Authorship：Corresponding author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：SAGE PUBLICATIONS INC  

Endometriosis is a benign gynecologic disease characterized by the presence of ectopic endometrium and associated with inflammation and immune abnormalities. However, the molecular basis for endometriosis is not well understood. To address this issue, the present study examined the expression of high-mobility group box (HMGB) 1 in menstrual blood to investigate its role in the ectopic growth of human endometriotic stromal cells (ESCs). A total of 139 patients were enrolled in this study; 84 had endometriosis and 55 were nonendometriotic gynecological patients (control). The HMGB1 levels in various fluids were measured by enzyme-linked immunosorbent assay. Expression of receptor for advanced glycation end products (RAGE) in eutopic and ectopic endometrium was assessed by immunohistochemistry, and RAGE and vascular endothelial growth factor (VEGF) messenger RNA expression in HMGB1- and lipopolysaccharide (LPS)-treated ESCs was evaluated by real-time polymerase chain reaction. The HMGB1 concentration was higher in menstrual blood than in serum or peritoneal fluid (P < .001 for both). RAGE was expressed in both normal and ectopic endometrium. Administration of 1000 ng/mL HMGB1 or coadministration of 100 ng/mL HMGB1 and 100 ng/mL LPS induced VEGF production in ESCs relative to the control (P < .05). These results suggest that menstrual fluid has naturally high levels of HMGB1 and may promote endometriosis following retrograde menstruation when complexed with other factors such as LPS by inducing inflammation and angiogenesis.

DOI： 10.1177/1933719117692042

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：PERGAMON-ELSEVIER SCIENCE LTD  

Excess androgen and insulin-like growth factor (IGF)-I in the ovarian follicle has been suggested to be involved in the pathophysiology of polycystic ovary syndrome (PCOS). Here we investigated the impact of androgen and IGF-I on the regulatory mechanism of ovarian steroidogenesis using rat primary granulosa cells. It was revealed that androgen treatment with dihydrotestosterone (DHT) amplified progesterone synthesis in the presence of FSH and IGF-I, whereas it had no significant effect on estrogen synthesis by rat granulosa cells. In accordance with the effects of androgen on steroidogenesis, DHT enhanced the expression of progesterogenic factors and enzymes, including StAR, P450scc and 3 beta HSD, and cellular cAMP synthesis induced by FSH and IGF-I. Of note, treatment with DHT and IGF-I suppressed Smad1/5/8 phosphorylation and transcription of the BMP target gene Id-1, suggesting that androgen and IGF-I counteract BMP signaling that inhibits FSH-induced progesterone synthesis in rat granulosa cells. DHT was revealed to suppress the expression of BMP-6 receptors, consisting of ALK-2, ALK-6 and ActRII, while it increased the expression of inhibitory Smads in rat granulosa cells. In addition, IGF-I treatment upregulated androgen receptor (AR) expression and DHT treatment suppressed IGF-I receptor expression on rat granulosa cells. Collectively, the results indicate that androgen and IGF-I mutually interact and accelerate progesterone production, at least in part, by regulating endogenous BMP signaling in rat granulosa cells. Cooperative effects of androgen and IGF-I counteract endogenous BMP-6 activity in rat granulosa cells, which is likely to be functionally linked to the steroidogenic property shown in the PCOS ovary.

DOI： 10.1016/j.jsbmb.2017.07.002

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Authorship：Corresponding author   Language：Japanese   Publishing type：Research paper (scientific journal)   Publisher：中国四国産科婦人科学会  

緒言 ジェノゲスト(DNG)の一日投与量は2mgと規定されているが、治療費や副作用の問題から、減量を検討する症例はしばしば経験される。本研究では、DNGの至適投与量を、血中エストラジオール(E2)値を指標として決定することができるかどうかにつき検討した。方法 当科外来に通院中の子宮内膜症患者38例に対し、血清中E2値30-50pg/mlを目標値に定め、DNG投与量を決定した。DNG2mg投与開始後のE2を3ヵ月毎に測定し、50pg/ml以下となった時点で1mgへの減量を施行した。減量した症例では、減量後3ヵ月以降のE2値と臨床所見より、1mg継続の可否を判断した。結果 29例に1mgへの減量を行った。23例は1mgで良好な管理が得られた(A群、「1mg群」)。また不正出血などの副作用のため2mgに再増量した6例(B群)および、減量基準を満たさず減量しなかった9例(C群)を合わせて「2mg群」とした。1mg群と2mg群では、平均年齢、体重、BMIに有意差はなかった。A群とB群の比較では、減量直前のE2はA群で有意に低かった(A:19.0±12.8pg/ml B:30.1±22.0pg/ml、P=0.037)。また、減量までに要した期間は、A群で有意に短かった(A:3.0±2.9ヵ月、B:6.0±2.3ヵ月、P=0.042)。1mg/dayで使用中にCA125・CA19-9の上昇、子宮内膜症性嚢胞の増大などの臨床所見の悪化を認めた症例はなく、3例において2mg使用時に見られた更年期様症状やうつ症状が減量に伴い改善した。結論 血中E2値を指標にDNGの至適投与量が決定できる可能性が示唆された。またDNG至適投与量は年齢、体重、BMIには規定されず、減量前の血中E2値が低い症例、および、2mg投与開始後短期間で血中E2値が低下する症例において、1mgでの良好な管理が得られやすい可能性が示唆された。(著者抄録)

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Authorship：Lead author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：Elsevier USA  

Background: Although preparation of a potential vaginal space between the bladder and rectum is a pivotal step in various vaginal reconstructions for patients with vaginal agenesis, few papers have mentioned the importance of this procedure. Case: We report the successful creation of a neovagina in 3 Japanese patients with Mayer-Rokitansky-Küster-Hauser syndrome using a novel modified McIndoe procedure that involved separation between the bladder and the rudimentary uterus in a laparoscopically assisted manner. Summary and Conclusion: Opening "the anterior vaginal vault" between the bladder and uterus is a novel concept of vaginal reconstruction
this approach has not been described hitherto in the literature. Based on the outcome of our cases, we conclude that this procedure is advantageous in creating a large and soft neovagina.

DOI： 10.1016/j.jpag.2014.02.016

Scopus

PubMed

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：OXFORD UNIV PRESS  

Vaginal agenesis is an uncommon, but not rare, condition. Although there are many methods for creating a neovagina, the optimal treatment is unknown. An 18-year-old woman with Mayer-Rokitansky-Kuster-Hauser syndrome received vaginoplasty with a modified Wharton procedure using an artificial dermis (atelocollagen sponge). From 10 days after the operation, the patient was administered human recombinant basic fibroblast growth factor (bFGF) spray to accelerate epithelialization on the neovagina. At 50 days after the operation, we confirmed histological squamous epithelialization of the vaginal epithelium. At 12 months after the operation, the neovagina was at least 3.5 cm in width and similar to8 cm in length. In this case, use of artificial dermis and recombinant bFGF to create a neovagina was an easy, less invasive and useful method.

DOI： 10.1093/humrep/deh254

Web of Science

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Authorship：Lead author   Language：English   Publishing type：Research paper (scientific journal)  

Because overproduction of nitric oxide (NO) and peroxynitrite is known to cause tissue injury, the expression of NO synthases (NOS) and generation of peroxynitrite were investigated in adenomyosis. Immunoreactivities to endothelial and inducible NOS demonstrated phase-dependent changes in normal endometrium, and in eutopic endometrium of adenomyosis. However, NOS were expressed throughout the menstrual cycle in ectopic endometrium from the majority of patients with adenomyosis. Nitrotyrosine, a footprint of peroxynitrite, was detected concomitantly with NOS protein. This suggested that high doses of NO and superoxide are produced in the ectopic endometrium, presumably by stimulation with bioactive molecules such as cytokines and growth factors. The expression of NOS and generation of peroxynitrite were markedly reduced by administration of gonadotrophin-releasing hormone agonists (GnRHa). The suppression of serum concentrations of nitrite/nitrate, stable metabolites of NO, by long-term administration of GnRHa was also demonstrated. The suppression of synthesis of NO and/or peroxynitrite may be part of both the therapeutic and adverse effects of GnRHa therapy.

PubMed

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Language：English   Publishing type：Research paper (scientific journal)  

This study investigated the correlation of Apolipoprotein-B mRNA-editing complex 3B (APOBEC3B) expression with hypoxia inducible factor 1α (HIF-1α), Kirsten rat sarcoma virus (KRAS) and phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA) in endometriosis patients, and the inhibitory effects of APOBEC3B knockdown in a human endometriotic cell line. Here, APOBEC3B, HIF-1α, KRAS, and PIK3CA were examined in patients with and without endometriosis using reverse transcription polymerase chain reaction (RT-PCR). The apoptosis, cell proliferation, invasion, migration, and biological function of APOBEC3B knockdown were explored in 12Z immortalized human endometriotic cell line. We observed APOBEC3B, HIF-1α, KRAS and PIK3CA expressions were significantly higher in endometriosis patients (p < 0.001, p < 0.001, p = 0.029, p = 0.001). Knockdown of APOBEC3B increased apoptosis, which was 28.03% and 22.27% higher than in mock and control siRNA samples, respectively. APOBEC3B knockdown also decreased PIK3CA expression and increased Caspase 8 expression, suggesting a potential role in the regulation of apoptosis. Furthermore, knockdown of APOBEC3B significantly inhibited cell proliferation, invasion, and migration compared to mock and control siRNA. (Cell proliferation: mock: p < 0.001 and control siRNA: p = 0.049. Cell invasion: mock: p < 0.001 and control siRNA: p = 0.029. Cell migration: mock: p = 0.004, and control siRNA: p = 0.014). In conclusion, this study suggests that APOBEC3B may be a new potential therapeutic target for endometriosis.

