研究者詳細 - 藤野　明浩

論文 - 藤野　明浩

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【出生前診断の倫理と実際】先天性横隔膜ヘルニアにおける出生前診断リスク評価の最先端

高安, 肇, 北野, 良博, 黒田, 達夫, 森川, 信行, 田中, 秀明, 藤野, 明浩, 種村, 比呂子 and 武藤, 充

小児外科 41 （ 5 ） 476 - 480 2009年05月

ISSN 0385-6313

【知っているようで知らない、これら疾患の違い】先天性嚢胞性腺腫様奇形(CCAM)と肺分画症、肺葉性肺気腫、気管支嚢胞

黒田, 達夫, 本名, 敏郎, 森川, 信行, 田中, 秀明, 高安, 肇, 藤野, 明浩, 種村, 比呂子 and 武藤, 充

小児外科 41 （ 4 ） 333 - 335 2009年04月

ISSN 0385-6313

中腸軸捻転後の遷延する胆汁鬱滞に対し胆嚢外瘻・胆道洗浄が有効であった1例

森川, 信行, 黒田, 達夫, 本名, 敏郎, 細井, 健一郎, 伊藤, 裕司, 中村, 知夫, 田中, 秀明, 高安, 肇, 藤野, 明浩, 種村, 比呂子 and 武藤, 充

日本小児外科学会雑誌 45 （ 2 ） 282 - 283 2009年04月

ISSN 0288-609X

【呼吸器症候群(第2版)　その他の呼吸器疾患を含めて】縦隔疾患　縦隔腫瘍　リンパ管腫

藤野, 明浩 and 森川, 康英

日本臨床別冊（呼吸器症候群III ） 531 - 533 2009年03月

ISSN 0047-1852

【小児外科手術手技　創意と工夫】短腸症候群に対する複数回STEP手術

森川, 信行, 本名, 敏郎, 黒田, 達夫, 柴田, 祐充子, 種村, 比呂子, 田中, 秀明, 高安, 肇, 藤野, 明浩 and 武藤, 充

小児外科 41 （ 3 ） 268 - 274 2009年03月

ISSN 0385-6313

Positive association of genetic variants in the upstream region of NKX2-3 with Crohn's disease in Japanese patients

Yamazaki K., Takahashi A., Takazoe M., Kubo M., Onouchi Y., Fujino A., Kamatani N., Nakamura Y., Hata A.

Gut 58 （ 2 ） 228 - 232 2009年02月

ISSN 0017-5749

Background and aims: A number of genome-wide association studies have been performed as a robust means of identifying susceptibility loci for Crohn's disease (CD). The loci detected after the completion of the HapMap project are quite concordant among these studies, suggesting that the results are reliable. Recently, the Wellcome Trust Case Control Consortium (WTCCC) reported the primary scanning of 17 000 individuals for seven diseases, including CD, and a subsequent study has validated these susceptible genetic variants in independent UK sample sets. The purpose of this study was to study the possible association of the variants reported by the WTCCC with CD in a Japanese population. Patients and methods: A total of 484 patients with CD and 470 healthy controls were examined. Seventeen genetic variants at eight newly identified loci, including IRGM. NKX2-3 and PTPN2, were genotyped using the TaqMan assay or the invader assay. Results: A positive association signal presumably common to different ethnic groups for rs10883365 was detected in the upstream region of NKX2-3 (p = 0.019 under the genotypic model, p = 0.0065 under the allelic model, p = 0.019 under the recessive model, p = 0.036 under the dominant model). In addition to rs10883365, marginal associations for two single nucleotide polymorphisms (SNPs) were detected in the Japanese population; rs6887695 near IL12B and rs10761659 on 10q21. Further genotype-phenotype analysis found a significant association between rs6887695 and patients with pure ileal CD. Conclusions: The results indicate that the three loci are possible candidates for conferring susceptibility to CD in people of different ethnicities.

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Cell migration and activated PI3K/AKT-directed elongation in the developing rat Müllerian duct

Fujino Akihiro, Arango Nelson A., Zhan Yong, Manganaro Thomas F., Li Xianlin, MacLaughlin David T., Donahoe Patricia K.

