論文 - 池ノ上　学

Predictors of later insulin therapy for gestational diabetes diagnosed in early pregnancy

Tamagawa M., Kasuga Y., Saisho Y., Tanaka Y., Hasegawa K., Oishi M., Endo T., Sato Y., Ikenoue S., Tanaka M., Ochiai D.

Endocrine Journal （Endocrine Journal）  68 （ 11 ） 1321 - 1328 2021年

ISSN  09188959

　概要を見る

Interventions for gestational diabetes mellitus (GDM), diagnosed in early pregnancy, have been a topic of controversy. This study aimed to elucidate factors that predict patients with GDM diagnosed before 24 gestational weeks (early GDM: E-GDM) who require insulin therapy later during pregnancy. Furthermore, we identified patients whose impaired glucose tolerance should be strictly controlled from early gestation onward. Women diagnosed with GDM were categorized based on the gestational age at diagnosis into E-GDM (n = 388) or late GDM (L-GDM, diagnosed after 24 weeks, n = 340) groups. Clinical features were compared between the groups, and the predictors for insulin therapy was evaluated in the E-GDM group. There were no significant between-group differences in terms of perinatal outcomes (e.g., gestational weeks at delivery, fetal growth, hypertensive disorder of pregnancy), with the exception of the Apgar score at 5 min. Moreover, there was no significant difference in the frequency of insulin therapy during pregnancy between the two groups. Using multiple logistic regression analysis, pre-pregnancy body mass index (BMI) ≥25 kg/m2, a family history of diabetes, and higher fasting plasma glucose (FPG), 1 h-plasma glucose (PG), and 2 h-PG values increased insulin therapy risk during pregnancy in the E-GDM group. Furthermore, since E-GDM patients with abnormal levels of FPG, as well as 1 h-PG or 2 h-PG, and those with pre-pregnancy BMI ≥25 kg/m2 and a family history of diabetes had a higher risk of later insulin therapy during pregnancy, they may require more careful follow-up in the perinatal period.

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Prophylactic therapy with human amniotic fluid stem cells improves long-term cognitive impairment in rat neonatal sepsis survivors

Abe Y., Ochiai D., Sato Y., Kanzaki S., Ikenoue S., Kasuga Y., Tanaka M.

International Journal of Molecular Sciences （International Journal of Molecular Sciences）  21 （ 24 ） 1 - 12 2020年12月

ISSN  16616596

　概要を見る

A systemic inflammatory response induces multiple organ dysfunction and results in poor long-term neurological outcomes in neonatal sepsis. However, there is no effective therapy for treating or preventing neonatal sepsis besides antibiotics and supportive care. Therefore, a novel strategy to improve neonatal sepsis-related morbidity and mortality is desirable. Recently, we reported that prophylactic therapy with human amniotic stem cells (hAFSCs) improved survival in a rat model of lipopolysaccharide (LPS)-induced neonatal sepsis through immunomodulation. Besides improving the mortality, increasing survival without major morbidities is an important goal of neonatal intensive care for neonatal sepsis. This study investigated long-term neurological outcomes in neonatal sepsis survivors treated with hAFSCs using the LPS-induced neonatal sepsis model in rats. We found that prophylactic therapy with hAFSCs improved spatial awareness and memory-based behavior in neonatal sepsis survivors at adolescence in rats. The treatment suppressed acute reactive gliosis and subsequently reduced astrogliosis in the hippocampal region over a long period of assessment. To the best of our knowledge, this is the first report that proves the concept that hAFSC treatment improves cognitive impairment in neonatal sepsis survivors. We demonstrate the efficacy of hAFSC therapy in improving the mortality and morbidity associated with neonatal sepsis.