DOI： 10.1038/s41598-024-76589-2

PubMed

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Language：Japanese   Publisher：(株)メジカルビュー社  

19歳未婚、0妊。月経困難症、下腹部痛を主訴とした。総排泄腔遺残症(cloaca)にて人工肛門造設術、腎瘻造設術、尿道・腟形成術、肛門形成術、腟拡張術の既往があり、腟入口部の狭窄にて紹介受診した。術前診断はcloaca術後、重複子宮、右子宮留血症(非交通性)、右卵巣チョコレート嚢胞、右卵管留血症、腟狭窄症(下1/2)、左片腎であり、非交通性機能性子宮・腟狭窄症に対して腹腔鏡下手術(非交通性機能性子宮摘出術と右付属器腫瘍摘出術)と腟再建術を行った。腟再建術では会陰は切開せず、腟壁の3時9時を長軸方向に切開して腟円蓋部付近まで十分に拡張した後、陰唇の切開創を縫合修復し、腟と腟前庭粘膜の欠損部を人工真皮で修復した。排泄機能の温存を確認後、1日1回の自己拡張と定期的な腟洗浄を行った。その結果、術後4ヵ月で拡張時の疼痛はなく、現時点で性交可能な状態にある。

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Language：Japanese   Publisher：(公社)日本産科婦人科学会  

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Language：English   Publisher：John Wiley & Sons Australia, Ltd  

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Language：English   Publisher：John Wiley & Sons Australia, Ltd  

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Language：Japanese   Publisher：中国四国産科婦人科学会  

【緒言】アンドロゲン不応症(androgen insensitivity syndrome,AIS)はX染色体長腕上のAR遺伝子変異による46,XY性分化疾患である。アンドロゲン作用の障害の程度により表現型は完全女性型から様々な程度の男性型を呈する。また将来的な性腺の悪性化も知られている。完全型アンドロゲン不応症(complete AIS,CAIS)と診断し,予防的性腺摘出術を施行した1例につき報告する。【症例】17歳,0妊。初経遅延を主訴に前医を受診し,精査目的に紹介となった。身長162cm,体重59.7kg,MRI検査で子宮は欠損し,腟は盲端に終わり,骨盤内に両側性腺を認めた。乳房TannerIV度,恥毛TannerI度で腋毛を欠き男性型発毛は認めなかった。外性器は女性型で腟が存在した。血液検査にてエストラジオール23.3pg/mLであったが,テストステロン5.67ng/mLと異常高値であった。染色体検査は46,XYであったが,性自認は女性であった。CAISと診断し,高校卒業時に予防的性腺摘出術を腹腔鏡下に施行した。性腺は卵巣様であったが円靱帯に連続して内鼠径輪へと向かうように存在し,正常女性のみならず,Mayer-Rokitansky-Kuester-Hauser(MRKH)症候群の骨盤解剖とも異なっていた。病理組織診断は,性腺は精巣であり卵管様構造も認めた。術後経過は良好で,現在エストロゲン補充療法を施行中である。【考察】AISでは将来的な性腺の悪性化が知られており,予防的性腺摘出術の検討が必要となる。しかし,患者,家族の精神的負担も大きく,診断の告知や予防的性腺摘出術の時期など,慎重に個別対応する必要がある。また,男性生殖器の解剖及び発生学の知識を要し,性腺摘出術の際には,通常の付属器切除術とは骨盤解剖を異にすることに留意すべきである。(著者抄録)

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Other Link： https://search.jamas.or.jp/default/link?pub_year=2022&ichushi_jid=J05038&link_issn=&doc_id=20221221480009&doc_link_id=%2Fcv0mtrob%2F2022%2F007101%2F009%2F0057-0061%26dl%3D0&url=https%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fcv0mtrob%2F2022%2F007101%2F009%2F0057-0061%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

Language：Japanese   Publisher：(一社)日本女性心身医学会  

胎児先天性心疾患の妊婦への多職種による介入と、倫理的配慮を2例(26歳初産婦、35歳3回経産婦)報告した。26歳の妊婦は長期の不妊治療を経ての妊娠であり、夫婦双方の両親が健在であった。35歳の妊婦は夫婦の希望で4人目を自然妊娠し、上の子どもは入学を控え、夫婦の両親は遠方在住で持病があった。26歳の妊婦は心疾患への積極的治療を選択し、地域保健師、医療ソーシャルワーカーとも連携しながら分娩の日を迎え、父親の愛着形成、両親の受け入れも良好であった。35歳の妊婦は「家族のサポートはなく、この子にかかりきりになれない。経済的不安もあり手術は望まない」と心疾患への治療を拒否していた。多職種からの情報提供を繰り返し行ったが、治療拒否の意思は変わらなかった。妊娠37週に分娩となり、生後2日間、児が永眠するまで母児同室を行い、家族で看取った。方針を一律に定めることは難しく、議論を重ねていくことが重要と考えられた。

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Other Link： https://search.jamas.or.jp/default/link?pub_year=2022&ichushi_jid=J03327&link_issn=&doc_id=20221206110006&doc_link_id=10.18977%2Fjspog.27.2_172&url=https%3A%2F%2Fdoi.org%2F10.18977%2Fjspog.27.2_172&type=J-STAGE&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00007_2.gif

Authorship：Lead author  

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Language：Japanese   Publisher：中国四国産科婦人科学会  

【緒言】抗リン脂質抗体症候群(APS)は、抗リン脂質抗体に関連して起こる動静脈血栓症あるいは習慣性流産・子宮内胎児死亡などの妊娠合併症を主症状とし不妊・不育の原因ともなる全身性自己免疫疾患である。今回APS合併で標準的な抗凝固療法を行っていたにもかかわらず下肢静脈血栓症を生じた一例を報告する。【症例】31歳、4妊1産。第1子は常位胎盤早期剥離で緊急帝王切開術の既往あり。第2子は妊娠22週に子宮内胎児死亡となったため、精査のため当院の不育症外来を受診した。精査にて2回ループスアンチコアグラント陽性でありAPSと診断した。第3子は低用量アスピリン内服しながら自然妊娠成立し妊娠判明時より未分画ヘパリン自己注射を開始したが、妊娠7週で稽留流産となった。第4子も同様に低用量アスピリン内服しながら自然妊娠成立。妊娠判明時より未分画ヘパリンを自己注射していたが、妊娠9週突然の左下肢腫脹・変色、歩行時の痺れ、息切れを自覚し外来受診した。血液検査でDダイマー高値を認め、超音波検査で左大腿静脈から下腿静脈内まで連続する下肢静脈血栓が指摘された。入院し未分画ヘパリン持続静注を開始した。APTTの値を参考に未分画ヘパリンを22500単位/日自己注射に調整し退院した。その後自覚症状は消失しDダイマー低下し、下肢血栓も縮小した。妊娠38週4日で選択帝王切開術を行った。胎盤病理ではフィブリン沈着は軽度で小梗塞巣を認めるのみであった。術後はヘパリン持続点滴からワルファリン内服に切り替えて術後10日目に退院した。【結論】標準的な抗凝固療法を行っていたにもかかわらず妊娠中に深部静脈血栓を発症したAPS合併妊娠例を経験した。血栓性素因がある患者は、抗凝固療法を行っていても血栓症の発症に注意する必要がある。(著者抄録)

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Language：English   Publishing type：Research paper (scientific journal)  

To elucidate the impact of glucocorticoids on ovarian steroidogenesis and its molecular mechanism by focusing on bone morphogenetic proteins (BMPs), we examined the effect of dexamethasone (Dex) on estradiol and progesterone synthesis by using primary culture of rat granulosa cells. It was revealed that Dex treatment dose-dependently decreased estradiol production but increased progesterone production induced by follicle-stimulating hormone (FSH) by granulosa cells. In accordance with the effects of Dex on estradiol synthesis, Dex suppressed P450arom mRNA expression and cAMP synthesis induced by FSH. Dex treatment in turn enhanced basal as well as FSH-induced levels of mRNAs encoding the enzymes for progesterone synthesis including P450scc and 3βHSD but not StAR and 20αHSD. Of note, Dex treatment significantly upregulated transcription of the BMP target gene Id-1 and Smad1/5/9 phosphorylation in the presence of BMP-15 among the key ovarian BMP ligands. It was also found that Dex treatment increased the expression level of BMP type-I receptor ALK-6 among the type-I and -II receptors for BMP-15. Inhibitory Smad6/7 expression was not affected by Dex treatment. On the other hand, BMP-15 treatment upregulated glucocorticoid receptor (GR) expression in granulosa cells. Collectively, it was revealed that glucocorticoids elicit differential effects on ovarian steroidogenesis, in which GR and BMP-15 actions are mutually enhanced in granulosa cells.

