to preterm birth among monochorionic biamniotic and bichorionic biamniotic twin pregnancies

  Mamoru Morikawa, Takashi Yamada, Takahiro Yamada, Shoji Sato, Hisanori Minakami

  JOURNAL OF PERINATAL MEDICINE 39 5 557 - 561 2011年09月 [査読有り][通常論文]
   

  Aims: To determine the contribution of twin-to-twin transfusion syndrome (TTTS) to preterm birth (PTB) at <37 weeks of gestation among Japanese twin pregnancies. Methods: An observational study using 3241 MC-BA (monochorionic biamniotic) and 6581 BC (bichorionic biamniotic) twin pregnancies. We focused on TTTS, preterm premature rupture of membranes (PPROM), pregnancy-induced hypertension (PIH), and fetal sex as possible causes of PTB. Results: PTB was more common in MC-BA than in BC twin pregnancies (66.9% vs. 57.6%, P<0.0001) whereas PTB after PPROM (8.0% vs. 10.0%) and PIH (5.7% vs. 5.9%) was not. PTB after TTTS occurred in 7.3% of women with MC-BA twins. PTB was significantly more common for male-male pairs than for female-female pairs among both MC-BA (69.2% vs. 64.7%) and BC (59.6% vs. 56.3%) twins. Conclusion: The elevated risk of PTB among MC-BA twins could be explained by the occurrence of TTTS.
• Candidates for the determination of antithrombin activity in pregnant women

  Hisanori Minakami, Mamoru Morikawa, Takahiro Yamada, Takashi Yamada

  JOURNAL OF PERINATAL MEDICINE 39 4 369 - 374 2011年07月 [査読有り][通常論文]
   

  Background: Some women exhibit a gradual decrease in antithrombin activity until the time of delivery, with antithrombin activity reaching < 65% of the normal level (pregnancy- induced antithrombin deficiency, PIATD). However, the clinical features of such women are not well understood and are unfamiliar to many obstetricians. Findings: PIATD is more likely to occur as the number of fetuses increases (approx. 1.0%, 10%, and 40% for singleton, twin, and triplet pregnancies, respectively) and in women with hypertension, isolated proteinuria and/or edema. However, normotensive women account for 60% of women with PIATD. Antithrombin can escape from the blood into the interstitial space. Women with PIATD suffer from a decreased plasma volume and are more likely to develop liver dysfunction, irrespective of the presence or absence of hypertension. Because antithrombin activity continues to decrease until the time of delivery in women with PIATD, women with unrecognized PIATD may be identified as patients with so-called "acute fatty liver of pregnancy'' if delivery is delayed. Conclusion: Knowledge of AT activity in obstetrical practice may improve management of pregnant women. The determination of AT activity should be considered in women with multifetal pregnancies, hypertension, isolated proteinuria and/or edema.
• 帝王切開術施行前後における D-dimer 値の正常域の検討-第2報

  森川 守, 山田 俊, 山田 崇弘, 赤石 理奈, 小山 貴弘, 武田 真光, 西田 竜太郎, 荒木 直人, 長 和俊, 水上 尚典

  日本産婦人科・新生児血液学会誌 = The Japanese journal of obstetrical, gynecological & neonatal hematology 21 1 "S - 19"-"S-20" 2011年06月01日 [査読無し][通常論文]
  
• Do uterotrophic drugs increase the risk of fatal hemorrhagic brain stroke?

  Takashi Yamada, Takahiro Yamada, Mamoru Morikawa, Masamitsu Takeda, Rina Akaishi, Ryutaro Nishida, Naoto Araki, Takahiro Koyama, Hisanori Minakami

  JOURNAL OF PERINATAL MEDICINE 39 1 23 - 26 2011年01月 [査読有り][通常論文]
   

  Objective: To evaluate whether uterotrophic agents increase the risk of fatal hemorrhagic brain stroke. Methods: Between 1991 and 1992, there were 230 maternal deaths among 2,420,000 pregnant women in Japan and the causes of these deaths was investigated in 1994. Using information provided in this report, we identified 35 women who died from or were assumed to die from hemorrhagic brain stroke. We assumed that 93% of women would have tried vaginal delivery. The risk of fatal hemorrhagic brain stroke after uterotrophic agent use was calculated according to the assumption that 5.0-40% of women received uterotrophic agents. Results: Use of uterotrophic agents for induction/augmentation of labor was confirmed in five (14.3%) of the 35 women who died from hemorrhagic brain stroke. The incidence of fatal brain stroke after the use of uterotrophic agents was only significantly higher than that for spontaneous hemorrhagic brain stroke if these agents were administered in <= 6.0% of women. Conclusions: Because more than 6.0% of women received uterotrophic agents, these agents are unlikely to increase the risk of fatal hemorrhagic brain stroke.
• Isolated proteinuria as an initial sign of severe preeclampsia

  Yamada T, Yamada T, Morikawa M, Takeda M, Nishida R, Akaishi R, Minakami H

  Open Journal of Obstetrics and Gynecology 1 13 - 16 2011年 [査読有り][通常論文]
  
• インフルエンザ．母体感染症up to date

  山田崇弘, 水上尚典

  周産期医学 41 2 271 - 276 東京医学社 2011年 [査読無し][招待有り]
  
• 早剥の疫学−最近の傾向

  山田崇弘, 水上尚典

  臨床婦人科産科 65 1298 - 1300 2011年 [査読無し][招待有り]
  
• 【羊水の臨床】 羊水過多の臨床(解説/特集)

  山田崇弘, 山田俊, 水上尚典

  産科と婦人科 78 1199 - 1203 2011年 [査読無し][招待有り]
  
• 札幌圏における未受診妊婦の実態調査 : 札幌市の未受診妊婦対策啓発活動の紹介

  山田 俊, 長 和俊, 小山 貴弘, 赤石 理奈, 武田 真光, 山田 崇弘, 島田 茂樹, 森川 守, 遠藤 俊明, 館石 宗隆, 斉藤 豪, 水上 尚典

  日本周産期・新生児医学会雑誌 = Journal of Japan Society of Perinatal and Neonatal Medicine 46 4 1097 - 1099 2010年12月20日 [査読無し][通常論文]
  
• Change in the number of patients after the adoption of IADPSG criteria for hyperglycemia during pregnancy in Japanese women

  Mamoru Morikawa, Takashi Yamada, Takahiro Yamada, Rina Akaishi, Ryutaro Nishida, Kazutoshi Cho, Hisanori Minakami

  DIABETES RESEARCH AND CLINICAL PRACTICE 90 3 339 - 342 2010年12月 [査読有り][通常論文]
   

  Aims: To assess how the number of Japanese pregnant women with hyperglycemia changes after the adoption of the criteria proposed by the IADPSG. Methods: The study subjects comprised 228 Japanese women with a plasma glucose level >= 7.8 mmol/L on a glucose challenge test and who subsequently underwent a glucose tolerance test among 1038 women with singleton pregnancies. Gestational diabetes mellitus (GDM) is currently diagnosed using the JSOG criteria in Japan. Results: Of the 228 women, all 25 women with GDM and an additional 43 women without GDM according to the JSOG criteria were classified as having hyperglycemia according to the IADPSG criteria, resulting in an increase of patients with hyperglycemia from 2.4% (25/1038) to 6.6% (68/1038). The number of infants with a birthweight >= 3600 g was significantly larger among the 43 women with newly diagnosed GDM than among the 160 women who remained normoglycemic (14% [6/43] vs. 3.8% [6/160], p = 0.02). The calculated number of patients requiring treatment for a reduction of one infant with a birthweight >= 3600 g was at least 9.8 for women with newly diagnosed GDM. Conclusion: The IADPSG criteria increase the number of patients by at least 2.7-fold but may be cost-effective with respect to the resulting reduction in macrosomia. (C) 2010 Elsevier Ireland Ltd. All rights reserved.
• Evidence of the escape of antithrombin from the blood into the interstitial space in pregnant women

  Mamoru Morikawa, Takashi Yamada, Takahiro Yamada, Takahiro Koyama, Rina Akaishi, Masamitsu Takeda, Naoto Araki, Kazutoshi Cho, Hisanori Minakami

  JOURNAL OF PERINATAL MEDICINE 38 6 613 - 615 2010年11月 [査読有り][通常論文]
   

  Objective: We investigated whether ascites samples obtained from pregnant women during cesarean sections contained antithrombin because it is unknown whether antithrombin escapes from the blood and passes into the interstitial space during pregnancy. Methods: The concentration and activity levels of antithrombin were determined in six ascites samples obtained from six consecutive women who exhibited generalized edema, ascites, and a gradual decline in antithrombin activity. Results: All six ascites samples contained antithrombin (mean +/- SD, 4.9 +/- 2.2 mg/dL; range, 2.7-8.8 mg/dL) and exhibited an antithrombin activity level of 15.5 +/- 6.0% (range, 10-24%). Conclusions: Antithrombin escapes from the blood into the interstitial space in pregnant women. This phenomenon partially explains the gradual decline in antithrombin activity observed in these six pregnant women with generalized edema and large volumes of ascites.
• Marked gestational edema as a clinical sign of life-threatening condition

  Takahiro Koyama, Takashi Yamada, Mamoru Morikawa, Rieko Tanaka, Mie Yamamura, Naoto Araki, Takahiro Yamada, Shigeki Shimada, Hisanori Minakami

  JOURNAL OF OBSTETRICS AND GYNAECOLOGY RESEARCH 36 4 861 - 865 2010年08月 [査読有り][通常論文]
   

  A 35-year-old Japanese nulliparous woman exhibited rapid weight gain (6 kg/7 days), reduced antithrombin activity and platelet count at 37 weeks of gestation without hypertension or proteinuria, and underwent cesarean section. Postnatally, pulmonary edema developed for 7 days, with transient hypertension and proteinuria, and bodyweight loss (14.6 kg) by 14 days postpartum. Platelet count and antithrombin activity normalized promptly postpartum. Despite a life-threatening clinical condition due to enhanced vascular permeability, neither hypertension nor proteinuria appeared antenatally. Determining antithrombin activity and platelet count may be useful for distinguishing between women with pathological edema and physiological edema.
• 日本においてはPandemic (H1N1) 2009による妊婦死亡はなかった

  Yamada T, Yamada T, Saito T, Sengoku K, Minakami H

  BMJ http://www.bmj.com/rapid-response/2011/11/02/no-maternal-mortality-pandemic-h1n1-2009-occurred-japan 2010年08月
• Pregnancy-induced antithrombin deficiency

  Mamoru Morikawa, Takashi Yamada, Takahiro Yamada, Shigeki Shimada, Takahiro Koyama, Kazutoshi Cho, Hisanori Minakami

  JOURNAL OF PERINATAL MEDICINE 38 4 379 - 385 2010年07月 [査読有り][通常論文]
   

  Objective: This retrospective study was performed to characterize the laboratory features and water metabolism of women with pregnancy-induced antithrombin deficiency (PIATD). Methods: Among 1493 women who gave birth to a singleton infant at our institution, 114 women who developed PIATD and/or pregnancy-induced hypertension (PIH) were reviewed with respect to perinatal changes in laboratory variables (hematocrit value, fibrinogen, fibrinogen degradation product, D-dimer, uric acid, aspartate aminotransferase, lactate dehydrogenase) and body weight. PIATD was defined as a gradual decline in antithrombin (AT) activity to <= 65% of normal activity levels. One hundred and fourteen women with neither PIATD nor PIH and matched for the cesarean delivery rate were selected as a control group. Results: Of the 81 women who developed PIH, 19 (23.4%) also developed PIATD. Thirty-three women developed PIATD in the absence of PIH. Coagulation-fibrinolysis was significantly more enhanced and the postpartum reduction in the hematocrit value was significantly larger in women with PIATD, irrespective of the presence or absence of hypertension, than in women without PIATD. The postpartum decrease in body weight was significantly smaller in women with PIATD, irrespective of the presence or absence of hypertension. Conclusions: A decrease in AT activity may occur in the absence of hypertension. Even in the absence of hypertension, a decreased plasma volume and enhanced coagulation-fibrinolysis seem to characterize women with PIATD. The monitoring of AT activity may help in distinguishing pregnant women with these insidious risks.
• 妊婦における血中から間質へのアンチトロンビンの漏出の根拠

  森川 守, 山田 俊, 山田 崇弘, 赤石 理奈, 小山 貴弘, 武田 真光, 西田 竜太郎, 荒木 直人, 水上 尚典

  日本産婦人科・新生児血液学会誌 = The Japanese journal of obstetrical, gynecological & neonatal hematology 20 1 "S - 51"-"S-52" 2010年06月01日 [査読無し][通常論文]
  
• Invasive group A streptococcal infection in pregnancy

  Takahiro Yamada, Takashi Yamada, Mie K. Yamamura, Kenichi Katabami, Mineji Hayakawa, Utano Tomaru, Shigeki Shimada, Mamoru Morikawa, Toshio Seki, Satoshi Ariga, Kaoru Ishikawa, Tadayoshi Ikebe, Satoshi Gando, Hisanori Minakami

  JOURNAL OF INFECTION 60 6 417 - 424 2010年06月 [査読有り][通常論文]
   

  We conducted a literature review of 55 pregnancies with symptomatic Group A streptococcus (Streptococcus pyogenes) infection reported in English (20 cases), French (2 cases) and Japanese (33 cases) to seek ways of improving prognosis. Multiparous women (83% [39/47]) in the third trimester (90% [47/52]) were prone to infection from winter to spring (75% [21/28]). Onset was heralded by flu-like symptoms, such as high fever (94% [46/49]), with upper respiratory (40% [22/55]) and/or gastrointestinal symptoms (49% [27/55]). Characteristic findings were early onset of shock (91% [50/55]) and infection-induced strong uterine contraction (73% [40/55]) suggestive of placental abruption. The clinical course was too acute and severe to rescue the mother (58% [32/55] died) and/or infant (66% [39/59] died). However, outcome has improved over the last decade, with rescue of 68% (15/22) of the mothers since 2000, and early use of antibiotics (71% [22/31] survived) and use of intravenous immunoglobulin (91% [10/11] survived) were associated with favourable outcome. Early use of antibiotics and intravenous immunoglobulin may improve outcome of pregnant women suffering from flu-like symptoms, shock and strong uterine contractions suggestive of placental abruption. (C) 2010 The British Infection Society. Published by Elsevier Ltd. All rights reserved.
• Invasive group A streptococcal infection in pregnancy.

  Yamada T, Yamamura MK, Katabami K, Hayakawa M, Tomar U, Ahimada S, Morikawa M, Seki T, Ariga S, Ishikawa K, Ikebe T, Gando S, Minakami H

  The Journal of infection 60 6 417 - 424 2010年06月 [査読有り][通常論文]
  
• 妊娠性血小板減少症 (gestational thrombocytopenia) の臨床的意義

  森川 守, 山田 俊, 山田 崇弘, 島田 茂樹, 荒木 直人, 小山 貴弘, 水島 正人, 長 和俊, 水上 尚典

  日本産婦人科・新生児血液学会誌 = The Japanese journal of obstetrical, gynecological & neonatal hematology 19 2 19 - 25 2010年03月01日 [査読無し][通常論文]
  
• 妊娠性アンチトロンビン欠乏症

  水上 尚典, 森川 守, 島田 茂樹, 山田 崇弘, 長 和俊, 小山 貴弘, 水島 正人, 山田 俊

  日本産婦人科・新生児血液学会誌 = The Japanese journal of obstetrical, gynecological & neonatal hematology 19 2 7 - 17 2010年03月01日 [査読無し][通常論文]
  
• A type of familial cleft of the soft palate maps to 2p24.2-p24.1 or 2p21-p12

  Masayoshi Tsuda, Takahiro Yamada, Tadashi Mikoya, Izumi Sogabe, Mitsuko Nakashima, Hisanori Minakami, Tatsuya Kishino, Akira Kinoshita, Norio Niikawa, Akiyoshi Hirano, Koh-ichiro Yoshiura

  JOURNAL OF HUMAN GENETICS 55 2 124 - 126 2010年02月 [査読有り][通常論文]
   

  Cleft of the soft palate (CSP) and the hard palate are subtypes of cleft palate. Patients with either condition often have difficulty with speech and swallowing. Nonsyndromic, cleft palate isolated has been reported to be associated with several genes, but to our knowledge, there have been no detailed genetic investigations of CSP. We performed a genome-wide linkage analysis using a single-nucleotide polymorphism-based microarray platform and successively using microsatellite markers in a family in which six members, across three successive generations, had CSP. A maximum LOD score of 2.408 was obtained at 2p24.2-24.1 and 2p21-p12, assuming autosomal dominant inheritance. Our results suggest that either of these regions is responsible for this type of CSP. Journal of Human Genetics (2010) 55, 124-126; doi: 10.1038/jhg.2009.131; published online 15 January 2010
• 妊娠中の薬剤投与：一大学病院からの調査報告

  小山貴弘, 山田俊, 山村満恵, 荒木直人, 山田崇弘, 島田茂樹, 森川守, 山田秀人, 水上尚典

  北海道産科婦人科学会会誌 54 1 25 - 31 北海道産科婦人科学会 2010年 [査読有り]
   

  周産期三次施設において、妊娠中の薬剤使用について調査した。対象は2008年1〜12月に22週以降で分娩した妊婦277名で、55.9%(155名)がハイリスク妊婦であった。薬剤を投与されていたのは84.8%で、1名当たりの薬剤数は平均4.2±3.6剤であった。投与頻度は、子宮収縮抑制剤:52.3%(145例)、緩下剤:39.0%(108例)、鉄剤:36.8%(102例)、抗菌剤:26.2%(74例)、葉酸製剤:20.2%(56例)の順であった。平均分娩週数は36.6週であったが、降圧剤、副腎皮質ステロイド、ヘパリンを投与された妊婦は妊娠持続週数が短い傾向がみられ、合併した原疾患が妊娠持続週数に影響を与えたことが推測された。ハイリスク妊婦が集中する周産期三次施設では、薬剤の処方を要する妊婦が多いことが示唆された。
• Prenatal diagnosis of short-rib polydactyly syndrome type 3 (Verma-Naumoff type) by three-dimensional helical computed tomography.

  Yamada T, Nishimura G, Nishida K, Sawai H, Omatsu T, Kimura T, Nishihara H, Shono R, Shimada S, Morikawa M, Mizushima M, Yamada T, Cho K, Tanaka S, Shirato H, Minakami H

  J. Obstet. Gynecol. Res. 37 151 - 155 2010年 [査読有り][通常論文]
  
• 常位胎盤早期剥離．−胎盤と疾患−

  山田崇弘, 水上尚典

  周産期医学 40 1101 - 1104 2010年 [査読無し][招待有り]
  
• 母体血を用いた胎児性別診断．産科医療における遺伝学

  山田崇弘, 古田伊都子, 水上尚典

  産婦人科の実際 59 12 2029 - 2033 金原出版 2010年 [査読無し][招待有り]
  
• 妊娠中の暫定的診断「妊娠蛋白尿」の病的意義(第2報)

  森川 守, 山田 俊, 山田 崇弘, 島田 茂樹, 小山 貴弘, 長 和俊, 水上 尚典

  日本周産期・新生児医学会雑誌 = Journal of Japan Society of Perinatal and Neonatal Medicine 45 4 1125 - 1128 2009年12月20日 [査読無し][通常論文]
  
• Platyspondylic lethal skeletal dysplasia San Diego type (thanatophoric dysplasia type 1) associated with trisomy 21 presenting with nuchal translucency: a case report

  Takahiro Yamada, Hideaki Sawai, Gen Nishimura, Hironao Numabe, Kazutoshi Cho, Hisanori Minakami

  PRENATAL DIAGNOSIS 29 7 715 - 717 2009年07月 [査読有り][通常論文]
  
• 妊娠性血小板減少症 gestational thrombocytopenia(GP) の臨床的意義

  森川 守, 山田 俊, 山田 崇弘, 島田 茂樹, 荒木 直人, 小山 貴弘, 山村 満恵, 長 和俊, 山田 秀人, 水上 尚典

  日本産婦人科・新生児血液学会誌 = The Japanese journal of obstetrical, gynecological & neonatal hematology 19 1 "S - 107"-"S-108" 2009年05月01日 [査読無し][通常論文]
  
• 双胎妊娠において Late Preterm Birth (LPB) は異常分娩か?