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腹腔鏡下術後、生児を得た正所異所同時妊娠の2例

片倉 慧美, 山田 満稔, 池ノ上 学, 田中 守

日本産科婦人科内視鏡学会雑誌 （(一社)日本産科婦人科内視鏡学会）  36 （ Suppl.I ） [O - 383] 2020年11月

ISSN  1884-9938

妊娠糖尿病と正常耐糖能例における胎児Fractional limb volumeの発育の比較

池ノ上 学, 秋葉 洋平, 遠藤 豊英, 春日 義史, 落合 大吾, 宮越 敬, 矢久保 和美, 田中 守

超音波医学 （(公社)日本超音波医学会）  47 （ Suppl. ） S170 - S170 2020年11月

ISSN  1346-1176

前置血管との鑑別を要した子宮頸管内静脈瘤合併妊娠の1例

遠藤 豊英, 宮越 敬, 玉川 真澄, 長谷川 慶太, 大石 真希, 大谷 利光, 池ノ上 学, 春日 義史, 落合 大吾, 田中 守

超音波医学 （(公社)日本超音波医学会）  47 （ Suppl. ） S406 - S406 2020年11月

ISSN  1346-1176

Placenta accreta indexによる前置癒着胎盤発症予測に関する検討

長谷川 慶太, 池ノ上 学, 玉川 真澄, 大石 真希, 遠藤 豊英, 大谷 利光, 春日 義史, 落合 大吾, 宮越 敬, 田中 守

超音波医学 （(公社)日本超音波医学会）  47 （ Suppl. ） S374 - S374 2020年11月

ISSN  1346-1176

Survey on the use of personal protective equipment and COVID-19 testing of pregnant women in Japan

Umazume T., Miyagi E., Haruyama Y., Kobashi G., Saito S., Hayakawa S., Kawana K., Ikenoue S., Morioka I., Yamada H.

Journal of Obstetrics and Gynaecology Research （Journal of Obstetrics and Gynaecology Research）  46 （ 10 ） 1933 - 1939 2020年10月

査読有り,  ISSN  13418076

　概要を見る

Aim: To clarify the status of personal protective equipment (PPE) and coronavirus disease 2019 (COVID-19) tests for pregnant women, we conducted an urgent survey. Methods: The survey was conducted online from April 27 to May 1, 2020. Questionnaires were sent to core facilities and affiliated hospitals of the obstetrics and gynecology training program and to hospitals of the national perinatal medical liaison council. Results: A total of 296 institutions participated in our survey; however, 2 institutions were excluded. Full PPE was used by doctors in 7.1% of facilities and by midwives in 6.8%. Our study also determined that around 65.0% of facilities for doctors and 73.5% of facilities for midwives used PPE beyond the “standard gown or apron, surgical mask, goggles or face shield” during labor of asymptomatic women. N95 masks were running out of stock at 6.5% of the facilities and goggles and face shields at 2.7%. Disposable N95 masks and goggles or face shields were re-used after re-sterilization in 12% and 14% of facilities, respectively. Polymerase chain reaction (PCR) testing of asymptomatic patients was performed for 9% of vaginal deliveries, 14% of planned cesarean sections and 17% of emergency cesarean sections. The number of PCR tests for obstetrics and gynecology per a week ranged from zero to five in 92% of facilities. Conclusion: The shortage of PPE in Japan is alarming. Sufficient stockpiling of PPE is necessary to prevent unnecessary disruptions in medical care. Appropriate guidelines for PPE usage and COVID-19 testing of pregnant women at delivery are needed in Japan.

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Universal screening for SARS-CoV-2 in asymptomatic obstetric patients in Tokyo, Japan

Ochiai D., Kasuga Y., Iida M., Ikenoue S., Tanaka M.

International Journal of Gynecology and Obstetrics （International Journal of Gynecology and Obstetrics）  150 （ 2 ） 268 - 269 2020年08月

査読有り,  ISSN  00207292

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Prophylactic therapy with human amniotic fluid stem cells improved survival in a rat model of lipopolysaccharide-induced neonatal sepsis through immunomodulation via aggregates with peritoneal macrophages

Sato Y., Ochiai D., Abe Y., Masuda H., Fukutake M., Ikenoue S., Kasuga Y., Shimoda M., Kanai Y., Tanaka M.