Developmental Biology 325 （ 2 ） 351 - 362 2009年01月

ISSN 0012-1606

In vertebrates, the Müllerian duct elongates along the Wolffian duct, a mesonephric structure that is required for Müllerian duct formation. Recently, several genes required for initial Müllerian duct formation have been identified. However, the precise mechanism of Müllerian duct elongation remains to be elucidated. In this study, we investigated dynamic morphological changes in the elongating Müllerian duct in rat urogenital ridges in organ culture manipulated by microincision and/or chemical inhibitors. Mechanical division of the developing Müllerian duct showed that epithelial cells of the Müllerian duct actively migrate along the anterior-posterior axis independent of the proliferative expansion of the anterior portion of the duct. We found that the PI3K/AKT signaling pathway is activated in the Müllerian duct epithelium and is required for elongation of the tip of the duct; however, migration of Müllerian duct epithelial cells proximal to the tip remains intact when PI3K/AKT is inactivated. Although much is known about the molecular and cellular mechanisms leading to Müllerian duct regression, the present findings provide a fuller understanding of the mechanisms contributing to Müllerian duct formation and to the general process of early tubulogenesis. © 2008.

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【この治療法のメリット・デメリット】胃食道逆流症に対する腹腔鏡下噴門形成術

黒田, 達夫, 本名, 敏郎, 森川, 信行 and 藤野, 明浩

小児外科 40 （ 12 ） 1320 - 1323 2008年12月

ISSN 0385-6313

Prognostic significance of circulating tumor cells and bone marrow micrometastasis in advanced neuroblastoma

Kuroda Tatsuo, Morikawa Nobuyuki, Matsuoka Kentaro, Fujino Akihiro, Honna Toshiro, Nakagawa Atsuko, Kumagai Masaaki, Masaki Hidekazu, Saeki Morihiro

Journal of Pediatric Surgery 43 （ 12 ） 2182 - 2185 2008年12月

ISSN 0022-3468

Purpose: The aim of this study was to study the prognostic significance of circulating tumor cells (CTC) and the appropriate indications for aggressive surgery in advanced neuroblastoma. Materials and Methods: Micrometastasis was sequentially explored using our reverse transcriptase-polymerase chain reaction method in 29 neuroblastoma patients (International Neuroblastoma Staging System stage 4, n = 24; stage 3, n = 5) who treated at our department with the united chemotherapeutic regimen since 1991. Their medical records and detection of CTC and/or the bone marrow micrometastasis were retrospectively reviewed then analyzed statistically. Results: The overall survival rate was 58.6% (17/29). Circulating tumor cells were detected in 55.6% of the stage 4 patients, and all deaths were related to systemic metastases in the CTC-positive patients. The detection of CTC scarcely associated with MYCN amplification. In the patients showing MYCN amplification but no CTC, all deaths were related to local relapse or chemotherapy-associated complications. The survival rate was not significantly different between the patients with and without MYCN amplification (56.8% vs 52.7%). However, it was significantly lower in the patients with CTC and/or persistent bone marrow micrometastasis compared to those without detectable micrometastasis (33.8% vs 87.5%; P < .05). Conclusions: The presence of CTC and/or persistent micrometastasis may indicate a significantly high risk, regardless of MYCN amplification. Patients with MYCN amplification but no micrometastasis would be most benefited by highly intensive surgery. © 2008 Elsevier Inc. All rights reserved.

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High dose intravenous methylprednisolone resolves esophageal stricture resistant to balloon dilatation with intralesional injection of dexamethasone

Morikawa Nobuyuki, Honna Toshiro, Kuroda Tatsuo, Watanabe Koji, Tanaka Hideaki, Takayasu Hajime, Fujino Akihiro, Tanemura Hiroko, Matsukubo Makoto