DOI： 10.1016/j.bbrc.2021.04.085

PubMed

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Language：Japanese   Publisher：(株)メジカルビュー社  

J-GLOBAL

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Language：Japanese   Publisher：中国四国産科婦人科学会  

腹腔鏡下子宮全摘出術(total laparoscopic hysterectomy;TLH)において、子宮内膜症等によるダグラス窩の高度癒着症例に対する逆行性子宮全摘出術は文献で目にする機会も多く有用な術式として馴染み深くなってきているが、膀胱子宮窩の高度癒着を認めた場合、通常の前腟壁切開からアプローチする子宮全摘出術は困難である。今回我々は既往手術が原因と思われる膀胱子宮窩の高度癒着を認めた症例に対し、腹腔鏡下に子宮腟上部切断術を行い、術中二期的に後腟壁からのアプローチによる逆行性子宮頸部摘出術を行った症例を経験したので、文献的考察を踏まえて報告する。症例は46歳、2妊1産。診断は多発子宮筋腫、過多月経および月経困難症を伴っており手術適応と判断した。帝王切開術および帝王切開術後の子宮筋層の縫合不全による再手術の既往を有していた。内診にて膀胱子宮窩に高度癒着が疑われるもTLHは可能と判断し、手術を行った。膀胱子宮窩の高度癒着にて膀胱子宮窩の剥離が困難であり、上記手順にて子宮摘出を行った。ダグラス窩の癒着がなく、膀胱子宮窩の癒着が高度である場合、後腟壁からのアプローチによる逆行性子宮全摘出を行える可能性はあるが、前腟壁切除に至る過程で子宮腟部を反転させる必要があり、子宮体部を限られた膀胱子宮窩のスペースに持ち上げるのは困難と思われる。子宮腟上部切断術を行うことで、子宮頸部のみが残存する状態となれば、スペースの問題が解決されるため、後腟壁からの逆行性子宮頸部摘出が容易となる。これまでに同様の術式の報告例はみられず、膀胱子宮窩、子宮前壁側のみの強固な癒着症例に対し、子宮腟上部切断術に引き続き後腟壁側からのアプローチによる逆行性子宮頸部摘出術はTLHを完遂する上での有用な方法と考えられた。(著者抄録)

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Authorship：Lead author   Language：Japanese   Publishing type：Research paper (scientific journal)   Publisher：(株)メジカルビュー社  

日本産婦人科手術学会の会員が所属する全国421病院を対象とし、2016〜2018年における子宮腺筋症手術の実施状況について、手術の様式別に調査した。手術の様式は、結節状または嚢胞状の子宮腺筋症に対する手術(以下「限局性」)と、びまん性の子宮腺筋症に対する手術に大別し、後者については、前後壁のいずれかが正常筋層の場合(「びまん性」)と、前後壁とも子宮腺筋症の場合(「全周性」)に細分類した。164施設から回答が得られ、子宮腺筋症手術の施行経験が「ある」と答えたのは61施設(37%)であった。2016〜2018年の3年間に「限局性」は42施設(26%)で計552例に施行され、うち開腹術が511例(93%)であった。「びまん性」は3年間に37施設(23%)で計320例に施行され、うち開腹術が295例(92%)であった。「全周性」は3年間に10施設(6%)で計170例に施行され、うち開腹術が169例(99%)であった。

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Language：Japanese   Publisher：(株)メジカルビュー社  

日本産婦人科手術学会の会員が所属する421施設を対象とし、2018年1月〜12月の手術について調査した。開腹手術については、良性疾患に対する4術式、悪性疾患に対しては体癌・頸癌・卵巣癌別に計9術式に分類した。腹腔鏡下手術については、良性疾患に対する13術式、悪性疾患に対しては診断的腹腔鏡を含め、体癌・頸癌・卵巣癌別に計9術式に分類した。ダヴィンチ支援下手術については、良性疾患に対する5術式、悪性疾患は体癌・頸癌・卵巣癌別に計9術式に分類した。169施設から回答が得られ、腹腔鏡手術を「行っている」と答えたのは159施設(94%)、ダヴィンチ支援下手術を「行っている」と答えたのは45施設(27%)であった。総手術数56763件のうち、開腹手術が18373件(32%)、腹腔鏡下手術26324件(46%)、経腟手術11494件(20%)、ダヴィンチ支援下手術572件(1%)であった。前年の調査と手術割合を比較したところ、経腟手術は横ばいで、開腹手術が漸減し、腹腔鏡下手術が漸増していた。

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Language：Japanese   Publishing type：Research paper (scientific journal)   Publisher：中国四国産科婦人科学会  

【緒言】抗リン脂質抗体症候群など不育症の治療法として、現在は低用量アスピリンとヘパリンカルシウムの併用療法が主流となっている。しかしながら抗凝固療法だけでは流産を反復する難治性の症例も存在する。当院で施行している不育症患者に対するステロイド治療につき検討する。【対象】2008年4月から2018年12月までに当院不育症外来を受診し、妊娠中にプレドニゾロンの投与を行った60症例について倫理委員会の承認のもと後方視的に検討した。患者の背景、スクリーニング検査で施行した不育症リスク因子の検査、妊娠が成立した場合の妊娠予後や妊娠中の合併症、流産した場合の染色体異常の有無につき検討した。【結果】症例の年齢は36.7±4.0(mean±SD)歳、妊娠回数4.1±2.4回、流産回数3.6±2.5回、生児の数は0.30±0.5人であった。生化学妊娠は妊娠回数から除外した。妊娠予後として、妊娠経過が判明した51症例のうち、34症例は生児を得られた。17症例は流産となり、そのうち6症例には染色体異常を認めた。染色体異常を除いた全体の生児を得た率としては75.6%であった。また当院では治療方針としてのステロイドの内服量を妊娠前に決定しているが、プレドニゾロンの内服量として5mgと10mg、20mgの症例が存在した。それぞれの染色体異常による流産を除いた生児獲得率としては81.8%、71.4%、75.0%となった。全体として、1例に早産を認め、6例に妊娠糖尿病を認めた。【結語】抗凝固療法のみでは生児を得られていなかった症例においても、副腎皮質ステロイドを併用することで生児を得られており、不育症の患者に対するステロイド治療の有用性が示された。易感染性による切迫早産や、耐糖能異常などのリスクに注意して投与することが必要であるが、通常の治療法では流産を反復する難治性の症例などについては治療のステップアップとしてステロイド治療を提示することが可能と考えられる。(著者抄録)

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Language：English   Publishing type：Research paper (scientific journal)  

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Language：Japanese   Publisher：(一社)日本女性医学学会  

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Language：Japanese   Publisher：(株)メジカルビュー社  

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Language：Japanese   Publisher：(株)メジカルビュー社  

全国511の周産期医療中核病院施設に頸管縫縮術困難症例の背景および工夫についてアンケート用紙を送付し、172施設より回答を得て162施設を解析対象とした。日常臨床で頸管縫縮が困難と感じた症例は、胎胞形成78%、円錐切除後73%、肥満43%であった。胎胞形成症例の工夫として、膀胱充満(44%)、ミニメトロによる還納(43%)が多かった。円錐切除後で経腟的腹膜開放は2施設(1%)のみで行われ、頸部把持鉗子は25施設(16%)が選択していた。肥満症例に対しては27施設が助手を増やし複数の機器を使用する、12施設が大きな機器を用いると回答した。開腹による頸管縫縮術が1年間で18例(12施設)に行われ、妊娠期15例のうち2例(16.7%)は28週未満で分娩に至った。非妊娠期の開腹頸管縫縮術は3例行われ、うち1例は妊娠成立し生児を獲得した。腹腔鏡による頸管縫縮術は6例(2施設)で行われた。

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Language：English   Publisher：ELSEVIER IRELAND LTD  

DOI： 10.1016/j.jri.2018.09.045

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Language：English   Publishing type：Research paper (scientific journal)  

The involvement of orexins in reproductive function has been gradually uncovered. However, the functional role of orexins in ovarian steroidogenesis remains unclear. In the present study, we investigated the effects of orexin A on ovarian steroidogenesis by using rat primary granulosa cells that express both OX1 and OX2 receptors for orexins. Treatment with orexin A enhanced progesterone, but not estradiol, biosynthesis induced by FSH, whereas it did not affect basal levels of progesterone or estradiol. In accordance with the effects on steroidogenesis, orexin A increased the mRNA levels of progesterogenic enzymes, including StAR, P450scc and 3βHSD, but not P450arom, and cellular cAMP synthesis induced by FSH. Under the condition of blockage of endogenous BMP actions by noggin or BMP-signaling inhibitors, orexin A failed to increase levels of progesterone synthesis induced by FSH treatment, suggesting that endogenous BMP activity in granulosa cells might be involved in the enhancement of progesterone synthesis by orexin A. Treatment with orexin A impaired Smad1/5/9 activation as well as Id-1 mRNA expression stimulated by BMP-6 and BMP-7, the latter of which was reversed by treatment with an OX1 antagonist. It was also found that orexin A suppressed the mRNA expression of both type-I and -II receptors for BMPs and increased that of inhibitory Smad6 and Smad7 in granulosa cells. On the other hand, treatments with BMP-6 and -7 suppressed the expression of OX1 and OX2. Collectively, the results indicated that orexin A enhances FSH-induced progesterone production, at least in part, by downregulating BMP signaling in granulosa cells. Thus, a new role of orexin A in facilitating progesterone synthesis and functional interaction between the orexin and BMP systems in granulosa cells were revealed.

DOI： 10.1016/j.jsbmb.2018.03.004

PubMed

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Language：Japanese   Publishing type：Research paper (scientific journal)  

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Language：English   Publishing type：Research paper (bulletin of university, research institution)  

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：WILEY  

Acquired idiopathic chylous ascites is extremely rare in women of reproductive age. This is the first report describing successful infertility and pregnancy management in a patient with idiopathic chylous ascites. A 23-year-old woman presented with abdominal distention and was diagnosed with idiopathic fluid collection. A lymphogram revealed lymphatic leakage from the right renal hilum. Lymphatic-venous anastomosis of the thoracic duct was performed thrice, but the chylous ascites persisted. In vitro fertilization was performed because natural conception was not possible. Just prior to oocyte retrieval, transvaginal drainage of ascites was performed. In total, nine blastocysts were obtained and cryopreserved. Single frozen embryo transfer was performed, including hormone replacement therapy. The patient became pregnant and the ascites spontaneously decreased as the pregnancy progressed, finally disappearing around gestational week 20. A healthy baby was delivered transvaginally. Ascites began to reaccumulate on post-partum day 1 and returned to the pre-pregnancy level within a month.