Stem Cell Research and Therapy （Stem Cell Research and Therapy）  11 （ 1 ） 300 - 300 2020年07月

査読有り

　概要を見る

Background: Despite recent advances in neonatal care, sepsis remains a leading cause of mortality in neonates. Mesenchymal stem cells derived from various tissues, such as bone marrow, umbilical cord, and adipose tissue, have beneficial effects on adult sepsis. Although human amniotic fluid stem cells (hAFSCs) have mesenchymal stem cell properties, the efficacy of hAFSCs on neonatal sepsis is yet to be elucidated. This study aimed to investigate the therapeutic potential of hAFSCs on neonatal sepsis using a rat model of lipopolysaccharide (LPS)-induced sepsis. Methods: hAFSCs were isolated as CD117-positive cells from human amniotic fluid. Three-day-old rat pups were intraperitoneally treated with LPS to mimic neonatal sepsis. hAFSCs were administered either 3 h before or at 0, 3, or 24 h after LPS exposure. Serum inflammatory cytokine levels, gene expression profiles from spleens, and multiple organ damage were analyzed. hAFSC localization was determined in vivo. In vitro LPS stimulation tests were performed using neonatal rat peritoneal macrophages co-cultured with hAFSCs in a cell-cell contact-dependent/independent manner. Immunoregulation in the spleen was determined using a DNA microarray analysis. Results: Prophylactic therapy with hAFSCs improved survival in the LPS-treated rats while the hAFSCs transplantation after LPS exposure did not elicit a therapeutic response. Therefore, hAFSC pretreatment was used for all subsequent studies. Inflammatory cytokine levels were elevated after LPS injection, which was attenuated by hAFSC pretreatment. Subsequently, inflammation-induced damages in the brain, lungs, and liver were ameliorated. hAFSCs aggregated with peritoneal macrophages and/or transiently accumulated in the liver, mesentery, and peritoneum. Paracrine factors released by hAFSCs induced M1-M2 macrophage polarization in a cell-cell contact-independent manner. Direct contact between hAFSCs and peritoneal macrophages further enhanced the polarization. Microarray analysis of the spleen showed that hAFSC pretreatment reduced the expression of genes involved in apoptosis and inflammation and subsequently suppressed toll-like receptor 4 signaling pathways. Conclusions: Prophylactic therapy with hAFSCs improved survival in a rat model of LPS-induced neonatal sepsis. These effects might be mediated by a phenotypic switch from M1 to M2 in peritoneal macrophages, triggered by hAFSCs in a cell-cell contact-dependent/independent manner and the subsequent immunomodulation of the spleen.

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臨床的羊水塞栓症を契機に発症した腹部コンパートメント症候群の1例

平田 桃, 長谷川 慶太, 春日 義史, 秋田 啓介, 大石 真希, 遠藤 豊英, 大谷 利光, 池ノ上 学, 落合 大吾, 宮越 敬, 田中 守, 青木 大輔

関東連合産科婦人科学会誌 （(一社)関東連合産科婦人科学会）  57 （ 2 ） 233 - 233 2020年06月

ISSN  2186-0610

妊娠中に発症した特発性中枢性尿崩症の1例

島田 紗也葵, 春日 義史, 吉村 拓馬, 山下 博, 長谷川 慶太, 大石 真希, 遠藤 豊英, 池ノ上 学, 落合 大吾, 宮越 敬, 田中 守, 青木 大輔

関東連合産科婦人科学会誌 （(一社)関東連合産科婦人科学会）  57 （ 2 ） 226 - 226 2020年06月

ISSN  2186-0610

頭痛および視野欠損を契機に診断に至った脳動脈解離による脳梗塞合併妊娠の1例

秋田 啓介, 春日 義史, 玉川 真澄, 上條 慎太郎, 大石 真希, 遠藤 豊英, 大谷 利光, 池ノ上 学, 落合 大吾, 宮越 敬, 田中 守, 青木 大輔

