出口 雅士 | ![]() |
デグチ マサシ | |
大学院医学研究科 医科学専攻 | |
教授 | |
医学 |
2006年07月 兵庫県産科婦人科学会, 兵庫県産科婦人科学会学術奨励賞, Lack of association between endometriosis and N-acetyl transferase 1 (NAT1) and 2 (NAT2) polymorphisms in a Japanese population.
AIM: The aim of this prospective cohort study was to evaluate the risk factors for postpartum glucose intolerance (GI) in women with gestational diabetes mellitus (GDM). METHOD: A total of 140 women with GDM were enrolled. Of these, 115 underwent a 75-g oral glucose tolerance test (OGTT) at 12 weeks after delivery. Clinical factors and parameters in the antepartum 75-g OGTT associated with postpartum GI were evaluated by logistic regression analyses. RESULTS: Twenty-two (19.1%) of the 115 women with GDM developed postpartum GI. The univariate and multivariable logistic regression analyses revealed that low oral disposition index (DI) was a risk factor for postpartum GI (OR, 0.2; 95% CI, 0.04-0.7; p < 0.05), and that no clinical factors were associated with postpartum GI. CONCLUSIONS: Lower oral DI on the antepartum 75-g OGTT may be a useful marker for identifying GDM women who are at high risk for postpartum GI.
2022年01月20日, The journal of obstetrics and gynaecology research, 英語, 国際誌研究論文(学術雑誌)
INTRODUCTION: The aims were to investigate the clinical characteristics of Toxoplasma gondii (T. gondii) immunoglobulin (Ig) M-positive mothers and to clarify the incidences of serum T. gondii IgM or blood T. gondii DNA positivity in newborns born to the mothers and the actual congenital T. gondii infection. METHODS: Mothers with T. gondii IgM positivity and newborns born to the mothers from 2013 to 2020 were prospectively investigated. Serum T. gondii IgG and IgM were measured by enzyme-linked immunosorbent assay. Blood T. gondii DNA was detected by semi-nested polymerase chain reaction. Congenital T. gondii infection was diagnosed based on clinical characteristic manifestations with serum T. gondii IgG positivity at any age or T. gondii IgG positivity after 12 months of age. RESULTS: Among 71 T. gondii IgM-positive mothers, including one with triplets, 41% had low T. gondii IgG avidity index and 73% received maternal therapy. Among 73 newborns who were examined for serum T. gondii IgG and IgM at birth, none had clinical manifestations, and one (1.4%) had T. gondii IgM positivity. Among 32 newborns who were examined for blood T. gondii DNA at birth, two (6.3%) were positive. All patients with serum T. gondii IgM or blood T. gondii DNA positivity showed T. gondii IgG negativity within 12 months of age. CONCLUSIONS: A few newborns born to T. gondii IgM-positive mothers were suspected of having congenital T. gondii infection based on serum T. gondii IgM or blood T. gondii DNA testing at birth. However, none developed congenital T. gondii infection.
2021年12月17日, Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy, 英語, 国際誌研究論文(学術雑誌)
INTRODUCTION: Placenta accreta spectrum (PAS) is a life-threating obstetric complication, and prenatal prediction of PAS can decrease maternal morbidity and mortality. The aim of this prospective cohort study was to determine the clinical factors associated with PAS. METHODS: Pregnant women who delivered at a university hospital were enrolled. Clinical data were collected from medical records, and logistic regression analyses were performed to determine which clinical factors were associated with PAS. RESULTS: Eighty-seven (2.1%) of the 4146 pregnant women experienced PAS. Multivariable analyses revealed that a prior history of cesarean section (CS) (OR 3.3; 95% CI 1.9-5.7; p < 0.01), dilation and curettage (D&C) (OR 2.8; 95% CI 1.7-4.6; p < 0.01), hysteroscopic surgery (OR 5.7; 95% CI 2.3-14.4; p < 0.01), uterine artery embolization (UAE) (OR 44.1; 95% CI 13.8-141.0; p < 0.01), current pregnancy via assisted reproductive technology (ART) (OR 4.1; 95% CI 2.4-7.1; p < 0.01), and the presence of placenta previa in the current pregnancy (OR 13.1; 95% CI 7.9-21.8; p < 0.01) were independently associated with the occurrence of PAS. CONCLUSION: Pregnant women who have a prior history of CS, D&C, hysteroscopic surgery, UAE, current pregnancy via ART, and the presence of placenta previa in the current pregnancy are high risk for PAS.
2021年09月01日, Placenta, 112, 180 - 184, 英語, 国際誌研究論文(学術雑誌)
Triiodothyronine (T3)-predominant Graves' disease is characterized by increased serum free T3 (FT3) levels after free thyroxine (FT4) levels become normal or even low during antithyroid drug treatment. We encountered a 34-year-old pregnant woman, gravida 5 para 4, who was complicated by T3-predominant Graves' disease. She was diagnosed with Graves' disease at 20 years old, and had received methimazole. Methimazole was changed to potassium iodide to reduce the risk of congenital anomalies during the first trimester. The dose of antithyroid drugs was adjusted based on maternal FT4 levels, so that maternal Graves' disease deteriorated and fetal goitrous hyperthyroidism appeared during the second trimester. Since the fetus presented goiter and tachycardia at 27-28 gestational weeks, doses of methimazole and potassium iodide were increased. A male newborn weighing 2604 g was delivered by a cesarean section at 35 gestational weeks. The newborn was diagnosed with neonatal hyperthyroidism, and received methimazole for six months. He developed normally with normal thyroid function at 1 year old. In pregnancies complicated by T3-predominant Graves' disease, the kinds and doses of antithyroid drugs have to be carefully selected to maintain maternal levels of FT4 as well as FT3 within the normal range, considering trimesters of pregnancy, teratogenicity of medication, and maternal levels of thyroid-stimulating hormone receptor antibody.
2021年02月08日, The Kobe journal of medical sciences, 66 (4), E153-E158, 英語, 国内誌研究論文(学術雑誌)
Infants with symptomatic congenital cytomegalovirus infection (cCMV) suffer from long-term sequelae. This study aimed at evaluating the efficacy of combining immunoglobulin (Ig) fetal therapy (FT) and neonatal therapy (NT) with antiviral drugs to improve neurological outcomes of affected infants. Women whose fetuses had symptomatic cCMV received Ig injection into the fetal peritoneal cavity and/or maternal blood as FT, while affected newborns received oral valganciclovir or intravenous ganciclovir as NT. We compared the neurological outcomes at ≥18 months old between infants receiving FT with or without NT (FT group) and those receiving NT only (NT group). From 2009-2019, 15 women whose fetuses had symptomatic cCMV received FT, while 19 newborns received NT only. In FT group, two newborns died, and two were <18 months old. Neurological outcomes of the remaining 11 infants in FT group were as follows: normal 45.5 %, mild impairments 36.4 %, and severe impairments 18.2 %. In NT group, one newborn died, one's parents refused the follow-up, one was <18 months old, and two had only chorioretinitis as symptoms. Neurological outcomes of the remaining 14 infants in NT group were as follows: normal 21.4 %, mild impairments 14.3 %, and severe impairments 64.3 %. The proportion of infants with severe impairments in FT group was significantly lower than that in NT group (18.2 % vs 64.3 %, p < 0.05). This is the first trial demonstrating that the combination of Ig FT and NT with antiviral drugs may be more effective in improving neurological outcomes of newborns with symptomatic cCMV as compared to NT only.
2020年12月16日, Journal of reproductive immunology, 143, 103263 - 103263, 英語, 国際誌研究論文(学術雑誌)
<文献概要>血栓性素因のうち抗リン脂質抗体症候群のみ,不育症の明らかな原因といえる。そのほかの血栓性素因としては,わが国ではプロテインS低下,凝固第XII因子低下が代表的である。これらの(抗)凝固因子低下と不育症には弱い関連があるものの,治療が妊娠予後を改善するエビデンスは乏しい。不妊症と血栓性素因との関連についてはさらにエビデンスに乏しく,血栓性素因のある不妊・不育症患者の全例に抗凝固療法を行うべきではない。抗リン脂質抗体症候群については確立された治療法(低用量アスピリンとヘパリンの併用)があり,不育症(生化学的妊娠の反復を含む)や妊娠34週未満早産,胎児発育不全,妊娠高血圧症候群,常位胎盤早期剥離,HELLP症候群などの妊娠合併症があれば,不妊治療施設でもプレコンセプションケアとして積極的に診断検査基準に含まれる抗リン脂質抗体(aPL)を測定する。一方,血栓症の既往からみつかった血栓性素因についてはまったく対応が異なり,不妊治療に伴う卵巣過剰刺激症候群(OHSS)の徴候がみられた場合や妊娠が明らかとなった場合は,積極的にヘパリンを含む抗凝固療法を行う必用がある。また,凝固検査の評価においては,本検査が非常に繊細な検査であり,採血・検体処理手技により検査値が大きく変動する可能性があることに留意し,より正確な凝固検査を実施する体制を整備していくことが重要である。
金原出版(株), 2020年12月, 産婦人科の実際, 69 (13), 1605 - 1614, 日本語This prospective cohort study aimed to determine clinical factors associated with congenital cytomegalovirus (CMV) infection in pregnancy. Newborns born at a perinatal medical center received PCR analyses for CMV-DNA in their urine with informed consent. Clinical data, including age, maternal fever or flu-like symptoms, complications, ultrasound fetal abnormality, gestational weeks at delivery, and birth weight, were collected. Logistic regression analyses determined clinical findings associated with congenital CMV infection (cCMV). cCMV was diagnosed in 32 of 4380 pregnancies. Univariate and multivariable analyses revealed that age < 25 years old (OR 2.7, 95% CI 1.1-6.6; p < 0.05), the presence of maternal fever or flu-like symptoms (5.4, 2.6-11.2; p < 0.01), ultrasound fetal abnormalities (12.7, 5.8-27.7; p < 0.01), and preterm delivery at less than 34 gestational weeks (2.6, 1.1-6.0; p < 0.05) were independent clinical findings associated with cCMV. A combination of maternal fever/flu-like symptoms, ultrasound fetal abnormalities, or preterm delivery at less than 34 gestational weeks as optimal predictive factors showed 90.6% sensitivity, 66.4% specificity, and a maximum Youden index of 0.57. CMV-DNA tests in the urine of newborns born to mothers with these clinical manifestations may be an effective method in detecting cCMV as a targeted screening with a high sensitivity.
2020年11月12日, Scientific reports, 10 (1), 19706 - 19706, 英語, 国際誌研究論文(学術雑誌)
Objective The clinical manifestations of antiphospholipid syndrome (APS) include vascular thrombosis and pregnancy morbidity as well as recurrent pregnancy loss (RPL). However, in more than half of patients with RPL, the cause is never determined. Recently, beta(2)-glycoprotein I (beta(2)GPI) complexed with HLA class II molecules (beta(2)GPI/HLA-DR) was found to be a major autoantibody target in APS. The present study was undertaken to assess the serum levels of autoantibodies against the beta(2)GPI/HLA II complex as a potential risk factor for RPL in women. Methods Serum levels of antiphospholipid antibodies (aPLs), including IgG/IgM anticardiolipin antibodies, IgG/IgM anti-beta(2)GPI antibodies, and lupus anticoagulant as well as anti-beta(2)GPI/HLA-DR antibodies, were measured in 227 women with RPL. In this prospective, multicenter, cross-sectional study, women with RPL and their partners underwent HLA-DR immunotyping and analysis to identify potential causes and risk factors associated with RPL. The normal range for anti-beta(2)GPI/HLA-DR antibody levels was determined using serum samples obtained from a control population of female subjects (208 women of childbearing potential). Results Of the 227 women with RPL, aPL antibodies were detected in 19.8%, and 52 (22.9%) tested positive for anti-beta(2)GPI/HLA-DR antibodies. Among the 227 women, 121 (53.3%) had no risk factors for RPL, and among these women with unexplained RPL, 24 (19.8%) were positive for anti-beta(2)GPI/HLA-DR antibodies. Of the 112 women who had clinical symptoms of APS but did not have levels of aPLs that met the diagnostic criteria for APS, 21 (18.8%) were positive for anti-beta(2)GPI/HLA-DR antibodies. Conclusion The anti-beta(2)GPI/HLA-DR antibody is frequently associated with RPL. Detection of these autoantibodies is useful in understanding the pathogenesis of RPL. Our findings may provide potential new therapeutic strategies for addressing RPL in patients with obstetric APS.