  森川 守, 山田 俊, 山田 崇弘, 小山 貴弘, 山村 満恵, 長 和俊, 山田 秀人, 水上 尚典

  日本周産期・新生児医学会雑誌 = Journal of Japan Society of Perinatal and Neonatal Medicine 44 4 1074 - 1077 2008年12月25日 [査読無し][通常論文]
  
• 症例から見た妊娠高血圧症候群の病態とその管理

  水上 尚典, 山田 俊, 森川 守, 島田 茂樹, 山田 崇弘, 山田 秀人, 長 和俊

  日本周産期・新生児医学会雑誌 = Journal of Japan Society of Perinatal and Neonatal Medicine 44 4 799 - 803 2008年12月25日 [査読無し][通常論文]
  
• Ileal atresia after fetoscopic laser photocoagulation for twin-to-twin transfusion syndrome-a case report

  Mamoru Morikawa, Haruhiko Sago, Takashi Yamada, Satoshi Hayashi, Takahiro Yamada, Kazutoshi Cho, Hideto Yamada, Michihiro Kitagawa, Hisanori Minakami

  PRENATAL DIAGNOSIS 28 11 1072 - 1074 2008年11月 [査読有り][通常論文]
  
• HELLP症候群関連疾患 : 妊娠性アンチトロンビン欠乏症

  森川 守, 山田 俊, 山田 崇弘, 島田 茂樹, 長 和俊, 山田 秀人, 櫻木 範明, 水上 尚典

  日本産婦人科・新生児血液学会誌 = The Japanese journal of obstetrical, gynecological & neonatal hematology 18 1 "S - 65"-"S-66" 2008年06月01日 [査読無し][通常論文]
  
• TESE-ICSI後に発生した二絨毛膜性双胎と共存した全胞状奇胎

  山田 崇弘, 松田 貴雄, 工藤 正尊, 山田 俊, 森脇 征史, 西 信也, 蝦名 康彦, 山田 秀人, 加藤 秀則, 伊藤 智雄, 和氣 徳夫, 櫻木 範明, 水上 尚典

  日本産科婦人科學會雜誌 60 3 999 - 999 2008年03月01日 [査読無し][通常論文]
  
• Complete hydatidiform mole with coexisting dichorionic diamniotic twins following testicular sperm extraction and intracytoplasmic sperm injection

  Takahiro Yamada, Takao Matsuda, Masataka Kudo, Takashi Yamada, Masashi Moriwaki, Shinya Nishi, Yasuhiko Ebina, Hideto Yamada, Hidenori Kato, Tomoo Ito, Norio Wake, Noriaki Sakuragi, Hisanori Minakami

  JOURNAL OF OBSTETRICS AND GYNAECOLOGY RESEARCH 34 1 121 - 124 2008年02月 [査読有り][通常論文]
   

  We present the first report of complete hydatidiform mole (HM) with coexisting dichorionic diamniotic twins. This pregnancy was achieved after testicular sperm extraction and intracytoplasmic sperm injection (ICSI) for azoospermia in the woman's husband. Standard in vitro fertilization may cause multisperm fertilization and increase triploid partial HM and complete HM, which arise from dispermic fertilization. In contrast, ICSI can avoid multisperm fertilization. In our case, paternal isodisomy in the molar tissue was confirmed by microsatellite analysis suggesting that it resulted from duplication of a haploid paternal genome following monospermic fertilization of an inactivated oocyte or from monospermic fertilization of an inactivated oocyte with a diploid sperm. Although the patient was eager to continue the pregnancy, the size of the HM component increased rapidly and termination of the pregnancy was required for pre-eclampsia-like symptoms at 15 weeks of gestation. After the operation, chemotherapy was initiated for persistent trophoblastic disease.
• Pregnancy outcome of women who developed proteinuria in the absence of hypertension after mid-gestation

  Mamoru Morikawa, Takashi Yamada, Takahiro Yamada, Kazutoshi Cho, Hideto Yamada, Noriaki Sakuragi, Hisanori Minakami

  JOURNAL OF PERINATAL MEDICINE 36 5 419 - 424 2008年 [査読有り][通常論文]
   

  Objective: To characterize the clinical features of women with singleton pregnancies who develop proteinuria in the absence of hypertension after mid-gestation. Methods: Seventy-nine women who developed proteinuria and/or hypertension at and after 20 weeks of gestation were reviewed, focusing on the gestational week at which significant proteinuria (>0.3 g/day) and/or hypertension developed. Results: Thirty-seven (47%) women exhibited new-onset proteinuria (>0.3 g/day) in the absence of hypertension, 33 (42%) exhibited new-onset hypertension in the absence of proteinuria, and 9 (11%) exhibited both proteinuria and hypertension. Nineteen (51%) of 37 women who exhibited new proteinuria in the absence of hypertension and 5 (15%) of 33 women who exhibited new hypertension in the absence of proteinuria progressed to preeclampsia (P=0.002). Among women who exhibited new proteinuria, 10 (77%) out of 13 women and 9 (38%) out of 24 women who developed proteinuria at <32 weeks and >= 32 weeks, respectively, progressed to preeclampsia (P=0.022). Conclusions: Women with new-onset proteinuria in the absence of hypertension may be more likely to progress to preeclampsia than women with a presumptive diagnosis of gestational hypertension, and the likelihood of progression may be significantly greater among women with earlier presentation.
• 妊娠性血小板減少症ならびに妊娠性アンチトロンビン欠乏症の分娩前後のフィブリノーゲン、FDP、D-dimer、Ht 値の推移 : 妊娠高血圧症候群との対比

  森川 守, 山田 俊, 山田 崇弘, 佐々木 尚子, 鈴木 賀博, 荒木 直人, 長 和俊, 山田 秀人, 櫻木 範明, 水上 尚典

  日本産婦人科・新生児血液学会誌 = The Japanese journal of obstetrical, gynecological & neonatal hematology 17 1 "S - 51"-"S-52" 2007年06月01日 [査読無し][通常論文]
  
• Identification of the imprinted KLF14 transcription factor undergoing human-specific accelerated evolution

  Layla Parker-Katiraee, Andrew R. Carson, Takahiro Yamada, Philippe Arnaud, Robert Feil, Sayeda N. Abu-Amero, Gudrun E. Moore, Masahiro Kaneda, George H. Perry, Anne C. Stone, Charles Lee, Makiko Meguro-Horike, Hiroyuki Sasaki, Keiko Kobayashi, Kazuhiko Nakabayashi, Stephen W. Scherer

  PLOS GENETICS 3 5 665 - 678 2007年05月 [査読有り][通常論文]
   

  Imprinted genes are expressed in a parent- of- origin manner and are located in clusters throughout the genome. Aberrations in the expression of imprinted genes on human Chromosome 7 have been suggested to play a role in the etiologies of Russell- Silver Syndrome and autism. We describe the imprinting of KLF14, an intronless member of the Kru " ppel- like family of transcription factors located at Chromosome 7q32. We show that it has monoallelic maternal expression in all embryonic and extra- embryonic tissues studied, in both human and mouse. We examine epigenetic modifications in the KLF14 CpG island in both species and find this region to be hypomethylated. In addition, we perform chromatin immunoprecipitation and find that the murine Klf14 CpG island lacks allele- specific histone modifications. Despite the absence of these defining features, our analysis of Klf14 in offspring from DNA methyltransferase 3a conditional knockout mice reveals that the gene's expression is dependent upon a maternally methylated region. Due to the intronless nature of Klf14 and its homology to Klf16, we suggest that the gene is an ancient retrotransposed copy of Klf16. By sequence analysis of numerous species, we place the timing of this event after the divergence of Marsupialia, yet prior to the divergence of the Xenarthra superclade. We identify a large number of sequence variants in KLF14 and, using several measures of diversity, we determine that there is greater variability in the human lineage with a significantly increased number of nonsynonymous changes, suggesting humanspecific accelerated evolution. Thus, KLF14 may be the first example of an imprinted transcript undergoing accelerated evolution in the human lineage.
• 偽性バーター症候群合併妊娠の1例 : 妊娠高血圧症候群モデル?

  森川 守, 山田 俊, 山崎 綾野, 太田 智佳子, 山田 崇弘, 長 和俊, 山田 秀人, 櫻木 範明, 水上 尚典

  日本産婦人科・新生児血液学会誌 = The Japanese journal of obstetrical, gynecological & neonatal hematology 16 1 "S - 9"-"S-10" 2006年06月01日 [査読無し][通常論文]
  
• Prenatal diagnosis and therapy of persistent cloaca: A case report

  M Morikawa, T Yamada, K Cho, H Yamada, H Minakami

  FETAL DIAGNOSIS AND THERAPY 21 4 343 - 347 2006年 [査読有り][通常論文]
   

  Persistent cloaca is a rare abnormality that occurs only in females and is characterized by a direct communication between the gastrointestinal, urinary, and genital structures resulting in a single perineal opening. A case with massive ascites, two cystic structures arising from the fetal pelvis, bilateral hydroureters, calcified meconium, and cardiac anomalies, in which this condition was diagnosed prenatally is presented here. Copyright (c) 2006 S. Karger AG, Basel.
• Association between preterm birth and vaginal colonization by mycoplasmas in early pregnancy

  S Kataoka, T Yamada, K Chou, R Nishida, M Morikawa, M Minami, H Yamada, N Sakuragi, H Minakami

  JOURNAL OF CLINICAL MICROBIOLOGY 44 1 51 - 55 2006年01月 [査読有り][通常論文]
   

  To examine the association between colonization by two newly classified species of genital ureaplasmas (Ureaplasma parvum and U. urealyticum) in early pregnancy and subsequent late abortion or preterm birth at < 34 weeks of gestation, four species of genital mycoplasmas-Mycoplasma genitalium, M. hominis, U. parmin, and U. urealyticum-as well as Chlamydia trachomatis and Neisseria gonorrhoeae were examined by PCR-based methods in a prospective cohort study of 877 women with singleton pregnancies at < 11 weeks of gestation. Antibiotics were used only in cases in which C. trachomatis and/or N. gonorrhoeae was detected. Multivariate logistic-regression analysis was used to assess independent risk factors after taking maternal low body weight and past history of preterm birth into account. M. genitalium, M. hominis, U. parvum, U. urealyticum, C. trachomatis, and N. gonorrhoeae were detected in 0.8%, 11.2%, 52.0%, 8.7%, 3.2%, and 0.1% of these 877 women, respectively. Twenty-one (2.4%) women experienced late abortion or preterm birth at < 34 weeks of gestation. Three factors-detection of U. parmin in the vagina (odds ratio [OR), 3.0; 95% confidence interval [CI], 1.1 to 8.5); use of antibiotics, such as penicillin and cefatrizine, for incidental inflammatory complications before 22 weeks of gestation (OR, 4.2; 95% CI, 1.6 to 10.0); and past history of preterm birth (OR, 10.4; 95% CI, 2.7 to 40.5)-were independently associated with late abortion and preterm birth. In conclusion, vaginal colonization with U. parmin, but not U. urealyticum, is associated with late abortion or early preterm birth.
• Changes in antithrombin activity and platelet counts in the late stage of twin and triplet pregnancies

  M Morikawa, T Yamada, S Kataoka, K Cho, H Yamada, S Suzuki, N Sakuragi, H Minakami

  SEMINARS IN THROMBOSIS AND HEMOSTASIS 31 3 290 - 296 2005年06月 [査読有り][通常論文]
   

  It is possible that women with triplet pregnancies are more likely to exhibit pregnancy-induced antithrombin deficiency, gestational thrombocytopenia, and perinatal elevation in serum aspartate aminotransferase (AST) than women with twin pregnancies. We retrospectively reviewed changes in antithrombin activity, platelet count, and blood chemistry in 23 twin and seven triplet pregnancies in which the mothers received antenatal care and gave birth in our hospital during 1999 and 2001. Both antithrombin activity and platelet counts gradually decreased until delivery, then promptly increased after delivery in both twin and triplet pregnancies. A significantly larger number of women developed gestational thrombocytopenia of < 100 x 10(9)/L (43% [three of seven] versus 4.3% [one of 23]; p < 0.01) and pregnancy-induced antithrombin deficiency of < 60% of normal activity (57% [four of seven] versus 17% [four of 23]; p < 0.05) in triplet than in twin pregnancies. Eight women with pregnancy-induced antithrombin deficiency, including three women with gestational thrombocytopenia, were significantly more likely to develop perinatal elevations of AST, lactate dehydrogenase, serum creatinine, fibrin/fibrinogen degradation products, and D-dimer than were those without pregnancy-induced antithrombin deficiency. These findings suggest that women with triplet pregnancies are at an increased risk of the HELLP syndrome and acute fatty liver of pregnancy compared with women with twin pregnancies.
• Endothelial nitric-oxide synthase antisense (NOS3AS) gene encodes an autophagy-related protein (APG9-like2) highly expressed in trophoblast

  T Yamada, AR Carson, Caniggia, I, K Umebayashi, T Yoshimori, K Nakabayashi, SW Scherer

  JOURNAL OF BIOLOGICAL CHEMISTRY 280 18 18283 - 18290 2005年05月 [査読有り][通常論文]
   

  Macroautophagy is an intracellular degradation system for the majority of proteins and some organelles that is conserved in all eukaryotic species. The precise role of autophagy in mammalian development and potential involvement in disease remain to be discerned. Yeast Atg9p is the first integral membrane protein shown to be essential for the cytoplasm to vacuole targeting (Cvt) pathway and autophagy, whereas its mammalian functional orthologue has yet to be identified. We have identified two human genes homologous to yeast Atg9p and designated these as APG9L1 and APG9L2. We have previously identified APG9L2 as NOS3AS, which participates in the post-transcriptional regulation of the endothelial nitric-oxide synthase (NOS3) gene on chromosome 7 through its antisense overlap. In human adult tissues, APG9L1 was ubiquitously expressed, whereas APG9L2 was highly expressed in placenta (trophoblast cells) and pituitary gland. In transient transfection assays we found that both proteins were primarily localized to the perinuclear region and also scattered throughout the cytosol as dots, a subset of which colocalized with an autophagosome-specific marker LC3 under starvation conditions. Finally, by the small interfering RNA-mediated knockdown of APG9L1 in HeLa cells, we demonstrated that APG9L1 is essential for starvation-induced autophagosome formation. In addition, APG9L2 can functionally complement APG9L1 in this process. These results, taken together with those of phylogenetic and sequence analyses, suggest that both APG9L1 and APG9L2 are functionally orthologous to the yATG9 in autophagosome formation. Moreover, APG9L2 is a vertebrate-specific gene that may have gained critical roles in mammalian-specific developmental events, such as placentation, through rapid evolution.
• Magnetic resonance image findings of placental lake: report of two cases

  M Morikawa, K Cho, S Kataoka, EH Kato, T Yamada, H Yamada, H Minakami

  PRENATAL DIAGNOSIS 25 3 250 - 252 2005年03月 [査読有り][通常論文]
   

  Two cases with a large cystic mass within the placenta are reported. By ultrasonography, it was found that both women had a subchorionic hypoechoic lesion (11.0 x 4.8 x 4.0 cm and 6.6 x 3.7 x 2.2 cm, respectively) at 24 and 35 weeks of gestation, respectively. In both cases, turbulent blood flow generated by a pulsatile jet flow (pulse rate; 40 to 60 beats per minute) into the cystic lesion seen on real-time imaging and lesions being low intensity on T1-weighted and isointensity on T2-weighted magnetic resonance image suggested that they contained fresh maternal blood. In both cases, the sonolucency of the lesions did not change until cesarean deliveries of females, both of whom were small-for-gestational-age infants (1940 a at 37 weeks and 2195 g at 37 weeks, respectively). Biochemical analysis of the fluid in the cystic lesion sampled during the cesarean section in the latter case confirmed that the fluid had originated from the maternal blood. These lesions histologically corresponded to large avillous areas surrounded by normal villi. Thus, a huge placental lake was diagnosed in both cases. Copyright (c) 2005 John Wiley T Sons, Ltd.
• トロントからの留学報告

  山田 崇弘

  北海道醫學雜誌 = Acta medica Hokkaidonensia 79 6 789 - 790 2004年11月01日 [査読無し][通常論文]
  
• Embryo loss pattern is predominant in miscarriages with normal chromosome karyotype among women with repeated miscarriage

  M Morikawa, H Yamada, EH Kato, S Shimada, T Yamada, H Minakami

  HUMAN REPRODUCTION 19 11 2644 - 2647 2004年11月 [査読有り][通常論文]
   

  Objective: The aim of this study was to assess pregnancy loss patterns in women with repeated miscarriage (RM), according to fetal chromosome karyotypes and aetiologies of RM. Methods: In this cohort study, 168 fetal chromosome karyotypes of miscarriages were investigated. The pregnancy loss patterns were compared between 75 miscarriages from RM women who had a history of two or more consecutive miscarriages and 93 miscarriages from control women whose previous pregnancies ended in live births without a history of RM. By serial ultrasonography, embryo loss (EL) was defined as miscarriage before fetal heat movement was identified and fetal loss (FL) as miscarriage after fetal heat movement was identified. The EL rate was calculated as EL/(EL+FL). Results: The EL rate (66.7%) in miscarriages with normal karyotypes among RM women (n=42) was higher (P<0.05) than that (45.7%) in controls (n=46), while the EL rate (30.3%) in miscarriages with abnormal karyotypes among RM women (n=33) did not differ from that (25.5%) in the controls (n=47). The EL rate (71.4%) in miscarriages with normal karyotypes among unexplained RM women (n=21) was much higher (P<0.05) than that in the controls. Conclusions: By evaluating fetal karyotypes, we demonstrated for the first time that EL was predominant in miscarriages with normal karyotype among RM women.
• Post-transcriptional regulation of endothelial nitric-oxide synthase by an overlapping antisense mRNA transcript

  GB Robb, AR Carson, SC Tai, JE Fish, S Singh, T Yamada, SW Scherer, K Nakabayashi, PA Marsden

  JOURNAL OF BIOLOGICAL CHEMISTRY 279 36 37982 - 37996 2004年09月 [査読有り][通常論文]
   

  Endothelial nitric-oxide synthase ( eNOS) mRNA levels are abnormal in diseases of the cardiovascular system, but changes in gene expression cannot be accounted for by transcription alone. We found evidence for the existence of an antisense mRNA (sONE) that is derived from a transcription unit ( NOS3AS) on the opposite DNA strand from which the human eNOS (NOS3) mRNA is transcribed at human chromosome 7q36. The genes are oriented in a tail-to-tail configuration, and the mRNAs encoding sONE and eNOS are complementary for 662 nucleotides. The mRNA for sONE could be detected in a variety of cell types, both in vivo and in vitro, but not vascular endothelial cells. In contrast, expression of eNOS is highly restricted to vascular endothelium. Most surprisingly, interrogation of transcriptional events across NOS3/NOS3AS genomic regions, using single- and double-stranded probes for nuclear run-off analyses and chromatin immunoprecipitation-based assessments of RNA polymerase II distribution, indicated that NOS3 and NOS3AS gene transcription did not correlate with steady-state mRNA levels. We found strong evidence supporting a role for NOS3AS in the post-transcriptional regulation of NOS3 expression. RNA interference-mediated inhibition of sONE expression in vascular smooth muscle cells increased eNOS expression. Overexpression of sONE in endothelial cells blunted eNOS expression. Finally, the histone deacetylase inhibitor trichostatin A is known to regulate the expression of eNOS via a post-transcriptional mechanism. We found that trichostatin A treatment of vascular endothelial cells increased expression of sONE mRNA levels prior to the observed decrease in eNOS mRNA expression. Taken together, these results indicate that an antisense mRNA ( sONE) participates in the post-transcriptional regulation of eNOS and provide a newer model for endothelial cell-specific gene expression.
• A previously unidentified MECP2 open reading frame defines a new protein isoform relevant to Rett syndrome

  GN Mnatzakanian, H Lohi, Munteanu, I, SE Alfred, T Yamada, PJM MacLeod, Jones, JR, SW Scherer, NC Schanen, MJ Friez, JB Vincent, BA Minassian

  NATURE GENETICS 36 4 339 - 341 2004年04月 [査読有り][通常論文]
   

  Rett syndrome is caused by mutations in the gene MECP2 in 80% of affected individuals. We describe a previously unknown MeCP2 isoform. Mutations unique to this isoform and the absence, until now, of identified mutations specific to the previously recognized protein indicate an important role for the newly discovered molecule in the pathogenesis of Rett syndrome.
• Imprinting analysis of 10 genes and/or transcripts in a 1.5-Mb MEST-flanking region at human chromosome 7q32

  T Yamada, K Mitsuya, T Kayashima, K Yamasaki, T Ohta, K Yoshiura, N Matsumoto, H Yamada, H Minakami, M Oshimura, N Niikawa, T Kishino

  GENOMICS 83 3 402 - 412 2004年03月 [査読有り][通常論文]
   

  MEST is one of the imprinted genes in human. With the assistance of our integration map and the complete sequence in the registry, we mapped a total of 16 genes/transcripts at the 1.5-Mb MEST-flanking region at 7q32. This region has been suggested to form an imprinted gene cluster, because MEST and its three flanking genes/transcripts (MESTIT1, CPA4, and COPG2IT1) were reported to be imprinted, although two (TSGA14 and COPG2) were shown to escape imprinting. In this study, 10 other genes/transcripts were examined for their imprinting status in human fetal tissues. The results indicated that 8 genes/transcripts (NRF1, UBE2H, HSPC216, KIAA0265, FLJ14803, CPA2, CPA1, and DKFZp667F0312) were expressed biallelically. The imprinting status of two (TSGA13 and CPA5) was not conclusive, because of their weak and/or tissue-specific expression and inconstant results. These findings provided evidence that only 4 of the 16 genes/ transcripts located to the region show monoallelic expression, while others are not involved in imprinting. Therefore, it is less likely that the MEST-flanking 7q32 region forms a large imprinted domain. (C) 2003 Elsevier Inc. All rights reserved.
• A polymorphism in the CYP17 gene and intrauterine fetal growth restriction