東京産科婦人科学会会誌 （(一社)東京産科婦人科学会）  69 （ 2 ） 212 - 217 2020年04月

ISSN  2186-0599

　概要を見る

緒言:脳動脈解離は若年発症脳梗塞の原因となり、リスク因子としては片頭痛や高血圧が挙げられるが、妊婦における初発例は稀である。今回我々は妊娠中に発症した脳動脈解離による脳梗塞の1例を経験したので報告する。症例:31歳、3妊1産。既往歴として片頭痛を認めた。妊娠26週0日に激しい頭痛が出現し、その1週間後に右側半盲を認めた。頭部MRI/MRA検査で左後大脳動脈の狭小化と左後頭葉の虚血性変化が認められ、脳動脈解離による脳梗塞の診断となった。神経学的症状の増悪や血圧の変動なく経過し、妊娠37週5日に経腟分娩に至った。児は2926gの女児でApgar score 8/10点(1/5分値)であった。分娩中や分娩後に血圧の変動や新規の神経学的異常所見の出現は認めなかった。結論:神経学的異常所見を伴う頭痛を認める際には脳動脈解離を含めた脳血管障害を念頭に頭蓋内病変精査を行う必要があると考えられた。(著者抄録)

妊娠中期に卵巣癌と診断し、手術療法と化学療法治療後に生児を得られた1例

田中 邦生, 長谷川 慶太, 吉村 拓馬, 大石 真希, 大谷 利光, 池ノ上 学, 春日 義史, 落合 大吾, 岩田 卓, 宮越 敬, 田中 守, 青木 大輔

東京産科婦人科学会会誌 （(一社)東京産科婦人科学会）  69 （ 2 ） 387 - 391 2020年04月

ISSN  2186-0599

　概要を見る

緒言:卵巣癌合併妊娠は1万から5万例に1例と頻度が低く、対応に一定の見解はない。今回我々は妊娠中期に卵巣癌を診断され、手術療法と化学療法を行い生児を得られた症例を経験した。症例:44歳、1妊0産。妊娠16週時に卵巣癌を疑われ、妊娠18週時に右付属器摘出術、左卵巣腫瘍摘出術、大網生検を施行した。右卵巣原発の高異型度漿液性癌IIIC期の診断にて術後パクリタキセルとカルボプラチン(TC)併用療法を4サイクル施行し、妊娠35週5日時に選択的帝王切開術とinterval debulking surgeryを同時に施行した。2118gの女児を娩出し、術後TC療法を2サイクル施行した。術後母体は再発を認めず、児の発育も良好である。結論:卵巣癌合併妊娠に対して、予め分娩時期を想定した管理・治療を行ったことで母児ともに合併症なく手術療法と化学療法を行うことができた。(著者抄録)