DOI： 10.1111/jog.13434

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Language：Japanese   Publisher：(一社)日本内分泌学会  

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：OKAYAMA UNIV MED SCHOOL  

Vascular dysfunction has been reported in women with recurrent pregnancy loss (RPL). We investigated the severity of vascular dysfunction in non-pregnant women with RPL and its correlation with anti-heat shock protein (HSP) antibodies that are known to induce arteriosclerosis. We measured the serum anti-HSP60 antibodies, anti-HSP70 antibodies, and anti-phospholipid antibodies (APA) in 68 women with RPL and 29 healthy controls. Among the women with RPL, 14 had a diagnosis of antiphospholipid syndrome (APS), and in the remaining 54, the causes for RPL were unexplained. Compared to the controls, the brachial-ankle pulse wave velocity (baPWV), carotid augmentation index (cAI), and uterine artery pulsatility index (PI) were all significantly higher in the women with both APS and unexplained RPL. Compared to the controls, the anti-HSP60 antibody levels were significantly higher in the APA-positive group of women with unexplained RPL, and the anti-HSP70 antibody levels were significantly higher in APS and APA-positive group of women with unexplained RPL. However, the anti-HSP60 and anti-HSP70 antibody levels did not correlate with the values of baPWV or cAI. Our results demonstrated anti-HSP60 and anti-HSP70 antibodies are increased in women with unexplained RPL. Further studies are needed to elucidate the roles of anti-HSP antibodies and their pathophysiology in unexplained RPL.

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Language：Japanese   Publishing type：Research paper (scientific journal)   Publisher：中国四国産科婦人科学会  

近年40歳以下の若年子宮内膜癌患者は増加しており、その妊孕性温存が注目されている。我々は子宮内膜癌IA期発症後にmedroxyprogesterone acetate(MPA)による高用量黄体ホルモン療法後の再発に対し再度MPA療法を行い、生殖補助医療により生児を得た症例を経験したので報告する。症例は32歳女性既婚、未経妊。不正性器出血を主訴に前医を受診した。子宮内膜組織診でendometrioid adenocarcinoma、Grade 1と診断され、当科紹介となった。当院での精査で、子宮内膜癌IA期相当と診断、妊孕性温存希望のため、MPA療法を6ヵ月間行った。子宮内膜組織診で悪性所見の消失を確認後、妊娠を試みるも妊娠成立せず、初回治療から3年2ヵ月後に組織診断でendometrioid adenocarcinomaの再発が指摘された。依然挙児希望は強く、リスクを十分に説明した上で再度MPA療法を6ヵ月間行った。子宮内膜組織診で悪性所見の消失を確認し、不妊治療を再開した。生殖補助医療を選択し、GnRHアンタゴニスト法で14個の卵子を採取し体外受精した。受精後6日目に胚盤胞まで達した3AA胚1個を凍結した。子宮内膜組織診で陰性を確認後、ホルモン補充周期で凍結融解胚移植を行い、妊娠成立した。妊娠経過は順調で、妊娠40週4日に胎児機能不全の適応で帝王切開術を施行した。MPA療法は治療後1〜3年以内に再発する症例が多く、寛解後早期の不妊治療開始が推奨され、体外受精により妊娠する症例が多い。本症例のように子宮内膜癌再発後にMPA療法と生殖補助医療を行い、生児を得た症例の報告は散見されるが、本邦のガイドラインでは推奨されていないため、十分な説明と同意のもとに慎重に行われるべきである。(著者抄録)

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Other Link： https://search-tp.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2017&ichushi_jid=J05038&link_issn=&doc_id=20170612460016&doc_link_id=%2Fcv0mtrob%2F2016%2F006502%2F016%2F0217-0221%26dl%3D0&url=https%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fcv0mtrob%2F2016%2F006502%2F016%2F0217-0221%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

Authorship：Lead author   Publishing type：Research paper (conference, symposium, etc.)  

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：JAPAN ENDOCRINE SOC  

Polycystic ovary syndrome (PCOS) is a common endocrine disorder characterized by insulin resistance and hyperandrogenism. The interaction of these factors might result in increased risks of miscarriage and pregnancy complications such as gestational diabetes mellitus (GDM). To examine the pregnancy risks in women with PCOS, we compared obstetrical outcomes between patients with and without PCOS. We also studied the differences in maternal characteristics, glucose intolerance and pregnancy complications between PCOS patients with and without GDM, with and without obesity, and between successful pregnancies and miscarriages. We observed a high incidence of GDM and prevalence of GDM diagnosis in the first trimester in PCOS. Patients with GDM had higher body mass index (BMI) and lower homeostasis model assessment of beta-cell function (HOMA-beta) at preconception than those without GDM. Obese pregnant women with PCOS demonstrated a high incidence of GDM with severe insulin resistance, including high fasting insulin, HOMA of insulin resistance (HOMA-IR), and HOMA-beta at preconception compared with normal-weight patients. BMI was significantly correlated with HOMA-IR or HOMA-beta, and both indices were lower in PCOS patients with than without GDM for the same BMI. There were no significant differences in maternal characteristics (excluding maternal age) between PCOS patients with successful pregnancy and PCOS patients with miscarriages. Our data suggest that pregnant women with PCOS have an increased risk of GDM, especially if they have obesity and/or poorer insulin secretion. Measure of beta-cell function, such as HOMA-beta, at preconception might be a useful predictor of the risk of GDM in pregnant PCOS patients.

DOI： 10.1507/endocrj.EJ15-0364

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：WILEY  

AimAutonomic nervous system activity was studied to evaluate the physical and mental state of women with unexplained recurrent pregnancy loss (RPL).
MethodsHeart rate variability (HRV) is a measure of beat-to-beat temporal changes in heart rate and provides indirect insight into autonomic nervous system tone and can be used to assess sympathetic and parasympathetic tone. We studied autonomic nervous system activity by measuring HRV in 100 women with unexplained RPL and 61 healthy female volunteers as controls. The degree of mental distress was assessed using the Kessler 6 (K6) scale.
ResultsThe K6 score in women with unexplained RPL was significantly higher than in control women. HRV evaluated on standard deviation of the normal-to-normal interval (SDNN) and total power was significantly lower in women with unexplained RPL compared with control women. These indices were further lower in women with unexplained RPL 4. On spectral analysis, high-frequency (HF) power, an index of parasympathetic nervous system activity, was significantly lower in women with unexplained RPL compared with control women, but there was no significant difference in the ratio of low-frequency (LF) power to HF power (LF/HF), an index of sympathetic nervous system activity, between the groups.
ConclusionsThe physical and mental state of women with unexplained RPL should be evaluated using HRV to offer mental support. Furthermore, study of HRV may elucidate the risk of cardiovascular diseases and the mechanisms underlying unexplained RPL.

DOI： 10.1111/jog.12653

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Authorship：Corresponding author   Language：Japanese   Publishing type：Research paper (scientific journal)   Publisher：中国四国産科婦人科学会  

【目的】当科外来で施行する径3.8mmの子宮ファイバースコープによる検査(HFS)に関して、特に腹腔鏡下手術前に施行する有用性につき後方視的に検討した。【方法】不妊症や不育症、月経異常などの精査のため当科を受診した患者のうち、111例に説明と同意のもとにHFSを月経終了直後に施行した。そしてHFSの検査結果と患者の診療情報との関連につき解析を行った。【成績】HFS施行患者の年齢は35.0±5.0歳(mean±SD)で、うち未産婦が89例(80.2%)であった。主訴は、過多月経34例(30.6%)、不妊69例(62.2%)、反復流産35例(31.5%)など(重複有)であった。なお前医で子宮腔内病変を疑われ、当科を受診したのは65例(58.6%)であった。HFS結果は、異常なし38例(34.2%)、粘膜下筋腫24例(21.6%)、子宮内膜ポリープ33例(29.7%)、アッシャーマン症候群(子宮腔癒着症)15例(13.5%)など(重複有)であった。HFS前に超音波画像診断は全例に施行されており、感度80.8%、特異度57.9%で、14例(12.6%)はHFSでのみ異常を認めた。子宮卵管造影法は52例で同時期に施行されていたが、感度50.0%、特異度83.3%であり、17例(32.7%)はHFSでのみ異常を認めた。さらに111例中、腹腔鏡下手術を予定していた42例にHFSを施行したところ、新たな子宮腔内病変が判明したため、5例に対して子宮鏡下手術が追加された。HFSの合併症は、検査後の強い気分不良2例、検査継続困難な疼痛1例であり、子宮穿孔等の重篤な合併症はなかった。【結論】HFSは頸管拡張などの前処置が不要で、疼痛などの患者負担も少ない。そしてHFS施行により初めて得られる情報も多く、特に腹腔鏡下手術を予定する不妊症症例では術前に施行する意義の高い検査と考えられた。(著者抄録)

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Other Link： https://search-tp.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2015&ichushi_jid=J05038&link_issn=&doc_id=20150709460024&doc_link_id=%2Fcv0mtrob%2F2014%2F006302%2F024%2F0299-0303%26dl%3D0&url=https%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fcv0mtrob%2F2014%2F006302%2F024%2F0299-0303%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