Pediatric Surgery International 24 （ 10 ） 1161 - 1164 2008年10月

ISSN 0179-0358

One of the most serious problems in patients with long-gap esophageal atresia or corrosive esophagitis is esophageal stricture, which may require esophageal resection and replacement. We describe two cases with persistent esophageal stricture successfully managed by high dose intravenous methylprednisolone following balloon dilatation. High-dose methylprednisolone with gradual tapering (daily 25, 15, 10, 5, 2 mg/kg for 4 days each) plus cimetidine and ampicillin for 1 week was intravenously administrated immediately after balloon dilatation of the esophageal stenosis. This was followed by oral prednisolone (daily 2, 1, 0.5 mg/kg for 1 week each) for persistent esophageal stricture. High dose intravenous methylprednisolone therapy was given to two patients. One patient was a 5-year-old boy with long-gap esophageal atresia who had undergone repair of the esophagus resulting in severe anastomotic stenosis of 3 cm in length. The other case was a 10-year-old boy with corrosive stenosis caused by alkali ingestion. Both patients had been requiring balloon dilatation of the esophagus with intralesional injection of dexamethasone every 3 weeks for more than 1 year to tolerate oral feeding. After the high-dose methylprednisolone protocol was initiated, the symptoms of dysphagia or choking dramatically improved in both patients, and they remained symptom-free for 8 and 7 months. There were complications of moon faces that resolved concomitantly with the withdrawal of oral prednisolone in both cases. High dose intravenous methylprednisolone in addition to intralesional injection of dexamethasone following balloon dilation is an effective therapeutic strategy for persistent esophageal strictures. © 2008 Springer-Verlag.

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【産科医が見逃したくない小児外科疾患】胎便性腹膜炎

黒田, 達夫, 本名, 敏郎, 森川, 信行, 田中, 秀明, 高安, 肇, 藤野, 明浩, 種村, 比呂子, 武藤, 充, 左合, 治彦 and 林, 聡

産科と婦人科 75 （ 9 ） 1111 - 1116 2008年09月

ISSN 0386-9792

幼児期に発見された胆嚢重複症の1例

藤野, 明浩, 本名, 敏郎, 黒田, 達夫, 森川, 信行, 田中, 秀明, 高安, 肇, 種村, 比呂子, 武藤, 充, 野坂, 俊介 and 松岡, 健太郎

日本膵・胆管合流異常研究会プロシーディングス 31 71 - 72 2008年09月

ISSN 1883-4116

Normal ovarian surface epithelial label-retaining cells exhibit stem/progenitor cell characteristics

Szotek Paul P., Chang Henry L., Brennand Kristen, Fujino Akihiro, Pieretti-Vanmarcke Rafael, Celso Cristina Lo, Dombkowski David, Preffer Frederic, Cohen Kenneth S., Teixeira Jose, Donahoe Patricia K.

Proceedings of the National Academy of Sciences of the United States of America 105 （ 34 ） 12469 - 12473 2008年08月

ISSN 0027-8424

Ovulation induces cyclic rupture and regenerative repair of the ovarian coelomic epithelium. This process of repeated disruption and repair accompanied by complex remodeling typifies a somatic stem/progenitor cell-mediated process. Using BrdU incorporation and doxycycline inducible histone2B-green fluorescent protein pulse-chase techniques, we identify a label-retaining cell population in the coelomic epithelium of the adult mouse ovary as candidate somatic stem/progenitor cells. The identified population exhibits quiescence with asymmetric label retention, functional response to estrous cycling in vivo by proliferation, enhanced growth characteristics by in vitro colony formation, and cytoprotective mechanisms by enrichment for the side population. Together, these characteristics identify the label-retaining cell population as a candidate for the putative somatic stem/progenitor cells of the coelomic epithelium of the mouse ovary. © 2008 by The National Academy of Sciences of the USA.

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【新生児外科と周術期管理-Up-to-date】巨大仙尾部奇形腫の新生児期手術と周術期管理

田中, 秀明, 高安, 肇, 藤野, 明浩, 森川, 信行, 黒田, 達夫, 本名, 敏郎, 左合, 治彦, 林, 聡, 中村, 知夫, 伊藤, 裕司, 宮嵜, 治 and 野坂, 俊介

小児外科 40 （ 7 ） 823 - 828 2008年07月

ISSN 0385-6313

巨大仙尾部奇形腫(SCT)の新生児期手術と周術期管理について検討した。胎児SCTは9例で、1例が妊娠中断、8例が帝王切開分娩となった。腫瘍切除術は平均日齢5.25に施行され1例が死亡、7例が生存退院した。胎児水腫合併2例中、1例は妊娠20週にSCTを疑われた。出生後は腫瘤内出血により循環動態が不安定で、同日摘出術を施行したが術中大量出血による心停止を繰り返し術中死した。残りの1例は妊娠24週にSCTを疑われた。妊娠30週4日に全身麻酔下に母体に超音波ガイド下で経皮的に穿刺針を腫瘍内の栄養血管周囲に刺入し、RFAを施行した。術後胎児心拍出量の低下を認め、腫瘍の増大は止まった。日齢4に腫瘍切除術を施行した。術後経過は順調で日齢73に退院となった。