自然陣痛発来群におけるivPCAを用いた和痛分娩の有用性に関する後方視的検討

長谷川 慶太, 春日 義史, 玉川 真澄, 大石 真希, 遠藤 豊英, 佐藤 佑, 大谷 利光, 池ノ上 学, 落合 大吾, 宮越 敬, 田中 守, 青木 大輔

日本産科婦人科学会雑誌 （(公社)日本産科婦人科学会）  72 （ 臨増 ） S - 369 2020年03月

ISSN  0300-9165

自然陣痛発来群におけるivPCAを用いた和痛分娩の有用性に関する後方視的検討

長谷川 慶太, 春日 義史, 玉川 真澄, 大石 真希, 遠藤 豊英, 佐藤 佑, 大谷 利光, 池ノ上 学, 落合 大吾, 宮越 敬, 田中 守, 青木 大輔

日本産科婦人科学会雑誌 （(公社)日本産科婦人科学会）  72 （ 臨増 ） S - 369 2020年03月

ISSN  0300-9165

当院における高用量黄体ホルモン療法後妊娠の周産期臨床像

大石 真希, 春日 義史, 山上 亘, 長谷川 慶太, 遠藤 豊英, 佐藤 佑, 大谷 利光, 池ノ上 学, 落合 大吾, 宮越 敬, 田中 守, 青木 大輔

日本産科婦人科学会雑誌 （(公社)日本産科婦人科学会）  72 （ 臨増 ） S - 547 2020年03月

ISSN  0300-9165

妊娠初期に診断された妊娠糖尿病の臨床像に関する検討

玉川 真澄, 春日 義史, 長谷川 慶太, 遠藤 豊英, 大石 真希, 佐藤 佑, 大谷 利光, 池ノ上 学, 落合 大吾, 宮越 敬, 田中 守, 青木 大輔

日本産科婦人科学会雑誌 （(公社)日本産科婦人科学会）  72 （ 臨増 ） S - 458 2020年03月

ISSN  0300-9165

妊娠初期に診断された妊娠糖尿病の臨床像に関する検討

玉川 真澄, 春日 義史, 長谷川 慶太, 遠藤 豊英, 大石 真希, 佐藤 佑, 大谷 利光, 池ノ上 学, 落合 大吾, 宮越 敬, 田中 守, 青木 大輔

日本産科婦人科学会雑誌 （(公社)日本産科婦人科学会）  72 （ 臨増 ） S - 458 2020年03月

ISSN  0300-9165

当院における高用量黄体ホルモン療法後妊娠の周産期臨床像

大石 真希, 春日 義史, 山上 亘, 長谷川 慶太, 遠藤 豊英, 佐藤 佑, 大谷 利光, 池ノ上 学, 落合 大吾, 宮越 敬, 田中 守, 青木 大輔

日本産科婦人科学会雑誌 （(公社)日本産科婦人科学会）  72 （ 臨増 ） S - 547 2020年03月

ISSN  0300-9165

In Utero Amniotic Fluid Stem Cell Therapy Protects Against Myelomeningocele via Spinal Cord Coverage and Hepatocyte Growth Factor Secretion

Abe Y., Ochiai D., Masuda H., Sato Y., Otani T., Fukutake M., Ikenoue S., Miyakoshi K., Okano H., Tanaka M.

Stem Cells Translational Medicine （Stem Cells Translational Medicine）  8 （ 11 ） 1170 - 1179 2019年08月

ISSN  2157-6564

　概要を見る

© 2019 The Authors. Stem Cells Translational Medicine published by Wiley Periodicals, Inc. on behalf of AlphaMed Press Despite the poor prognosis associated with myelomeningocele (MMC), the options for prenatal treatments are still limited. Recently, fetal cellular therapy has become a new option for treating birth defects, although the therapeutic effects and mechanisms associated with such treatments remain unclear. The use of human amniotic fluid stem cells (hAFSCs) is ideal with respect to immunoreactivity and cell propagation. The prenatal diagnosis of MMC during early stages of pregnancy could allow for the ex vivo proliferation and modulation of autologous hAFSCs for use in utero stem cell therapy. Therefore, we investigated the therapeutic effects and mechanisms of hAFSCs-based treatment for fetal MMC. hAFSCs were isolated as CD117-positive cells from the amniotic fluid of 15- to 17-week pregnant women who underwent amniocentesis for prenatal diagnosis and consented to this study. Rat dams were exposed to retinoic acid to induce fetal MMC and were subsequently injected with hAFSCs in each amniotic cavity. We measured the exposed area of the spinal cord and hepatocyte growth factor (HGF) levels at the lesion. The exposed spinal area of the hAFSC-treated group was significantly smaller than that of the control group. Immunohistochemical analysis demonstrated a reduction in neuronal damage such as neurodegeneration and astrogliosis in the hAFSC-treated group. Additionally, in lesions of the hAFSC-treated group, HGF expression was upregulated and HGF-positive hAFSCs were identified, suggesting that these cells migrated to the lesion and secreted HGF to suppress neuronal damage and induce neurogenesis. Therefore, in utero hAFSC therapy could become a novel strategy for fetal MMC. Stem Cells Translational Medicine 2019;8:1170–1179.

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