WILEY, 2020年11月, ARTHRITIS & RHEUMATOLOGY, 72 (11), 1882 - 1891, 英語研究論文(学術雑誌)
OBJECTIVE: The clinical manifestations of antiphospholipid syndrome (APS) include vascular thrombosis and pregnancy morbidity as well as recurrent pregnancy loss (RPL). However, in more than half of patients with RPL, the cause is never determined. Recently, β2 -glycoprotein I (β2 GPI) complexed with HLA class II molecules (β2 GPI/HLA-DR) was found to be a major autoantibody target in APS. The present study was undertaken to assess the serum levels of autoantibodies against the β2 GPI/HLA II complex as a potential risk factor for RPL in women. METHODS: Serum levels of antiphospholipid antibodies (aPLs), including IgG/IgM anticardiolipin antibodies, IgG/IgM anti-β2 GPI antibodies, and lupus anticoagulant as well as anti-β2 GPI/HLA-DR antibodies, were measured in 227 women with RPL. In this prospective, multicenter, cross-sectional study, women with RPL and their partners underwent HLA-DR immunotyping and analysis to identify potential causes and risk factors associated with RPL. The normal range for anti-β2 GPI/HLA-DR antibody levels was determined using serum samples obtained from a control population of female subjects (208 women of childbearing potential). RESULTS: Of the 227 women with RPL, aPL antibodies were detected in 19.8%, and 52 (22.9%) tested positive for anti-β2 GPI/HLA-DR antibodies. Among the 227 women, 121 (53.3%) had no risk factors for RPL, and among these women with unexplained RPL, 24 (19.8%) were positive for anti-β2 GPI/HLA-DR antibodies. Of the 112 women who had clinical symptoms of APS but did not have levels of aPLs that met the diagnostic criteria for APS, 21 (18.8%) were positive for anti-β2 GPI/HLA-DR antibodies. CONCLUSION: The anti-β2 GPI/HLA-DR antibody is frequently associated with RPL. Detection of these autoantibodies is useful in understanding the pathogenesis of RPL. Our findings may provide potential new therapeutic strategies for addressing RPL in patients with obstetric APS.
2020年11月, Arthritis & rheumatology (Hoboken, N.J.), 72 (11), 1882 - 1891, 英語, 国際誌研究論文(学術雑誌)
OBJECTIVES: This prospective cohort study aimed to evaluate the efficacy of the universal neonatal urine screening, followed by diagnosis, workup and antiviral therapy for symptomatic congenital cytomegalovirus (CMV) infection to reduce neurological impairments and sequelae. METHODS: Neonates born in three facilities underwent the universal urine screening of PCR analyses for CMV-DNA. Neonates with symptomatic congenital CMV infection (cCMV) received oral valganciclovir (VGCV) of 32 mg/kg/day for six weeks or six months, and were evaluated for neurological outcomes including developmental quotient (DQ) and hearing function at around 18 months of corrected age. RESULTS: cCMV was diagnosed in 56 (0.48%) of 11,736 neonates, consisting of 23 neonates with symptomatic and 33 with asymptomatic cCMV. The incidence of cCMV in the general perinatal medical center (0.69%) was higher than that in the primary maternity hospital (0.23%, p<0.01%). Twenty of the 23 infants with symptomatic cCMV received VGCV therapy, and 19 underwent neurological assessment. Eight neonates (42%) had severe sequelae of DQ < 70, bilateral hearing dysfunction, and/or epilepsy. Four neonates (21%) had mild sequelae of DQ 70-79 or unilateral hearing dysfunction only, and seven (37%) showed normal development without any impairment. CONCLUSIONS: This study on a large scale demonstrated that a series of universal neonatal urine screening, diagnosis, workup, and VGCV therapy for neonates with symptomatic cCMV may decrease neurological impairments, because 58% of the treated infants had normal development or mild sequelae. The universal urine screening likely identifies subclinical symptomatic cCMV. Mothers with fetuses of cCMV seem to be selectively transferred to perinatal medical centers before deliveries.
2020年04月06日, Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy, 26 (8), 790 - 794, 英語, 国際誌[査読有り]
研究論文(学術雑誌)
子宮頸部小細胞癌は子宮頸部に発生する高異型度神経内分泌腫瘍であり、子宮頸癌の1〜3%を占めるに過ぎないが、早期に再発・転移をきたすことが多く予後不良な疾患として知られている。統一した治療方針は確立されていない。一方で子宮頸癌の治療において、腫瘍径が大きく、摘出が困難な進行症例では、術前化学療法が考慮される。今回我々は、局所進行子宮頸部小細胞癌に術前後の化学療法を施行し、良好な経過を得られたので報告する。症例は76歳。多量の不正出血を主訴に来院した。子宮傍組織に至る86mm大の腫瘤を認め、IIB期と診断した。組織診はsmall cell carcinomaであった。術前化学療法としてイリノテカン+シスプラチン(CPT-P)療法を1コース施行したところ、著明な縮小を認めたため、直ちに広汎子宮全摘術、両側付属器摘出術、骨盤リンパ節郭清、傍大動脈リンパ節郭清を行った。術後に2コースを追加し、術後7ヵ月で再発なく外来経過観察中である。転移のない局所進行子宮頸部小細胞癌では、術前後の化学療法が奏功し、予後を改善する可能性がある。(著者抄録)
(公社)日本婦人科腫瘍学会, 2020年04月, 日本婦人科腫瘍学会雑誌, 38 (2), 193 - 199, 日本語Primary peritoneal carcinosarcomas which arise from extragenital locations are extremely rare. Carinosarcomas contain both carcinomatous and sarcomatous elements and can be mainly detected in the female genital tract. We herein report a case of primary peritoneal carcinosarcoma diagnosed by laparoscopic surgery and treated with olaparib. A 62-year-old woman referred to our hospital due to abdominal distension. From imaging findings, we suspected advanced primary peritoneal carcinoma, and laparoscopic surgery was thereafter performed. The pathological diagnosis was carcinosarcoma, and the patient received chemotherapy with docetaxel and carboplatin. After three cycles of chemotherapy, the interval debulking surgery was attempted but resulted in suboptimal results. Because the bilateral ovaries were observed with a normal size and normal findings, we considered that the most likely diagnosis was primary peritoneal carcinosarcoma. After the additional chemotherapy and a 6-month observation period, the tumor relapsed. The patient received chemotherapy again, and the peritoneal carcinosarcoma was judged to be a platinum-sensitive tumor. Oral administration of olaparib was thus initiated. Although a dose reduction was needed due to anemia, olaparib was effective, and the patient could continue the drug for another 7 months. This is the first report of primary peritoneal carcinosarcoma treated with olaparib and shows that it could be a treatment option for platinum-sensitive tumors.
2020年, Case reports in obstetrics and gynecology, 2020, 9106390 - 9106390, 英語, 国際誌OBJECTIVE: This study aimed to evaluate the neurodevelopmental outcomes of infants with symptomatic congenital cytomegalovirus (SCCMV) disease after antiviral treatment and investigate the symptoms at birth associated with a developmental quotient (DQ) < 70. METHODS: In this prospective study conducted from 2009 to 2018, infants with SCCMV disease who received oral valganciclovir (VGCV; 32 mg/kg/day) for 6 weeks (November 2009 to June 2015) or 6 months (July 2015 to March 2018) were evaluated for their neurodevelopmental outcomes at around 18 months of corrected age. Sequelae were categorized as follows: no impairment with a DQ ≥ 80 and no hearing dysfunction; mild sequelae including unilateral hearing dysfunction or a DQ of 70-79; and severe sequelae with a DQ < 70, bilateral hearing dysfunction requiring hearing aids, blindness or epilepsy requiring anti-epileptic drugs. DQ was assessed using the Kyoto Scale of Psychological Development. Symptoms at birth associated with a DQ < 70 were determined using univariate and receiver operating characteristic curve analyses. RESULTS: Of the 24 treated infants, 21 reached > 18 months of corrected age. Six (29%) were no impairment, 4 (19%) had mild sequelae, and 11 (52%) developed severe sequelae. The symptoms at birth associated with a DQ < 70 were microcephaly and/or small for gestational age. CONCLUSION: In our cohort of infants with SCCMV disease after VGCV treatment, the incidence of severe sequelae at 18 months of corrected age was around 50%. When microcephaly and/or small for gestational age are seen at birth, a low DQ may appear even after oral VGCV treatment.
2019年10月, Brain & development, 41 (9), 743 - 750, 英語, 国際誌[査読有り]
研究論文(学術雑誌)
The aims of this study were to assess the effect of maternal screening for hepatitis B (HB) virus and a perinatal prevention program of mother-to-child transmission, and to identify clinical characteristics and findings associated with HB exacerbation during pregnancy. This prospective cohort study enrolled 3796 pregnant women and their neonates with informed consent. Pregnant women underwent maternal universal screening for HBs antigen (Ag) in the first trimester. If HBs Ag was positive, serum levels of HBe Ag, alanine transaminase (AST), aspartate aminotransferase (ALT), and HB virus (HBV) DNA were measured. All neonates delivered from HBs Ag-positive women were given HB immune globulin and HB vaccine based on the guidelines of the perinatal prevention program. Of the 3796 pregnant women, 40 (1.05%) tested positive for HBs Ag. Three (7.5%) of the 40 HBs Ag-positive women experienced exacerbation of HBV infection during pregnancy. Serum levels of AST (median 776 vs. 22 mIU/ml, p < 0.01), ALT (median 325 vs. 15 mIU/ml, p < 0.01), and HBV-DNA (median 9.1 vs. 5.4 log copies/ml, p < 0.05), and frequencies of HBe Ag-positive (100% vs. 29.7%, p < 0.05) and symptoms of itching or general fatigue (66.7% vs. 0%, p < 0.01) in three women with exacerbation of HBV infection were significantly higher than those in 37 women without exacerbation. There was no case of mother-to-child transmission, suggesting the perinatal HBV prevention program was effective. Levels of HBe Ag, liver enzymes, and HBV-DNA as well as symptoms of itching and general fatigue should be carefully monitored for HBs Ag-positive women during pregnancy and the postpartum period.
2019年08月, Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy, 25 (8), 621 - 625, 英語, 国際誌[査読有り]
研究論文(学術雑誌)
Primary infection with Toxoplasma gondii (T. gondii) during pregnancy may cause congenital infection of the infant. This study evaluated whether screening using IgG avidity and multiplex-nested polymerase chain reaction (PCR) methods was effective for detecting a high-risk pregnancy for congenital T. gondii infection. In a prospective cohort study serum T. gondii IgG avidity was measured in 469 pregnant women who had a positive test for T. gondii antibody plus a positive or equivocal test for IgM. Multiplex-nested PCR for T. gondii DNA on amniotic fluid, maternal blood, and neonatal blood was performed with informed consent. Low (<30%), borderline (30-35%), and high (>35%) IgG avidity indices were found in 104 (22.2%), 30 (6.4%), and 305 (71.4%), respectively. A total of 12 cases had a positive PCR test for amniotic fluids of the prenatal amniocentesis or at birth, or neonatal blood. Seven of the 12 cases were diagnosed as having congenital T. gondii infection, and they had low IgG avidity indices. Congenital T. gondii infection screening using of IgG avidity and multiplex-nested PCR methods for pregnant women with a positive test for T. gondii antibody plus a positive or equivocal test for T. gondii IgM was useful for detecting a high-risk pregnancy and diagnosing congenital T. gondii infection.
2019年06月, Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy, 25 (6), 427 - 430, 英語, 国際誌[査読有り]
研究論文(学術雑誌)
The aim of this prospective cohort study was to evaluate clinical factors associated with pregnancy outcomes in women with recurrent pregnancy loss (RPL). Women with a history of two or more pregnancy losses underwent workups for clinical factors of RPL and their pregnancies were followed-up with informed consent. Two hundred eleven (81.5%) of 259 women with RPL became pregnant. The multivariable analyses demonstrated that age (p < .01, OR 0.9, 95%CI 0.97-0.83), uterine abnormality (p < .05, OR 0.3, 95%CI 0.11-0.8), and protein C (PC) deficiency (p < .01, OR 0.14, 95%CI 0.03-0.6) were independent factors for becoming pregnancy in women with RPL. The number of previous pregnancy loss (p < .01, OR 0.57, 95%CI 0.43-0.75) and natural killer (NK) cell activity ≥33% (p < .01, OR 0.31, 95%CI 0.13-0.73) were independent factors for live birth in the subsequent pregnancy. Advanced age, the presence of uterine abnormality, and PC deficiency were risk factors for reduced pregnancy rate in women with RPL. Increased number of previous pregnancy loss and high NK cell activity were risk factors for miscarriage in the subsequent pregnancy. These results involve important information and are helpful for clinical practitioners.