  H Yamada, F Sata, EH Kato, Y Saijo, S Kataoka, M Morikawa, S Shimada, T Yamada, R Kishi, H Minakami

  MOLECULAR HUMAN REPRODUCTION 10 1 49 - 53 2004年01月 [査読有り][通常論文]
   

  Intrauterine fetal growth restriction is a multifactorial disorder, and its aetiology includes both environmental and genetic components. We aimed to investigate whether maternal genetic polymorphisms of metabolic enzymes affects fetal growth and pregnancy duration. Genomic DNA was obtained from 134 women who experienced singleton deliveries beyond 24 weeks of gestation. Maternal age, birth weight, gestational age at birth and frequencies of fetal growth restriction, prematurity and pregnancy-induced hypertension were compared among genotypic subgroups of cytochrome P450 (CYP) and glutathione S-transferase (GST) genes. The polymorphisms of CYP1A1 (MspI), CYP17 (MspAI) and GSTP1 (BsmAI) genotypes, and the presence or absence of GSTM1 and GSTT1 genes were analysed by PCR-based methods. The frequency of fetal growth restriction (<10th percentile/<-1.5 SD; 22.7%/11.4%) in 44 women who were homozygous for the A1 allele (A1A1) of CYP17 was significantly higher than that (7.8%/2.2%) in 90 women who carried the A2 allele (A1A2/A2A2) of CYP17 (P < 0.05), with an odds ratio =3.41 (95% confidence interval = 1.18-9.84). The gestational age at birth (mean +/- SD, 37.5 +/- 3.1 weeks) in 67 women with GSTM1 null genotype was significantly lower than that (38.5 +/- 2.4 weeks) in 67 women who carried GSTM1 (P < 0.05). The polymorphism of CYP17 that encodes the cytochrome P450c17alpha enzyme might be associated with the pathophysiology underlying fetal growth restriction.
• Atp10a, the mouse ortholog of the human imprinted ATP10A gene, escapes genomic imprinting

  T Kayashima, K Yamasaki, K Joh, T Yamada, T Ohta, K Yoshiura, N Matsumoto, Y Nakane, T Mukai, N Niikawa, T Kishino

  GENOMICS 81 6 644 - 647 2003年06月 [査読有り][通常論文]
   

  The mouse Atp10a gene is located at the border of an imprinted domain distal to the p-locus on mouse chromosome 7. The localization of Atp10a neighboring the maternally expressed gene Ube3a in the imprinted domain and an unusual inheritance pattern of the obesity phenotype with a p-locus deletion have suggested that Atp10a might be imprinted and associated with body fat. Recently, its human ortholog, ATP10A, was identified as the second imprinted gene with maternal expression in the human chromosome 15q11-q13 imprinted domain. To elucidate the imprinting status of Atp10a, we performed expression analysis in various tissues from reciprocal crosses between C57BL/6 and PWK (divergent strains of Mus musculus) mice. The results revealed that Atp10a was biallelically expressed in all tissues examined. Furthermore, there was no differential methylation in the CpG island and no antisense transcripts of the gene. These findings suggest that the mouse Atp10a gene escapes genomic imprinting. (C) 2003 Elsevier Science (USA). All rights reserved.
• The novel imprinted carboxypeptidase A4 gene (CPA4) in the 7q32 imprinting domain

  T Kayashima, K Yamasaki, T Yamada, H Sakai, N Miwa, T Ohta, K Yoshiura, N Matsumoto, Y Nakane, H Kanetake, F Ishino, N Niikawa, T Kishino

  HUMAN GENETICS 112 3 220 - 226 2003年03月 [査読有り][通常論文]
   

  By a search for novel human imprinted genes in the vicinity of the imprinted gene MEST, at chromosome 7q32, we identified the carboxypeptidase A4 gene (CPA4) in a gene cluster of the carboxypeptidase family, 200kb centromeric to MEST. Because CPA4 was originally identified as a protein induced in a prostate cancer cell line (PC-3) by histone deacetylase inhibitors, and was located at the putative prostate cancer-aggressiveness locus at 7q32, we investigated its imprinting status in fetal tissues and in adult benign hypertrophic prostate (BPH). RT-PCR using four intragenic polymorphisms as markers showed that CPA4 was expressed preferentially from the maternal allele in the fetal heart, lung, liver, intestine, kidney, adrenal gland, and spleen, but not in the fetal brain. It was also preferentially expressed in the BPH. These findings support that CPA4 is imprinted and may become a strong candidate gene for prostate cancer-aggressiveness. As a Silver-Russell syndrome (SRS) locus has been proposed to be located to a region near MEST and to be involved in imprinting, CPA4 would have been a candidate gene for SRS. However, analysis of ten SRS patients revealed no mutations in CPA4.
• <学位論文>MEST周囲7q32領域におけるインプリンティングドメインの解析

  山田 崇弘

  北海道医学雑誌 77 6 517 - 526 北海道大学 2002年11月01日 [査読無し][通常論文]
  
• [Analysis of the imprinted domain in the vicinity of MEST at chromosomal 7q32].

  Yamada T

  [Hokkaido igaku zasshi] The Hokkaido journal of medical science 77 6 517 - 526 6 2002年11月 [査読有り][通常論文]
  
• The gene TSGA14, adjacent to the imprinted gene MEST, escapes genomic imprinting

  T Yamada, T Kayashima, K Yamasaki, T Ohta, K Yoshiura, N Matsumoto, S Fujimoto, N Niikawa, T Kishino

  GENE 288 1-2 57 - 63 2002年04月 [査読有り][通常論文]
   

  We identified the gene TSGA14, encoding the testis-specific protein A14 and located 50 kb proximal to the imprinted gene MEST in a head-to-head orientation. TSGA14 has at least two transcripts: a long-type (I-type) transcript, and a short-type (s-type) transcript. Since the COPG2IT1 gene in the vicinity of MEST has been reported to be imprinted, we presumed that TSGA14 might also be imprinted. We thus analyzed the imprinting status of TSGAI41-type and s-type transcripts in various fetal tissues. TSGAI41-type transcript, which consists of 11 exons and encodes a 1-type isoform with 373 amino acids, is biallelically expressed in the fetal tissues including the testis. TSGA14 s-type transcript, which consists of three exons and encodes a s-type isoform with 54 amino acids, also showed biallelic expression in the fetal brain and liver. No allele-specific methylation in the TSGA14 CpG island was detected. The fact that COPG2 and TSGA14, both neighbors of MEST, escape genomic imprinting suggests that the 7q32 imprinted region may be small and not similar to other imprinted domains, such as those at 15q11-13 and 11p15.5. (C) 2002 Elsevier Science B.V. All rights reserved.
• A catalog of 106 single-nucleotide polymorphisms (SNPs) and 11 other types of variations in genes for transforming growth factor-beta 1 (TGF-beta 1) and its signaling pathway

  Y Watanabe, A Kinoshita, T Yamada, T Ohta, T Kishino, N Matsumoto, M Ishikawa, N Niikawa, K Yoshiura

  JOURNAL OF HUMAN GENETICS 47 9 478 - 483 2002年 [査読有り][通常論文]
   

  Transforming growth factor-beta1 (TGF-beta1) is a multifunctional cytokine that is produced in the platelet, bone, placenta, and other tissues. It acts as a growth inhibitor in many types of cells, and also mediates extracellular matrix production and immunosuppression. Mutations in the specific domain of its gene (TGFBI) cause Camurati-Engelmann disease, a bone-sclerosing disorder, and those in other domains may be associated with osteoporosis. We identified 106 single-nucleotide polymorphisms and 11 other types of variations in TGFBI and six other genes. These genes were TGF-beta type I receptor gene (TGFBR1), TGF-beta type II receptor gene (TGFBR2), SMAD2 gene (SMAD2), SMAD3 gene (SMAD3), SMAD4 gene (SMAD4), and SMAD7 gene (SMAD7), all of which compose the TGF-beta1 signaling pathway. We also estimated allele frequencies of these DNA polymorphisms among 48 Japanese individuals. Our data will provide a useful resource for the study of disease susceptibility.
• Massive intravenous immunoglobulin treatment in women with four or more recurrent spontaneous abortions of unexplained etiology: Down-regulation of NK cell activity and subsets

  M Morikawa, H Yamada, EH Kato, S Shimada, T Kishida, T Yamada, G Kobashi, S Fujimoto

  AMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY 46 6 399 - 404 2001年12月 [査読有り][通常論文]
   

  Problem: The aims of this study were to investigate the efficacy of massive intravenous immunoglobulin (MIVIg) treatment for women with recurrent spontaneous abortion (RSA) of unexplained etiology, and to investigate changes in peripheral natural killer (NK) cell activity and subsets. Method of study: MIVIg treatment was performed in 18 pregnancies from 15 women with 4 or more consecutive RSA of unexplained etiology. NK cell activity and subsets were assessed in 8 of the pregnancies. ResultS: 14 pregnancies resulted in live births and 4 resulted in abortions with chromosome abnormality. The pre-infusion NK cell activity (mean +/- SID, 40.9 +/- 17.0%) at 4.4 +/-0.5 weeks of gestation (GW) decreased to 15.0 +/-7.9% at post-infusion status (5.4 +/-0.5 GW). Pre-infusion percentages of CD56(+)CD16(-) cells (3.5 +/-2.1%) and CD56(+)CD16(-) cells (16.8 +/-8.8%) decreased to 3.0 +/-2.2% and 11.1 +/-6.9%, respectively. after MIVIg treatment. Conclusions: MIVIg treatment was effective in all 14 pregnancies from RSA women of unexplained etiology, excluding 4 abortions with chromosome abnormality. Peripheral NK cell activity and subsets were suppressed by MIVIg treatment.
• Management of pregnancy with congenital antithrombin III deficiency: Two case reports and a review of the literature

  T Yamada, H Yamada, M Morikawa, EH Kato, T Kishida, Y Ohnaka, H Nikaido, T Ozawa, S Fujimoto

  JOURNAL OF OBSTETRICS AND GYNAECOLOGY RESEARCH 27 4 189 - 197 2001年08月 [査読有り][通常論文]
   

  Women with antithrombin (AT) III deficiency are prone to pregnancy-associated venous thromboembolism. We report 2 cases with genetically confirmed ATIII deficiency, one with a mutation in exon 3A and the other with an exon 4 deletion, in whom the pregnancies were successfully managed with prophylactic therapies for thrombosis. A 35-year-old pregnant woman was treated with intravenous infusions of ATIII concentrate alone, and the other 22-year-old pregnant woman was mainly treated with subcutaneous injections of heparin and oral low-dose aspirin therapy. Both pregnancies resulted in vaginal deliveries of healthy neonates. The literature concerning prophylactic therapies for thrombosis in ATIII deficiency-complicated pregnancy is reviewed, and the clinical problems, including the adverse effects of the therapies, are discussed.
• 子宮筋腫合併妊娠の取り扱いについて

  山田崇弘, 山田秀人, 北澤克彦, 藤本征一郎

  産婦人科手術 12 97 - 103 2001年
• NK cell activity and subsets in women with a history of spontaneous abortion. Cause, number of abortions, and subsequent pregnancy outcome.

  Morikawa M, Yamada H, Kato EH, Shimada S, Ebina Y, Yamada T, Sagawa T, Kobashi G, Fujimoto S

  Gynecologic and obstetric investigation 52 163 - 167 3 2001年 [査読有り][通常論文]
  
• Recurrent pregnancy loss: etiology of thrombophilia.

  Yamada H, Kato EH, Kobashi G, Ebina Y, Shimada S, Morikawa M, Yamada T, Sakuragi N, Fujimoto S

  Semin Thromb Hemost 27 121 - 129 2001年 [査読有り][通常論文]
  
• 大量の胸腹水のため全身管理が困難であったCA19-9の著明高値を伴うpseudo-Meigs症候群の1症例

  山田崇弘, 櫻木範明, 藤本征一郎, 岩城雅範, 大中吉人, 福士貞男, 松野伸哉

  産婦人科の実際 50 5 645 - 649 金原出版 2001年 [査読有り][通常論文]
  
• 腫瘍合併妊娠の取り扱い 乳房腫瘍

  山田崇弘, 佐川 正, 齋藤千奈美, 日下 剛, 小橋 元, 藤本征一郎

  産科と婦人科 68 633 - 638 2001年 [査読無し][招待有り]
  
• Relation between viability of vaginal polymorphonuclear leukocytes and presence of histologic chorioamnionitis

  T Yamada, S Matsubara, H Minakami, A Ohkuchi, M Hiratsuka, Sato, I

  ACTA OBSTETRICIA ET GYNECOLOGICA SCANDINAVICA 79 10 818 - 823 2000年10月 [査読有り][通常論文]
   

  Background. The number and percentage of viable vaginal polymorphonuclear leukocytes (vPMNs) are known to be increased in women who experience preterm labor. Whether those parameters may be associated with the presence of histologic chorioamnionitis (CAM) is not known. Methods. We investigated prospectively 39 women at 26.3 +/- 6.2 weeks of gestation. The following were determined in vaginal washings. total number of vPMNs and the percent that were viable, the pH, and the concentrations of granulocyte elastase and interleukin-8 (IL-8). In addition, the while blood cell count and the serum level of C-reactive protein were determined in peripheral blood. The placenta and the umbilical cord were examined histologically with special reference to the presence of CAM. The optimal cutoff value for prediction of histologic CAM was obtained for each variable using receiver operating characteristic curves. A multivariate logistic-regression model was used to determine the independent risk factors for this disorder. Results. Histologic CAM was present in ten women (37.1+/-3.8 weeks) and absent in 29 women (38.2+/-1.5 weeks). The total number of vPMNs, the percent of viable vPMNs, and the IL-8 level were all significantly increased in the women with CAM, in contrast to those without CAM. When the optimal cutoff value for each of seven covariates was entered into the model, only the percent of viable vPMNs, greater than or equal to 11%, demonstrated a significant relationship with histologic CAM (odds ratio 26.9; 95% confidence interval 1.3 to 545; p<0.05). Conclusions. Women with a % viability of vPMNs of greater than or equal to 11% were at a significantly higher risk for histologic CAM. Data suggest that an influx of PMNs into the vagina occurs continuously in patients with histologic CAM.
• 心筋炎を確認したヒトパルボウイルスB19胎内感染の1例

  山田崇弘, 岩城雅範, 大中吉人, 田中 敏

  苫小牧市立病院医誌 14 18 - 21 2000年 [査読有り][通常論文]
  
• Recent trends in the prevalence of Down syndrome in Japan, 1980-1997

  Nobuhiko Hoshi, Rifumi Hattori, Kaoru Hanatani, Kazuhiko Okuyama, Hideto Yamada, Tatsuro Kishida, Takahiro Yamada, Tadashi Sagawa, Yoshio Sumiyoshi, Seiichiro Fujimoto

  American Journal of Medical Genetics 84 4 340 - 345 1999年06月04日 [査読有り][通常論文]
   

  The aims of the present study were to determine recent trends in the prevalence of Down syndrome (DS) in Japan, and to determine whether recent changes in demographic and social habits and access to prenatal diagnosis have influenced the livebirth rates of DS. Livebirth statistics indicate that the birth rate in Japan has decreased for women in their 20s and has increased for those in their 30s and 40s. During an 18-year period between 1980 and 1997, 1,299 consecutive DS infants were born among a total of 2,232,694 births, a rate corresponding to approximately 10% of all births in Japan over the same period. The increasing risk of DS with advancing maternal age was confirmed. The overall prevalence was 5.82 DS births per 10,000 livebirths (8.3-9.7 per 10,000 after correction according to the estimated ascertainment ratio: 60-70%). The prevalence rate by year of child birth represents a statistically significant increase (P = 0.001). In conclusion, recent trends in the prevalence of DS in Japan from 1980 to 1997 failed to show a consistent tendency to decrease, probably because of the concomitant increase in pregnancy in advanced maternal age.
• わが教室における乳癌検診

  佐川 正, 山田崇弘, 日下 剛, 山下陽一郎, 藤本俊郎, 山田秀人, 星 信彦, 櫻木範明, 藤本征一郎

  産婦人科治療 79 200 - 208 1999年
• Morphological aspects of ectopia cordis: Four case reports and a review of the literature

  Takahiro Yamada, Nobuhiko Hoshi, Kazuhiko Okuyama, Hiroaki Negishi, Satoko Sudo, Tatsuro Kishida, Hideto Yamada, Tadashi Sagawa, Hiroaki Fujii, Akihiro Ishizu, Hiroshi Ishikura, Seiichiro Fujimoto

  Journal of Obstetrics and Gynaecology Research 25 4 237 - 243 1999年 [査読有り][通常論文]
   

  Ectopia cordis is a rare congenital anomaly. We present 4 cases of ectopia cordis, 1 of which is the first report of an affected fetus in a triplet pregnancy. The morphological relationship between the types of ectopia cordis and their outcomes were investigated in all 4 cases. In addition, the literature on ectopia cordis in Japan was reviewed and discussed.
• 両側内腸骨動脈結紮後妊娠の一症例

  山田崇弘, 菊地 研, 岩城雅範, 大中吉人

  苫小牧市立病院医誌 13 12 - 16 1999年 [査読有り][通常論文]
  
• 出生前診断した致死性四肢短縮型小人症の一症例

  山田崇弘, 菊地 研, 岩城雅範, 大中吉人

  苫小牧市立病院医誌 12 17 - 21 1999年 [査読有り][通常論文]
  
• 子宮内反症の4例を経験して

  山田崇弘, 星 信彦, 岸田達朗, 奥山和彦, 山崎綾野, 横尾洋一, 相馬 彰, 大久保 仁, 高後 亮, 藤本征一郎

  周産期医学 1999年 [査読有り][通常論文]
  
• 産婦人科における乳癌検診の意義と穿刺吸引細胞診に関する検討

  山田 崇弘, 佐川 正, 星 信彦, 晴山 仁志, 藤本 征一郎

  日本産科婦人科學會雜誌 50 4 155 - 160 社団法人日本産科婦人科学会 1998年04月01日 [査読無し][通常論文]
   

  我が国では, 乳癌検診は外科医によって行われてきたが, 近年, 産婦人科領域においても乳癌検診が取り入れられるようになった.今回, 産婦人科における乳癌検診の特徴と意義を明らかにすると共に, 穿刺吸引細胞診(Aspiration Biopsy Cytology, 以下ABCとする)の有用性について検討した.今回の検討には1990年6月より1996年2月までに, 当科の乳房外来を初診した2, 106症例を対象とした.乳癌は両側性1症例を含む19症例(0.90%)であり, 乳癌発見率は集団検診による発見率(0.41%:北海道対がん協会, 1992年)と比較して高率であった.対象の特徴として, 乳癌症例全例および非乳癌症例1, 747症例の計1, 766症例(83。9%)において, 乳癌腫瘍, 子宮体癌, 子宮頸癌, 更年期障害などの婦人科疾患の合併を有していた.問診及び, 視診, 触診による一次検診, 超音波断層法あるいはマンモグラフィーによって抽出された127症例(全症例の6.0%)にABCが施行され, 組織学的検索の適用となったものは乳癌症例全例を含む31症例であった.細胞診陰性例には, 乳癌は1例も認められず, 疑陽性症例で27.3%(3/11), 陽性症例で93.8%、(15/16)に乳癌が確定診断された.以上のことより, 乳癌のスクリーニングの見地より産婦人科領域におけ...
• Prenatal identification of mos 45,X/46,X,+mar in a normal male baby by cytogenetic and molecular analysis

  Nobuhiko Hoshi, Hidefumi Tonoki, Yasushi Handa, Takafumi Fujino, Kazuhiko Okuyama, Yasutsugu Koga, Yoshinori Matsumoto, Takahiro Yamada, Hideto Yamada, Tatsuro Kishida, Tadashi Sagawa, Kenji Fujieda, Yutaka Nakahori, Jeffrey A. Kant, Sehchiro Fujimoto

  Prenatal Diagnosis 18 12 1316 - 1322 1998年 [査読有り][通常論文]
   