Authorship：Lead author   Language：Japanese   Publishing type：Research paper (scientific journal)  

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Language：Japanese   Publishing type：Research paper (scientific journal)   Publisher：金原出版  

CiNii Article

CiNii Books

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Other Link： http://search.jamas.or.jp/link/ui/2015407185

DOI： 10.11477/mf.1409103611

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Language：Japanese   Publishing type：Research paper (scientific journal)  

CiNii Article

CiNii Books

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Other Link： http://search.jamas.or.jp/link/ui/2015075867

Language：Japanese   Publisher：金原出版  

CiNii Article

CiNii Books

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Other Link： http://search.jamas.or.jp/link/ui/2014106777

Language：English   Publishing type：Research paper (scientific journal)   Publisher：WILEY-BLACKWELL  

Aim: Male-to-female (MTF) transsexuals are treated with estrogen with and without progestin through a variety of routes. The aim of this study is to evaluate the arterial stiffness in MTF transsexuals undergoing hormonal treatment. Methods: We evaluated the arterial stiffness in 156 MTF transsexuals (22 untreated and 129 treated with estrogen only or plus progestin) using a volume-plethysmographic apparatus equipped with a multi-element applanation tonometry sensor. Results: MTF transsexuals treated with parenteral estrogen were significantly older than untreated MTF transsexuals. Hematocrit, uric acid and activated partial thromboplastin time in treated MTF transsexuals were significantly lower than in untreated MTF transsexuals. The level of high-density lipoprotein cholesterol in MTF transsexuals treated with oral estrogen was significantly higher than in untreated MTF transsexuals or those treated with parenteral estrogen with and without progestin. The systolic blood pressure in MTF transsexuals treated with estrogen only is significantly lower than that in untreated MTF transsexuals. The brachialankle pulse wave velocity was significantly decreased in MTF transsexuals treated with estrogen compared to that in untreated MTF transsexuals or in those treated with estrogen plus progestin. The carotid augmentation index in MTF transsexuals treated with oral estrogen was significantly lower than that in MTF transsexuals treated with parenteral estrogen or oral estrogen plus progestin. Conclusions: Estrogen treatment is likely to have some beneficial effects on lipid metabolism and vascular function in MTF transsexuals; however, progestin administered with estrogen may have adverse effects on arterial stiffness.

DOI： 10.1111/j.1447-0756.2011.01815.x

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Language：Japanese   Publishing type：Research paper (scientific journal)  

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Language：Japanese   Publishing type：Research paper (scientific journal)  

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Language：Japanese   Publishing type：Research paper (scientific journal)  

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：WILEY-BLACKWELL  

Aim:
Although risk factors for cardiovascular disease, such as obesity, hyperinsulinemia, and dyslipidemia, are commonly observed in women with polycystic ovary syndrome (PCOS), impairment of vascular function is still controversial. We evaluated the vascular function in young women with PCOS.
Methods:
We evaluated arterial stiffness in 54 women with PCOS and 24 healthy control women using a volume-plethysmographic apparatus equipped with a multi-element applanation tonometry sensor for the left common carotid artery and studied the correlations of various factors.
Results:
There was no significant difference in age or body mass index between the controls and the women with PCOS. These women with PCOS had a significantly higher serum testosterone and C-reactive protein levels and showed insulin resistance and dyslipidemia. The mean blood pressure in women with PCOS was within the normal range, but still significantly higher than those in the controls. Women with PCOS had a significantly higher brachial-ankle pulse wave velocity (baPWV) than that for the controls (P &lt; 0.02), whereas there was no significant difference in the carotid augmentation index between the two groups. Stepwise multiple regression analysis revealed that blood pressure influences the baPWV in women with PCOS. Arterial stiffness evaluated using the baPWV in mildly-hypertensive women (systolic blood pressure &gt;= 120 mmHg or diastolic blood pressure &gt;= 90 mmHg) with PCOS was significantly higher than that in the controls or normotensive women with PCOS.
Conclusions:
Early changes in vascular function were detected in mildly-hypertensive women with PCOS. Lifestyle interventions to prevent hypertension, such as diet and exercise, should be the first-line of treatment in women with PCOS.

DOI： 10.1111/j.1447-0756.2010.01375.x

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We report a rare case of polycystic ovary syndrome (PCOS) complicated with acromegaly due to a growth hormone (GH)-producing pituitary adenoma. Complete removal of the pituitary adenoma Successfully reduced circulating levels of GH and insulin-like growth factor (IGF)-1, which, in turn, resulted in the amelioration of gonadal dysfunction, hyperandrogenism, lutenizing hormone hypersecretion, and severe insulin resistance. This clinical complication suggests that activation of systemic GH-IGF-1 axis is potentially involved in the development of PCOS.

DOI： 10.1507/endocrj.K08E-215

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：OKAYAMA UNIV MED SCHOOL  

We studied the effects of advanced glycation end products (AGEs), which are known to accumulate in patients with diabetes, autoimmune diseases, or those who smoke, on embryonal development. Pronuclear (PN) embryos were obtained by flushing the fallopian tubes of rats after superovulation and mating. The cleavage rate and blastocyst yield were evaluated at 24, 72, 96, and 120 h of culture. Glyoxal, an AGE-forming aldehyde, suppressed embryonal development at every stage from PN to blastocyst in a concentration-dependent manner. The cleavage rate of the embryo was also significantly decreased by treatment with glyoxal at concentrations of 1 mM or higher. The blastocyst yield was significantly decreased by treatment with glyoxal at concentrations of 0.5 mM or higher. N-acetyl-L-cysteine (L-NAC) at I mM significantly suppressed the glyoxal-induced embryonal toxicity. BSA-AGEs at 5 mu g/ml or higher concentration significantly reduced the cleavage rate and blastocyst yield compared to those for BSA-treated embryos. L-NAC at I mM significantly suppressed BSA-AGE-induced embryonal toxicity. Because AGEs are embryo-toxic, AGE contamination may influence the pregnancy rate of in vitro fertilization and embryo transfer. AGEs, which are increased in women under pathological conditions, may also be involved in their infertility.

DOI： 10.18926/AMO/30960

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Language：Japanese   Publisher：(一社)日本生殖医学会  

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Language：Japanese   Publisher：Okayama Medical Association  

DOI： 10.4044/joma.119.315

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Other Link： http://search.jamas.or.jp/link/ui/2008137203

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Other Link： http://search.jamas.or.jp/link/ui/2009005747

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DOI： 10.11477/mf.1409101464

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DOI： 10.11477/mf.1409101465

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Advanced glycation end products (AGEs) are known to cause oxidative damage in various cells by binding with its receptor, RAGE. We measured the serum level of AGEs and examined the AGEs, RAGE, and the other biomarkers of oxidative stress in the placentas from preeclamptic women.
Competitive ELISA was carried out to measure the AGEs in serum. Western blotting was performed to analyze AGEs and RAGE in the placenta. Immunohistochemical analyses were performed to examine the localization of AGEs, RAGE, and other biomarkers of oxidative stress in the placenta.
The mean level of serum AGEs in preeclamptic women was significantly higher than that in healthy non-pregnant women or healthy pregnant women. Western blotting revealed that the level of AGEs or RAGE in preeclamptic placenta was significantly higher than that in normal placenta. Immunohistochemical analyses showed that levels of nitrotyrosine and nitroguanosine, which are formed by reactive nitrogen species, in preeclamptic placenta were higher than those in normal placenta. Accumulation of 4-hydroxy-2-nonenal and 8-hydroxy-2'-deoxyguanosine indicated enhanced oxidative modifications of lipids and DNA in preeclamptic placenta.
The AGE-RAGE system, which is upregulated in preeclampsia, is likely to be involved in the oxidative stress of preeclampsia. (c) 2005 Elsevier Ltd. All rights reserved.

DOI： 10.1016/j.placenta.2005.02.016

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Tetrahydrobiopterin is a necessary cofactor for the synthesis of nitric oxide by the hemeprotein enzyme, NO-synthase (NOS). It is widely thought that inadequate levels of tetrahydrobiopterin lead to tissue injury and organ dysfunction due, in part, to formation of superoxide from pterin-deficient NOS. In the course of studies on the ubiquitylation of neuronal NOS (nNOS), we have found that certain substrate analogs, such as N-G-nitro-L-arginine, stabilize the dimeric form of nNOS and protect the enzyme from ubiquitylation. Since tetrahydrobiopterin is known to bind near heme and confers stability to the active dimeric structure of nNOS, we wondered if the loss of tetrahydrobiopterin could be an endogenous signal for nNOS ubiquitylation and degradation. We show here in HEK293 cells stably transfected with nNOS that depletion of tetrahydrobiopterin by treatment with 2,4-diamino-6-hydroxypyrimidine leads to destabilization of the dimeric form and enhances ubiquitylation of nNOS. Sepiapterin, a precursor to tetrahydrobiopterin in the salvage pathway, completely reverses the effect of 2,4-diamino-6-hydroxypyrimidine on nNOS ubiquitylation. Consistent with that found in cells, the in vitro ubiquitylation of nNOS by reticulocyte proteins decreases when tetrahydrobiopterin is present. Thus, inadequate amounts of tetrahydrobiopterin may lead to a sustained decrease in the steady state level of nNOS that is not readily reversed. (c) 2005 Elsevier B.V. All rights reserved.