2019年04月23日, Gynecological endocrinology : the official journal of the International Society of Gynecological Endocrinology, 35 (10), 1 - 6, 英語, 国際誌[査読有り]
研究論文(学術雑誌)
Although earlier studies have shown that antiviral treatment regimens using valganciclovir (VGCV) improved hearing function in some infants with congenital cytomegalovirus (CMV) infection; its efficacy on the severity of hearing dysfunction is unclear. We conducted a prospective study among 26 infants with congenital CMV infections from 2009 to 2018. Oral VGCV (32 mg/kg/day) was administered for 6 weeks (November 2009 to June 2015; n = 20) or 6 months (July 2015 to March 2018, n = 6). Hearing function was evaluated by measuring the auditory brainstem response before VGCV treatment and at 6 months. Hearing dysfunction, defined as a V-wave threshold >40 dB, was categorized into: most severe, ≥91 dB; severe, 61⁻90 dB; and moderate, 41⁻60 dB. Hearing improvement was defined as a decrease of ≥20 dB from the pretreatment V-wave threshold. Of 52 ears in 26 infants with congenital CMV infection, 29 (56%) had hearing dysfunction, and of 29 ears, 16 (55%) improved after VGCV treatment. Although, 16 (84%) of 19 ears with moderate or severe hearing dysfunction improved after treatment (p < 0.001), 10 ears with the most severe form did not. In conclusion, VGCV treatment is effective in improving moderate and severe hearing dysfunction in infants with congenital CMV infection.
2019年03月19日, International journal of molecular sciences, 20 (6), 英語, 国際誌[査読有り]
研究論文(学術雑誌)
Antibodies against fetal platelet alloantigens in maternal blood cause neonatal alloimmune thrombocytopenia (NAIT). We encountered four newborns with NAIT from three women. A woman carried anti-human platelet antigen (HPA)-1a antibody, and vaginally delivered a newborn who had subarachnoid hemorrhage and platelet transfusions. She delivered the second newborn by a cesarean section who had no symptom. The second woman carried anti-human leukocyte antigen-A2 antibody and vaginally delivered a newborn who had no symptom. The third woman with a history of recurrent pregnancy losses carried anti-HPA-4b antibody, and delivered a newborn by a cesarean section who received platelet transfusions and immunoglobulin infusions. Antiplatelet antibody screening may be helpful in women who have a history of blood transfusion, or previous neonates with thrombocytopenia or intracranial hemorrhage.
2019年03月, The Kobe journal of medical sciences, 64 (6), E197 - E199, 英語, 国内誌[査読有り]
研究論文(学術雑誌)
抗リン脂質抗体(aPL)は1980年代中頃に発見され、不育症や妊娠合併症、血栓塞栓症との関連が解析されてきた。抗リン脂質抗体症候群(APS)は1986年に誕生した疾患群で、aPLを有し、かつ臨床症状として血栓症や妊娠高血圧腎症、子癇、胎盤機能不全、胎児発育不全(FGR)による早産、および不育症といった妊娠合併症をきたす疾患である。APS合併妊娠は治療が可能であり、妊娠合併症の原因検索の一つとしてaPLの検索は重要である。(著者抄録)
(株)診断と治療社, 2019年02月, 産科と婦人科, 86 (2号), 223 - 229, 日本語[招待有り]
Fetal intestinal volvulus is a rare condition, and fetal diagnosis of this disease is still challenging, especially in primary cases not accompanied by other comorbidities, such as intestinal malformations. Herein, we report a case of fetal primary small bowel volvulus associated with acute gastric dilatation detected by ultrasonography. We speculate that the mechanism of acute gastric dilatation in our case was peristatic malfunction of the whole intestine caused by a strangulated ileus resulting from fetal intestinal volvulus. In conclusion, acute gastric dilatation detected by fetal ultrasound can indicate the fetal intestinal volvulus.
2019年01月11日, The Kobe journal of medical sciences, 64 (4), E157-E159 - E159, 英語, 国内誌[査読有り]
研究論文(学術雑誌)
INTRODUCTION: Cytomegalovirus (CMV) infection is the most common cause of congenital viral infections in humans. The unusual structure of the placenta plays a pivotal role in CMV transmission from mothers to fetuses. The aim of this study was to evaluate the histopathological findings of placentas with congenital CMV infections. METHODS: We obtained placental specimens from 35 women who had newborns with congenital CMV infections. Placental specimens, extraplacental membranes, and umbilical cords were stained with hematoxylin and eosin, and subjected to immunohistochemical analysis. We evaluated the localization of CMV-infected cells and other histological parameters. RESULTS: Thirty (86%) of the 35 placentas tested positive for CMV-infected cell proteins by immunohistochemistry. A majority of CMV-positive cells were present in fibroblasts and endothelial cells in the villi. The number of CMV-infected cells was inversely correlated to gestational age at delivery. The frequency of chronic villitis (65% vs. 11%; p < 0.01) and changes of the villi (38% vs. 0%; p < 0.05) in the placentas from mothers with symptomatic congenital CMV infections was higher than those observed in samples from mothers with asymptomatic congenital infections. The frequency of changes of the decidua (43% vs. 5%; p < 0.01) in the placentas from mothers with non-primary CMV infections was higher than those from mothers with primary infections. DISCUSSION: Chronic villitis and changes of the villi were associated with symptomatic congenital CMV infections. The changes of the decidua were associated with congenital CMV infections, in mothers with non-primary CMV infections.
2019年01月, Placenta, 75, 62 - 67, 英語, 国際誌[査読有り]
研究論文(学術雑誌)
2008年から7月から2016年12月までにHBs抗原検査を行い、分娩した妊婦3796名とその新生児を対象に、前向き研究を実施した。B型肝炎(HBV)キャリア妊婦における妊娠中のB型肝炎増悪(Flare)の発生頻度および臨床的特徴、HBVスクリーニングによる母子感染予防対策の有用性も調査した。対象となったHBs抗原陽性40名を分析対象とした。HBs抗原陽性妊婦からの出生児40名中、転院5名を除く35名に垂直感染予防策が完遂されて、全例で垂直感染は見られなかった。分析対象40名のうち、3名(7.5%)でFlareがみられ、Flareがみられた3名中2名で皮膚そう痒感や全身倦怠感などの臨床症状を呈し、3名ともHBV-DNA量が増加した。HBVスクリーニングによる母子感染予防対策は有効であると考えられた。HBs抗原陽性妊婦がFlareを起こすことは稀ではなく、劇症化する場合もあり、内科のある高次施設での妊娠管理が望ましいと考えられた。
兵庫県母性衛生学会, 2018年12月, 兵庫県母性衛生学会雑誌, (27号), 67 - 68, 日本語[査読有り]
The aim of this nested case-control study was to evaluate clinical factors associated with the occurrence of congenital cytomegalovirus (CMV) infection in pregnant women with non-primary CMV infection. In a cohort study of CMV screening for 2193 pregnant women and their newborns, seven newborns with congenital CMV infection were identified among 1287 pregnant women with non-primary CMV infection that was defined as negative IgM and positive IgG with IgG avidity index >45%. In the 1287 women with non-primary CMV infection, clinical findings and complications were compared between pregnancies with and without congenital CMV infection. Clinical factors associated with the occurrence of congenital CMV infection were evaluated. The birth weight of newborns with congenital CMV infection was less than that of newborns without congenital infection (p < 0.05). Univariate logistic regression analyses demonstrated that threatened premature delivery (OR 10.6, 95%CI 2.0-55.0; p < 0.01) and multiple pregnancy (OR 7.1, 95%CI 1.4-37.4; p < 0.05) were associated with congenital infection. Multivariable logistic regression analyses demonstrated that threatened premature delivery (OR 8.4, 95%CI 1.5-48.1; p < 0.05) was a single risk factor for congenital CMV infection in pregnant women with non-primary CMV infection. This study revealed for the first time that threatened premature delivery was associated with the occurrence of congenital CMV infection in pregnant women with non-primary CMV infection, the pathophysiology of which may be closely associated with CMV reactivation during pregnancy.
2018年09月, Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy, 24 (9), 702 - 706, 英語, 国際誌[査読有り]
研究論文(学術雑誌)
妊娠30週未満で分娩となった胎児発育不全児(FGR)16例を対象に、予後不良に関連する因子について検討した。その結果、後遺症なし生存中の予後良好群は8例、後遺症あり生存または、子宮内胎児死亡、新生児死亡の予後不良群は8例であった。予後良好群に比べ予後不良群では、妊娠回数が少なく、FGR診断時胎児推定体重のSD値が小さく、高度の胎児血流異常ありの割合が高かった。FGRの原因やリスク因子としては妊娠高血圧症候群が62.4%を占めていた。また、FGR診断後にHDP(妊娠高血圧症候群)を発症した症例もみられた。
「産婦人科の進歩」編集室, 2018年08月, 産婦人科の進歩, 70 (3), 270 - 277, 日本語[査読有り]
PURPOSE: To justify a classification system for angiographic images of uterine artery embolization (UAE) for postpartum hemorrhage (PPH) and identify new risk factors associated with failed embolization. MATERIALS AND METHODS: A retrospective analysis of 63 consecutive patients who underwent UAE for severe PPH was performed. Uterine artery angiography (UA) before embolization was classified into two types: type 1 was defined as complete staining and type 2 was defined as partial staining of the uterine arteries. The clinical outcome, UA classification, and other possible factors previously reported were evaluated. Univariate and multivariate analyses were performed to determine the factors related to clinical outcomes. RESULTS: Sixty-three patients were enrolled (type 1, 22; type 2, 41). The clinical success rates of the primary UAE session were 90.9% (20/22) for type 1 and 61.0% (25/41) for type 2 (p = 0.018). Univariate and multivariate analyses demonstrated that the only UA classification was significantly associated with primary UAE failure (p = 0.033). CONCLUSIONS: The UA classification is an independent predictive factor of the clinical success rate of the primary UAE session for PPH; thus, it is an intuitive and optimal predictor for interventional radiologists to decide whether additional therapy is necessary.
2018年06月, Japanese journal of radiology, 36 (6), 394 - 400, 英語, 国内誌[査読有り]
研究論文(学術雑誌)
Purpose: This study aimed to assess the efficacy of high-dose i.v. immunoglobulin (HIVIg) therapy in pregnant women with antiphospholipid syndrome (APS) secondary to systemic lupus erythematosus with a history of pregnancy failure, despite receiving low-dose aspirin plus unfractionated heparin therapy, of which condition being designated as "aspirin-heparin-resistant APS" (AHRAPS). Methods: The HIVIg therapy (20 g/d, 5 days) was performed for the pregnancies of five women with AHRAPS. Results: Five of the eight pregnancies ended in live births. The gestational ages of delivery in four of the five pregnancies were extended, compared with previous pregnancies. The HIVIg therapy was considered to be successful for these four pregnancies. Excluding one pregnancy that ended in miscarriage with an abnormal chromosome karyotype of the villi, the HIVIg therapy was considered to be successful in four (57.1%) of the seven pregnancies of the women with AHRAPS. Although all the live newborns were prematurely delivered, no adverse effect of the HIVIg therapy was observed. Conclusions: The HIVIg therapy might be beneficial as an immune modifier for pregnant women with AHRAPS. However, the precise indication of which women with AHRAPS who should receive HIVIg therapy remains unknown.