  We report a case of mos 45,X/46,X,+mar, diagnosed prenatally by amniocentesis, whose physical examination, including external and internal organs, along with serum testosterone values were normal five years after delivery. The mosaic karyotype was seen in 146 of 240 cells examined (amniotic fluid cells, 110/65 placental chorionic vilii: 5/4 cord blood, 21/81 cultured skin fibroblasts, 10/90) from 386 metaphases, and the marker chromosome appeared as a small non-fluorescent acrocentric chromosome. All autosomes appeared normal, and no normal Y chromosome could be demonstrated. Analysis of 26 Y-chromosome loci by molecular techniques such as PCR, Southern analysis using multiple Y-specific DNA probes, and Hae III restriction endonuclease assessment of male-specific repeated DNA in the heterochromatic region of the Y chromosome, and fluorescence in situ hybridization (FISH), revealed the marker was derived from a Y chromosome including p terminal to q11.23, and paracentric inversion in the remaining Y long arm. The formation of testes can be considered as existence of SRY (sex-determining region of Y) as a testis-determining factor. The present report illustrates the importance of FISH and molecular techniques as a complement to cytogenetic methods for accurate identification and characterization of chromosome rearrangements in prenatal diagnosis.
• 妊娠経過中に突然母体にDIC傾向を認めた胎便性腹膜炎の一症例

  山田崇弘, 酒井慶一郎, 小口健一, 田畑雅章, 花谷 馨, 後藤史郎, 藤本征一郎

  周産期医学 28 1527 - 1530 1998年 [査読有り][通常論文]
  
• 反復臍帯穿刺によるRh (D)不適合妊娠の管理

  山田 崇弘, 山田 秀人, 平山 恵美, 根岸 広明, 奥山 和彦, 佐川 正, 藤本 征一郎

  日本産科婦人科學會雜誌 49 2 129 - 132 社団法人日本産科婦人科学会 1997年02月01日 [査読無し][通常論文]
  
• 巨大筋腫の為に胎児変形をきたした子宮筋腫合併妊娠の１症例

  山田崇弘, 花谷 馨, 半田 康, 田畑雅章, 藤田博正, 山田良隆, 後藤史郎

  市立札幌病院医誌 57 37 - 40 1997年 [査読有り][通常論文]
  
• 症例から学ぶ：乳癌と妊娠

  佐川 正, 齋藤千奈美, 山田崇弘, 藤本征一郎

  産婦人科の実際 46 837 - 843 1997年 [査読無し][招待有り]
  
• 乳房外来における穿刺吸引細胞診

  佐川 正, 山田崇弘, 藤本征一郎

  産婦人科治療 73 564 - 568 1996年
• 臍帯穿刺を用いたRh(D)不適合双胎妊娠管理の１例

  山田崇弘, 奥山和彦, 山田秀人, 平山恵美, 根岸広明, 松田 直, 長 和俊, 大湯淳功, 松本憲則, 佐川 正, 藤本征一郎

  周産期医学 26 1181 - 1184 1996年 [査読有り][通常論文]
  
• 不育症

  山田秀人, 山田崇弘, 平山恵美

  ペリネイタルケア 14 827 - 831 1995年 [査読無し][招待有り]
  
• 若年妊娠

  渡利英道, 山田崇弘, 齋藤千奈美, 藤本征一郎

  産婦人科の実際 44 1620 - 1625 1995年 [査読無し][招待有り]
  
• 日常生活における性分化の診かた

  田島敏弘, 柴田有花, 山田崇弘, 矢部一郎

  小児内科 [査読有り][通常論文]
  

MISC

• 産科編 胎盤の病態生理 前置胎盤の病態・成因はどこまでわかっているか

  神谷亮雄, 山田崇弘 周産期医学 53 2023年
• 単一三次施設における34歳以下妊婦の出生前遺伝学的検査の受検動向調査

  島田咲, 佐藤智佳, 佐藤智佳, 吉田彩, 吉田彩, 神谷亮雄, 黒田優美, 矢内洋次, 山田崇弘, 山田崇弘, 山田崇弘, 岡田英孝, 岡田英孝 日本人類遺伝学会大会プログラム・抄録集 67th (CD-ROM) 2022年
• 前置胎盤における子宮頸部静脈叢体積と術中出血量の関連についての検討

  神谷亮雄, 山田崇弘, 吉田彩, 奥楓, 西端修平, 森川守, 岡田英孝 日本周産期・新生児医学会雑誌(Web) 58 (Suppl.1) 2022年
• 難病領域における次世代シークエンサーを用いた網羅的遺伝子解析出検施設の二次的所見開示の現状と困難:アンケート調査

  洪本加奈, 洪本加奈, 山田崇弘, 山田崇弘, 土屋実央, 土屋実央, 川目裕, 川目裕, 川目裕, 難波栄二, 難波栄二, 後藤雄一, 後藤雄一, 小杉眞司, 小杉眞司 日本遺伝カウンセリング学会誌 43 (2) 2022年
• がん遺伝子パネル検査の運用に関する現状と課題:多施設対象アンケート調査-二次的所見への対応を中心に-

  源明理, 山田崇弘, 山田崇弘, 吉岡正博, 吉岡正博, 近藤知大, 金井雅史, 春山瑳依子, 佐々木佑菜, 島田咲, 川崎秀徳, 川崎秀徳, 和田敬仁, 和田敬仁, 武藤学, 平沢晃, 小杉眞司, 小杉眞司 日本遺伝カウンセリング学会誌 42 (2) 2021年
• 当院で遺伝学的に診断された骨系統疾患の検討

  森貞直哉, 森貞直哉, 河本和泉, 衣笠真紀, 坂田亮介, 小林大介, 尾崎佳代, 洪本加奈, 片桐岳信, 西村玄, 池川志郎, 山田崇弘, 飯島一誠, 薩摩眞一 日本小児遺伝学会学術集会プログラム・抄録集 43rd 2021年
• 新生児マススクリーニングで見つかった遺伝性疾患をもつ子の親の生殖意思決定の複雑さと支援

  洪本加奈, 山田崇弘, 山田崇弘, 西垣昌和, 小杉眞司, 小杉眞司, 山田崇弘, 山田崇弘 日本人類遺伝学会大会プログラム・抄録集 65th (CD-ROM) 2020年
• 保険収載されたがん遺伝子パネル検査における実施状況と,生殖細胞系列バリアントへの対応状況に関する現状調査と課題提起

  小林明理, 山田崇弘, 山田崇弘, 吉岡正博, 吉岡正博, 近藤知大, 近藤知大, 金井雅史, 金井雅史, 木下一郎, 青木洋子, 青木洋子, 織田克利, 織田克利, 植木有紗, 植木有紗, 森川真紀, 森川真紀, 佐藤友紀, 佐藤友紀, 小川昌宣, 小川昌宣, 東川智美, 武藤学, 平沢晃, 平沢晃, 小杉眞司, 小杉眞司, 小杉眞司, 小林明理 日本人類遺伝学会大会プログラム・抄録集 65th (CD-ROM) 2020年
• PALB2遺伝子変異による遺伝性乳癌9例に関する検討

  樋上明音, 川口展子, 仙田典子, 川田有希子, 村上裕美, 本田明夏, 山田崇弘, 吉田健一, 橘強, 山上和彦, 露木茂, 岡村隆仁, 小杉眞司, 小川誠司, 戸井雅和 日本癌治療学会学術集会(Web) 58th PS -6 2020年
• がん遺伝子パネル検査での二次的所見疑い症例における生殖細胞系列の確認検査実施の促進要因と阻害要因

  近藤知大, 近藤知大, 近藤知大, 山田崇弘, 山田崇弘, 吉岡正博, 吉岡正博, 吉岡正博, 西垣昌和, 西垣昌和, 山本佳宏, 山本佳宏, 金井雅史, 金井雅史, 武藤学, 武藤学, 小杉眞司, 小杉眞司 日本遺伝カウンセリング学会誌 41 (2) 2020年
• 新生児マススクリーニングで子の遺伝性疾患が見つかった親の感情:自身が保因者である可能性と再発率の告知について

  洪本加奈, 山田崇弘, 小杉眞司 日本遺伝カウンセリング学会誌 41 (3) 107 -114 2020年 [査読有り][通常論文]
  
• 出生前診断における遺伝カウンセリング体制の構築に関する研究【第2分科会】遺伝カウンセリングに関する知識及び技術向上に関する医療従事者向けの研修プログラムの開発

  小西郁生, 久具宏司, 山田重人, 山田崇弘, 西垣昌和, 三宅秀彦, 久具宏司, 池田真理子, 左合治彦, 佐々木愛子, 佐々木規子, 鈴森伸宏, 福島明宗, 福嶋義光, 蒔田芳男, 三宅秀彦, 山田重人, 山田崇弘, 西垣昌和, 伊尾紳吾 出生前診断における遺伝カウンセリング体制の構築に関する研究 平成31/令和元年度 研究報告書(Web) 2020年
• ゲノム医療における二次的所見の取り扱いに関する実態調査-遺伝医療専門家を対象とした質問票調査より倫理問題検討委員会報告-

  土屋実央, 山田崇弘, 赤石理奈, 井本逸勢, 梅村啓史, 清水健司, 浜之上はるか, 平沢晃, 吉田晶子, 吉橋博史, 四元淳子, 渡邉淳, 小杉眞司 日本遺伝カウンセリング学会誌 41 (2) 2020年
• Placenta-specific epimutation at H19-DMR among common pregnancy complications: its frequency and effect on the expression patterns of H19 and IGF2.

  Yamaguchi Y, Tayama C, Tomikawa J, Akaishi R, Kamura H, Matsuoka K, Wake N, Minakami H, Kato K, Yamada T, Nakabayashi K, Hata K Clinical epigenetics 11 (1) 113 -113 2019年08月 [査読有り][通常論文]
  
• Charcot-Marie-Tooth病患者から子どもへの情報伝達に対する遺伝カウンセリングの検討

  馬場 遥香, 十川 麗美, 永田 美保, 松川 愛未, 本田 明夏, 鳥嶋 雅子, 山田 崇弘, 和田 敬仁, 中川 正法, 小杉 眞司 日本遺伝カウンセリング学会誌 40 (2) 67 -67 2019年07月 [査読無し][通常論文]
  
• 日本における18トリソミーあるいは13トリソミーを合併した極低出生体重児の予後

  川崎 秀徳, 山田 崇弘, 和田 敬仁, 小杉 眞司 日本遺伝カウンセリング学会誌 40 (2) 75 -75 2019年07月 [査読無し][通常論文]
  
• がんゲノム医療に対する一般市民のリテラシー向上を目的としたまんが教材開発

  十川 麗美, 和田 敬仁, 金井 雅史, 近藤 知大, 本田 明夏, 永田 美保, 馬場 遥香, 山田 崇弘, 平沢 晃, 武藤 学, 小杉 眞司 日本遺伝カウンセリング学会誌 40 (2) 76 -76 2019年07月 [査読無し][通常論文]
  
• 一般地域住民で検出された低ホスファターゼ症原因遺伝子のバリアントと骨形質との関連 ながはまスタディ

  永田 美保, 山田 崇弘, 和田 敬仁, 川崎 秀徳, 澤井 英明, 瀬藤 和也, 川口 喬久, 日笠 幸一郎, 田原 康玄, 松田 文彦, 中山 健夫, 小杉 眞司 日本遺伝カウンセリング学会誌 40 (2) 81 -81 2019年07月 [査読無し][通常論文]
  
• クライエントの背景に関わらずコミュニケーションが満足につながった 当院の出生前遺伝カウンセリングより

  佐藤 智佳, 吉田 晶子, 玉置 知子, 稲葉 慧, 笠松 敦, 吉田 彩, 黒田 優美, 矢内 洋次, 村上 裕美, 鳥嶋 雅子, 山田 崇弘, 小杉 眞司, 岡田 英孝 日本遺伝カウンセリング学会誌 40 (2) 83 -83 2019年07月 [査読無し][通常論文]
  
• 国内外の多発性内分泌腫瘍I型(MEN1)患者データベースを用いたMEN1の遺伝子型-表現型相関についての文献調査

  幅野 愛理, 小池 佳菜子, 洪本 加奈, 横田 恵梨, 川崎 秀徳, 山田 崇弘, 和田 敬仁, 小杉 眞司 日本遺伝カウンセリング学会誌 40 (2) 98 -98 2019年07月 [査読無し][通常論文]
  
• 遺伝性疾患の当事者または保因者の生殖意思決定の遺伝形式による相違点・類似点

  洪本 加奈, 小池 佳菜子, 幅野 愛理, 横田 恵梨, 川崎 秀徳, 山田 崇弘, 和田 敬仁, 小杉 眞司 日本遺伝カウンセリング学会誌 40 (2) 140 -140 2019年07月 [査読無し][通常論文]
  
• 若年心臓突然死者に対する遺伝学的剖検により明らかになる遺伝性不整脈の頻度 系統的レビュー

  小池 佳菜子, 幅野 愛理, 洪本 加奈, 横田 恵梨, 川崎 秀徳, 山田 崇弘, 和田 敬仁, 小杉 眞司 日本遺伝カウンセリング学会誌 40 (2) 162 -162 2019年07月 [査読無し][通常論文]
  
• 実臨床における遺伝性乳癌の拾い上げ

  仙田 典子, 川田 有希子, 川口 展子, 川島 雅央, 高田 正泰, 本田 明夏, 鈴木 栄治, 村上 弘美, 山田 崇弘, 露木 茂, 山内 清明, 高原 祥子, 芳林 浩史, 山神 和彦, 岡村 隆仁, 加藤 大典, 眞島 奨, 小杉 眞司, 小川 誠司, 戸井 雅和 日本乳癌学会総会プログラム抄録集 27回 711 -711 2019年07月 [査読無し][通常論文]
  
• 遺伝性乳がん卵巣がん症候群に対するリスク低減卵巣卵管切除の後方視的検討

  山口建, 本田明夏, 山村幸, 堀江昭史, 山田崇弘, 北村幸子, 千草義継, 堀川直城, 濱西潤三, 小杉眞司, 万代昌紀 日本人類遺伝学会大会プログラム・抄録集 64th 2019年
• 羊水染色体検査で経験した真性モザイク型トリソミーの2例(9トリソミー,20トリソミー)

  井田憲蔵, 清水喜一, 宮元勝則, 孫田信一, 鈴森薫, 川崎秀徳, 川崎秀徳, 山田崇弘, 山田崇弘, 小杉眞司, 小杉眞司 日本人類遺伝学会大会プログラム・抄録集 64th 2019年
• 日本における21トリソミーを合併した極低出生体重児の予後

  川崎秀徳, 川崎秀徳, 山田崇弘, 山田崇弘, 和田敬仁, 和田敬仁, 小杉眞司, 小杉眞司 日本人類遺伝学会大会プログラム・抄録集 64th 2019年
• 腫瘍細胞がん遺伝子パネル検査でCDH1の病的バリアントが検出され生殖細胞系列遺伝学的検査を希望したびまん性胃がん患者の1例

  幅野愛理, 西垣昌和, 西垣昌和, 山田崇弘, 山田崇弘, 松原淳一, 武藤学, 小杉眞司, 小杉眞司 日本人類遺伝学会大会プログラム・抄録集 64th 2019年
• 出生前診断における遺伝カウンセリング体制の構築に関する研究 遺伝カウンセリングに関する知識及び技術向上に関する医療従事者向けの研修プログラムの開発

  小西郁生, 久具宏司, 山田重人, 山田崇弘, 西垣昌和, 三宅秀彦, 池田真理子, 左合治彦, 佐々木愛子, 佐々木規子, 鈴森伸宏, 福島明宗, 福嶋義光, 蒔田芳男, 伊尾紳吾 出生前診断における遺伝カウンセリング体制の構築に関する研究 平成30年度 研究報告書(Web) 2019年
• ゲノム医療における情報伝達プロセスに関する提言 がん遺伝子パネル検査と生殖細胞系列全ゲノム 全エクソーム解析について【初版】

  小杉 眞司, 金井 雅史, 川目 裕, 後藤 雄一, 櫻井 晃洋, 武藤 学, 宮本 恵宏, 三宅 秀彦, 孫 徹, 和田 敬仁, 山田 崇弘, 平沢 晃, 松本 繁巳, 高 忠之, 西垣 昌和, 佐藤 智佳, 赤羽 智子, 清水 玲子, 宮崎 幸子, 本田 明夏, 稲葉 慧, 松川 愛未, AMED「医療現場でのゲノム情報の適切な開示のための体制整備に関する研究」班 臨床病理レビュー 160 (160) 23 -34 2018年11月 [査読無し][通常論文]
  
• がんゲノム医療における二次的所見の取扱について(Genetic counseling Secondary findings in clinical cancer genome sequencing)

  山田 崇弘, 小杉 眞司 日本癌学会総会記事 77回 1185 -1185 2018年09月 [査読無し][通常論文]
  
• がんゲノム医療における二次的所見の取扱について(Genetic counseling Secondary findings in clinical cancer genome sequencing)

  山田 崇弘, 小杉 眞司 日本癌学会総会記事 77回 1185 -1185 2018年09月 [査読無し][通常論文]
  
• 産科一次施設において出生前診断の相談を受ける際の問題点

  山田 崇弘, 関沢 明彦, 金井 誠, 佐村 修, 澤井 英明, 高田 史男, 吉橋 博史, 伊尾 紳吾, 三宅 秀彦, 山田 重人, 小西 郁生, 厚労科研出生前診断実施時の遺伝カウンセリング体制の構築に関する研究班 日本周産期・新生児医学会雑誌 54 (2) 542 -542 2018年06月 [査読無し][通常論文]
  
• 遺伝学的に未診断の遺伝性間質性肺疾患同胞例に対する出生前遺伝カウンセリング

  川崎秀徳, 山田崇弘, 鳥嶋雅子, 友滝清一, 松倉崇, 千草義継, 小杉眞司, 小杉眞司 日本遺伝カウンセリング学会誌 39 (2) 81 -81 2018年05月31日 [査読無し][通常論文]
  
• X連鎖性疾患の保因者リスクのある女性が自身と娘の保因者診断受検を検討する際に影響を及ぼす要因の探索

  佐藤優, 小名徹, 田口育, 松浦香里, 松川愛未, 本田明夏, 中川奈保子, 鳥嶋雅子, 山田崇弘, 和田敬仁, 小杉眞司 日本遺伝カウンセリング学会誌 39 (2) 64 -64 2018年05月31日 [査読無し][通常論文]
  
• ヒト受精卵におけるゲノム編集に関する意識 臨床遺伝専門家を対象とした質問票調査を用いて

  田口 育, 山田 崇弘, 赤石 理奈, 井本 逸勢, 黒澤 健司, 中谷 中, 野村 文夫, 浜之上 はるか, 兵頭 麻希, 村上 裕美, 吉橋 博史, 四元 淳子, 小杉 眞司 日本遺伝カウンセリング学会誌 39 (2) 60 -60 2018年05月 [査読無し][通常論文]
  
• ヒト受精卵におけるゲノム編集に関する意識 臨床遺伝専門家を対象とした質問票調査を用いて

  田口 育, 山田 崇弘, 赤石 理奈, 井本 逸勢, 黒澤 健司, 中谷 中, 野村 文夫, 浜之上 はるか, 兵頭 麻希, 村上 裕美, 吉橋 博史, 四元 淳子, 小杉 眞司 日本遺伝カウンセリング学会誌 39 (2) 60 -60 2018年05月 [査読無し][通常論文]
  
• 一般地域住民における低ホスファターゼ症の未診断罹患者および非発症キャリアの研究:ながはまスタディ

  永田美保, 山田崇弘, 山田崇弘, 十川麗美, 馬場遥香, 川崎秀徳, 川崎秀徳, 和田敬仁, 和田敬仁, 澤井英明, 澤井英明, 瀬藤和也, 川口喬久, 日笠幸一郎, 中山健夫, 田原康玄, 松田文彦, 小杉眞司, 小杉眞司 日本人類遺伝学会大会プログラム・抄録集 63rd 2018年
• 遺伝性疾患罹患者から血縁者へのリスク伝達に関わる心理的・状況的要素の疾患特性による相違点・類似点についての文献調査

  馬場遥香, 十川麗美, 永田美保, 川崎秀徳, 川崎秀徳, 山田崇弘, 山田崇弘, 和田敬仁, 和田敬仁, 小杉眞司, 小杉眞司 日本人類遺伝学会大会プログラム・抄録集 63rd 2018年
• ハンチントン病の発症前診断に関わる遺伝カウンセリング

  松島 理明, 柴田 有花, 中川 伸, 山田 崇弘, 矢部 一郎, 佐々木 秀直 日本遺伝カウンセリング学会誌 38 (2) 100 -100 2017年05月 [査読無し][通常論文]
  
• 体細胞変異を対象とした網羅的がん遺伝子検査におけるIncidental Findingsとしての生殖細胞系列変異への対応

  柴田 有花, 山田 崇弘, 西原 広史, 林 秀幸, 秋田 弘俊, 矢部 一郎 日本遺伝カウンセリング学会誌 38 (2) 107 -107 2017年05月 [査読無し][通常論文]
  
• 出生前診断における遺伝カウンセリングの実施体制及び支援体制に関する研究【第2分科会】一般産科診療から専門レベルに至る出生前診断に関する診療レベルの向上

  小西 郁生, 福嶋 義光, 山田 重人, 三宅 秀彦, 伊尾 紳吾, 山田 崇弘, 藤井 庸祐 2017年03月 [査読無し][通常論文]
   

  平成28年度厚生労働科学研究費補助金成育疾患克服等次世代育成基盤研究事業（健やか次世代育成総合研究事業）平成28年度総括・分担研究報告書およびシンポジウム報告書
• 酵素補充療法導入後における低ホスファターゼ症周産期型の新しい重症度分類の提案

  永岡 晋一, 小堀 周作, 室本 仁, 室月 淳, 山田 崇弘, 澤井 英明, 八重樫 伸生 日本産科婦人科学会雑誌 69 (2) 660 -660 2017年02月 [査読無し][通常論文]
  
• Pseudo-homozygous mutation due to a primer site polymorphism in hereditary ATTR amyloidosis: a pitfall of PCR-based genetic testing.