DOI： 10.1016/j.molbrainres.2005.09.003

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Background. Risk factors for cardiovascular disease, including chronic anovulation, obesity, hyperandrogenism, hyperinsulinemia, and dyslipidemia, are commonly observed in women with polycystic ovary syndrome (PCOS). We evaluated uterine perfusion and its correlation with clinical and biochemical parameters in women with PCOS.
Methods. We performed a pulsed Doppler study on uterine arterial blood flow in 25 women with PCOS and 45 control women with regular menstrual cycles. PCOS was diagnosed based on oligomenorrhea, polycystic ovaries determined by means of ultrasonography, and elevated luteinizing hormone (LH)/follicle-stimulating hormone (FSH) ratio.
Results. Women with PCOS had a significantly higher body mass index (BMI) and serum testosterone, and showed insulin resistance and dyslipidemia, including increased total cholesterol, triglyceride, low-density lipoprotein-cholesterol (LDL-C), and decreased high-density lipoprotein-cholesterol (HDL-C). The uterine arterial pulsatility index (PI) in women with PCOS was significantly higher than that in the control women during the follicular phase. The PI was correlated with BMI, LH/FSH ratio, or LDL-C/HDL-C ratio, whereas it was inversely correlated with the HDL-C level. Women with PCOS had reduced endometrial thickness and elevated uterine arterial PI in the luteal phase, in which implantation occurs.
Conclusions. Elevation of uterine arterial blood flow resistance is associated with risk factors for cardiovascular events. Furthermore, the impaired uterine perfusion in the luteal phase may cause endometrial dysfunction in women with PCOS.

DOI： 10.1111/j.0001-6349.2005.00678.x

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Language：Japanese   Publisher：永井書店  

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It is established that neuronal NO synthase (nNOS) is ubiquitinated and proteasomally degraded. The metabolism-based inactivation of nNOS and the inhibition of heat shock protein 90 (hsp90)-based chaperones, which are known to regulate nNOS, both lead to enhanced proteasomal degradation of nNOS. The mechanism of this selective proteolytic degradation, or in essence how the nNOS becomes labilized and recognized for ubiquitination and subsequent degradation, has not been determined. In the current study, we used a crude preparation of reticulocyte proteins, which contains ubiquitin-conjugating enzymes and the proteasome, to determine how nNOS is labilized. We found that the inactive monomeric heme-deficient nNOS (apo-nNOS) is rapidly degraded in vitro, consistent with the finding that both metabolism-based inactivation and inhibition of hsp90-based chaperones cause the formation of apo-nNOS and enhance its degradation in vivo. In the current study, we discovered that destabilization of the dimeric nNOS, as determined by measuring the SDS-resistant dimer, is sufficient to trigger ubiquitin-proteasomal degradation. Treatment of nNOS with NG-nitro-L-arginine or 7-nitroindazole led to stabilization of the dimeric nNOS and decreased proteasomal degradation of the enzyme, consistent with that observed in cells. Thus, it seems that the dimeric structure is a major determinant of nNOS stability and proteolysis.

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Language：English   Publishing type：Research paper (international conference proceedings)   Publisher：MEDIMOND PUBLISHING CO  

We evaluated the uterine arterial blood flow resistance (pulsatility index:PI) by transvaginal pulsed Doppler ultrasonography of women with recurrent pregnancy loss (RPL). We also measured concentrations of plasma adrenomedullin or serum thrombomodulin, biomarkers for vascular dysfunction, of these women. Both plasma adrenomedullin concentration and uterine arterial PI of a non-pregnant cycle were significantly high in women with antiphospholipid antibodies (APA) in RPL group. Plasma level of adrenomedullin had a significant positive correlation with uterine arterial PI. Women in the RPL group had significantly higher uterine arterial PI at 4-5 weeks of gestation as compared with women in the control group. Pregnant women with APA and increased serum thrombomodulin in their early gestation resulted in fetal growth restriction.

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：ELSEVIER SCIENCE BV  

Nafamostat mesilate (NM), a clinically used serine protease inhibitor, Suppressed the overproduction of nitric oxide (NO) and the expression of inducible nitric oxide synthase (iNOS) in RAW264.7 murine macrophages treated with lipopolysaccharide (LPS, 100 ng/ml); however, it had little effect oil endothelial NOS (eNOS) in human umbilical vein endothelial cells (HUVEC). Electrophoretic mobility shift assay (EMSA) revealed that LPS activated nuclear factor-kappaB (NF-kappaB) in RAW264.7 cells and that this activation was suppressed by nafamostat mesilate. Western blotting showed that nafamostat mesilate suppressed the phosphorylation and degradation of inhibitor kappaB-alpha (IkappaB-alpha), which holds NF-kappaB in the cytoplasm in an inactivated state. Our observations suggest that nafamostat mesilate is a candidate agent for various diseases such as ischemia-reperfusion, graft rejection, inflammatory diseases, and autoimmune diseases, in which iNOS and/or NF-kappaB are upregulated. (C) 2003 Elsevier B.V. All rights reserved.

DOI： 10.1016/S1567-5769(03)00146-2

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It has been shown that administration of cigarette smoke to rats leads to loss of neuronal nitric-oxide synthase (nNOS) activity and nNOS protein in penile tissue. The exact mechanism for this loss of activity and protein is not known. In the current study, we investigated whether extracts prepared from cigarette smoke or from the cigarette itself could directly inhibit nNOS activity. We discovered that the cigarette smoke extract and the cigarette extract cause a time-, concentration-, and calmodulin-dependent inactivation of nNOS in an in vitro system containing the purified enzyme. L-Arginine, but not D-arginine, protects nNOS from this time-dependent inactivation, suggesting an active site directed event. The kinetics of inactivation are consistent with the metabolism-based or suicide inactivation of nNOS. Based on studies with other metabolism-based inactivators, this cigarette-mediated inactivation may render nNOS more susceptible to proteasomal degradation and thereby may explain the loss of nNOS protein in vivo. The component(s) responsible for nNOS inactivation is not volatile, is not retained by a 3,000 molecular weight cut-off membrane, binds to activated charcoal, and is highly water-soluble under both acidic and basic conditions. The discovery of a direct inactivation of nNOS by an organic, cationic compound(s) present in tobacco and tobacco smoke provides a basis for further study of not only the mechanisms responsible for the biological effects of tobacco but also a search for a potentially novel inactivator of nNOS.

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Language：Japanese   Publisher：医学書院  

DOI： 10.11477/mf.1409100824

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Other Link： http://search.jamas.or.jp/link/ui/2004134268

Language：English   Publishing type：Research paper (scientific journal)   Publisher：ELSEVIER SCIENCE INC  

The heme prosthetic group of NO synthase is critical for catalytic activity as well as assembly of the enzyme to the native homodimeric form. In the current study, we examined if structurally different metal porphyrins could substitute for the native heme prosthetic group in neuronal NO synthase (nNOS) with regard to assembly and catalysis. We established, with the use of a recently developed in vitro method that functionally reconstitutes heme-deficient apo-nNOS, that Fe-mesoporphyrin IX or Fe-deuteroporphyrin IX can substitute for heme and lead to assembly of a functional nNOS, albeit with lower activity. Fe-protoporphyrin IX dimethyl ester or the metal free protoporphyrin IX, however, lead to minimal assembly of nNOS. Protoporphyrin IX compounds where the native Fe was substituted with Zn, Mn, Co, or Sn lead to assembly of nNOS, but no detectable NO was synthesized in the presence of NADPH and L-arginine. Thus, the presence of the metal and propionic acid groups, but not the vinyl moieties, of heme are important structural features in assembly of nNOS. These studies establish that the mechanism of assembly and catalysis of nNOS can be probed with structurally diverse metal porphyrins. (C) 2002 Elsevier Science Inc. All rights reserved.

DOI： 10.1016/S0162-0134(02)00430-0

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS  

It is established that N-G-amino-L-arginine (NAA) is a metabolism-based inactivator of all three major nitric-oxide synthase (NOS) isoforms. The mechanism by which this inactivation occurs, however, is not well understood. In the current study, we discovered that inactivation of the neuronal isoform of NOS (nNOS) by NAA in vitro results in covalent alteration of the heme prosthetic group, in part, to products that contain an intact porphyrin ring and are either dissociable from or irreversibly bound to the protein. The alteration of the heme is concomitant with the loss of nNOS activity. Studies with nNOS containing a C-14-labeled prosthetic heme moiety indicate that the major dissociable product and the irreversibly bound heme adduct account for 21 and 28%, respectively, of the heme that is altered. Mass spectral analysis of the major dissociable product gave a molecular ion of m/z 775.3 that is consistent with the mass of an adduct of heme and NAA minus a hydrazine group. Peptide mapping of the irreversibly bound heme adduct indicates that the heme is bound to a residue in the oxygenase domain of nNOS. We show for the first time that metabolism-based inactivation of nNOS occurs in vivo as highly similar heme products are formed. Because inactivation and alteration may trigger ubiquitination and proteasomal degradation of nNOS, NAA may be a useful biochemical tool for the study of these basic regulatory processes.