2018年04月, Reproductive medicine and biology, 17 (2), 149 - 154, 英語, 国内誌[査読有り]
研究論文(学術雑誌)
INTRODUCTION: Placenta previa (PP) is one of the most significant risk factors for adherent placenta (AP). The aim of this study was to evaluate the diagnostic efficacy of a novel scoring system for predicting AP in pregnant women with PP. METHODS: This prospective cohort study enrolled 175 women with PP. The placenta previa with adherent placenta score (PPAP score) is composed of 2 categories: (1) past history of cesarean section (CS), surgical abortion, and/or uterine surgery; and (2) ultrasonography and magnetic resonance imaging findings. Each category is graded as 0, 1, 2, or 4 points, yielding a total score between 0 and 24. When women with PP had PPAP score ≥8, they were considered to be at a high risk for AP and received placement of preoperative internal iliac artery occlusion balloon catheters. If they were found to have AP during CS, they underwent hysterectomy or placenta removal using advanced bipolar with balloon catheter occlusion. The predictive accuracy of PPAP score was evaluated. RESULTS: In total, 23 of the 175 women with PP were diagnosed as having AP, histopathologically or clinically. Twenty-one of 24 women with PPAP score ≥8 had AP, whereas two of 151 women with PPAP score <8 had AP. The scoring system yielded 91.3% sensitivity, 98.0% specificity, 87.5% positive predictive value, and 98.7% negative predictive value for predicting AP in women with PP. DISCUSSION: This prospective study demonstrated that PPAP scoring system may be useful for predicting AP in women with PP.
2018年04月, Placenta, 64, 27 - 33, 英語, 国際誌[査読有り]
研究論文(学術雑誌)
Congenital complete atrioventricular block (CCAVB) is a condition in which the atria and ventricles beat independently of each other. CCAVB cases require permanent pacemaker implantation until adulthood. Nevertheless, consensus regarding postnatal medical therapy for bradycardia has not been reached. Here we report the case of a newborn with CCAVB, whose intractable bradycardia was successfully treated with transdermal tulobuterol. Tulobuterol is a selective β2-adrenoceptor agonist, widely used safely as bronchodilator in children. It also has positive inotropic and chronotropic effect via β1-adrenoceptors. We believe the tulobuterol patch can be used as an optional therapy for CCAVB where pacemaker implantation is not available.
2018年04月, Kobe J Med Sci, 63 (4), E109 - E112, 英語, 国内誌[査読有り]
研究論文(学術雑誌)
The aim of this prospective study was to determine clinical factors associated with adverse pregnancy outcomes in women with systematic lupus erythematosus (SLE). Fifty-six pregnancies from 46 women with SLE were enrolled. Risk factors for pregnancy loss, premature delivery, hypertensive disorders of pregnancy (HDP), and light-for-date neonate (LFD), were evaluated. Univariate and multivariate logistic regression analyses revealed a history of two or more pregnancy losses before 10 gestational weeks (GW) (OR 11.5, 95%CI 1.72-76.8) as a risk factor for pregnancy loss; low levels of blood complements (OR 7.55, 95%CI 1.10-51.9) and antiphospholipid syndrome (OR 26.5, 95%CI 3.17-219) as risk factors for premature delivery before 37 GW; SLEDAI score at conception (OR 1.68, 95%CI 1.05-2.68) and positive tests for two or more antiphospholipid antibodies (OR 6.89, 95%CI 1.13-41.9) as risk factors for premature delivery before 34 GW; prednisolone therapy >14mg/day (OR 7.55, 95%CI 1.10-51.9) as a risk factor for HDP; and low dose aspirin therapy (OR 0.21, 95%CI 0.05-0.97) decreased the risk for LFD neonate. These results have important implications for clinicians managing SLE complicated pregnancy.
2018年02月, Journal of reproductive immunology, 125, 39 - 44, 英語, 国際誌[査読有り]
研究論文(学術雑誌)
PROBLEM: Is an abnormal increase or decrease of M1/M2 macrophages observed in the deciduae of miscarriages with normal fetal chromosome (MN)? METHODS OF STUDY: Deciduae of 18 MN and 26 miscarriages with abnormal fetal chromosome (MA) were obtained. Additionally, deciduae from 15 women whose pregnancies ended in induced abortions (IA) and endometriums at the mid-luteal phase from 19 non-pregnant women endomeriums of mid-luteal phases (EM) were obtained. Macrophages were analyzed by flow cytometry using monoclonal antibodies for CD68, HLA-DR, and CD163. RESULTS: M1 macrophages, defined as CD68+ HLA-DR+ CD163- cells, increased in MN compared with MA or IA. M2 macrophages, defined as CD68+ HLA-DR- CD163+ cells, increased in the deciduae of MA and IA compared with EM. However, this increase was not observed in the deciduae of MN. CONCLUSION: Our findings of phenotypic characters of decidual macrophages in MN provide additional evidence that M2 polarization is favorable for the maintenance of early stages of pregnancy.
2018年02月, American journal of reproductive immunology (New York, N.Y. : 1989), 79 (2), 英語, 国際誌[査読有り]
研究論文(学術雑誌)
[査読有り]
研究論文(学術雑誌)
We report two cases of pulmonary hypoplasia due to fetal ascites in symptomatic congenital cytomegalovirus (CMV) infections despite fetal therapy. The patients died soon after birth. The pathogenesis of pulmonary hypoplasia in our cases might be thoracic compression due to massive fetal ascites as a result of liver insufficiency. Despite aggressive fetal treatment, including multiple immunoglobulin administration, which was supposed to diminish the pathogenic effects of CMV either by neutralization or immunomodulatory effects, the fetal ascites was uncontrollable. To prevent development of pulmonary hypoplasia in symptomatic congenital CMV infections, further fetal intervention to reduce ascites should be considered.
FRONTIERS MEDIA SA, 2017年11月, FRONTIERS IN PEDIATRICS, 5, 241, 英語[査読有り]
研究論文(学術雑誌)
Background: The aim of this prospective cohort study was to evaluate the efficacy of maternal screening for congenital cytomegalovirus infection (CCI) using cytomegalovirus (CMV) immunoglobulin G (IgG) and the IgG avidity index (AI). Methods: Pregnant women underwent screening of CMV IgG and AI measurements. IgG-negative women underwent remeasurement of IgG after educational intervention. Women with an AI ≤45% received further examinations, including measurement of CMV IgM. All newborns received polymerase chain reaction analyses of the urine, and CCI was diagnosed by the detection of CMV-DNA in the urine. Primary infection was defined as an AI <35% and/or positive IgM (>1.20 index). Serum samples from women with an AI >45% were stored, and the IgM levels were measured after delivery. The efficacy of AI and IgM for CCI screening was compared. Results: A total of 1562 (71.2%) women tested positive for IgG. In this study, 10 newborns with CCI were detected. The presence of infection in 3 newborns from mothers with primary infection was predicted by screening of IgG and AI <35%. However, infection in 7 newborns from women with nonprimary infection could not be predicted by screening of CMV IgG, AI <35%, or IgM. The application of an AI <35% for CCI screening yielded 22.2% sensitivity, 95.0% specificity, 2.5% positive predictive value, and 99.5% negative predictive value and was similar to that of IgM (11.1% sensitivity, 93.2% specificity, 0.9% positive predictive value, and 92.7% negative predictive value). Conclusions: Maternal screening using CMV IgG and AI can identify pregnancies with CCI from primary infection, but overlooks a number of those from nonprimary infection.
2017年10月30日, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, 65 (10), 1652 - 1658, 英語, 国際誌[査読有り]
研究論文(学術雑誌)
[招待有り]
研究論文(学術雑誌)
[招待有り]
研究論文(学術雑誌)
The aim of this study was to understand the clinical features of antiphospholipid syndrome (APS)-complicated pregnancies and evaluate risk factors for the adverse pregnancy outcomes. This multicenter study evaluated live-birth rates according to therapy modality for APS and risk factors of pregnancy loss in 81 pregnancies. Risk factors for pregnancy complications, including premature delivery before 34 gestational weeks, hypertensive disorders of pregnancy, thrombocytopenia, and light-for-date neonate, were evaluated in 51 women who received low dose aspirin (LDA) plus unfractionated heparin (UFH) and delivered after 24 GW. The live-birth rate in APS pregnancies with LDA+UFH therapy was 92.6%. A multiple logistic regression analysis demonstrated that LDA+UFH therapy decreased the risk of pregnancy loss (OR 0.13, 95%CI 0.03-0.62), and that a history of pregnancy loss despite LDA+UFH therapy increased the risk of pregnancy loss (OR 8.74, 95%CI 1.69-45.2). LDA therapy prior to pregnancy decreased the risk of premature delivery (OR 0.14, 95%CI 0.03-0.69). Positive tests for two or more anti-phospholipid antibodies increased the risks of premature delivery (OR 9.61, 95%CI 1.78-51.8) and thrombocytopenia (OR 4.90, 95%CI 1.11-21.7). Laboratory findings of low complements increased the risk of hypertensive disorders of pregnancy (OR 12.1, 95%CI 1.61-91.0). Standard therapy yielded high live-birth rates. Positive tests for two or more anti-phospholipid antibodies and low complements were associated with adverse pregnancy outcomes. These results have important implications for clinicians.
ELSEVIER IRELAND LTD, 2017年08月, Journal of reproductive immunology, 122, 21 - 27, 英語, 国際誌[査読有り]
研究論文(学術雑誌)
[招待有り]
研究論文(学術雑誌)
Epithelial ovarian carcinomas account for more than 90% of human ovarian cancers and have become the primary cause of death for gynecological malignancies. Unlimited cell proliferation and resistance to cell apoptosis contribute to the development of ovarian cancers. However, the underlying mechanisms involved in these processes in epithelial ovarian carcinomas are yet poorly understood. In the present study, we examined the Hippo signaling gene expression and investigated the effects of Sphingosine 1-phosphate (S1P) on cell proliferation and the underlying mechanisms in human ovarian cancer cell lines, OVCAR3 and SKOV3. Our results demonstrate that S1P disrupts Hippo signaling by reducing YAP phosphorylation and increasing the expression of CCN1 and CCN2 in both ovarian cancer cells. Furthermore, the increase in CCN1/CCN2 expression contributes to the S1P-induced increase in cancer cell proliferation.
IMPACT JOURNALS LLC, 2017年04月18日, Oncotarget, 8 (16), 27166 - 27176, 英語, 国際誌[査読有り]
研究論文(学術雑誌)
This study aimed to evaluate whether natural killer (NK) cell activity was associated with the etiology of recurrent miscarriage (RM), and to evaluate the predictive value of NK cell activity for outcomes of following pregnancies in women with RM. Peripheral NK cell activity was measured in 160 non-pregnant women with a history of two or more miscarriages. This activity was compared according to the etiology of RM and to pregnancy outcomes in women who became pregnant. NK cell activity in women with unexplained RM was significantly higher than that in those with known etiologies of RM. NK cell activity in women whose next pregnancies ended in miscarriage of fetuses with a normal chromosome karyotype (MN) was higher than that in those with live births (p<0.05). Women with NK cell activity ≥33% had a higher risk for MN (relative risk 3.4, 95% confidence interval 1.3-8.7). An increase in peripheral NK cell activity was associated with MN. This increase might be involved in the pathophysiology underlying RM.
ELSEVIER IRELAND LTD, 2017年04月, Journal of reproductive immunology, 120, 42 - 47, 英語, 国際誌[査読有り]
研究論文(学術雑誌)
BACKGROUND: This prospective study aimed to determine maternal clinical, laboratory, and ultrasound findings that effectively predict the occurrence of congenital cytomegalovirus (CMV) infection (CCI) in high-risk pregnant women. METHODS: Three hundred CMV immunoglobulin (Ig) M-positive pregnant women were enrolled. The maternal clinical and laboratory findings, including serum CMV IgM and IgG; IgG avidity index (AI); antigenemia assay (C7-HRP); polymerase chain reaction (PCR) for the detection of CMV-DNA in the maternal serum, urine, and uterine cervical secretion; and prenatal ultrasound findings, were evaluated. To determine predictive factors for the occurrence of CCI, logistic regression analyses were performed. RESULTS: In 22 of the 300 women, CCI was confirmed using PCR for CMV-DNA in newborn urine. Univariate analyses demonstrated that the presence of maternal flu-like symptoms, presence of ultrasound fetal abnormalities, serum titers of CMV IgM, positive results for C7-HRP, CMV IgG AI <40%, and positive PCR results in the uterine cervical secretion were statistically associated with the occurrence of CCI. Multivariable analysis revealed that the presence of ultrasound fetal abnormalities (odds ratio [OR], 31.9; 95% confidence interval [CI], 8.5-120.3; P < .001) and positive PCR results in the uterine cervical secretion (OR, 16.4; 95% CI, 5.0-54.1; P < .001) were independent predictive factors of CCI in CMV IgM-positive women. CONCLUSIONS: This is the first prospective cohort study to suggest that the presence of CMV-DNA in the maternal uterine cervical secretion and ultrasound fetal abnormalities are predictive of the occurrence of congenital CMV infection in high-risk pregnant women.