  Shibata Y, Matsushima M, Yabe I, Matsuda K, Nagai A, Kano T, Yamada T, Sekijima Y, Sasaki H Amyloid 24 (1) 66 -67 2017年01月02日 [査読無し][通常論文]
  
• 京都大学医学部附属病院における乳がん・卵巣がんに関する遺伝カウンセリング状況

  本田明夏, 村上裕美, 鳥嶋雅子, 松川愛未, 山田崇弘, 山田崇弘, 山田重人, 小杉眞司, 小杉眞司 日本人類遺伝学会大会プログラム・抄録集 62nd 2017年
• NIPTにおけるfetal fractionについての検討~cfDNA解析結果と臨床データの照合解析~

  鈴森伸宏, 榎原毅, 山田崇弘, 佐村修, 四元淳子, 西山深雪, 三浦清徳, 澤井英明, 室月淳, 北川道弘, 亀井良政, 増崎英明, 平原史樹, SALDIVAR Juan‐Sebastian, DHARAJIYA Nilesh, 左合治彦, 関沢明彦 日本周産期・新生児医学会雑誌 52 22‐23 2017年01月01日 [査読無し][通常論文]
  
• 当院における神経・筋疾患の遺伝カウンセリングの現状と役割の検討

  柴田 有花, 松島 理明, 山田 崇弘, 矢部 一郎, 佐々木 秀直 臨床神経学 56 (Suppl.) S263 -S263 2016年12月 [査読無し][通常論文]
  
• Alterations in cardiac morphology and function in pregnancy and their association with cardiovascular biomarkers

  T. Umazume, S. Yamada, T. Yamada, T. Hayashi, D. Murai, H. Iwano, H. Tsutsui, H. Minakami EUROPEAN HEART JOURNAL 37 1156 -1157 2016年08月 [査読無し][通常論文]
  
• 日本人妊婦における2014〜2015シーズンの季節性インフルエンザ 初産婦と経産婦の比較

  山田 崇弘, 河上 祥一, 吉田 悠晋, 川村 裕士, 太田 志代, 安部 加奈子, 濱田 洋実, 土肥 聡, 市塚 清健, 瀧田 寛子, 馬場 洋介, 松原 茂樹, 望月 純子, 海野 信也, 前川 有香, 前田 眞, 犬走 英介, 芥川 典之, 久保 隆彦, 小田 泰也, 山田 俊, 山岸 絵美, 中井 章人, 淵 直樹, 増崎 英明, 占部 智, 工藤 美樹, 野溝 万吏, 佐川 典正, 前田 隆嗣, 上塘 正人, 川端 公輔, 片岡 宙門, 塩崎 有宏, 斎藤 滋, 関沢 明彦, 水上 尚典 日本周産期・新生児医学会雑誌 52 (2) 568 -568 2016年06月 [査読無し][通常論文]
  
• 随時尿中タンパク/クレアチニン比が推奨される妊婦とは?1033妊婦(2212検体)の解析 多施設前向き観察研究

  馬場 洋介, 山田 崇弘, 小畠 真奈, 安田 俊, 大野 泰正, 川端 公輔, 皆川 詩織, 平井 千裕, 日下 秀人, 村林 奈緒, 印出 佑介, 奈倉 道和, 濱田 洋実, 板倉 敦夫, 大口 昭英, 前田 眞, 佐川 典正, 中井 章人, 片岡 宙門, 藤森 敬也, 工藤 美樹, 池田 智明, 水上 尚典 日本周産期・新生児医学会雑誌 52 (2) 500 -500 2016年06月 [査読無し][通常論文]
  
• 日本における2年間の無侵襲的出生前遺伝学検査(NIPT)の現況

  佐村 修, 左合 治彦, 北川 道弘, 和田 誠司, 佐々木 愛子, 関沢 明彦, 浜之上 はるか, 三浦 清徳, 山下 隆博, 永松 健, 澤井 英明, 山田 崇弘, 室月 淳, 鈴森 伸宏, 種元 智洋, 遠藤 俊明, 福島 明宗, 生野 寿史, 平久 進也, 松原 圭一, 吉里 俊幸, 前田 和寿, 加地 剛, 小川 昌宣, 佐世 正勝, 難波 聡, 長田 久夫, 西澤 春紀, 岡本 陽子, 金川 武司, 柿ヶ野 藍子, 小川 正樹, 中村 博昭, 和泉 俊一郎, 片桐 由起子, 笠井 靖代, 成瀬 勝彦, 吉松 淳, 早田 桂, 兵頭 麻希, 近藤 朱音, 川野 由紀枝, 大場 隆, 横浜 祐子, 市塚 清健, 川島 英理子, 三春 範夫, 川上 浩介, 日本NIPTコンソーシアム 日本産科婦人科学会雑誌 68 (2) 738 -738 2016年02月 [査読無し][通常論文]
  
• P2-35-1 絨毛細胞由来exosomeが内包するsmall RNA量に及ぼすtoll-like receptor agonistの影響について(Group35 胎盤1,一般演題,公益社団法人日本産科婦人科学会第68回学術講演会)

  古田 伊都子, 山田 崇弘, 金内 優典, 櫻木 範明, 水上 尚典 日本産科婦人科學會雜誌 68 (2) 708 -708 2016年
• ISP-38-6 Platelet aggregation in citrated whole blood of the first trimester of pregnancy(Group 38 Reproduction Perinatology,International Session Poster) :

  Umazume Takeshi, Yamada Takahiro, Furuta Itsuko, Akaishi Rina, Ishikawa Satoshi, Koyama Takahiro, Morikawa Mamoru, Minakami Hisanori 日本産科婦人科學會雜誌 68 (2) 589 -589 2016年
• MW12-1 両親のALP値を用いた胎児低アルカリフォスファターゼ血症の補助診断(ミニワークショップ12 胎児診断と治療,一般演題,公益社団法人日本産科婦人科学会第68回学術講演会)

  高橋 雄一郎, 澤井 英明, 山田 崇弘, 早川 博生, 上妻 友隆, 佐藤 秀平, 室月 淳 日本産科婦人科學會雜誌 68 (2) 610 -610 2016年
• 当院における遺伝性乳がん・卵巣がん症候群の遺伝カウンセリングの現状

  柴田 有花, 細田 充主, 三田村 卓, 山田 崇弘, 矢部 一郎, 山下 啓子, 三田村 卓, 山田 崇弘, 渡利 英道, 櫻木 範明, 炭山 峰華 北海道外科雑誌 60 (2) 231 -231 2015年12月 [査読無し][通常論文]
  
• 筋強直性ジストロフィーの遺伝カウンセリング 3症例の報告

  柴田 有花, 松島 理明, 山田 崇弘, 田島 敏広, 矢部 一郎, 佐々木 秀直 神経治療学 32 (5) 868 -868 2015年09月 [査読無し][通常論文]
  
• タナトフォリック骨異形成症の長期生存例の発育調査

  澤井 英明, 山田 崇弘, 堤 誠司, 篠塚 憲男, 高橋 雄一郎, 佐世 正勝, 室月 淳, 厚生労働科学研究費補助金, 胎児, 新生児骨系統疾患の診断と予後に関する研究班 日本周産期・新生児医学会雑誌 51 (2) 936 -936 2015年06月 [査読無し][通常論文]
  
• 母体血清マーカーテスト(クアトロテスト),コンバインド検査(NT+血清マーカー) (特集 出生前診断と生命倫理 : 染色体異常を中心として) -- (目でみる出生前診断)

  赤石 理奈, 山田 崇弘 周産期医学 45 (5) 670 -672 2015年05月
• 本邦妊婦のインフルエンザ感染とその予防・治療の現況 多施設共同研究

  馬場 洋介, 松原 茂樹, 水上 尚典, 山田 崇弘, 濱田 洋実, 安部 加奈子, 芥川 典之, 犬走 英介, 片岡 宙門, 川端 公輔, 久保 隆彦, 前田 真, 前川 由香, 増崎 英明, 淵 直樹, 佐川 典正, 野溝 万吏, 中井 章人, 島田 学, 斉藤 滋, 塩崎 有宏 日本産婦人科感染症学会学術講演会プログラム・抄録集 32回 46 -46 2015年05月 [査読無し][通常論文]
  
• 胎児異常の諸問題 タナトフォリック骨異形成症の長期生存例の発育調査

  潮田 まり子, 山田 崇弘, 堤 誠司, 室月 淳, 篠塚 憲男, 高橋 雄一郎, 佐世 正勝, 澤井 英明 日本産科婦人科学会雑誌 67 (2) 527 -527 2015年02月 [査読無し][通常論文]
  
• P3-42-4 妊娠経過中に未破裂脳動脈瘤の存在が判明し帝王切開で娩出した一例(Group144 合併症妊娠7,一般演題,公益社団法人日本産科婦人科学会第67回学術講演会)

  山田 竜太郎, 赤石 理奈, 山田 崇弘, 荒木 直人, 馬詰 武, 小島 崇史, 石川 聡司, 小山 貴弘, 西田 竜太郎, 森川 守, 水上 尚典 日本産科婦人科學會雜誌 67 (2) 929 -929 2015年
• NW-7-2 Atg9aノックアウトマウス胎盤におけるオートファジー活性化の検討(ミニワークショップ7 胎盤関連分子,一般演題,公益社団法人日本産科婦人科学会第67回学術講演会)

  小島 崇史, 赤石 理奈, 山田 崇弘, 古田 伊都子, 森川 守, 山田 俊, 櫻木 範明, 水上 尚典 日本産科婦人科學會雜誌 67 (2) 509 -509 2015年
• P3-57-2 出生前診断の選択に影響を与える因子に関する検討(Group 159 出生前診断2,一般演題,公益社団法人日本産科婦人科学会第67回学術講演会)

  赤石 理奈, 山田 崇弘, 小島 崇史, 小山 貴弘, 河口 哲, 水上 尚典 日本産科婦人科學會雜誌 67 (2) 974 -974 2015年
• P1-25-2 妊娠婦人の血漿中exosomeに内包されるsmall RNA濃度の変動(Group25 妊娠の生理2,一般演題,公益社団法人日本産科婦人科学会第67回学術講演会)

  古田 伊都子, 山田 崇弘, 金内 優典, 櫻木 範明, 水上 尚典 日本産科婦人科學會雜誌 67 (2) 593 -593 2015年
• P1-37-7 間葉性異形成胎盤の妊娠週数毎予後予測(Group37 胎盤3,一般演題,公益社団法人日本産科婦人科学会第67回学術講演会)

  石川 聡司, 山田 崇弘, 山田 竜太郎, 馬詰 武, 小島 崇史, 小山 貴弘, 赤石 理奈, 西田 竜太郎, 荒木 直人, 森川 守, 水上 尚典 日本産科婦人科學會雜誌 67 (2) 633 -633 2015年
• P1-30-3 周産期心筋症の経過を心エコーで観察しえた1症例(Group30 合併症妊娠1,一般演題,公益社団法人日本産科婦人科学会第67回学術講演会)

  馬詰 武, 山田 崇弘, 山田 竜太郎, 荒木 直人, 小島 崇史, 小山 貴弘, 石川 聡司, 赤石 理奈, 西田 竜太郎, 森川 守, 水上 尚典 日本産科婦人科學會雜誌 67 (2) 610 -610 2015年
• P3-60-7 新生児低酸素性虚血性脳症による脳性麻痺の分娩時リスクファクター(Group 162 胎児,新生児の脳神経,一般演題,公益社団法人日本産科婦人科学会第67回学術講演会)

  山田 崇弘, 長 和俊, 森川 守, 山田 俊, 水上 尚典 日本産科婦人科學會雜誌 67 (2) 986 -986 2015年
• NW-8-4 疾患特異的iPS細胞を活用した胎児・新生児骨系統疾患の治療薬開発(ミニワークショップ8 胎児の評価と治療,一般演題,公益社団法人日本産科婦人科学会第67回学術講演会)

  澤井 英明, 山田 崇弘, 室月 淳, 岡田 稔, 山下 晃弘, 妻木 範行 日本産科婦人科學會雜誌 67 (2) 511 -511 2015年
• 出生前診断による胎児染色体異常の診断後のクライアントの意思決定

  西山深雪, 中村博昭, 鈴森伸宏, 中山摂子, 山田崇弘, 片桐由起子, 岡本陽子, 難波聡, 浜之上はるか, 小川昌宣, 三浦清徳, 和泉俊一郎, 関沢明彦, 左合治彦 日本人類遺伝学会大会プログラム・抄録集 60th 232 2015年 [査読無し][通常論文]
  
• 胎児・新生児骨系統疾患の診断と予後に関する研究 症例の収集と診断の支援システム構築

  室月淳, 澤井英明, 山田崇弘, 堤誠司, 篠塚憲男, 高橋雄一郎, 佐世正勝, 鬼頭浩史, 宮嵜治, 渡邉淳, 芳賀信彦, 大薗恵一, 西村玄 胎児・新生児骨系統疾患の診断と予後に関する研究 平成26年度 総括・分担研究報告書 11‐12 2015年 [査読無し][通常論文]
  
• 妊娠高血圧腎症 (Preeclampsia : PE)の診断と取り扱い (特集 『産婦人科診療ガイドライン : 産科編2014』の改訂ポイント解説)

  山田 崇弘, 水上 尚典 助産雑誌 68 (11) 956 -961 2014年11月
• 出生前遺伝学的検査 : 非確定検査について (ミニ特集 出生前診断について考える)

  山田 崇弘, 赤石 理奈 小児科臨床 67 (10) 1626 -1630 2014年10月
• PROSPECTIVE RISK OF STILLBIRTH IN WOMEN WITH PLACENTAL MESENCHYMAL DYSPLASIA

  Satoshi Ishikawa, Takahiro Yamada, Takeshi Umadume, Takahiro Koyama, Rina Akaishi, Mamoru Morikawa, Hisanori Minakami PLACENTA 35 (10) A21 -A22 2014年10月 [査読無し][通常論文]
  
• 本邦における2012-2013年風疹流行時の日本人風疹抗体保有状況 多施設共同研究

  山田 崇弘, 久保 隆彦, 望月 純子, 橋本 恵理子, 大口 昭英, 伊藤 実香, 花岡 正智, 中井 章人, 齋藤 滋, 海野 信也, 松原 茂樹, 水上 尚典 日本周産期・新生児医学会雑誌 50 (2) 778 -778 2014年06月 [査読無し][通常論文]
  
• 致死性骨異形成症からタナトフォリック骨異形成症への名称変更とその背景に関する報告

  澤井 英明, 山田 崇弘, 堤 誠司, 篠塚 憲男, 高橋 雄一郎, 佐世 正勝, 佐藤 秀平, 室月 淳 日本周産期・新生児医学会雑誌 50 (2) 822 -822 2014年06月 [査読無し][通常論文]
  
• 致死性骨異形成症からタナトフォリック骨異形成症への名称変更とその背景に関する報告

  澤井 英明, 潮田 まり子, 山田 崇弘, 佐藤 秀平, 室月 淳, 堤 誠司, 篠塚 憲男, 高橋 雄一郎, 佐世 正勝 日本産科婦人科学会雑誌 66 (2) 730 -730 2014年02月 [査読無し][通常論文]
  
• 妊婦静脈血栓症診断のためのD-dimerの意義

  河口哲, 山田俊, 遠藤大介, 千葉健太郎, 小島崇史, 荒木直人, 武田真光, 西田竜太郎, 山田崇弘, 森川守, 櫻木範明, 水上尚典 北海道産科婦人科学会会誌 58 (1) 2014年
• P3-2-2 本邦における胎児数別の妊娠期間中の母体体重増加(Group 99 ハイリスク妊娠2,一般演題,公益社団法人日本産科婦人科学会第66回学術講演会)

  森川 守, 山田 崇弘, 山田 俊, 長 和俊, 水上 尚典 日本産科婦人科學會雜誌 66 (2) 757 -757 2014年
• P3-4-2 妊娠高血圧腎症モデルマウスの胎盤におけるオートファジーの活性化の検討(第2報)(Group 101 妊娠高血圧症候群4,一般演題,公益社団法人日本産科婦人科学会第66回学術講演会)

  小島 崇史, 赤石 理奈, 山田 崇弘, 古田 伊都子, 森川 守, 山田 俊, 櫻木 範明, 水上 尚典 日本産科婦人科學會雜誌 66 (2) 762 -762 2014年
• P3-6-6 妊娠婦人血漿におけるエクソソーム内封RNAの変動(Group 103 羊水塞栓症,一般演題,公益社団法人日本産科婦人科学会第66回学術講演会)

  古田 伊都子, 山田 崇弘, 金内 優典, 櫻木 範明, 水上 尚典 日本産科婦人科學會雜誌 66 (2) 770 -770 2014年
• P2-44-6 当院における出生前診断の現状 : 外来の開設からNIPT開始まで(Group 82 出生前診断2,一般演題,第66回学術講演会)

  赤石 理奈, 山田 崇弘, 小島 崇史, 小山 貴弘, 河口 哲, 水上 尚典 日本産科婦人科學會雜誌 66 (2) 708 -708 2014年
• P1-37-9 品胎妊娠における周産期肝機能障害についての検討 : 妊娠中のアンチトロンビン活性と血小板数との関連について(Group37 多胎妊娠2,一般演題,公益社団法人日本産科婦人科学会第66回学術講演会)

  西田 竜太郎, 嶋田 知紗, 馬詰 武, 小島 崇史, 荒木 直人, 赤石 理奈, 小山 貴弘, 山田 崇弘, 森川 守, 山田 俊, 櫻木 範明, 水上 尚典 日本産科婦人科學會雜誌 66 (2) 577 -577 2014年
• P1-38-10 低酸素性虚血性脳症による脳性麻痺リスクは巨大児と関連する(Group38 胎児・新生児の病理,一般演題,公益社団法人日本産科婦人科学会第66回学術講演会)

  山田 崇弘, 赤石 理奈, 山田 俊, 森川 守, 水上 尚典 日本産科婦人科學會雜誌 66 (2) 581 -581 2014年
• ISP-9-3 Association of Antithrombin Activity with Plasma Aldosterone Concentration and Plasma Renin Activity in Pregnant Women(Group 9 Perinatology 1,IS Poster,International Session) :

  Koyama Takahiro, Yamada Takashi, Furuta Itsuko, Yamada Takahiro, Morikawa Mamoru, Minakami Hisanori 日本産科婦人科學會雜誌 66 (2) 943 -943 2014年
• P1-29-3 本態性血小板血症合併妊娠における胎児死亡リスク(Group29 合併症妊娠5,一般演題,公益社団法人日本産科婦人科学会第66回学術講演会)

  馬詰 武, 山田 崇弘, 赤石 理奈, 嶋田 知紗, 荒木 直人, 小島 貴弘, 小山 貴弘, 西田 竜太郎, 森川 守, 水上 尚典 日本産科婦人科學會雜誌 66 (2) 549 -549 2014年
• 公益社団法人北海道看護協会2013年助産師職能集会 遺伝医学の基礎知識と最新の出生前診断について

  山田 崇弘 Best nurse 24 (10) 26 -31 2013年10月
• PTCH1遺伝子の変異(c.2497delA)を確認した22歳女性のGorlin症候群

  三田村 卓, 小田切 哲二, 金野 陽輔, 加藤 達矢, 保坂 昌芳, 山田 崇弘, 小林 範子, 武田 真人, 首藤 聡子, 渡利 英道, 金内 優典, 工藤 正尊, 宮下 俊之, 櫻木 範明 日本婦人科腫瘍学会雑誌 31 (3) 500 -500 2013年06月 [査読無し][通常論文]
  
• 胎児骨系統疾患の診断に有用な胎児CTの被ばく線量軽減の試み

  澤井 英明, 山田 崇弘, 堤 誠司, 篠塚 憲男, 高橋 雄一郎, 佐世 正勝, 佐藤 秀平, 室月 淳, 厚生労働科学研究費補助金, 難治性疾患克服研究事業, 致死性骨異形成症の診断と予後に関する研究班 日本周産期・新生児医学会雑誌 49 (2) 758 -758 2013年06月 [査読無し][通常論文]
  