DOI： 10.1124/mol.62.1.110

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC  

It is established that neuronal NO synthase (nNOS) is associated with the chaperone hsp90, although the functional role for this interaction has not been defined. We have discovered that inhibition of hsp90 by radicicol or geldanamycin nearly prevents the heme-mediated activation and assembly of heme-deficient apo-nNOS in insect cells. This effect is concentration-dependent with over 75% inhibition achieved at 20 pm radicicol. The ferrous carbonyl complex of nNOS is not formed when hsp90 is inhibited, indicating that functional heme insertion is prevented. We propose that the hsp90-based chaperone machinery facilitates functional heme entry into apo-nNOS by the opening of the hydrophobic heme-binding cleft in the protein. Previously, it has been reported that the hsp90 inhibitor geldanamycin uncouples endothelial NOS activity and increases endothelial NOS-dependent O-2(.-) production. Geldanamycin is an ansamycin benzoquinone, and we show here that it causes oxidant production from nNOS in insect cells as well as with the purified protein. At a concentration of 20 mum, geldanamycin causes a 3-fold increase in NADPH oxidation and hydrogen peroxide formation from purified nNOS, whereas the non-quinone hsp90 inhibitor radicicol had no effect. Thus, consistent with the known propensity of other quinones, geldanamycin directly redox cycles with nNOS by a process independent of any action on hsp90, cautioning against the use of geldanamycin as a specific inhibitor of hsp90 in redox-active systems.

DOI： 10.1074/jbc.M201940200

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Mosby Inc.  

We measured the total concentration of nitrite and nitrate, metabolites of nitric oxide, in vaginal secretions from pregnant women at 22 to 32 weeks' gestation. Total nitrite and nitrate concentrations in patients with preterm premature rupture of membranes and in those with preterm labor and subsequent premature delivery were significantly higher than concentrations in patients who were delivered at term. Elevated total nitrite and nitrate concentration may predict premature delivery.

DOI： 10.1067/mob.2000.104223

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Objective: To make a prognosis for pregnant women with uterine cervical cancer. Subjects and Methods: Thirty-two women with cervical cancer diagnosed during pregnancy were treated at Okayama University Hospital between 1976 and 1995. Results: Squamous cell carcinoma was detected in the majority of these patients (93.7%). Approximately 80% of them were in an early stage (stage 0 or Ia). The number of patients in an early stage increased in the 10 years from 1986 to 1995 compared with the ten years from 1976 to 1985. More than half of the patients were diagnosed by a positive cervical smear without symptoms. We carried out conization in all of 16 patients who hoped to maintain gestation. Although 2 patients had preterm labor and in one patient there was fetal death at 14 weeks, 15 patients had term delivery. On pathological examination of specimens, residual neoplastic lesion was suspected in 42% of the patients in stage 0 and in all patients in stage Ia, but most of them were considered to be in an earlier stage. Pregnancy did not affect the five year survival rate of the patients with cervical cancer detected in an early stage. Conclusion: Our results suggest that pregnant women with cervical cancer in an early stage (0 and Ia) can be treated without termination of pregnancy.

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The reaction of nitric oxide (NO) and superoxide results in the formation of peroxynitrite, a potent and relatively long-lived oxidant. In infectious diseases, these molecules are not only bactericidal but also toxic to host cells. Chorioamnionitis is often complicated by premature rupture of membranes and can be associated with placental abruption. These diseases are significant causes of premature low-birth-weight deliveries and consequently the morbidity and mortality of neonates. Lipopolysaccharide, bacterial endotoxin, is known to be elevated in the amniotic fluid of patients with chorioamnionitis. Lipopolysaccharide is known to induce the formation of NO and superoxide. We report here that nitrite/nitrate, stable metabolites of NO, were increased in serum from patients with chorioamnionitis. Immunohistochemical studies demonstrated enhanced expression of inducible NO synthase and formation of nitrotyrosine, a footprint of peroxynitrite, in the placentae from patients with chorioamnionitis and also in patients with placental abruption. Furthermore, apoptotic cell death was also increased in the placentae from patients with both diseases. These results suggest that chorioamnionitis and a portion of placental abruption may share a common cascade of placental injury. Nitric oxide and its metabolites may play an important role in this cascade.

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：KARGER  

Isosorbide dinitrate (ISDN), a nitric oxide donor, was applied transdermally for 4-16 days to 4 preeclamptic women with oligohydramnios, intrauterine fetal growth retardation (IUGR), and elevated resistance of blood flow in the uterine arteries. Pulsed Doppler ultrasonography revealed immediate and drastic improvement of pulsatility index (PI) of uterine arteries following treatment with ISDN, The average PI in uterine arteries of the 4 patients was reduced to approximately 67% of that of the untreated state. In 2 patients the amniotic fluid gradually increased over a few days which suggested improvement of fetoplacental circulation during administration of ISDN, This study suggests that long-term transdermal ISDN is an effective therapy, at least in a portion of preeclamptic women, to avoid maternal hypertension, fetal distress, oligohydramnios, and IUGR, and consequentially to prolong the gestational period.

DOI： 10.1159/000010055

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Language：Japanese   Publisher：(一社)日本生殖医学会  

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Language：Japanese   Publisher：[広島] : 日本産科婦人科学会中国四国合同地方部会  

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Language：Japanese   Publisher：[広島] : 日本産科婦人科学会中国四国合同地方部会  

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Other Link： https://search.jamas.or.jp/link/ui/2024074672

Language：Japanese   Publisher：(一社)日本女性医学学会  

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Language：Japanese   Publisher：(一社)日本女性医学学会  

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Language：Japanese   Publisher：中国四国産科婦人科学会  

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Language：Japanese   Publisher：(株)メジカルビュー社  

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Language：Japanese   Publisher：日本女性栄養・代謝学会  

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Language：Japanese   Publisher：(一社)日本産科婦人科内視鏡学会  

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Event date： 2021

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Event date： 2020.11.9 - 2020.11.23

Language：Japanese   Presentation type：Symposium, workshop panel (public)  

Venue：WEB開催  

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Event date： 2020.8

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Event date： 2020.4.23 - 2020.4.28

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Venue：WEB開催  

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Event date： 2019.11.13 - 2019.11.16

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Venue：奈良春日野国際フォーラム甍 ?I・RA・KA?  

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Event date： 2019.11.2 - 2019.11.3

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Venue：ヒルトン福岡シーホーク  

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Event date： 2019.5.29

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Venue：鹿児島大学医学部 鶴陵会館「中会議室」  

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Event date： 2019.4.11 - 2019.4.14

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Venue：名古屋国際会議場  

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Event date： 2023.4

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Event date： 2022.11.11 - 2022.11.12

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Event date： 2022.10.1

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Event date： 2022.10

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Event date： 2022.10

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Event date： 2022.9.8 - 2022.9.10

Presentation type：Oral presentation (general)  

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Event date： 2022.9

Language：Japanese  

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Event date： 2022.8.28

Presentation type：Oral presentation (general)  

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Event date： 2022.8.28

Presentation type：Oral presentation (general)  

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Event date： 2022.8.28

Presentation type：Oral presentation (general)  

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Event date： 2022.6

Language：Japanese  

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Event date： 2022.4.16

Presentation type：Oral presentation (general)  

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Event date： 2022.2

Language：Japanese  

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Event date： 2022.2

Language：English  

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Event date： 2022.2

Language：English  

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Event date： 2022.2

Language：English  

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Event date： 2022.2

Language：English  

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Event date： 2022.2

Language：English  

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Event date： 2022

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Event date： 2022

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Event date： 2022

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Event date： 2021.11.11 - 2021.11.12

Presentation type：Poster presentation  

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Event date： 2021.11.11 - 2021.11.12

Presentation type：Oral presentation (general)  

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Event date： 2021.11.11 - 2021.11.12

Presentation type：Poster presentation  

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Event date： 2021.10

Language：Japanese  

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Event date： 2021.10

Language：Japanese  

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Event date： 2021.10

Language：Japanese  

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Event date： 2021.9.18 - 2021.9.19

Presentation type：Oral presentation (general)  

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Event date： 2021.9.18 - 2021.9.19

Presentation type：Oral presentation (general)  

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Event date： 2021.9.18 - 2021.9.19

Presentation type：Oral presentation (general)  

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Event date： 2021.9.11 - 2021.9.13

Presentation type：Oral presentation (general)  

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Event date： 2021.9.11 - 2021.9.13

Presentation type：Oral presentation (general)  

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Event date： 2021.9.3 - 2021.9.4

Presentation type：Oral presentation (general)  

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Event date： 2021.9

Language：Japanese  

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Event date： 2021.9

Language：Japanese  

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Event date： 2021.6.26 - 2021.6.27

Presentation type：Oral presentation (general)  

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Event date： 2021.4.22 - 2021.4.25

Presentation type：Poster presentation  

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Event date： 2021.4.22 - 2021.4.25

Presentation type：Poster presentation  

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Event date： 2021.4.22 - 2021.4.25

Presentation type：Poster presentation  

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Event date： 2021.4.22 - 2021.4.25

Presentation type：Poster presentation  

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Event date： 2021.4.22 - 2021.4.24

Presentation type：Poster presentation  

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Event date： 2021.4

Language：Japanese  

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Event date： 2021.4

Language：Japanese  

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Event date： 2021.3.20 - 2021.3.23

Language：English   Presentation type：Poster presentation  

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Event date： 2021.3

Language：Japanese  

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Event date： 2021.3

Language：Japanese  

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Event date： 2021.3

Language：Japanese  

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Event date： 2021.2.11

Presentation type：Poster presentation  

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Event date： 2021.1.29 - 2021.2.11

Presentation type：Poster presentation  

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Event date： 2020.12.14 - 2020.12.28

Language：Japanese   Presentation type：Oral presentation (general)  

Venue：WEB開催  

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Event date： 2020.12.12 - 2020.12.25

Language：Japanese   Presentation type：Oral presentation (general)  

Venue：WEB開催  

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Event date： 2020.12.3 - 2020.12.4

Language：Japanese   Presentation type：Oral presentation (general)  

Venue：WEB開催  

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Event date： 2020.12.3 - 2020.12.4

Language：Japanese   Presentation type：Oral presentation (general)  