OXFORD UNIV PRESS INC, 2017年01月15日, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, 64 (2), 159 - 165, 英語, 国際誌[査読有り]
研究論文(学術雑誌)
[招待有り]
研究論文(学術雑誌)
[招待有り]
研究論文(学術雑誌)
OBJECTIVES: To determine the risk factors for glucose intolerance (GI) during the postpartum period in women with gestational diabetes mellitus (GDM). METHODS: This prospective cohort study included 72 Japanese women with GDM who underwent 75 g oral glucose tolerance tests (OGTT) at 12 weeks after delivery. These women were divided into the GI group and the normal group based on postpartum OGTT. Risk factors for GI, including levels of blood glucose (BG), area under the curve (AUC) of glucose, AUC insulin, HbA1c, homeostasis model assessment-insulin resistance (HOMA-IR), HOMA-β, insulinogenic index (II) and the oral disposition index (DI) in antepartum OGTT, were analyzed by logistic regression analyses. RESULTS: Of the 72 women, 60 (83.3%) were normal and 12 (16.7%) had GI. By univariate logistic regression analyses, fasting BG, AUC glucose, HOMA-β, II and oral DI were selected as risk factors for GI. Multivariate logistic regression analysis revealed that the level of II in antepartum OGTT was a significant factor that predicted GI after delivery (odds ratio, 0.008; 95% CI, 0.0001-0.9; p < 0.05). CONCLUSIONS: II measured by OGTT during pregnancy might be a useful predictor of GI within the early postpartum period in women with GDM.
2016年10月, Gynecological endocrinology : the official journal of the International Society of Gynecological Endocrinology, 32 (10), 803 - 806, 英語, 国際誌[査読有り]
研究論文(学術雑誌)
PROBLEM: The aim of this prospective study was to evaluate phenotypic differences of helper T (Th), cytotoxic T (Tc), and regulatory T (Treg) cells in the deciduae of missed miscarriage with a normal chromosome karyotype of a fetus (MN) and missed miscarriage with an abnormal chromosome karyotype of a fetus (MA). METHODS OF STUDY: The decidua of 19 MN and 28 MA was obtained. Additionally, the decidua of 15 induced abortion (IA) and the endometrium of 19 non-pregnant women (EM) were obtained. IFN-γ(+) , IL-17(+) , CD25(high) Foxp3(+) cells in CD4(+) (Th) cells, and IFN-γ(+) cells in CD8(+) (Tc) cells were evaluated by flow cytometry. RESULTS: The percentages of IFN-γ(+) Tc and CD4(+) CD25(high) Foxp3(+) (Treg) cells in MN were significantly increased as compared with MA and IA. The percentage of IFN-γ(+) Th in MN was increased as compared with IA. CONCLUSION: Activation of IFN-γ(+) Tc and Treg cells in the decidua might be associated with the pathophysiology underlying MN.
2016年09月, American journal of reproductive immunology (New York, N.Y. : 1989), 76 (3), 199 - 204, 英語, 国際誌[査読有り]
研究論文(学術雑誌)
This prospective study aimed to evaluate pregnancy outcome and complications in women with recurrent pregnancy loss (RPL) and protein S (PS) deficiency, who received low dose aspirin (LDA) or LDA plus heparin (LDA/H) therapies. Clinical characteristics, pregnancy outcome and complications of 38 women with two or more RPL and <60% of plasma free PS antigen were compared among three groups: antiphospholipid antibody (aPL)-negative women who received LDA (group A), aPL-negative women who received LDA/H (group B) and aPL-positive women who received LDA/H (group C). Gestational weeks (GW) at delivery in group C (median 32 GW) were earlier than 40 GW in group A and 38.5 GW in group B (p < 0.05). The birth weight in group C (median 1794 g) was less than 2855 g in group B (p < 0.05). The incidences of fetal growth restriction (37.5%), pregnancy-induced hypertension (37.5%), and preterm delivery (62.5%) in group C were higher than those (4.5%, 0%, and 4.5%, respectively) in group B (p<0.05). Women with RPL, PS deficiency, and positive aPL had high risks for adverse pregnancy outcome and complications, even when they received LDA/H therapy. Among women with RPL, PS, and negative aPL, there was no difference in these risks between LDA alone and LDA/H therapies.
2016年08月, Gynecological endocrinology : the official journal of the International Society of Gynecological Endocrinology, 32 (8), 672 - 674, 英語, 国際誌[査読有り]
研究論文(学術雑誌)
[査読有り]
研究論文(学術雑誌)
[査読有り]
BACKGROUND: Newborn screening for urinary cytomegalovirus (CMV) and early introduction of antiviral treatment are expected to improve neurological outcomes in symptomatic congenital CMV-infected infants. This cohort study prospectively evaluated neurological outcomes in symptomatic congenital CMV-infected infants following the introduction of hospital-based newborn urinary CMV screening and antiviral treatment. SUBJECTS/METHODS: Following institutional review board approval and written informed consent from their parents, newborns were prospectively screened from 2009 to 2014 for urinary CMV-DNA by PCR within 1 week after birth at Kobe University Hospital and affiliated hospitals. CMV-positive newborns were further examined at Kobe University Hospital, and those diagnosed as symptomatic were treated with valganciclovir for 6 weeks plus immunoglobulin. Clinical neurological outcomes were evaluated at age ⩾12 months and categorized by the presence and severity of neurologic sequelae. RESULTS: Urine samples of 6348 newborns were screened, with 32 (0.50%) positive for CMV. Of these, 16 were diagnosed with symptomatic infection and 12 received antiviral treatment. Four infants developed severe impairment (33%), three developed mild impairment (25%), and five developed normally (42%). CONCLUSIONS: This is the first Japanese report of neurological assessments in infants with symptomatic congenital CMV infection who received early diagnosis and antiviral treatment. Urinary screening, resulting in early diagnosis and treatment, may yield better neurological outcomes in symptomatic congenital CMV-infected infants.
2016年02月, Brain & development, 38 (2), 209 - 16, 英語, 国際誌[査読有り]
研究論文(学術雑誌)
Background: Few studies have targeted psychomotor development and associated perinatal risk factors in Japanese very low birth weight (VLBW) infants who are severely small for gestational age (SGA). Design/subjects: A single-center study was conducted in 104 Japanese VLBW infants who were born preterm, due to maternal, umbilical cord, or placental abnormalities, between 2000 and 2007. Psychomotor development as a developmental quotient (DQ) was assessed using the Kyoto Scale of Psychological Development at 3 years corrected age. Severely SGA was defined as birth weight or length below -2 standard deviation values of the mean values at the same gestation. VLBW infants were divided into 2 subgroups based on gestational age at birth: >= 28 weeks (n = 64) and <28 weeks (n = 40). DQs of infants with severe SGA were compared with those of infants who were appropriate for gestational age (AGA). Factors associated with developmental disabilities in VLBW infants with severe SGA (n = 23) were determined. Results: In the group born at >= 28 weeks gestation, infants with severe SGA had normal DQ values and did not significantly differ from those with AGA. However, in the group born at <28 weeks gestation, severe SGA infants had significantly lower postural motor DQ values than AGA infants. Gestational age <28 weeks was an independent factor for low postural motor DQ, regardless of the cause of severe SGA or pregnancy termination. Conclusions: Extremely preterm newborns with severe SGA are at risk of motor developmental disability at age 3 years. (C) 2015 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.
ELSEVIER SCIENCE BV, 2016年02月, BRAIN & DEVELOPMENT, 38 (2), 188 - 195, 英語[査読有り]
研究論文(学術雑誌)
[査読有り]
研究論文(学術雑誌)
[査読有り]
Primary Toxoplasma gondii (T. gondii) infection during pregnancy may lead to congenital toxoplasmosis. Maternal screening using T. gondii IgG avidity measurement and multiplex nested PCR was performed. The aim of this prospective cohort study was to determine a cut-off value of IgG avidity index (AI) for the prediction of the presence of T. gondii DNA in the amniotic fluid. One hundred thirty-nine women with positive or equivocal tests for IgM underwent both serum IgG avidity measurement and PCR analysis for the amniotic fluid. Nine had positive PCR results, and three of them were diagnosed as having congenital infection. A cut-off value of IgG AI was determined using receiver operating characteristic analysis. IgG AI (mean 13%) in women with positive PCR results was significantly lower than that (39%) in women with negative results. A cut-off value of <25% IgG AI yields the best results with 77.8% sensitivity and 81.5% specificity for the presence of T. gondii DNA in the amniotic fluid. None of women with IgG AI of ≥30% had a positive PCR result or congenital infection. This study firstly demonstrated that a cut-off value of 25-30% IgG AI might be useful for the prediction of the presence of T. gondii DNA in the amniotic fluid and congenital infection.
2015年09月, Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy, 21 (9), 668 - 71, 英語, 国際誌[査読有り]
研究論文(学術雑誌)
It was the study objective to evaluate whether low levels of plasma protein S (PS) activity, free PS, protein C (PC) activity and coagulation factor XII (FXII) during early pregnancy are related to adverse pregnancy outcomes. Peripheral blood samples were obtained at 8-14 gestational weeks (GW) from a consecutive series of 1,220 women. The levels of plasma PS activity, free PS, PC activity, and FXII were measured. Cut-off values were defined as < 1st, < 5th, and < 10th percentiles of values obtained from 933 women whose pregnancies ended in normal deliveries without complications. PS activity of < 10th percentile yielded risks of pregnancy-induced hypertension (PIH) and severe PIH, while free PS level of < 5th percentile yielded a risk of pre-eclampsia. FXII level of < 1st percentile yielded a risk of premature delivery (PD) at < 34 GW. None was associated with PD at < 37 GW, fetal growth restriction or fetal loss. A multivariate analysis demonstrated that PS activity of < 10th percentile (odds ratio 5.9, 95 % confidence interval 1.7-18.1) and body mass index (BMI) ≥ 25 kg/m² (4.3, 1.1-13.3) were independent risk factors for severe PIH. Similarly, free PS level of < 5th percentile (4.4, 1.0-14.3) and BMI ≥ 25 kg/m² (4.0, 1.3-10.9) were independent risk factors for pre-eclampsia. In conclusion, women with low levels of plasma PS activity and free PS during early pregnancy might have increased risks of PIH, severe PIH or pre-eclampsia. Women with low FXII level might have an increased risk of PD at < 34 GW.
20150416, 2015年07月, Thrombosis and haemostasis, 114 (1), 65 - 9, 英語, 国際誌[査読有り]
研究論文(学術雑誌)
研究論文(学術雑誌)
This study aimed to evaluate changes in natural killer (NK) cell activity and the percentage of monocytes in women with recurrent miscarriage who received medium-dose intravenous immunoglobulin (IVIg) therapy. Fourteen women with a history of six or more recurrent miscarriages of unexplained etiology received 60-g IVIg therapy (20 g daily, for three days) during early gestation. NK cell activity in the peripheral blood decreased to 12% one week after therapy compared with before therapy (median, 22%, P < 0.001) and the percentage of monocytes increased from 5.2% to 7.5% (P < 0.005). Four pregnancies ended in live births of healthy neonates, whereas the other ten pregnancies ended in miscarriages. Excluding one miscarriage with a chromosomal abnormality, the live birth rate was 30.8% (4/13). The rate of reduction of NK cell activity in the success group (-58.8%) tended to be greater than that in the failure group (-14.8%, P = 0.057).
2015年06月, Journal of reproductive immunology, 109, 48 - 51, 英語, 国際誌[査読有り]
研究論文(学術雑誌)
Hippo signaling pathway consists of conserved serine/threonine kinases to maintain optimal organ sizes. Studies have demonstrated that fragmentation of murine ovaries increases actin polymerization and disrupts Hippo signaling, leading to nuclear translocation of Hippo signaling effector Yes-associated protein (YAP) in ovarian follicles and follicle growth. For patients with polycystic ovarian syndrome showing follicle arrest, ovarian wedge resection and laser drilling promote follicle growth. Because these damaging procedures likely involve actin polymerization, we tested whether actin polymerization-promoting drugs could promote YAP translocation and stimulate follicle growth. Treatment of murine ovaries with μM Jasplakinolide (JASP), an actin polymerization-promoting cyclic peptide, or sphingosine-1-phosphate (S1P), a follicular fluid constituent known to promote actin polymerization, increased the conversion of globular actin to the filamentous form, followed by increased nuclear YAP and expression of downstream connective tissue growth factor (CCN2). After short-term treatments with JASP or S1P, in vitro cultured and in vivo grafted ovaries showed follicle growth. Furthermore, induction of constitutively active YAP in ovarian grafts of transgenic mice enhanced follicle development, whereas treatment of human ovarian cortices with JASP or S1P increased CCN2 expression. Thus, JASP and S1P stimulate follicle growth and are potential therapeutic agents for treating polycystic ovarian syndrome and other ovarian disorders.