• PTCH1遺伝子の変異(c.2497delA)を確認した22歳女性のGorlin症候群 症例報告

  蔵谷 美乃里, 三田村 卓, 小田切 哲二, 加藤 達矢, 山田 崇弘, 首藤 聡子, 武田 真人, 渡利 英道, 金内 優典, 工藤 正尊, 水上 尚典, 櫻木 範明 日本産科婦人科学会雑誌 65 (2) 520 -520 2013年02月 [査読無し][通常論文]
  
• 胎児骨系統疾患の診断に有用な3次元ヘリカルCTによる胎児被ばく線量の軽減に向けた取り組み 全国調査による診断参考レベルの推定

  澤井 英明, 山田 崇弘, 佐藤 秀平, 室月 淳, 堤 誠司, 篠塚 憲男, 林 聡, 高橋 雄一郎, 佐世 正勝, 宮嵜 治 日本産科婦人科学会雑誌 65 (2) 524 -524 2013年02月 [査読無し][通常論文]
  
• 脳性麻痺の原因としての常位胎盤早期剥離の臨床的特徴 : 産科医療補償制度原因分析委員会報告からの分析

  山田 崇弘, 山田 俊, 森川 守, 水上 尚典 北海道醫學雜誌 = Acta medica Hokkaidonensia 88 (1) 36 -36 2013年01月01日
• 双胎妊婦血中Nt-proBNP変動

  山田 俊, 小山 貴弘, 古田 伊都子, 武田 真光, 西田 竜太郎, 山田 崇弘, 森川 守, 水上 尚典 北海道醫學雜誌 = Acta medica Hokkaidonensia 88 (1) 33 -33 2013年01月01日
• 1絨毛膜2羊膜ならびに2絨毛膜2羊膜双胎妊娠における死産(ならびに早期新生児死亡)に関する後方視的検討

  森川 守, 山田 俊, 山田 崇弘, 水上 尚典 北海道醫學雜誌 = Acta medica Hokkaidonensia 88 (1) 37 -37 2013年01月01日
• 妊娠性血小板減少症(gestational thrombocytopenia) (特集 血栓・止血の異常と妊娠)

  水上 尚典, 森川 守, 山田 崇弘 産科と婦人科 80 (1) 27 -32 2013年01月
• P3-24-5 妊娠高血圧腎症モデルマウスの胎盤におけるオートファジーの活性化の検討(Group 129 胎盤・絨毛の基礎,一般演題,公益社団法人日本産科婦人科学会第65回学術講演会)

  小島 崇史, 赤石 理奈, 山田 崇弘, 古田 伊都子, 森川 守, 山田 俊, 山田 秀人, 櫻木 範明, 水上 尚典 日本産科婦人科學會雜誌 65 (2) 926 -926 2013年
• P2-40-8 1絨毛膜2羊膜双胎における1児胎児発育不全に関する後方視的検討(Group 92 多胎,一般演題,公益社団法人日本産科婦人科学会第65回学術講演会)

  遠藤 大介, 森川 守, 千葉 健太郎, 荒木 直人, 小島 崇史, 河口 哲, 武田 真光, 西田 竜太郎, 山田 崇弘, 長 和俊, 櫻木 範明, 水上 尚典 日本産科婦人科學會雜誌 65 (2) 812 -812 2013年
• 2.前置胎盤の管理(専攻医教育プログラム,公益社団法人日本産科婦人科学会第65回学術講演会)

  山田 崇弘 日本産科婦人科學會雜誌 65 (2) 418 -418 2013年
• P2-29-6 妊娠中の抗甲状腺抗体陽性および潜在性甲状腺機能低下症と産後甲状腺機能異常との関連について(Group 81 合併症妊娠3,一般演題,公益社団法人日本産科婦人科学会第65回学術講演会)

  西田 竜太郎, 山田 俊, 遠藤 大介, 千葉 健太郎, 小島 崇史, 荒木 直人, 河口 哲, 武田 真光, 山田 崇弘, 森川 守, 櫻木 範明, 水上 尚典 日本産科婦人科學會雜誌 65 (2) 777 -777 2013年
• P2-24-6 妊娠中の母体血中胎児ヘモグロビン値の変化(Group 76 妊娠・分娩・産褥の生理・病理,一般演題,公益社団法人日本産科婦人科学会第65回学術講演会)

  山田 俊, 遠藤 大介, 千葉 健太郎, 小島 崇史, 荒木 直人, 河口 哲, 武田 真光, 西田 竜太郎, 山田 崇弘, 森川 守, 櫻木 範明, 水上 尚典 日本産科婦人科學會雜誌 65 (2) 761 -761 2013年
• P1-32-6 妊婦健康診査における尿蛋白陽性および浮腫,過度体重増加の臨床的意義(Group 32 PIH2,一般演題,公益社団法人日本産科婦人科学会第65回学術講演会)

  千葉 健太郎, 山田 俊, 遠藤 大介, 小島 崇史, 荒木 直人, 河口 哲, 武田 真光, 西田 竜太郎, 山田 崇弘, 森川 守, 櫻木 範明, 水上 尚典 日本産科婦人科學會雜誌 65 (2) 618 -618 2013年
• 致死性骨異形成症の診断と予後に関する研究 症例の収集と診断の支援システム構築

  室月淳, 澤井英明, 山田崇弘, 堤誠司, 佐藤秀平, 林聡, 篠塚憲男, 高橋雄一郎, 佐世正勝, 鬼頭浩史, 沼部博直, 宮崎治, 緒方勤, 池川志郎, 妻木範行, 芳賀信彦, 西村玄 致死性骨異形成症の診断と予後に関する研究 平成24年度 総括・分担研究報告書 2013年
• 妊婦検診未受診で救急搬送されたところ、梅毒罹患が判明した1例

  西田 竜太郎, 山田 俊, 遠藤 大介, 千葉 健太郎, 小島 崇史, 河口 哲, 武田 真光, 山田 崇弘, 森川 守, 水上 尚典 日本性感染症学会誌 23 (2) 51 -51 2012年11月
• 妊娠糖尿病診断基準変更に伴う妊娠初期75g糖負荷試験の取り扱いに関する検討

  森川 守, 山田 俊, 山田 崇弘, 遠藤 大介, 千葉 健太郎, 小島 崇史, 河口 哲, 武田 真光, 西田 竜太郎, 荒木 直人, 水上 尚典 糖尿病と妊娠 12 (2) S -67 2012年10月
• 妊娠・産褥期の超音波検査による深部静脈血栓スクリーニング

  河口 哲, 山田 俊, 遠藤 大輔, 千葉 健太郎, 小島 崇史, 荒木 直人, 武田 真光, 西田 竜太郎, 山田 崇弘, 森川 守, 櫻木 範明, 水上 尚典 北日本産科婦人科学会総会・学術講演会プログラム・抄録集 60回 83 -83 2012年09月
• 一絨毛膜二羊膜双胎における1児胎児発育不全に関する後方視的検討

  遠藤 大介, 森川 守, 千葉 健太郎, 荒木 直人, 小島 崇史, 河口 哲, 武田 真光, 西田 竜太郎, 山田 崇弘, 山田 俊, 櫻木 範明, 水上 尚典 北日本産科婦人科学会総会・学術講演会プログラム・抄録集 60回 90 -90 2012年09月
• 3DCTが出生前診断に有用であったCampomelic dysplasiaの1例

  小島 崇史, 山田 崇弘, 長 和俊, 秋元 琢真, 石川 聡司, 武田 真光, 西田 竜太郎, 森川 守, 山田 俊, 兼次 洋介, 盛一 享徳, 水上 尚典 北日本産科婦人科学会総会・学術講演会プログラム・抄録集 60回 120 -120 2012年09月
• 筋強直性ジストロフィー1型罹患女性における一絨毛膜二羊膜性双胎妊娠管理の一例

  千葉 健太郎, 山田 崇弘, 小島 崇史, 嶋田 知紗, 石川 聡司, 武田 真光, 西田 竜太郎, 森川 守, 山田 俊, 長 和俊, 山口 辰美, 水上 尚典 北日本産科婦人科学会総会・学術講演会プログラム・抄録集 60回 126 -126 2012年09月
• 妊娠初期に静脈血栓塞栓症を来した2症例

  細川 亜美, 武田 真光, 遠藤 大介, 千葉 健太郎, 河口 哲, 西田 竜太郎, 山田 崇弘, 森川 守, 山田 俊, 家子 正裕, 櫻木 範明, 水上 尚典 北日本産科婦人科学会総会・学術講演会プログラム・抄録集 60回 129 -129 2012年09月
• 正常妊婦における経腟分娩直前のアンチトロンビン活性、血小板数、ヘモグロビン値、ヘマトクリット値

  森川 守, 山田 俊, 山田 崇弘, 小島 崇史, 小山 貴弘, 石川 聡司, 武田 真光, 西田 竜太郎, 荒木 直人, 長 和俊, 水上 尚典 日本産婦人科・新生児血液学会誌 22 (1) S -40 2012年06月
• 一絨毛膜二羊膜ならびに二絨毛膜二羊膜双胎妊娠における死産に関する後方視的検討

  森川 守, 山田 俊, 山田 崇弘, 長 和俊, 水上 尚典 日本周産期・新生児医学会雑誌 48 (2) 394 -394 2012年06月
• 一絨毛膜一羊膜双胎妊娠における短期周産期予後

  森川 守, 山田 俊, 山田 崇弘, 長 和俊, 水上 尚典 日本周産期・新生児医学会雑誌 48 (2) 394 -394 2012年06月
• 妊娠中の尿中蛋白尿の定量法についての検討

  山田 崇弘, 森川 守, 山田 俊, 石川 聡司, 武田 真光, 西田 竜太郎, 水上 尚典 日本周産期・新生児医学会雑誌 48 (2) 404 -404 2012年06月
• 妊娠中の出血傾向で発見された、後天性第XI因子欠乏症合併妊娠の一例

  小島 崇史, 山田 崇弘, 西田 竜太郎, 小山 貴弘, 石川 聡司, 武田 真光, 森川 守, 山田 俊, 水上 尚典 日本周産期・新生児医学会雑誌 48 (2) 406 -406 2012年06月
• 出生前に診断することができた先天性処女膜閉鎖症の1症例

  西田 竜太郎, 山田 俊, 小島 崇史, 小山 貴弘, 石川 聡司, 武田 真光, 山田 崇弘, 森川 守, 長 和俊, 水上 尚典 日本周産期・新生児医学会雑誌 48 (2) 472 -472 2012年06月
• 体重差のある一絨毛膜二羊膜双胎では臍帯血および羊水中B型ナトリウム利尿ペプチドが上昇している

  盛一 享徳, 長 和俊, 古瀬 優太, 秋元 琢真, 兼次 洋介, 山田 崇弘, 森川 守, 山田 俊, 水上 尚典 日本周産期・新生児医学会雑誌 48 (2) 492 -492 2012年06月
• 致死性骨異形成症の頻度と予後に関する全国調査から

  澤井 英明, 沼部 博直, 山田 崇弘, 堤 誠司, 篠塚 憲男, 林 聡, 高橋 雄一郎, 佐世 正勝, 室月 淳, 厚生労働科学研究費補助金, 難治性疾患克服研究事業, 致死性骨異形成症の診断と予後に関する研究班 日本周産期・新生児医学会雑誌 48 (2) 468 -468 2012年06月 [査読無し][通常論文]
  
• 致死性骨異形成症の頻度と予後に関する全国調査

  澤井 英明, 室月 淳, 山田 崇弘, 佐藤 秀平, 堤 誠司, 林 聡, 篠塚 憲男, 早川 博生, 高橋 雄一郎, 夫 律子, 佐世 正勝, 厚生労働科学研究, 致死性骨異形成症の診断と予後に関する研究班 日本産科婦人科学会雑誌 64 (2) 587 -587 2012年02月 [査読無し][通常論文]
  
• 妊娠高血圧症候群と双胎妊娠における胎盤性ロイシンアミノペプチダーゼ(P-LAP)及び水代謝の検討

  小山 貴弘, 山田 俊, 小島 崇史, 石川 聡司, 武田 真光, 西田 竜太郎, 山田 崇弘, 森川 守, 長 和俊, 水上 尚典 日本妊娠高血圧学会雑誌 19 111 -112 2012年01月
• P1-41-6 双胎妊娠における産褥に初発する高血圧の危険因子に関する後方視的検討(Group41 PIH2,一般演題,第64回日本産科婦人科学会学術講演会)

  森川 守, 山田 俊, 山田 崇弘, 小島 崇史, 小山 貴弘, 赤石 理奈, 石川 聡司, 武田 真光, 西田 竜太郎, 荒木 直人, 櫻木 範明, 水上 尚典 日本産科婦人科學會雜誌 64 (2) 537 -537 2012年
• 出生前3D-CTを用いた骨形成不全症の臨床的重症度推定

  山田崇弘, 山田崇弘, 長谷川奉延, 長谷川奉延, 西村玄, 西村玄, 池川志郎, 池川志郎, 室月淳, 室月淳, 室月淳, 澤井英明, 澤井英明 日本人類遺伝学会大会プログラム・抄録集 57th 2012年
• 致死性骨異形成症の診断と予後に関する研究 症例の収集と診断の支援システム構築

  室月淳, 澤井英明, 山田崇弘, 堤誠司, 佐藤秀平, 林聡, 篠塚憲男, 高橋雄一郎, 佐世正勝, 鬼頭浩史, 沼部博直, 宮崎治, 緒方勤, 池川志郎, 妻木範行, 西村玄 致死性骨異形成症の診断と予後に関する研究 平成23年度 総括・分担研究報告書 2012年
• 妊娠糖尿病(GDM)の発症予測

  森川 守, 山田 俊, 山田 崇弘, 小島 崇史, 小山 貴弘, 赤石 理奈, 石川 聡司, 武田 真光, 西田 竜太郎, 荒木 直人, 長 和俊, 水上 尚典 糖尿病と妊娠 11 (2) S -71 2011年10月
• 【周産期の血液をめぐる話題-母体・胎児編】母体の血液異常 妊娠性アンチトロンビン欠乏症

  水上 尚典, 森川 守, 山田 崇弘, 山田 俊 周産期医学 41 (8) 1021 -1025 2011年08月
• 社会的ハイリスク妊娠 札幌圏における未受診妊婦の実態調査 未受診妊婦対策啓発活動の効果は?

  山田 俊, 長 和俊, 小山 貴弘, 赤石 理奈, 武田 真光, 西田 竜太郎, 山田 崇弘, 森川 守, 遠藤 俊明, 矢野 公一, 斉藤 豪, 水上 尚典 日本周産期・新生児医学会雑誌 47 (2) 313 -313 2011年06月
• 妊娠高血圧症候群の病態生理 妊娠高血圧症候群と双胎妊娠における胎盤性ロイシンアミノペプチダーゼ(PLAP)及び水代謝の検討

  小山 貴弘, 山田 俊, 赤石 理奈, 武田 真光, 西田 竜太郎, 山田 崇弘, 森川 守, 長 和俊, 水上 尚典 日本周産期・新生児医学会雑誌 47 (2) 314 -314 2011年06月
• 双胎間輸血症候群の発症予知に母体体重増加量は有用である

  森川 守, 山田 俊, 平山 恵美, 山田 崇弘, 赤石 理奈, 小山 貴弘, 武田 真光, 西田 竜太郎, 長 和俊, 奥山 和彦, 水上 尚典 日本周産期・新生児医学会雑誌 47 (2) 360 -360 2011年06月
• 厳重な管理により生児を得ることができた子宮切開瘢痕部妊娠の1例

  西田 竜太郎, 山田 俊, 小山 貴弘, 赤石 理奈, 武田 真光, 山田 崇弘, 森川 守, 水上 尚典 日本周産期・新生児医学会雑誌 47 (2) 420 -420 2011年06月
• 先天性神経筋疾患を疑った胎児水腫・羊水過少の一例

  赤石 理奈, 山田 崇弘, 長 和俊, 武田 真光, 西田 竜太郎, 森川 守, 水島 正人, 山田 俊, 水上 尚典 日本周産期・新生児医学会雑誌 47 (2) 471 -471 2011年06月
• 妊娠中期に発見され、出生後meconium pseudocystの診断となった胎児腹腔内腫瘤の1例

  小山 貴弘, 山田 俊, 金野 陽輔, 荒木 直人, 山田 崇弘, 島田 茂樹, 森川 守, 櫻木 範明, 水上 尚典 北海道産科婦人科学会会誌 55 (1) 134 -135 2011年03月
• 耐糖能異常と胎児異常

  森川 守, 山田 俊, 山田 崇弘, 島田 茂樹, 小山 貴弘, 金野 陽輔, 荒木 直人, 長 和俊, 櫻木 範明, 水上 尚典 北海道産科婦人科学会会誌 55 (1) 142 -142 2011年03月
• 妊娠31週、急性腹症で発見された重複子宮、子宮静脈瘤破裂の一例

  金野 陽輔, 山田 俊, 小山 貴弘, 荒木 直人, 山田 崇弘, 島田 茂樹, 森川 守, 櫻木 範明, 水上 尚典 北海道産科婦人科学会会誌 55 (1) 147 -147 2011年03月
• 胎児三次元CT(3D‐CT)を用いた短肋骨骨異形成症の出生前診断

  山田崇弘, 澤井英明, 西村玄, 西田圭一郎, 尾松徳彦, 木村太一, 西原広史, 島田茂樹, 森川守, 山田俊, 長和俊, 田中伸哉, 白土博樹, 櫻木範明, 水上尚典 北海道産科婦人科学会会誌 55 (1) 135 2011年03月 [査読無し][通常論文]
  
• P1-22-2 北海道における妊娠中の新型インフルエンザ(Pandemic (H1N1) 2009)感染 : 日本における母体死亡ゼロの背景(Group48 妊娠・分娩・産褥の生理・病理13 感染症,一般演題,第63回日本産婦人科学会学術講演会)

  山田 崇弘, 山田 俊, 森川 守, 長 和俊, 遠藤 俊明, 佐藤 佐和子, 斎藤 豪, 千石 一雄, 水上 尚典 日本産科婦人科學會雜誌 63 (2) 613 -613 2011年
• P1-25-4 胎児に重症発育遅延と胎児水腫を認めた抗リン脂質抗体陽性・妊娠高血圧腎症・HELLP症候群の1例(Group57 PIH・HELLP症候群(症例),一般演題,第63回日本産科婦人科学会学術講演会)

  武田 真光, 吉井 一樹, 小山 貴弘, 赤石 理奈, 西田 竜太郎, 山田 崇弘, 森川 守, 荒木 直人, 山田 俊, 長 和俊, 櫻木 範明, 水上 尚典 日本産科婦人科學會雜誌 63 (2) 641 -641 2011年
• P1-13-8 妊娠高血圧症候群と双胎妊娠における胎盤性ロイシンアミノペプチダーゼ(PLAP)及び水代謝の検討(Group21 妊娠・分娩・産褥の生理・病理4 IUGR・PIH,一般演題,第63回日本産科婦人科学会学術講演会)

  小山 貴弘, 山田 俊, 古田 伊都子, 吉井 一樹, 荒木 直人, 赤石 理奈, 武田 真光, 西田 竜太郎, 山田 崇弘, 森川 守, 櫻木 範明, 水上 尚典 日本産科婦人科學會雜誌 63 (2) 527 -527 2011年
• P1-15-22 本邦双胎9937例の解析 : 前期破水,常位胎盤早期剥離,妊娠高血圧症候群による早産危険(Group29 多胎妊娠2,一般演題,第63回日本産婦人科学会学術講演会)

  森川 守, 山田 俊, 山田 崇弘, 佐藤 昌司, 斎藤 滋, 櫻木 範明, 水上 尚典 日本産科婦人科學會雜誌 63 (2) 552 -552 2011年
• P1-13-1 妊娠期から産褥期までの血清NT-proBNP値の変化(Group21 妊娠・分娩・産褥の生理・病理4 IUGR・PIH,一般演題,第63回日本産科婦人科学会学術講演会)

  山田 俊, 小山 貴弘, 古田 伊都子, 吉井 一樹, 赤石 理奈, 武田 真光, 西田 竜太郎, 山田 崇弘, 森川 守, 長 和俊, 櫻木 範明, 水上 尚典 日本産科婦人科學會雜誌 63 (2) 525 -525 2011年
• 骨形成不全症(Osteogenesis Imperfecta:OI)の診断と予後評価

  山田崇弘, 山田崇弘, 長谷川奉延, 西村玄, 池川志郎, 池川志郎, 室月淳, 室月淳, 室月淳, 澤井英明, 澤井英明 日本周産期・新生児医学会雑誌 47 (2) 2011年
• 致死性骨異形成症の診断と予後に関する研究 症例の収集と診断の支援システム構築