【小児科医が見逃したくない外科系疾患】頭頸部疾患　頸部瘻孔・嚢胞性疾患、斜頸

黒田, 達夫, 本名, 敏郎, 森川, 信行, 田中, 秀明, 高安, 肇 and 藤野, 明浩

小児科診療 71 （ 4 ） 595 - 599 2008年04月

ISSN 0386-9806

ITPKC functional polymorphism associated with Kawasaki disease susceptibility and formation of coronary artery aneurysms

Onouchi Yoshihiro, Gunji Tomohiko, Burns Jane C., Shimizu Chisato, Newburger Jane W., Yashiro Mayumi, Nakamura Yoshikazu, Yanagawa Hiroshi, Wakui Keiko, Fukushima Yoshimitsu, Kishi Fumio, Hamamoto Kunihiro, Terai Masaru, Sato Yoshitake, Ouchi Kazunobu, Saji Tsutomu, Nariai Akiyoshi, Kaburagi Yoichi, Yoshikawa Tetsushi, Suzuki Kyoko, Tanaka Takeo, Nagai Toshiro, Cho Hideo, Fujino Akihiro, Sekine Akihiro, Nakamichi Reiichiro, Tsunoda Tatsuhiko, Kawasaki Tomisaku, Nakamura Yusuke, Hata Akira

Nature Genetics 40 （ 1 ） 35 - 42 2008年01月

ISSN 1061-4036

Kawasaki disease is a pediatric systemic vasculitis of unknown etiology for which a genetic influence is suspected. We identified a functional SNP (itpkc_3) in the inositol 1,4,5-trisphosphate 3-kinase C (ITPKC) gene on chromosome 19q13.2 that is significantly associated with Kawasaki disease susceptibility and also with an increased risk of coronary artery lesions in both Japanese and US children. Transfection experiments showed that the C allele of itpkc_3 reduces splicing efficiency of the ITPKC mRNA. ITPKC acts as a negative regulator of T-cell activation through the Ca²⁺/NFAT signaling pathway, and the C allele may contribute to immune hyper-reactivity in Kawasaki disease. This finding provides new insights into the mechanisms of immune activation in Kawasaki disease and emphasizes the importance of activated T cells in the pathogenesis of this vasculitis. © 2008 Nature Publishing Group.

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【新生児の消化管疾患】新生児消化管出血　当院外科症例の検討

黒田, 達夫, 本名, 敏郎, 森川, 信行, 田中, 秀明, 高安, 肇, 藤野, 明浩, 種村, 比呂子, 松久保, 眞, 伊藤, 裕司 and 中村, 知夫

周産期医学 37 （ 11 ） 1413 - 1418 2007年11月

ISSN 0386-9881

当科で2007年7月までに経験した新生児消化管出血46例について臨床的検討を行った。原疾患は胃破裂が最も多く19例(41%)、次いで中腸軸捻転5例(11%)、胃穿孔4例(9%)、十二指腸穿孔3例(7%)、新生児メレナ3例(7%)の順であった。出生時体重を疾患別にみると胃破裂群は他の疾患より軽い傾向にあり、2500g未満の7例は全て胃破裂であった。一方、中腸軸捻転群は重い傾向にあり、胃破裂群とは有意差が認められた。入院時日齢を疾患別にみると、胃破裂や胃穿孔は日齢4日前後であるのに対して新生児メレナは日齢1日前後と早期に入院していた。症状を疾患別にみると、新生児メレナとアレルギー性疾患では下血や血便が多く、上部消化管穿孔性疾患では吐血や経鼻胃管からの出血が多いという特徴が認められた。

Sexual dimorphism of G-protein subunit Gng13 expression in the cortical region of the developing mouse ovary

Fujino Akihiro, Pieretti-Vanmarcke Rafael, Wong Anita, Donahoe Patricia K., Arango Nelson A.