2015年06月, FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 29 (6), 2423 - 30, 英語, 国際誌[査読有り]
研究論文(学術雑誌)
[招待有り]
研究論文(学術雑誌)
BACKGROUND: Human Cytomegalovirus (CMV) is the virus most frequently responsible for severe diseases of the fetus and newborn. The reported intrauterine transmission rate of CMV following primary maternal infection is approximately 40%. Invasive techniques are needed for the prenatal diagnosis of congenital CMV infection. OBJECTIVES: The aim of this study was to evaluate whether the rapidity of change in the CMV IgG avidity index (AI) is associated with the presence of congenital CMV infection among mothers with suspected primary CMV infection. STUDY DESIGN: The serum CMV IgG AI was repeatedly measured in 17 pregnant women with positive or borderline test results for CMV IgM together with an initial IgG AI value of <40%. Their neonates underwent polymerase chain reaction analyses for the presence of CMV DNA in the urine. The rapidity of change in the IgG AI per 4 weeks was defined as the ΔAI (%). The ΔAI of women with congenital CMV infection was compared with that of women with no infection. RESULTS: The ΔAI of nine mothers with congenital CMV infection (median,15.7%; range,7.8-42.8%) was significantly higher than that of eight mothers with no infection (median, 6.5%, range, 2.0-8.8%; p<0.001). The incidences of congenital CMV infection were 100.0%, 16.7%, and 0.0% among mothers with a ΔAI of >10, 5-10, and <5%, respectively. CONCLUSIONS: Measurement of the ΔAI in pregnant women might be useful for estimating the risk of mother-to-neonate CMV transmission.
2015年05月, Journal of clinical virology : the official publication of the Pan American Society for Clinical Virology, 66, 44 - 7, 英語, 国際誌[査読有り]
The aim of this study was to evaluate whether the presence of history of biochemical pregnancy (BP) was associated with clinical characteristics and the subsequent pregnancy outcome among women with recurrent spontaneous abortion (RSA). One-hundred and seventy-five RSA women with two or more clinical pregnancy losses were enrolled. The clinical characteristics were compared between 164 women with history of 0-1 BP (Group A) and 11 women with two or more BP (Group B). The frequency of previous pregnancy loss and history of in vitro fertilization and embryo transfer in Group B was higher than that in Group A; while frequency of secondary RSA in Group B was lower than Group A. The subsequent pregnancy outcome was assessed prospectively; and live-birth rate in Group A (72.9%) was higher (p < 0.05) than that in Group B (41.7%). The incidence of reproductive failure (58.3%, p < 0.05) and spontaneous abortion with normal chromosome (25.0%, p = 0.050) in Group B was higher than those (27.1 and 5.9%, respectively) in Group A. RSA women with two or more BP had higher risk of reproductive failure and spontaneous abortion with normal chromosome together with lower chance of live-birth. The results of the present study involve important information and are helpful for clinical practitioners.
2015年04月, Gynecological endocrinology : the official journal of the International Society of Gynecological Endocrinology, 31 (4), 306 - 8, 英語, 国際誌[査読有り]
研究論文(学術雑誌)
OBJECTIVE: Adherent placenta is a life-threatening condition in pregnancy, and is often complicated by placenta previa. The aim of this prospective study was to determine prenatal imaging findings that predict the presence of adherent placenta in pregnancies with placenta previa. STUDY DESIGN: The study included 58 consecutive pregnant women with placenta previa who underwent both ultrasonography and magnetic resonance imaging prenatally. Ultrasonographic findings of anterior placental location, grade 2 or higher placental lacunae (PL≥G2), loss of retroplacental hypoechoic clear zone (LCZ) and the presence of turbulent blood flow in the arteries were evaluated, in addition to MRI findings. Forty-three women underwent cesarean section alone; 15 women with adherent placenta underwent cesarean section followed by hysterectomy with pathological examination. To determine imaging findings that predict adherent placenta, univariate and multivariate logistic regression analyses were performed. RESULTS: Univariate logistic regression analyses demonstrated that anterior placental location, PL≥G2, LCZ, and MRI were associated with the presence of adherent placenta. Multivariate analyses revealed that LCZ (p<0.01, odds ratio 15.6, 95%CI 2.1-114.6) was a single significant predictor of adherent placenta in women with placenta previa. CONCLUSION: This prospective study demonstrated for the first time that US findings, especially LCZ, might be useful for identifying patients at high risk for adherent placenta among pregnant women with placenta previa.
2015年04月, European journal of obstetrics, gynecology, and reproductive biology, 187, 41 - 4, 英語, 国際誌[査読有り]
研究論文(学術雑誌)
Relaxin is essential for trophoblast development during pregnancy. Evidence shows that relaxin increases trophoblast cell migration capacity. Here, we show the effect of relaxin on protein kinase B (AKT) activation and glycogen synthase kinase 3-beta (GSK3β) inactivation as well as on the proliferation of HTR-8/SVneo cells, a model of human extravillous trophoblast (EVT). HTR-8/SVneo cells were treated with different doses of human recombinant (rH2) relaxin in serum-deprived conditions and treated for increasing time with 1 ng/mL of rH2 relaxin. Western blot analysis was performed to detect pAKT, AKT, pGSK3β, GSK3β, and actin expression. Proliferation of HTR-8/SVneo cells was analyzed by MTS assay. rH2 relaxin treatment increased the ratio of pAKT/AKT, pGSK3β/GSK3β, and proliferation in HTR-8/SVneo cells. Furthermore, AKT and GSK3β activation by rH2 relaxin was inhibited by a phosphoinositide 3-kinase (PI3K) inhibitor. This study suggests that rH2 relaxin induces AKT and GSK3β phosphorylation as well as proliferation in HTR-8/SVneo cells.
1, 2015年03月24日, The Kobe journal of medical sciences, 61 (1), E1-8 - 8, 英語, 国内誌[査読有り]
OBJECTIVES: The aim of this survey study was to evaluate a state of mother-to-child infections in Japan. METHODS: A nationwide survey on 2714 obstetric facilities where regular maternity checkups were carried out was conducted. A primary questionnaire assessed numbers of pregnancies including induced abortion, spontaneous abortion, still-birth as well as live-birth, which were affected by congenital infections of 6 pathogens during a year of 2011. The secondary questionnaire assessed clinical information, diagnostic modality, and the outcome for each case. The clinical features and diagnostic problems were evaluated. RESULTS: The high reply rates for the primary (73.7%) and the secondary questionnaire (100%) were achieved. The presence of congenital infections for 34 cases with cytomegalovirus (CMV), 1 with Toxoplasma gondii, 4 with rubella virus, 5 with Treponema pallidum, 8 with herpes simplex virus, and 69 with parvovirus B19 was confirmed after questionnaire assessment. The incidence of fetal demise among pregnancies with congenital parvovirus B19 infection was up to 71.0%. Eleven mothers with hydrops fetalis received prenatal fetal therapies involving fetal blood transfusion and immunoglobulin administration, whereas only three pregnancies (27.3%) ended in live-births. CONCLUSIONS: This survey study for the first time revealed the annual frequency of pregnancies with mother-to-child infections of 6 pathogens in Japan. The results involve important information and are helpful for clinical practitioners. The majority of neonates with congenital infection of CMV or T. gondii might be undiagnosed in obstetric facilities.
2015年03月, Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy, 21 (3), 161 - 4, 英語, 国際誌[査読有り]
研究論文(学術雑誌)
BACKGROUND AND PURPOSE: To investigate the diagnostic performance of diffusion-weighted imaging (DWI) and contrast-enhanced imaging in combination with T2-weighted imaging (T2WI) for magnetic resonance imaging (MRI) evaluation of intrapelvic recurrence of gynecological malignancies. MATERIALS AND METHODS: Sixty-two patients with suspected intrapelvic recurrence of gynecological malignancies underwent pelvic MRI including T2WI DWI, and contrast-enhanced imaging. Diagnostic performance for detection of local recurrence, pelvic lymph node and bone metastases, and peritoneal lesions was evaluated by consensus reading of two experienced radiologists using a 5-point scoring system, and compared among T2WI with unenhanced T1-weighted imaging (T1WI) (protocol A), a combination of protocol A and DWI (protocol B), and a combination of protocol B and contrast-enhanced imaging (protocol C). Final diagnoses were obtained by histopathological examinations, radiological imaging and clinical follow-up for at least 6 months. Receiver operating characteristic (ROC) analysis and McNemar test were employed for statistical analysis. RESULTS: Locally recurrent disease, lymph node recurrence, peritoneal dissemination and bone metastases were present in 48.4%, 29.0%, 16.1%, and 6.5% of the patients, respectively. The patient-based sensitivity, specificity, accuracy, and area under the ROC curve (AUC) for detection of intrapelvic recurrence were 55.0, 81.8, 64.5% and 0.753 for protocol A, 80.0, 77.3, 79.0% and 0.838 for protocol B, and 80.0, 90.9, 83.9% and 0.862 for protocol C, respectively. The sensitivity, accuracy, and AUC were significantly better for protocols B and C than for protocol A (p<0.001). There was no significant difference between protocols B and C. CONCLUSION: MRI using a combination of DWI and T2WI gives comparatively acceptable results for assessment of intrapelvic recurrence of gynecological malignancies.
2015年, PloS one, 10 (1), e0117411, 英語, 国際誌[査読有り]
研究論文(学術雑誌)
Viper bites in pregnant women have rarely been reported thus far. Moreover, there is no consensus regarding the treatment of such cases. In this paper, the authors report the successful treatment of viper bite during pregnancy without using antivenom.
I R O G CANADA, INC, 2015年, CLINICAL AND EXPERIMENTAL OBSTETRICS & GYNECOLOGY, 42 (2), 243 - 245, 英語[査読有り]
研究論文(学術雑誌)
研究論文(学術雑誌)
[招待有り]
研究論文(学術雑誌)
BACKGROUND: Cytomegalovirus (CMV) causes congenital infection with high mortality and morbidity rates in affected neonates. OBJECTIVES: To evaluate the maternal IgG avidity value for the prediction of congenital CMV infection. STUDY DESIGN: The serum IgG avidity in all mothers was measured, and the urine of their neonates was assessed for CMV DNA in a prospective cohort study. RESULTS: Of 759 women with a positive test for CMV IgG, 14 had congenital CMV infection. CMV IgG avidity indices in the congenital infection group (median 35.1%) were significantly lower than those in the non-congenital infection group (70.4%). A cutoff value of <40% IgG avidity index with 96.1% specificity and 64.3% sensitivity for congenital infection was determined by receiver operating characteristic curve analyses. The highest sensitivity (88.9%), 96.2% specificity, 27.6% positive predictive value, 99.8% negative predictive value, and 96.1% accuracy were found when IgG avidity was measured in <28 weeks of gestation. CONCLUSION: The IgG avidity measurement with a cutoff value of <40% IgG avidity index might be helpful in predicting congenital CMV infection, especially in <28 weeks of gestation.
2014年11月, Journal of perinatal medicine, 42 (6), 755 - 9, 英語, 国際誌[査読有り]
研究論文(学術雑誌)
研究論文(その他学術会議資料等)
研究論文(その他学術会議資料等)
研究論文(その他学術会議資料等)
The aim of this trial study was to assess the preventive efficacy of immunoglobulin with a high titer of anti-CMV antibody for mother-to-fetus cytomegalovirus (CMV) transmission among pregnant women with primary/acute CMV infection. The primary CMV infection in mothers was diagnosed by a positive test for CMV IgM and/or low IgG avidity. Intact type immunoglobulin with a high titer of anti-CMV antibody was injected intravenously at a dosage of 2.5-5.0 g/day for consecutive 3 days to mothers with primary CMV infection. Four pregnant women were enrolled. One pregnancy ended in no congenital infection, while two pregnancies ended in congenital CMV infection. The other one pregnancy was terminated. The mother-to-fetus CMV transmission rate was found to be high as 66.7% (2/3). This preliminary result suggests that intravenous immunoglobulin injections are not effective for the prevention of mother-to-fetus CMV transmission in the present protocol.