  室月淳, 澤井英明, 山田崇弘, 堤誠司, 佐藤秀平, 篠塚憲男, 高橋雄一郎, 早川博生, 夫律子, 岡本伸彦, 鬼頭浩史, 長谷川奉延, 河井昌彦, 沼部博直, 岡崎伸, 宮崎治, 緒方勤, 池川志郎, 西村玄 致死性骨異形成症の診断と予後に関する研究 平成22年度 総括・分担研究報告書 2011年
• COL1A1のモザイク変異によるII型骨形成不全症の再発例

  山田崇弘, 山田崇弘, 高木優樹, 西村玄, 赤石理奈, 赤石理奈, 古田伊都子, 小島崇史, 小島崇史, 石川聡司, 武田真光, 西田竜太郎, 森川守, 山田俊, 山田俊, 長和俊, 澤井英明, 池川志郎, 長谷川奉延, 水上尚典, 水上尚典 日本人類遺伝学会大会プログラム・抄録集 56th 2011年
• 妊娠管理における蛋白尿の扱い方 PIHとの関わりにおいて 蛋白尿と妊娠高血圧腎症 妊娠中の暫定的診断「妊娠蛋白尿」の病的意義

  森川 守, 山田 俊, 山田 崇弘, 赤石 理奈, 小山 貴弘, 武田 真光, 西田 竜太郎, 荒木 直人, 長 和俊, 水上 尚典 日本妊娠高血圧学会雑誌 18 67 -71 2010年12月
• 妊娠高血圧症候群と双胎妊娠における胎盤性ロイシンアミノペプチダーゼ(PLAP)及び水代謝の検討

  小山 貴弘, 山田 俊, 古田 伊都子, 吉井 一樹, 赤石 理奈, 武田 真光, 西田 竜太郎, 荒木 直人, 山田 崇弘, 森川 守, 櫻木 範明, 水上 尚典 日本妊娠高血圧学会雑誌 18 128 -129 2010年12月
• 新しいGDM診断基準採用後の日本人におけるGDM妊婦数の変化

  森川 守, 山田 俊, 山田 崇弘, 小山 貴弘, 赤石 理奈, 武田 真光, 西田 竜太郎, 荒木 直人, 長 和俊, 櫻木 範明, 水上 尚典 糖尿病と妊娠 10 (2) S -60 2010年10月
• 新しい妊娠糖尿病(GDM)診断基準に基づくOvert DM妊婦とDM妊婦におけるインスリン分泌能

  森川 守, 山田 俊, 山田 崇弘, 小山 貴弘, 赤石 理奈, 武田 真光, 西田 竜太郎, 荒木 直人, 長 和俊, 櫻木 範明, 水上 尚典 糖尿病と妊娠 10 (2) S -67 2010年10月
• 糖代謝異常合併妊娠の管理 妊娠中から産後のフォローまで 妊娠糖尿病gestational diabetes mellitus(GDM)におけるインスリン抵抗性と周産期予後の関連 胎児発育と胎児異常を中心に

  森川 守, 山田 俊, 山田 崇弘, 小山 貴弘, 荒木 直人, 島田 茂樹, 赤石 理奈, 水島 正人, 長 和俊, 水上 尚典 糖尿病と妊娠 10 (1) 57 -60 2010年08月 

  耐糖能異常ならびにインスリン抵抗性と児の出生体重ならびに胎児異常との関連について50gGCT陽性(.140mg/dL)であった228名を対象に検討した。75gOGTT結果により分類された妊娠糖尿病(GDM、25名)群、境界群(1点のみ異常39名、陰性群(3点すべて正常164名)のII(insulinogenic index)異常(<0.4)頻度はそれぞれ44.0%、23.1%、13.4%であり、HOMA-R異常(.2.5)頻度はそれぞれ40.0%、25.6%、10.4%であった。インスリン抵抗性増大(HOMA-R.2.5)は児出生体重.+2SDならびに胎児異常(とくに外胚葉由来)をよく予測(OR3.5[1.4-8.7]、7.6[1.6-35.5])した。GDM妊婦中、血糖調節不良例(分娩前1ヵ月以内HbA1c>5.8%)では良好例に比して児出生体重.+2SDの危険が高かった(4/8vs2/17)。GDM群25例中5例(20.0%)は後に糖尿病と診断された。これらの結果はGDM例中には高頻度に糖尿病妊婦が含まれていること、GDMはインスリン抵抗性増大ならびにインスリン分泌能低下と関連があること、インスリン抵抗性増大(HOMA-R.2.5)は児出生体重.+2SDならびに胎児異常(とくに外胚葉由来)を予測すること、ならびに血糖調節不良例では児出生体重.+2SDの危険が高いことを示した。(著者抄録)
• 社会的リスクと周産期医療 札幌圏における未受診妊婦の実態調査

  山田 俊, 長 和俊, 小山 貴弘, 赤石 理奈, 武田 真光, 山田 崇弘, 島田 茂樹, 森川 守, 遠藤 俊明, 館石 宗隆, 斉藤 豪, 水上 尚典 日本周産期・新生児医学会雑誌 46 (2) 280 -280 2010年06月
• 当科における近年の前置胎盤と癒着胎盤の検討 子宮底部横切開法を採用して

  山田 崇弘, 山田 俊, 森川 守, 赤石 理奈, 小山 貴弘, 長 和俊, 水上 尚典 日本周産期・新生児医学会雑誌 46 (2) 371 -371 2010年06月
• 補助生殖医療(ART)後成立妊娠の周産期短期予後に関する後方視的検討 一大学病院から

  森川 守, 山田 俊, 山田 崇弘, 小山 貴弘, 赤石 理奈, 武田 真光, 水島 正人, 長 和俊, 水上 尚典 日本周産期・新生児医学会雑誌 46 (2) 443 -443 2010年06月
• 臨床遺伝学の系統講義を経験していない医学生における遺伝カウンセリングロールプレイの試み

  山田 崇弘, 平塚 志保, 齋藤 伸治, 森川 守, 山田 俊, 水上 尚典 日本遺伝カウンセリング学会誌 31 (1) 68 -68 2010年04月
• 双胎妊娠における後期早産(Late Preterm Birth)の原因

  森川 守, 山田 俊, 山田 崇弘, 島田 茂樹, 田中 理恵子, 山村 満恵, 小山 貴弘, 荒木 直人, 長 和俊, 山田 秀人, 櫻木 範明, 水上 尚典 北海道産科婦人科学会会誌 54 (1) 75 -75 2010年03月
• 劇症型A群レンサ球菌(GAS)感染症(toxic shock like syndrome:TSLS)を発症し急激な経過をたどった一例

  山村 満恵, 山田 崇弘, 田中 理恵子, 小山 貴弘, 荒木 直人, 島田 茂樹, 森川 守, 山田 俊, 山田 秀人, 関 敏雄, 有賀 敏, 櫻木 範明, 水上 尚典 北海道産科婦人科学会会誌 54 (1) 76 -77 2010年03月
• 重篤な妊娠浮腫の一例

  田中 理恵子, 森川 守, 山田 俊, 山田 崇弘, 島田 茂樹, 山村 満恵, 小山 貴弘, 荒木 直人, 山田 秀人, 櫻木 範明, 水上 尚典 北海道産科婦人科学会会誌 54 (1) 77 -78 2010年03月
• 妊娠19週SLE flareを契機に胎児発育が停止した1例

  島田 茂樹, 山田 秀人, 小島 崇史, 山田 崇弘, 森川 守, 山田 俊, 櫻木 範明, 水上 尚典 北海道産科婦人科学会会誌 54 (1) 79 -79 2010年03月
• 治療抵抗性のため妊娠中期に中絶をした特発性血小板減少性紫斑病合併妊娠の1例

  小山 貴弘, 山田 俊, 田中 理恵子, 山村 満恵, 荒木 直人, 山田 崇弘, 島田 茂樹, 森川 守, 山田 秀人, 櫻木 範明, 水上 尚典, 今村 雅寛 北海道産科婦人科学会会誌 54 (1) 79 -80 2010年03月
• Insulin resistance is more increased in women with gestational diabetes mellitus (GDM) than in women without GDM

  Mamoru Morikawa, Takashi Yamada, Takahiro Yamada, Takahiro Koyama, Rina Akaishi, Masamitsu Takeda, Naoto Araki, Kazutoshi Cho, Hisanori Minakami ENDOCRINE JOURNAL 57 S382 -S382 2010年03月 [査読無し][通常論文]
  
• P2-88 ヒト胎盤におけるオートファジー関連遺伝子ATG9Bの発現と機能解析(Group54 妊娠高血圧2,一般演題,第62回日本産科婦人科学会学術講演会)

  赤石 理奈, 山田 崇弘, 古田 伊都子, 森川 守, 山田 俊, 山田 秀人, 櫻木 範明, 水上 尚典 日本産科婦人科學會雜誌 62 (2) 494 -494 2010年
• P1-81 帝王切開術施行前後におけるD-dimer値の正常域の検討(Group11 妊娠分娩産褥2,一般演題,第62回日本産科婦人科学会学術講演会)

  森川 守, 山田 俊, 山田 崇弘, 島田 茂樹, 小山 貴弘, 金野 陽輔, 荒木 直人, 長 和俊, 櫻木 範明, 水上 尚典 日本産科婦人科學會雜誌 62 (2) 375 -375 2010年
• 妊娠高血圧症候群におけるアンチトロンビン活性の意義、病態とその治療

  水上 尚典, 森川 守, 山田 崇弘, 山田 俊 日本妊娠高血圧学会雑誌 17 105 -109 2009年12月
• A CASE OF GROUP A STREPTOCOCCAL INFECTION IN LATE PREGNANCY

  Kenichi Katabami, Takahiro Yamada, Mineji Hayakawa, Hisanori Minakami, Satoshi Gando CRITICAL CARE MEDICINE 37 (12) A519 -A519 2009年12月 [査読無し][通常論文]
  
• 糖代謝異常合併妊娠の管理 妊娠中から産後のフォローまで 妊娠糖尿病におけるインスリン抵抗性と周産期予後の関連 胎児発育と胎児異常を中心に

  森川 守, 山田 俊, 山田 崇弘, 島田 茂樹, 小山 貴弘, 金野 陽輔, 荒木 直人, 長 和俊, 櫻木 範明, 水上 尚典 糖尿病と妊娠 9 (2) S -46 2009年10月
• 妊娠高血圧 妊娠中の暫定的診断「妊娠蛋白尿」の病的意義(第2報)

  森川 守, 山田 俊, 山田 崇弘, 島田 茂樹, 小山 貴弘, 山村 満恵, 長 和俊, 山田 秀人, 水上 尚典 日本周産期・新生児医学会雑誌 45 (2) 343 -343 2009年06月
• 出生前診断された重複臍帯静脈の1例

  森川 守, 山田 俊, 山田 崇弘, 島田 茂樹, 小山 貴弘, 山村 満恵, 長 和俊, 山田 秀人, 水上 尚典 日本周産期・新生児医学会雑誌 45 (2) 546 -546 2009年06月
• 羊水染色体検査を考慮しているクライエントに対する遺伝カウンセリング

  山田 崇弘, 山田 秀人, 島田 茂樹, 森川 守, 山田 俊, 水上 尚典 北海道医学雑誌 84 (2) 141 -141 2009年03月
• 前置胎盤および癒着胎盤に対する帝王切開術 子宮底部横切開法の経験

  鈴木 賀博, 山田 俊, 佐々木 尚子, 荒木 直人, 山田 崇弘, 森川 守, 山田 秀人, 櫻木 範明, 水上 尚典 北海道産科婦人科学会会誌 53 (1) 57 -58 2009年01月
• P3-237 切PCR法を用いた切迫早産症例の羊水中マイコプラズマ属の検出(Group105 周産期感染症3,一般演題,第61回日本産科婦人科学会学術講演会)

  古田 伊都子, 山田 秀人, 山田 崇弘, 島田 茂樹, 森川 守, 山田 俊, 櫻木 範明, 水上 尚典 日本産科婦人科學會雜誌 61 (2) 746 -746 2009年
• P1-162 アンチトロンビン活性(AT)低下や妊娠高血圧症候群(PIH)が産褥期母体体重(BW)減少に及ぼす影響(Group22 妊娠高血圧1,一般演題,第61回日本産科婦人科学会学術講演会)

  森川 守, 山田 俊, 島田 茂樹, 山田 崇弘, 荒木 直人, 小山 貴弘, 山村 満恵, 田中 理恵子, 長和 俊, 山田 秀人, 櫻木 範明, 水上 尚典 日本産科婦人科學會雜誌 61 (2) 500 -500 2009年
• Late pretermをめぐる諸問題 双胎妊娠においてLate Preterm Birth(LPB)は異常分娩か?

  森川 守, 山田 俊, 山田 崇弘, 長 和俊, 山田 秀人, 水上 尚典 日本周産期・新生児医学会雑誌 44 (2) 325 -325 2008年06月
• 妊娠高血圧症候群(PIH)が子宮内胎児発育遅延(IUGR)出現に及ぼす影響に関する検討

  森川 守, 山田 俊, 山田 崇弘, 長 和俊, 山田 秀人, 水上 尚典 日本周産期・新生児医学会雑誌 44 (2) 437 -437 2008年06月
• 子宮内胎児発育遅延(IUGR)出現に及ぼす諸因子の検討

  森川 守, 山田 俊, 山田 崇弘, 長 和俊, 山田 秀人, 水上 尚典 日本周産期・新生児医学会雑誌 44 (2) 439 -439 2008年06月
• 妊娠30週に発見された絨毛膜下血腫の1例

  庄野 理奈, 山崎 綾野, 佐々木 瑞恵, 太田 智佳子, 山田 崇弘, 森川 守, 山田 俊, 長 和俊, 山田 秀人, 櫻木 範明, 水上 尚典, 平山 恵美 日本産科婦人科学会東北連合地方部会誌 (55) 175 -175 2008年06月
• 16SrDNA領域PCR解析による妊娠女性の腟内乳酸桿菌・細菌性腟症関連細菌検出と細菌性腟症との関連について

  タムラカール・レヌカ, 山田 俊, 古田 伊都子, 太田 智佳子, 南 真志穂, 山崎 綾野, 山田 崇弘, 森川 守, 山田 秀人, 櫻木 範明, 水上 尚典 日本産科婦人科学会東北連合地方部会誌 (55) 185 -185 2008年06月
• 臍帯潰瘍からの出血により高度の胎児貧血をきたした胎児上部消化管閉鎖症の1例

  佐々木 瑞恵, 山田 俊, 庄野 理奈, 太田 智佳子, 山崎 綾野, 山田 崇弘, 森川 守, 長 和俊, 山田 秀人, 櫻木 範明, 水上 尚典 日本産科婦人科学会東北連合地方部会誌 (55) 188 -188 2008年06月
• 無心体双胎妊娠における正常児心不全に対する無心体の経皮的ラジオ波焼灼療法(RFA)の経験

  森川 守, 山田 俊, 山崎 綾野, 山田 崇弘, 太田 智佳子, 庄野 理奈, 佐々木 瑞恵, 長 和俊, 山田 秀人, 櫻木 範明, 水上 尚典 日本産科婦人科学会東北連合地方部会誌 (55) 200 -201 2008年06月
• 妊娠性血小板減少症(GT)/妊娠性アンチトロンビン欠乏症(PIATD)の分娩前後のフィブリノーゲン、FDP,D-dimer、ヘマトクリット値、尿酸値の推移 妊娠高血圧症候群(PIH)との関連

  森川 守, 山田 俊, 山田 崇弘, 鈴木 賀博, 荒木 直人, 佐々木 尚子, 島田 茂樹, 長 和俊, 山田 秀人, 櫻木 範明, 水上 尚典 日本産科婦人科学会雑誌 60 (2) 742 -742 2008年02月
• 胎児水腎症の産科学的特徴ならびに新生児予後に関する後方視的検討

  佐々木 尚子, 森川 守, 山田 俊, 山田 崇弘, 鈴木 賀博, 荒木 直人, 島田 茂樹, 長 和俊, 山田 秀人, 櫻木 範明, 水上 尚典 日本産科婦人科学会雑誌 60 (2) 748 -748 2008年02月
• 妊娠時の肝機能 (周産期臨床検査のポイント) -- (産科編 基本的な検査)

  山田 崇弘, 山田 俊, 水上 尚典 周産期医学 38 31 -34 2008年
• 臨床遺伝子診療部による遺伝カウンセリングと出生前遺伝子診断

  山田 崇弘, 山田 秀人, 佐々木 瑞恵, 庄野 理奈, 太田 智佳子, 山崎 綾野, 森川 守, 山田 俊, 古田 伊都子, 水上 尚典 北海道産科婦人科学会会誌 52 (1) 38 -39 2008年01月
• 出生前診断し生児を得た胎児腹壁破裂7例の検討 早産が多いか?

  森川 守, 佐々木 瑞恵, 庄野 理奈, 山崎 綾野, 太田 智佳子, 山田 崇弘, 山田 俊, 長 和俊, 山田 秀人, 櫻木 範明, 水上 尚典 北海道産科婦人科学会会誌 52 (1) 40 -40 2008年01月
• 妊娠性血小板減少症ならびに妊娠性アンチトロンビン欠乏症の分娩前後のフィブリノーゲン、FDP、D-dimer、ヘマトクリット値ならびに尿酸値の推移 妊娠高血圧症候群との対比

  森川 守, 山田 俊, 山田 崇弘, 島田 茂樹, 山田 秀人, 水上 尚典 日本妊娠高血圧学会雑誌 15 87 -88 2007年12月
• 出生前診断し生児を得た胎児腹壁破裂7例の検討

  森川 守, 佐々木 瑞恵, 庄野 理奈, 太田 智佳子, 山崎 綾野, 山田 崇弘, 山田 俊, 長 和俊, 山田 秀人, 櫻木 範明, 水上 尚典 北海道医学雑誌 82 (5) 355 -355 2007年09月
• 北海道大学病院産科・臨床遺伝子診療部による遺伝カウンセリングと出生前遺伝子診断

  山田 崇弘, 山田 秀人, 佐々木 瑞恵, 庄野 理奈, 太田 智佳子, 山崎 綾野, 森川 守, 山田 俊, 水上 尚典, 平塚 志保, 武市 紀人, 澤村 大輔, 矢部 一郎, 田島 敏広, 齋藤 伸治, 佐々木 秀直 北海道医学雑誌 82 (5) 356 -357 2007年09月
• 妊娠19-21週における臍帯動脈拡張期末期血流途絶ならびに逆流と子宮内胎児発育遅延との関係

  森川 守, 山田 俊, 佐々木 瑞恵, 庄野 理奈, 太田 智佳子, 山崎 綾野, 山田 崇弘, 長 和俊, 山田 秀人, 櫻木 範明, 水上 尚典 日本産科婦人科学会雑誌 59 (2) 522 -522 2007年02月
• P1-IS-66 The association between Lactobacillus species and bacterial vaginosis-related bacteria, and bacterial vaginosis scoring in Japanese pregnant women :

  Tamrakar Renuka, Yamada Takashi, Furuta Itsuko, Cho Kazutoshi, Yamazaki Ayano, Yamada Takahiro, Morikawa Mamoru, Yamada Hideto, Sakuragi Noriaki, Minakami Hisanori 日本産科婦人科學會雜誌 59 (2) 780 -780 2007年
• Functional maternal catechol-O-methyltransferase polymorphism and fetal growth restriction

  F. Sata, H. Yamada, K. Suzuki, Y. Saijo, T. Yamada, H. Minakami, R. Kishi EPIDEMIOLOGY 17 (6) S379 -S379 2006年11月 [査読無し][通常論文]
  
• 先天性カンジダ感染症の3例

  長 和俊, 岡嶋 覚, 上田 恵子, 小西 祥平, 塩野 展子, 山田 俊, 森川 守, 山崎 綾野, 山田 崇弘, 太田 智佳子, 庄野 理奈, 佐々木 瑞恵, 山田 秀人, 櫻木 範明, 水上 尚典 北海道医学雑誌 81 (5) 462 -462 2006年09月
• 臍帯潰瘍を合併し著明な胎児貧血を呈した先天性空腸閉鎖の一例

  塩野 展子, 長 和俊, 小西 祥平, 上田 恵子, 山崎 綾野, 山田 崇弘, 森川 守, 山田 俊, 山田 秀人, 水上 尚典 日本周産期・新生児医学会雑誌 42 (2) 405 -405 2006年06月
• 妊娠中の暫定的診断「妊娠性蛋白尿」の病的意義

  森川 守, 太田 智佳子, 山崎 綾野, 西田 竜太郎, 山田 崇弘, 山田 俊, 山田 秀人, 櫻木 範明, 水上 尚典 日本産科婦人科学会雑誌 58 (2) 718 -718 2006年02月
• P2-379 妊娠中の暫定的診断「妊娠性蛋白尿」の病的意義(Group 164 妊娠高血圧症候群IV,一般演題,講演要旨,第58回日本産科婦人科学会学術講演会)

  森川 守, 太田 智佳子, 山崎 綾野, 西田 竜太郎, 山田 崇弘, 山田 俊, 山田 秀人, 櫻木 範明, 櫻木 範明, 水上 尚典 日本産科婦人科學會雜誌 58 (2) 718 -718 2006年
• A previously unidentified MECP2 open reading frame defines a new protein isoform relevant to Rett syndrome (vol 36, pg 339, 2004)

  GN Mnatzakanian, H Lohi, Munteanu, I, SE Alfred, T Yamada, PJM MacLeod, Jones, JR, SW Scherer, NC Schanen, MJ Friez, JB Vincent, BA Minassian NATURE GENETICS 36 (5) 540 -540 2004年05月 [査読無し][通常論文]
  
• Previously unidentified MECP2 open reading frame defines a new protein isoform relevant in Rett syndrome

  GN Mnatzakanian, H Lohi, Munteanu, I, SE Alfred, T Yamada, PJM MacLeod, Jones, JR, SW Scherer, CN Schanen, MJ Friez, JB Vincent, BA Minassian ANNALS OF NEUROLOGY 56 S85 -S85 2004年 [査読無し][通常論文]
  
• Previously unidentified MECP2 open reading frame defines a new protein isoform relevant to Rett syndrome

  GN Mnatzakanian, H Lohi, Munteanu, I, SE Alfred, T Yamada, PJ MacLeod, Jones, JR, SW Scherer, CN Schanen, MJ Friez, JB Vincent, BA Minassian ANNALS OF NEUROLOGY 56 S29 -S29 2004年 [査読無し][通常論文]
  
• Imprinting analysis of genes flanking MEST at 7q32.