Venue：WEB開催  

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Event date： 2020.11

Language：Japanese  

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Event date： 2020.11

Language：Japanese  

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Event date： 2020.11

Language：Japanese  

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Event date： 2020.8

Language：Japanese  

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Event date： 2020.8

Language：Japanese  

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Event date： 2020.6.4 - 2020.6.6

Language：Japanese   Presentation type：Poster presentation  

Venue：WEB開催  

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Event date： 2020.4.23 - 2020.4.28

Language：English   Presentation type：Poster presentation  

Venue：WEB開催  

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Event date： 2020.4.23 - 2020.4.28

Language：English   Presentation type：Poster presentation  

Venue：WEB開催  

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Event date： 2020.4

Language：Japanese  

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Event date： 2020.2.22 - 2020.2.23

Language：Japanese   Presentation type：Symposium, workshop panel (public)  

Venue：メルパルク京都  

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Event date： 2020.2.22 - 2020.2.23

Language：Japanese   Presentation type：Oral presentation (general)  

Venue：メルパルク京都  

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Event date： 2020.2

Language：Japanese  

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Event date： 2020.1.18 - 2020.1.19

Language：Japanese   Presentation type：Oral presentation (general)  

Venue：海峡メッセ下関  

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Event date： 2020.1.18 - 2020.1.19

Language：Japanese   Presentation type：Oral presentation (general)  

Venue：海峡メッセ下関  

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Event date： 2020.1.11 - 2020.1.12

Language：Japanese   Presentation type：Oral presentation (general)  

Venue：砂防会館別館会議室  

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Event date： 2019.11.17

Language：Japanese   Presentation type：Oral presentation (general)  

Venue：川崎医科大学 別館6階 大会議室  

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Event date： 2019.11.7 - 2019.11.8

Language：Japanese   Presentation type：Poster presentation  

Venue：神戸国際会議場、神戸国際展示場  

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Event date： 2019.11.7 - 2019.11.8

Language：Japanese   Presentation type：Oral presentation (general)  

Venue：神戸国際会議場、神戸国際展示場  

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Event date： 2019.11.2 - 2019.11.3

Language：Japanese   Presentation type：Oral presentation (general)  

Venue：ヒルトン福岡シーホーク  

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Event date： 2019.10

Language：Japanese  

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Event date： 2019.10

Language：Japanese  

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Event date： 2019.10

Language：Japanese  

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Event date： 2019.9.21 - 2019.9.22

Language：Japanese   Presentation type：Oral presentation (general)  

Venue：米子コンベンションセンター  

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Event date： 2019.9.12 - 2019.9.14

Language：Japanese   Presentation type：Oral presentation (general)  

Venue：国立京都国際会館  

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Event date： 2019.9.12 - 2019.9.14

Language：Japanese   Presentation type：Oral presentation (general)  

Venue：国立京都国際会館  

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Event date： 2019.8.31

Language：Japanese   Presentation type：Oral presentation (general)  

Venue：TKPガーデンシティ岡山  

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Event date： 2019.8

Language：Japanese  

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Event date： 2019.8

Language：Japanese  

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Event date： 2019.8

Language：Japanese  

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Event date： 2019.7.20

Language：Japanese  

Venue：岡山大学鹿田キャンパス 臨床講義棟2階臨床第2講義室  

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Event date： 2019.5.15

Language：Japanese   Presentation type：Oral presentation (invited, special)  

Venue：リーガロイヤルホテル新居浜  

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Event date： 2019.5.9 - 2019.5.11

Language：Japanese   Presentation type：Poster presentation  

Venue：仙台国際センター  

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Event date： 2019.4.11 - 2019.4.14

Language：English   Presentation type：Poster presentation  

Venue：名古屋国際会議場  

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Event date： 2019.4

Language：Japanese  

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Event date： 2019.4

Language：Japanese  

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Event date： 2019.3.13

Language：Japanese   Presentation type：Oral presentation (invited, special)  

Venue：鳥取ワシントンホテルプラザ  

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Event date： 2019.2.9 - 2019.2.10

Language：Japanese   Presentation type：Oral presentation (general)  

Venue：じゅうろくプラザ(岐阜市文化産業交流センター)  

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Event date： 2019.2.2 - 2019.2.3

Language：Japanese   Presentation type：Oral presentation (general)  

Venue：都市センターホテル  

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Event date： 2019.2.2 - 2019.2.3

Language：Japanese  

Venue：都市センターホテル  

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Event date： 2019.1.19 - 2019.1.20

Language：Japanese   Presentation type：Oral presentation (general)  

Venue：虎ノ門ヒルズフォーラム  

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Event date： 2019.1

Language：Japanese  

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Event date： 2018.11.24 - 2018.11.25

Language：Japanese   Presentation type：Oral presentation (general)  

Venue：日本医科大学 千駄木校舎  

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Event date： 2018.11.18

Language：Japanese   Presentation type：Oral presentation (general)  

Venue：岡山県医師会館 三木記念ホール  

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Event date： 2018.9.12

Language：Japanese   Presentation type：Oral presentation (invited, special)  

Venue：ホテルセンチュリー21広島 4階「クリスタル」  

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Event date： 2018.8.25

Language：Japanese   Presentation type：Oral presentation (general)  

Venue：岡山国際交流センター  

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Event date： 2018.8.2 - 2018.8.4

Language：Japanese   Presentation type：Oral presentation (general)  

Venue：島根県民会館、サンラポーむらくま  

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Event date： 2018.8

Language：Japanese  

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Event date： 2018.7.24

Language：Japanese   Presentation type：Oral presentation (invited, special)  

Venue：グリーンヒルホテル尾道  

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Event date： 2018.6

Language：Japanese  

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Event date： 2018.5.24

Language：Japanese   Presentation type：Oral presentation (invited, special)  

Venue：福山ニューキャッスルホテル  

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Event date： 2018.5.10 - 2018.5.13

Language：English   Presentation type：Poster presentation  

Venue：仙台国際センター、東北大学百周年記念会館川内萩ホール  

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Event date： 2018.5.10 - 2018.5.13

Language：English   Presentation type：Poster presentation  

Venue：仙台国際センター、東北大学百周年記念会館川内萩ホール  

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Event date： 2018.5.10 - 2018.5.13

Language：English   Presentation type：Poster presentation  

Venue：仙台国際センター、東北大学百周年記念会館川内萩ホール  

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Event date： 2018.5.10 - 2018.5.13

Language：English   Presentation type：Poster presentation  

Venue：仙台国際センター、東北大学百周年記念会館川内萩ホール  

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Event date： 2018.5.10 - 2018.5.13

Language：Japanese   Presentation type：Poster presentation  

Venue：仙台国際センター、東北大学百周年記念会館川内萩ホール  

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Event date： 2018.4

Language：Japanese  

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Event date： 2018.3.17 - 2018.3.20

Language：English   Presentation type：Oral presentation (general)  

Venue：McCormick Place West Chicago Illinois  

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Event date： 2018.2.11

Language：Japanese   Presentation type：Poster presentation  

Venue：御茶ノ水ソラシティ カンファレンスセンター 2Fホール  

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Event date： 2018.2.10

Language：Japanese   Presentation type：Symposium, workshop panel (public)  

Venue：TKPガーデンシティ品川 1F「グリーンウィンド」  

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Event date： 2018.2

Language：Japanese  

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Event date： 2018.2

Language：Japanese  

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Event date： 2018.1.27 - 2018.1.28

Language：Japanese   Presentation type：Symposium, workshop panel (public)  

Venue：メルパルク京都  

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Event date： 2018.1.27 - 2018.1.28

Language：Japanese   Presentation type：Oral presentation (general)  

Venue：メルパルク京都  

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Event date： 2017.11.25 - 2017.11.26

Language：Japanese   Presentation type：Oral presentation (general)  

Venue：大阪国際交流センター  

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Event date： 2017.11.19

Language：Japanese   Presentation type：Oral presentation (general)  

Venue：川崎医科大学 現代医学教育博物館  

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Event date： 2017.11.16 - 2017.11.17

Language：Japanese   Presentation type：Oral presentation (general)  

Venue：海峡メッセ下関  

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Event date： 2017.11.16 - 2017.11.17

Language：Japanese   Presentation type：Oral presentation (general)  

Venue：海峡メッセ下関  

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Event date： 2017.11.16 - 2017.11.17

Language：Japanese   Presentation type：Oral presentation (general)  

Venue：海峡メッセ下関  

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Event date： 2017.11.4 - 2017.11.5

Language：Japanese   Presentation type：Poster presentation  

Venue：リーガロイヤルホテル大阪、大阪国際会議場  

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Event date： 2017.9.23 - 2017.9.24

Language：Japanese   Presentation type：Oral presentation (general)  

Venue：広島県医師会館  

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Event date： 2017.9.23 - 2017.9.24

Language：Japanese   Presentation type：Oral presentation (general)  

Venue：広島県医師会館  

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Event date： 2017.9.7 - 2017.9.9

Language：Japanese   Presentation type：Oral presentation (general)  

Venue：岡山コンベンションセンター、岡山県医師会館  

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Event date： 2017.9.7 - 2017.9.9

Language：Japanese   Presentation type：Oral presentation (general)  

Venue：岡山コンベンションセンター、岡山県医師会館  

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Event date： 2017.8.26

Language：Japanese   Presentation type：Poster presentation  

Venue：千葉大学医学部附属病院ガーネットホール  

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Event date： 2017.8

Language：Japanese  

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Event date： 2017.6

Language：Japanese  

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Event date： 2017.6

Language：Japanese