2014年07月11日, The Kobe journal of medical sciences, 60 (2), E25-9 - 9, 英語, 国内誌[査読有り]
研究論文(学術雑誌)
OBJECTIVE: The aim of this study was to determine the risk factors for hemorrhagic shock in women with placental polyp. MATERIALS AND METHODS: Twelve women (group A) developed hemorrhagic shock (shock index<1.5) and received uterine artery embolization (UAE). The other 25 women (group B) had shock index<1.5 and did not receive UAE. All women underwent transcervical resection (TCR). The risk factors for the development of hemorrhagic shock, including the age, conception mode, numbers of previous abortion, gestational weeks at termination of pregnancy (TOP), blood loss weights at TOP and at TCR, were analyzed. RESULTS: When compared with group B, group A had higher in vitro fertilization-embryo transfer (IVF-ET) pregnancy rate (58.3 versus 12.0%, p<0.01), number of previous abortion (median 1.58 versus 0.68, p<0.05), gestational weeks at TOP (median 36.5 versus 17.0 weeks, p<0.05), and blood loss weight at TOP (median 2151 versus 40 g, p<0.05). A logistic regression analysis reveled that IVF-ET (OR 41, 95% CI 1.3-1264) and blood loss weight at TOP (1.0025, 1.0006-1.0044) were independent risk factors for hemorrhagic shock. CONCLUSIONS: For the first time, IVF-ET pregnancy was found to be a risk factor for the development of hemorrhagic shock in women with placental polyp.
2014年07月, Gynecological endocrinology : the official journal of the International Society of Gynecological Endocrinology, 30 (7), 502 - 4, 英語, 国際誌[査読有り]
研究論文(学術雑誌)
Purpose: To investigate the fusion of pelvic magnetic resonance imaging (MRI) and fluorodeoxyglucose positron emission tomography (PET) for assessment of locoregional extension and nodal staging of cervical cancer. Methods: PET/computed tomography (CT), MRI, and non-fused and fusion of PET and MRI for assessing the extent of the primary tumor and metastasis to nodes were evaluated. Results: Accuracy for T-status was 83.3% for fused and non-fused PET/MRI and MRI proved significantly more accurate than PET/CT (53.3%) (P=.0077). Sensitivity, specificity, and accuracy for nodal metastasis were 92.3%, 88.2%, and 90.0% for fused PET/MRI and PET/contrast-enhanced CT; 84.6%, 94.1%, and 90.0% for nonfused PET/MRI; and 69.2%, 100%, and 86.7% for MRI. Conclusion: Fused PET/MRI combines the individual advantages of MRI and PET. (C) 2014 Elsevier Inc. All rights reserved.
ELSEVIER SCIENCE INC, 2014年07月, CLINICAL IMAGING, 38 (4), 464 - 469, 英語[査読有り]
研究論文(学術雑誌)
Mother-to-child infections cause congenital infection with disease and sequelae. To evaluate a state of maternal blood screening for mother-to-child infections in Japan, we for the first time conducted a nationwide survey on obstetric facilities where regular maternity checkups were carried out. A questionnaire assessment involved an annual number of deliveries, scale of facilities and a state of maternal blood screening for eight pathogens. A high rate (73.7%) of reply to the questionnaire was achieved from 1990 facilities, covering 75.1% of annual number of delivery in 2011. The performance rates of blood screening were more than 99% for rubella virus, Treponema pallidum, human immunodeficiency virus (HIV), human T cell leukemia virus type 1 (HTLV-1), hepatitis B virus, and hepatitis C virus, while the rate was found to be only 4.5% for cytomegalovirus (CMV), and 48.5% for Toxoplasma gondii with large differences in regions. Most of the facilities performed blood tests for rubella virus, Treponema pallidum, HIV, hepatitis B virus and hepatitis C virus once in early pregnancy, while approximately 28% of the facilities performed blood tests for HTLV-1 once during the 2nd or 3rd trimester. Most of the facilities used HA tests for Toxoplasma gondii, whereas there was a wide variation in antibody measurement methods for CMV. Generally, the obstetric facilities in Japan have performed maternal blood screening properly according to the current recommendations. The results of this survey involve important information and are helpful for clinical practitioners.
2014年05月, Congenital anomalies, 54 (2), 100 - 3, 英語, 国際誌[査読有り]
研究論文(学術雑誌)
[査読有り]
研究論文(学術雑誌)
研究論文(その他学術会議資料等)
研究論文(その他学術会議資料等)
研究論文(その他学術会議資料等)
研究論文(その他学術会議資料等)
Primary ovarian insufficiency (POI) and polycystic ovarian syndrome are ovarian diseases causing infertility. Although there is no effective treatment for POI, therapies for polycystic ovarian syndrome include ovarian wedge resection or laser drilling to induce follicle growth. Underlying mechanisms for these disruptive procedures are unclear. Here, we explored the role of the conserved Hippo signaling pathway that serves to maintain optimal size across organs and species. We found that fragmentation of murine ovaries promoted actin polymerization and disrupted ovarian Hippo signaling, leading to increased expression of downstream growth factors, promotion of follicle growth, and the generation of mature oocytes. In addition to elucidating mechanisms underlying follicle growth elicited by ovarian damage, we further demonstrated additive follicle growth when ovarian fragmentation was combined with Akt stimulator treatments. We then extended results to treatment of infertility in POI patients via disruption of Hippo signaling by fragmenting ovaries followed by Akt stimulator treatment and autografting. We successfully promoted follicle growth, retrieved mature oocytes, and performed in vitro fertilization. Following embryo transfer, a healthy baby was delivered. The ovarian fragmentation-in vitro activation approach is not only valuable for treating infertility of POI patients but could also be useful for middle-aged infertile women, cancer patients undergoing sterilizing treatments, and other conditions of diminished ovarian reserve.
2013年10月22日, Proceedings of the National Academy of Sciences of the United States of America, 110 (43), 17474 - 9, 英語, 国際誌[査読有り]
研究論文(学術雑誌)
R-spondin proteins are adult stem cell growth factors capable of stimulating gut development by activating LGR4, 5, and 6 receptors to promote Wnt signaling. Although multiple Wnt ligands and cognate Frizzled receptors are expressed in the ovary, their physiological roles are unclear. Based on bioinformatic and in situ hybridization analyses, we demonstrated the exclusive expression of R-spondin2 in oocytes of ovarian follicles. In cultured somatic cells from preantral follicles, R-spondin2 treatment (ED50: 3 ng/ml) synergized with Wnt3a to stimulate Wnt signaling. In cultured ovarian explants from prepubertal mice containing preantral follicles, treatment with R-spondin2, similar to follicle stimulating hormone, promoted the development of primary follicles to the secondary stage. In vivo administration of an R-spondin agonist stimulated the development of primary follicles to the antral stage in both immature mice and gonadotropin releasing hormone antagonist-treated adult mice. Subsequent treatment with gonadotropins allowed the generation of mature oocytes capable of undergoing early embryonic development and successful pregnancy. Furthermore, R-spondin agonist treatment of immune-deficient mice grafted with human cortical fragments stimulated the development of primary follicles to the secondary stage. Thus, oocyte-derived R-spondin2 is a paracrine factor essential for primary follicle development, and R-spondin agonists could provide a new treatment regimen for infertile women with low responses to the traditional gonadotropin therapy.
2013年06月, FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 27 (6), 2175 - 84, 英語, 国際誌[査読有り]
研究論文(学術雑誌)
[This corrects the article on p. e73763 in vol. 8.].
2013年, PloS one, 8 (9), 英語, 国際誌[査読有り]
研究論文(学術雑誌)
Hippo pathway controls the organ size by modulating cell proliferation and apoptosis. However, the upstream regulation of hippo signaling by actin cytoskeleton is not clear. To elucidate the role of actin as an upstream regulator of Hippo signaling, the levels of F (filamentous)-actin in cells were elevated using jasplakinolide, an actin-stabilizing drug. Induction of F-actin formation in HeLa cells resulted in decreased phosphorylation of YAP, a key effector molecule for Hippo signaling. The activated YAP is localized to the cell nucleus and YAP increase was associated with increased expression of downstream CCN growth factors CCN1/CYR61 and CCN2/CTGF. The effect of the actin-stabilizing drug was blocked when YAP levels were suppressed in YAP "knock-down" cells. In summary, using an actin-stabilizing drug we show that actin cytoskeleton is one of the upstream regulators of Hippo signaling capable of activating YAP and increasing its downstream CCN growth factors.
2013年, PloS one, 8 (9), e73763, 英語, 国際誌[査読有り]
研究論文(学術雑誌)
Neuroendocrine carcinomas (NEC) of the female genital tract are aggressive and uncommon tumors, which usually involve the uterine cervix and ovary, and are seen very rarely in the endometrium. Only less than 10 cases of large cell NEC (LCNEC) of the endometrium have been reported in the literature and their radiological findings are not well described. We report here two cases of pathologically proven LCNEC of the uterine endometrium. In both cases, the uterine body was enlarged and the tumor occupied part of the uterine cavity. Endometrial mass exhibited heterogeneous high intensity on T2-weighted magnetic resonance (MR) images, and diffusion-weighted MR images revealed high intensity throughout the tumor, consistent with malignancy. LCNEC is a highly malignant neoplasm without particular findings in terms of diagnostic imaging and pathology, so its preoperative definitive diagnosis is very difficult. However, when laboratory test, pathologic diagnosis and MR imaging suggest a poorly differentiated uterine malignancy, positron emission tomography-computed tomography scan should be performed as a general assessment to help with diagnosis.
2012年06月26日, Rare tumors, 4 (3), e37, 英語, 国際誌[査読有り]
研究論文(学術雑誌)
In addition to its role in blood coagulation, thrombin directly stimulates protease-activated receptors (PAR) or interacts with thrombomodulin (THBD) to activate membrane-bound protein C which stimulates PAR1 and PAR4 receptors to promote downstream pleiotropic effects. Our DNA microarray, RT-PCR, and immunostaining analyses demonstrated ovarian expression of THBD, activated protein C (APC) receptor [endothelial protein C receptor (EPCR)], as well as PAR1 and PAR4 receptors in mice. After treatment of gonadotropin-primed immature mice with an ovulatory dose of human chorionic gonadotropin (hCG) (a LH surrogate), major increases in the expression of THBD, EPCR, PAR1, and PAR4 were detected in granulosa and cumulus cells of preovulatory follicles. Immunoassay analyses demonstrated sustained increases in ovarian prothrombin and APC levels after hCG stimulation. We obtained luteinizing granulosa cells from mice treated sequentially with equine CG and hCG. Treatment of these cells with thrombin or agonists for PAR1 or PAR4 decreased basal and forskolin-induced cAMP biosynthesis and suppressed hCG-stimulated progesterone production. In cultured preovulatory follicles, treatment with hirudin (a thrombin antagonist) and SCH79797 (a PAR1 antagonist) augmented hCG-stimulated progesterone biosynthesis, suggesting a suppressive role of endogenous thrombin in steroidogenesis. Furthermore, intrabursal injection with hirudin or SCH79797 led to ipsilateral increases in ovarian progesterone content. Our findings demonstrated increased ovarian expression of key components of the thrombin-APC-PAR1/4 signaling system after LH/hCG stimulation, and this signaling pathway may allow optimal luteinization of preovulatory follicles. In addition to assessing the role of thrombin and associated genes in progesterone production by the periovulatory ovary, these findings provide a model with which to study molecular mechanisms underlying thrombin-APC-PAR1/4 signaling.