  T Yamada, K Mitsuya, T Kayashima, K Yamasaki, T Ohta, T Kishino, M Oshimura, N Niikawa AMERICAN JOURNAL OF HUMAN GENETICS 71 (4) 493 -493 2002年10月 [査読無し][通常論文]
  
• Altp10a, the mouse homologue of the human imprinted gene, ATP10C, escapes genomic imprinting

  T Kayashima, K Yamasaki, K Joh, T Yamada, T Ohta, T Kishino, T Mukai, N Niikawa AMERICAN JOURNAL OF HUMAN GENETICS 71 (4) 492 -492 2002年10月 [査読無し][通常論文]
  
• 産褥期における経腟超音波検査法を用いた経腟分娩・帝王切開分娩後の子宮サイズの変化

  小林 範子, 岸田 達朗, 根岸 広明, 山田 崇弘, 森川 守, 日下 剛, 平山 恵美, 山田 秀人, 奥山 和彦, 藤本 征一郎 北海道産科婦人科学会会誌 46 (1) 56 -56 2001年11月
• IS-124 Persistent Detection of Alfa-fetoprotein in the Vagina without Overt Preterm Premature Rupture of the Membranes : Clinical and Chemical Characterizations :

  YAMADA Takahiro, KISHIDA Tatsuro, YAMADA Hideo, FURUTA Itsuko, KOBAYASHI Noriko, MORIKAWA Mamoru, KUSAKA Tsuyoshi, HIRAYAMA Emi, CHO Kazutoshi, OKUYAMA Kazuhiko, FUJIMOTO Seiichiro 日本産科婦人科學會雜誌 53 (2) 600 -600 2001年
• P-416 産婦人科領域における性分化異常症例の表現型/遺伝子型の検討

  半田 康, 星 信彦, 山田 崇弘, 岸田 達朗, 平山 恵美, 蝦名 康彦, 長 和俊, 山田 秀人, 奥山 和彦, 佐川 正, 櫻木 範明, 藤本 征一郎 日本産科婦人科學會雜誌 52 (2) "511(S -435)" 2000年
• 253 産婦人科乳房外来における二次検診としての穿刺吸引細胞診の検討

  日下 剛, 山田 崇弘, 山下 陽一郎, 佐川 正, 遠藤 隆志, 藤田 美悧, 藤本 征一郎 日本臨床細胞学会雑誌 38 (1) 214 -214 1999年03月22日
• 120 卵巣癌の好発家系-家族性卵巣癌-の臨床的特徴

  山下 陽一郎, 佐川 正, 古屋 充子, 山田 崇弘, 山田 秀人, 山本 律, 藤野 敬史, 櫻木 範明, 藤本 征一郎 日本産科婦人科學會雜誌 50 (0) "S -183" 1998年02月20日 [査読無し][通常論文]
  
• P-164 ヒツジ胎仔における急性脱血性低血圧負荷による脳室周囲白質軟化(PVL)の誘起

  松田 直, 奥山 和彦, 山田 崇弘, 藤本 俊郎, 長 和俊, 根岸 広明, 星 信彦, 松本 憲則, 古林 与志安, 藤本 征一郎 日本産科婦人科學會雜誌 50 "S -443" 1998年
• 産婦人科における乳癌検診と穿刺吸引細胞診の有用性 : 第38回日本臨床細胞学会総会 : 乳腺I

  山田 崇弘, 佐川 正, 荒川 三紀雄, 藤田 美俐, 藤本 征一郎 日本臨床細胞学会雑誌 36 (1) 127 -127 1997年03月
• 412 産婦人科における乳癌検診と穿刺吸引細胞診の有用性について

  山田 崇弘, 佐川 正, 斎藤 千奈美, 藤本 征一郎 日本産科婦人科學會雜誌 49 "S -311" 1997年
• 妊婦における24時間自動血圧計を用いた血管作動性物質が血圧に及ぼす影響ならびに血圧が尿蛋白に及ぼす影響に関する検討(一般演題:ポスター)

  岸田 達朗, 根岸 広明, 山田 崇弘, 平山 恵美, 山田 秀人, 奥山 和彦, 佐川 正, 藤本 征一郎 日本妊娠中毒症学会雑誌 5 85 -86 1997年 

  The study group consisted of pregnant women at 20 weeks or more gestation with gestosis (G group, 12 cases with hypertension, 10 cases without hypertension) and 23 women without gestosis (N group). The blood pressure (BP) of each patient was recorded automatically by an ambulatory BP monitor (TM2421, A&D, Tokyo) to give 96 measurements a day. [Results] The mean BP (MBP) in the G group was negatively correlated with PRA (r=-0.551, p<0.05) and with PAC (r<-0.440, NS). There was a negative correlation between incidence showing abnormal BP (IABP, systolic BP;SBP above 140 mmHg, diastolic BP:DBP above 90 mmHg) and PRA in the G group (SBP, r=-0.528, p<0.05, DBP, r=-0.589, p<0.05). However, there was no correlation between the IABP and PAC in either group. There was a correlation between IABP and the urinary protein level (SBP, r=0.787, p
• 妊婦における24時間自動血圧計を用いた交感神経系が血圧ならびに血圧の夜間下降に及ぼす彩響に関する検討(一般演題:ポスター)

  根岸 広明, 岸田 達朗, 山田 崇弘, 平山 恵美, 山田 秀人, 奥山 和彦, 佐川 正, 藤本 征一郎 日本妊娠中毒症学会雑誌 5 83 -84 1997年 

  The study group consisted of pregnant women at 20 weeks or more gestation with gestosis (G group;12 cases with hypertension, 10 cases without hypertension) and 23 women without gestosis (N group). [Results] The night dip (ND) of the mean blood pressure (MBP) in the hypertension group was lower than that of the H group (3.4±6.3 mmHg, 8.7±5.6 mniHg, mean±SDf respectively, p<0.05). There was a negative correlation between the MBP and urinary adrenaline (UA) level (r=-0.686, p<0.001) in the G group. The degree of ND of the MBP was significantly correlated with the urinary noradrenaline (NA) level in the G group (r=0.534, p<0.05). Incidence showing abnormal BP (IABP, the systolic BP;SBP above 140 mmHg and the diastolic BP; DBP above 90 mmHg) a day were negatively correlated with UA level in the G group (r<-0.687, p<0.01, r=-0.732, p<0.001). The serum NA level at 6:00 am in the hypertension group tended to be negatively correlated with IABP during nighttime (SBP, r*-0.56; DBP, r=-0.69, NS) and at 9:00 am with IABP (DBP) during daytime (r<-0.752; p<0.05). [Conclusions] The fact that the ND of BP in the G group was not associated with sympathetic nerve activity suggests that the ND might be regulated by some other mechanisms. The MBP was negatively correlated with the UA level in the G group. The serum NA level at 6:00 am tended to be negatively correlated with the IABP during the night and at 9:00 am with the IABP (DBP) during the day. These results suggest that the activity of sympathetic nerve system might be inhibited according to the worsen of gestosis. Pulse rate was related to the sympathetic nerve.
• 40 産婦人科乳房外来における穿刺吸引細胞診

  山田 崇弘, 佐川 正, 藤本 征一郎 日本臨床細胞学会雑誌 35 (1) 102 -102 1996年03月22日
• 317 妊婦の頚管粘液中のサイトカイン動態について

  佐川 正, 古田 伊都子, 山田 崇弘, 金野 宏泰, 根岸 広明, 山田 秀人, 奥山 和彦, 藤本 征一郎 日本産科婦人科學會雜誌 48 "S -266" 1996年
• 妊娠中毒症の血圧夜間下降に影響を及ぼす血管作動性物質の関与に関する検討(ミニシンポジウムI : 血圧および尿蛋白測定の読みと意味)

  根岸 広明, 山下 陽一郎, 山田 秀人, 平山 恵美, 山田 崇弘, 奥山 和彦, 佐川 正, 藤本 征一郎 日本妊娠中毒症学会雑誌 4 69 -72 1996年

講演・口頭発表等

• P-416 産婦人科領域における性分化異常症例の表現型/遺伝子型の検討  [通常講演]

  半田 康, 星 信彦, 山田 崇弘, 岸田 達朗, 平山 恵美, 蝦名 康彦, 長 和俊, 山田 秀人, 奥山 和彦, 佐川 正, 櫻木 範明, 藤本 征一郎

  日本産科婦人科學會雜誌 2000年02月
• 253 産婦人科乳房外来における二次検診としての穿刺吸引細胞診の検討  [通常講演]

  日下 剛, 山田 崇弘, 山下 陽一郎, 佐川 正, 遠藤 隆志, 藤田 美悧, 藤本 征一郎

  日本臨床細胞学会雑誌 1999年03月
• P-164 ヒツジ胎仔における急性脱血性低血圧負荷による脳室周囲白質軟化(PVL)の誘起  [通常講演]

  松田 直, 奥山 和彦, 山田 崇弘, 藤本 俊郎, 長 和俊, 根岸 広明, 星 信彦, 松本 憲則, 古林 与志安, 藤本 征一郎

  日本産科婦人科學會雜誌 1998年02月
• 120 卵巣癌の好発家系-家族性卵巣癌-の臨床的特徴  [通常講演]

  山下 陽一郎, 佐川 正, 古屋 充子, 山田 崇弘, 山田 秀人, 山本 律, 藤野 敬史, 櫻木 範明, 藤本 征一郎

  日本産科婦人科學會雜誌 1998年02月
• 産婦人科における乳癌検診と穿刺吸引細胞診の有用性 : 第38回日本臨床細胞学会総会 : 乳腺I  [通常講演]

  山田 崇弘, 佐川 正, 荒川 三紀雄, 藤田 美俐, 藤本 征一郎

  日本臨床細胞学会雑誌 1997年03月
• 412 産婦人科における乳癌検診と穿刺吸引細胞診の有用性について  [通常講演]

  山田 崇弘, 佐川 正, 斎藤 千奈美, 藤本 征一郎

  日本産科婦人科學會雜誌 1997年02月
• 妊婦における24時間自動血圧計を用いた血管作動性物質が血圧に及ぼす影響ならびに血圧が尿蛋白に及ぼす影響に関する検討(一般演題:ポスター)  [通常講演]

  岸田 達朗, 根岸 広明, 山田 崇弘, 平山 恵美, 山田 秀人, 奥山 和彦, 佐川 正, 藤本 征一郎

  日本妊娠中毒症学会雑誌 1997年
• 妊婦における24時間自動血圧計を用いた交感神経系が血圧ならびに血圧の夜間下降に及ぼす彩響に関する検討(一般演題:ポスター)  [通常講演]

  根岸 広明, 岸田 達朗, 山田 崇弘, 平山 恵美, 山田 秀人, 奥山 和彦, 佐川 正, 藤本 征一郎

  日本妊娠中毒症学会雑誌 1997年
• 40 産婦人科乳房外来における穿刺吸引細胞診  [通常講演]

  山田 崇弘, 佐川 正, 藤本 征一郎

  日本臨床細胞学会雑誌 1996年03月
• 317 妊婦の頚管粘液中のサイトカイン動態について  [通常講演]

  佐川 正, 古田 伊都子, 山田 崇弘, 金野 宏泰, 根岸 広明, 山田 秀人, 奥山 和彦, 藤本 征一郎

  日本産科婦人科學會雜誌 1996年02月
• 妊娠中毒症の血圧夜間下降に影響を及ぼす血管作動性物質の関与に関する検討(ミニシンポジウムI : 血圧および尿蛋白測定の読みと意味)  [通常講演]

  根岸 広明, 山下 陽一郎, 山田 秀人, 平山 恵美, 山田 崇弘, 奥山 和彦, 佐川 正, 藤本 征一郎

  日本妊娠中毒症学会雑誌 1996年

所属学協会

• 日本遺伝性腫瘍学会   国際出生前診断学会   日本遺伝子診療学会   アメリカ人類遺伝学会   日本妊娠高血圧学会   日本周産期・新生児医学会   日本先天異常学会   日本遺伝カウンセリング学会   日本人類遺伝学会   日本産科婦人科学会   

共同研究・競争的資金等の研究課題

• 医療資源の少ない遠隔地におけるゲノム医療展開に関わる課題抽出と解決戦略の解明

  日本学術振興会：科学研究費助成事業

  研究期間 : 2024年04月 -2027年03月 

  代表者 : 山田 崇弘, 松島 理明, 蒔田 芳男, 柴田 有花, 矢部 一郎, 三田村 卓
• 周産期心筋症ハイリスク群同定を目指した臨床的有用性の高いリスク因子抽出の研究

  日本学術振興会：科学研究費助成事業

  研究期間 : 2014年04月 -2017年03月 

  代表者 : 山田 崇弘, 水上 尚典, 森川 守, 古田 伊都子

   

  周産期心筋症は、妊娠中から産後にかけて突然の心不全をきたす、妊産婦死亡の原因となる疾患である。本研究では、まず妊娠中の循環動態を観察し、心不全を診断するのに必要な、バイオマーカーや心エコー指標の正常妊娠中・産後の基準値を策定した。次に、正常妊娠と比較して妊娠高血圧症候群や双胎妊娠でどのような循環動態の違いがあるのかを解明し、心不全早期発見のためのバイオマーカーによるスクリーニング方法の一つの提言を行った。本研究成果は、妊娠中・産後の心不全がより簡便に早期発見され、周産期心筋症を発見する一つの端緒を開くものと考えられる。
• 異常胎児心拍パターンと胎児－母体輸血症候群の関係

  日本学術振興会：科学研究費助成事業

  研究期間 : 2013年04月 -2016年03月 

  代表者 : 水上 尚典, 森川 守, 山田 崇弘

   

  妊娠高血圧腎症などの合併症妊婦はplacental permeability dysfunction (PPD)を持ちやすいのでoccult fetematernal transfusion（FMH）が起こりやすい可能性がある。PPDが想定される11名妊婦（5名の妊娠高血圧腎症、3名の前置胎盤、2名の常位胎盤早期剥離、1名のPMD）ならびに対照妊婦35名の計46名妊婦から分娩前の41血液検体ならびに分娩後の39血液検体を得た。FMHはPPD群で対照群に比し有意に高かった（36% [4/11] vs. 2.9% [1/35]）。
• エクソゾーム内封小分子ＲＮＡを用いた妊娠早期における妊娠高血圧症候群の発症予知

  日本学術振興会：科学研究費助成事業

  研究期間 : 2012年04月 -2015年03月 

  代表者 : 古田 伊都子, 山田 崇弘, 金内 優典

   

  我々は,妊娠初期婦人血漿中exosomeに内封されているsmall RNA(Exo-RNA)を量的（RNA濃度）・質的（RNA塩基長）に解析し,妊娠高血圧症候群(PIH)の予知マーカーとしての可能性を検討した. Exo-RNAをchip電気泳動すると,サイズの異なる3分画(micro:20-40nt, medium:41-80nt, large:81nt<)が認められた.妊娠6-8wにおけるExo- micro RNAは非PIH発症検体(n=34, median1.55ng/ml)に対してPIH発症検体(n=2, median2.84ng/ml)では有意(p=0.038)に高値を示した.
• ヒト耳垢型決定遺伝子発現マウスモデルの解析

  日本学術振興会：科学研究費助成事業

  研究期間 : 2008年 -2010年 

  代表者 : 太田 亨, 及川 恒之, 長田 和実, 山田 崇弘

   

  ABCC11遺伝子は耳垢型決定遺伝子であり、SNP(c. 538G> A, rs17822931)により、乾型、湿型が決定される。今回、このSNP以外の多型である、Δ27(27bp欠失)の頻度を検出した。また、乳がんのエストロゲン非感受性グループと耳垢乾型の頻度の関連性を解析した。市販されているサプリメントAが、腋窩臭を抑制することを推定していたので腋窩臭官能評価をおこない、腋窩(腋臭)を予防できることが判明した。また、ヒトABCC11遺伝子を含むBAC cloneをマウスES細胞ゲノムに挿入したが、ABCC11遺伝子発現は認められなかった。現在もマウスES細胞のtransgeneを作成中である。
• 遺伝子解析による妊娠高血圧症候群の発症メカニズム解明と遺伝子型別介入研究

  日本学術振興会：科学研究費助成事業

  研究期間 : 2006年 -2007年 

  代表者 : 小橋 元, 羽田 明, 水上 尚典, 山田 崇弘, 岩田 昇, 太田 薫里

   

  1.従来から協力関係にある北海道内の産科施設において、(1)妊娠前・妊娠中の生活習慣、ストレス、ソーシャルサポート、エゴグラムなどの質問調査、(2)母体採血およびDNA抽出・タイピングを継続した。 2.PIH発症におけるいくつかの遺伝子多型要因の検討を行った。それぞれ、アンジオテンシノーゲン遺伝子(AGT)TT型、一酸化窒素合成酵素遺伝子(NOS3)GA+AA型、プラスミノーゲン・アクチベーター・インヒビター遺伝子(PAI-1)4G/5G 多型、Body Mass Index などと交絡も含めて検討したが、本研究期間においては、妊娠高血圧症候群の発症に有意に関連するものは、得られなかった。本研究分野において、あらためて文献レビューを行い、PIH発症のパスウエイおよびそこに関わる遺伝・環境要因を整理し今後の方向性を検討した。 3.妊娠女性に対する介入要因として重要な「妊娠中のストレス」に関する評価指標開発を目的として行った、妊婦を対象としたフォーカスグループインタビュー、個人インタビューから得られた、育児不安に関する項目、経済的問題に関する項目、職場などで先輩女性の理解不足、住居に関する問題、妊娠合計併症に対する不安やそれに対するフォロー体制に関する項目を用いて、妊娠中のストレス評価を試行中である。また、これらのインタビューの手法は、放射線治療目的にて入院中の患者集団における有害事象、QOL、ストレス評価においても応用されている。
• 胎盤の発生発達及び妊娠高血圧腎症におけるオートファジーの役割に関する研究

  文部科学省：科学研究費補助金(若手研究(B))

  研究期間 : 2006年 -2007年 

  代表者 : 山田 崇弘

   

  本年における研究実施状況と得られた結果は以下の通りであった.1.正常および妊娠高血圧腎症(preeclampsia:PE)や妊娠高血圧、(PIH)におけるオートファジー遺伝子APG9L1とAPG9L2の胎盤発現の検討APG9L1, APG9L2, NOS3の発現パターンを正常胎盤とPEおよびPIH胎盤で比較する為に胎盤絨毛を147検体収集.その内,正常69例,PE14検体,PIH12検体に関して定量RTPCR法で各遺伝子の発現量の比較を行った.まず正常検体でAPG9L1, APG9L2, NOS3の発現量の変化を検討した.各遺伝子の発現量は自然陣痛の有無で比較したところ自然陣痛有の群で有意に上昇し,週数による増減傾向を認めなかった.次にPEおよびPIHに関し検討した.週数による増減傾向が無いのは正常検体と同様であったが,PEの自然陣痛なし群でAPG9L1, APG9L2の発現量の上昇を認めた.2.正常およびPEにおけるオートファジー活性の検討正常胎盤とPE胎盤におけるオートファジー活性を比較するため上記の検体を使用し抗LC3抗体を用いたウェスタンブロットを行ったが現在のところ明らかな相関は確認出来ていない.3.PEモデルマウスを用いたPEとオートファジーの関わりについての検索.PEモデルマウス(p57KOマウス)とWTマウスより各妊娠段階における胎盤を収集した.定量RTPCR...