Developmental Dynamics 236 （ 7 ） 1991 - 1996 2007年07月

ISSN 1058-8388

In our search for genes required for the development and function of mouse gonads, we identified Gng13 (guanine nucleotide binding protein 13, gamma), a gene with an embryonic expression pattern highly restricted to the ovary. Based on reverse transcriptase-polymerase chain reaction (RT-PCR) and whole-mount in situ hybridization, Gng13 is expressed in both XX and XY gonads at embryonic day (E) 11.5, but becomes up-regulated in the XX gonad by E12.5. Expression is retained after treatment with busulfan, a chemical known to eliminate germ cells, pointing to the soma as a site of Gng13 transcription. In situ hybridization of embryonic ovarian tissue sections further localized the expression to the cortex of the developing XX gonad. Gng13 expression in the adult is also highly restricted. Northern blot analyses and Genomic Institute of the Novartis Research Foundation expression profiling of adult tissues detected very high expression in the cerebrum and cerebellum, in addition to, a weaker signal in the ovary. Gng13 belongs to a well-known family of signal transduction molecules with functions in many aspects of development and organ physiology. Here, we report that, in the developing mouse embryo, expression of Gng13 mRNA is highly restricted to the cortex of the XX gonad during sexual differentiation, suggesting a role for this gene during ovarian development. © 2007 Wiley-Liss, Inc.

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Expression analysis and evolutionary conservation of the mouse germ cell-specific D6Mm5e gene

Arango Nelson A., Huang Tiffany T., Fujino Akihiro, Pieretti-Vanmarcke Rafael, Donahoe Patricia K.

Developmental Dynamics 235 （ 9 ） 2613 - 2619 2006年09月

ISSN 1058-8388

During our search for genes required for gonadal development and function in the mouse, we identified D6Mm5e (DNA segment, Chr 6. Miriam Meisler 5, expressed), a gene with an expression pattern highly restricted to the embryonic ovary and the postnatal testis. Based on RT-PCR, Northern blot, and in situ hybridization analyses, we show that D6Mm5e is expressed in the germ cells of the female embryo upon their initial entry into meiosis, and in male germ cells during the last stages of spermatogenesis. Two transcripts are detected in the gonads resulting from the alternative splicing of exon 8. This splicing event does not introduce a frame shift, and creates an mRNA product that uses the same stop codon as the longer transcript. Although D6Mm5e does not belong to any known protein family and does not contain any known protein signature motifs, the high level of evolutionary conservation and the cellular and temporal expression suggest that D6Mm5e may have a role in male and female gametogenesis. Here we report the gonad-restricted mRNA expression profile of D6Mm5e in the mouse, and the evolutionary conservation of its amino acid sequence. © 2006 Wiley-Liss, Inc.

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Müllerian inhibiting substance regulates its receptors/SMAD signaling and causes mesenchymal transition of the coelomic epithelial cells early in Müllerian duct regression

Zhan Yong, Fujino Akihiro, MacLaughlin David T., Manganaro Thomas F., Szotek Paul P., Arango Nelson A., Teixeira Jose, Donahoe Patricia K.

Development 133 （ 12 ） 2359 - 2369 2006年06月

ISSN 0950-1991

Examination of Müllerian inhibiting substance (MIS) signaling in the rat in vivo and in vitro revealed novel developmental stage- and tissue-specific events that contributed to a window of MIS responsiveness in Müllerian duct regression. The MIS type II receptor (MISRII)-expressing cells are initially present in the coelomic epithelium of both male and female urogenital ridges, and then migrate into the mesenchyme surrounding the male Müllerian duct under the influence of MIS. Expression of the genes encoding MIS type I receptors, Alk2 and Alk3, is also spatiotemporally controlled; Alk2 expression appears earlier and increases predominantly in the coelomic epithelium, whereas Alk3 expression appears later and is restricted to the mesenchyme, suggesting sequential roles in Müllerian duct regression. MIS induces expression of Alk2, Alk3 and Smad8, but downregulates Smad5 in the urogenital ridge. Alk2-specific small interfering RNA (siRNA) blocks both the transition of MISRII expression from the coelomic epithelium to the mesenchyme and Müllerian duct regression in organ culture. Müllerian duct regression can also be inhibited or accelerated by siRNA targeting Smad8 and Smad5, respectively. Thus, the early action of MIS is to initiate an epithelial-to-mesenchymal transition of MISRII-expressing cells and to specify the components of the receptor/SMAD signaling pathway by differentially regulating their expression.

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