2012年02月, Molecular endocrinology (Baltimore, Md.), 26 (2), 331 - 40, 英語, 国際誌[査読有り]
研究論文(学術雑誌)
Development of ovarian follicles is regulated by pituitary-derived gonadotropins together with local ovarian paracrine factors. Based on DNA microarray data, we performed RT-PCR and immunostaining to demonstrate the expression of interleukin 7 transcripts in oocytes of preantral, antral, and preovulatory follicles in rats. We also found the expression of interleukin 7 receptor and the coreceptor interleukin 2 receptor gamma in granulosa cells, cumulus cells, and preovulatory oocytes. In cultured rat granulosa cells obtained from early antral and preovulatory follicles, treatment with interleukin 7 stimulated the phosphorylation of AKT, glycogen synthase kinase (GSK3B), and STAT5 proteins in a time- and dose-dependent manner. Furthermore, measurement of mitochondrial reductase activity indicated that treatment with interleukin 7, similar to gonadotropins, increased the number of viable granulosa cells during a 24-h culture period. Furthermore, monitoring of the activities of apoptotic enzymes (caspase 3/7) indicated that treatment with interleukin 7 suppressed apoptosis of cultured granulosa cells from both antral and preovulatory follicles following serum withdrawal. The apoptosis-suppressing actions of interleukin 7 were blocked by an inhibitor of the phosphoinositol-3-kinase (PIK3)/AKT pathway. Furthermore, treatment of cultured preovulatory follicles with interleukin 7, like treatment with human chorionic gonadotropin, induced germinal vesicle breakdown of oocytes. The stimulatory effect of interleukin 7 was also blocked by inhibitors of the PIK3/AKT pathway. The present findings suggest that oocyte-derived interleukin 7 could act on neighboring granulosa cells as a survival factor and promote the nuclear maturation of preovulatory oocytes through activation of the PIK3/AKT pathway.
2011年04月, Biology of reproduction, 84 (4), 707 - 14, 英語, 国際誌[査読有り]
研究論文(学術雑誌)
研究論文(国際会議プロシーディングス)
研究論文(国際会議プロシーディングス)
研究論文(国際会議プロシーディングス)
研究論文(国際会議プロシーディングス)
研究論文(国際会議プロシーディングス)
研究論文(国際会議プロシーディングス)
研究論文(国際会議プロシーディングス)
研究論文(国際会議プロシーディングス)
研究論文(国際会議プロシーディングス)
研究論文(国際会議プロシーディングス)
Objective: Vascular endothelial growth factor (VEGF) is one of the most potent endothelial cell mitogens and plays a critical role in angiogenesis of endometrial carcinomas. Several studies have demonstrated positive associations between VEGF gene polymorphisms and several carcinomas. In this study we investigated whether VEGF gene polymorphisms are associated with endometrial carcinomas in a Japanese population. Methods: The allele frequencies and genotype distributions of VEGF -460 C/T, +405 G/C, and +936 C/T polymorphisms were examined in 105 endometrial carcinomas and 179 controls using PCR-RFLP analysis. An association of these polymorphisms with three-year disease-free survival was evaluated using the Kaplan-Meier method. Results: No significant differences in the allele frequencies and genotype distributions of VEGF -460 C/T (p = 0.54, 0.90), +405 G/C (p = 0.31, 0.17), and +936 C/T polymorphisms (p = 0.46, 0.24) were observed between endometrial carcinoma patients and controls. There were no significant differences in the frequencies of haplotype -460 T/+405 C between patients and controls. Futhermore, VEGF 460 C/T, +405 G/C, and +936 C/T polymorphisms were not associated with three-year disease-free survival of endometrial carcinoma patients. Conclusions: Although limited by sample size, our study did not demonstrated any evidence that VEGF -460 C/T, +405 G/C, and +936 C/T polymorphisms are associated with an increased risk of endometrial carcinomas in Japanese women.
I R O G CANADA, INC, 2008年, EUROPEAN JOURNAL OF GYNAECOLOGICAL ONCOLOGY, 29 (4), 333 - 337, 英語[査読有り]
研究論文(学術雑誌)
Purpose: To investigate a possible association between uterine leiomyomas and catechol-O-methyltransferase (COMT) polymorphisms in a Japanese population. Methods: We compared the allele frequencies and genotype distributions of the exon 4 NlaIII restriction site polymorphism (RSP), the P2 promoter HindIII RSP at - 1217, and the exon 6 BglI RSP in the COMT gene in 250 leiomyoma cases and 182 controls using polymerase chain reaction-restriction fragment-length polymorphism analysis. Results: No significant differences in allele frequencies and genotype distributions of the exon 4 NlaIII RSP, the P2 promoter HindIII RSP at 1217, and the exon 6 BglI RSP were found between uterine leiomyoma cases and controls. Moreover, no associations were noted between these three polymorphisms in COMT genes and leiomyoma size or a family history of uterine leiomyomas. Conclusion: COMT gene polymorphisms are unlikely to be associated with an increased risk of uterine leiomyomas in a Japanese population.
I R O G CANADA, INC, 2008年, CLINICAL AND EXPERIMENTAL OBSTETRICS & GYNECOLOGY, 35 (1), 35 - 40, 英語研究論文(学術雑誌)
研究論文(学術雑誌)
Endometrial cancer is associated with both EGFR and HER2 receptor activation. The EGFR and HER2 genes could be disease susceptibility candidate genes for this cancer. This study was conducted to investigate a possible association between EGFR and HER2 gene polymorphisms and endometrial cancer and the influence of these polymorphisms on the clinical outcome of endometrial cancer patients in a Japanese population. The authors compare the genotype distributions and allele frequencies of the EGFR +2073 A/T and HER2 +655 A/G polymorphisms in 116 endometrial cancer patients and 213 controls using polymerase chain reaction-restriction fragment length polymorphism (RFLP) analysis. RFLP results were confirmed by direct DNA sequencing. Of the 116 patients, 76 (65.5%) could be followed free survival estimates were computed using the Kaplan-Meier method and differences between survival periods were assessed using the log-rank test. No significant differences were observed in either genotype distributions or allele frequencies in the EGFR +2073 A/T and HER2 +655 A /G polymorphisms between endometrial cancer patients and controls. The stratification by histological types and staging failed to identify significant differences between endometrial cancer patients and controls. No statistical differences were noted between these polymorphisms and disease-free survival (Kaplan-Meier log-rank test P = .55 and .66, for the EGFR +2073 A/T and HER2 +655 A/G, respectively). These results suggest that the EGFR +2073 A/T and HEM +655 A/G polymorphisms are not associated with endometrial cancer in a Japanese population. These conclusions arc based oil relatively small numbers and will require verification from additional independent studies.
SAGE PUBLICATIONS INC, 2007年05月, REPRODUCTIVE SCIENCES, 14 (4), 349 - 357, 英語研究論文(学術雑誌)
研究論文(国際会議プロシーディングス)
研究論文(国際会議プロシーディングス)
研究論文(国際会議プロシーディングス)
研究論文(国際会議プロシーディングス)
研究論文(国際会議プロシーディングス)
Background. Vascular endothelial growth factor (VEGF) concentration in endometriosis patients is higher than controls, in serum and ascites, suggesting that VEGF may play an important role in the pathogenesis of endometriosis. In this study, we investigated whether polymorphisms in the VEGF gene are associated with endometriosis in a Japanese population. Methods. Genotyping of VEGF -460 C/T, +405 G/C and +936 C/T polymorphisms were performed in 147 endometriosis cases diagnosed by laparotomy or laparoscopy at a university hospital, and 181 controls, by polymerase chain reaction-restriction fragment length polymorphism analysis. We compared the genotype distribution and allele frequency of these 3 polymorphisms between endometriosis patients and controls. Results. No significant differences in the frequency and genotype distribution of VEGF -460 C/T, +405 G/C and +936 C/T polymorphisms were found between the endometriosis patients ( all disease stages) and controls. However, a positive association was found between stage III-IV disease and the VEGF +936 Tallele (p = 0.018). Conclusions. The VEGF +936 Tallele is associated with an increased risk of stage III-IV endometriosis in a Japanese population.
TAYLOR & FRANCIS AS, 2007年, ACTA OBSTETRICIA ET GYNECOLOGICA SCANDINAVICA, 86 (11), 1352 - 1358, 英語研究論文(学術雑誌)
[査読有り]
研究論文(学術雑誌)
研究論文(国際会議プロシーディングス)
研究論文(国際会議プロシーディングス)
OBJECTIVE: The matrix metalloproteinases (MMPs) are a family of zinc-dependent proteases that degrade all the components of the extracellular matrix (ECM). Several studies have demonstrated association between MMP gene polymorphisms and various cancers. The object of this study was to investigate whether file MMP-1 and MMP-9 gene promoter polymorphisms are associated with endometrial carcinomas ill a Japanese population. METHODS: We compared the allele frequencies and genotype distributions Of each single nucleotide polymorphism in the promoter regions of MMP-1 (-1607 1G/2G) and MMP-9 (-1562 C/T) in 107 endometrial carcinoma cases and 213 controls using polymerase chain reaction-restriction fragment-length polymorphism (PCR-RFLP) analysis. RESULTS: The allele frequencies of MMP-1 -1607 2G and MMP-9 -1562T were 64.0% and 10.7% in the cases and 70.0% and 16.7% in the controls, respectively. No significant differences in the allele frequencies or genotype distributions were found between cases and controls for the MMP-1 -1607 1G/2G polymorphism. However, a small but significant difference in, the allele frequency of the MMP-9 -1562T allele was noted between cases and controls (P = .046; odds ratio [OR] = 1.01; 95% confidence interval [CI], 1.01 to 2.73). Stratification by histology revealed a significant difference in the frequency of the MMP-9 -1562T allele between endometrioid carcinoma cases (10.2%) and controls (P = .043; OR = 1.76; 95% CI, 1.02 to 3.03); we did not find a significant difference in the frequency of the MMP-9 -1562T allele between non-endometrioid carcinoma cases (13.2%) and controls. CONCLUSION: These results suggest that the MMP-9 -1562 C/T polymorphism may be associated with susceptibility to endometrioid carcinoma in the Japanese population.
ELSEVIER SCIENCE INC, 2006年10月, JOURNAL OF THE SOCIETY FOR GYNECOLOGIC INVESTIGATION, 13 (7), 523 - 529, 英語研究論文(学術雑誌)
研究論文(国際会議プロシーディングス)
研究論文(国際会議プロシーディングス)
研究論文(国際会議プロシーディングス)
[査読有り]
研究論文(学術雑誌)
OBJECTIVE: Matrix metalloproteinases (MMPs) play are important role in modeling and remodeling the extracellular matrix in leiomyomas. Hence, the investigated whether associations exist between leiomyomas and promoter polymorphisms in the MMP-1 and MMP-9 genes in a Japanese population. METHODS: We compared the distribution of polymorphisms in the promoter regions of MMP-1 (-1607 1G/2G) and MMP-9 (-1562 C/T) in 267 leiomyoma patients and 184 control patients using polymerase chain reaction-fragment-length polymorphism (PCP-RFLP) analysis. RESULTS: The allele frequencies of the MMP-1 - 1607 2G and MMP-9 - 1562 T polymorphisms were 74.6% and 18.6% in leiomyoma patients, anal 71.3% and 18.6% in control patients, respectively. No signs scant differences in allele frequencies or genotype distributions were found between leiomyoma and control patients. Moreover, no associations were found between MMP-1 and MMP-9 genotypes and leiomyoma size or a family history of the condition. CONCLUSION: These findings suggest that MMP-1 and MMP-9 promoter polymorphisms are unlikely to be associated with an increased risk of uterine leiomyomas in Japanese women.
ELSEVIER SCIENCE INC, 2006年04月, JOURNAL OF THE SOCIETY FOR GYNECOLOGIC INVESTIGATION, 13 (3), 232 - 236, 英語[査読有り]
研究論文(学術雑誌)
研究論文(国際会議プロシーディングス)
研究論文(国際会議プロシーディングス)
The CYP17 gene is thought to be a candidate gene for susceptibility to hormone-related diseases. A single (T -> C) nucleotide polymorphism in the promoter region of CYP17 is speculated to influence its transcription. The present study was conducted to investigate the possible association between uterine leiomyomas and CYP17 gene polymorphism in a Japanese population. Genotyping analysis of the CYP17 gene was performed in 138 leiomyoma cases, 183 unaffected controls and 179 population controls using polymerase chain reaction and restriction fragment length polymorphism analysis. No significant difference in CYP17 genotype distribution was noted between leiomyoma cases and controls. Women carrying the A2 allele were not at an increased risk of uterine leiomyoma compared with those carrying the A1 allele in unaffected controls (odds ratio, 1.26; 95% confidence interval, 0.92-1.72) and those carrying the A1 allele in population controls (odds ratio, 0.99; 95% confidence interval, 0.72-1.36). No significant difference in allele frequencies were found between leiomyoma cases and controls. These findings suggest that CYP17 gene polymorphism is unlikely to be associated with an increased risk of uterine leiomyomas in a Japanese population.
PARTHENON PUBLISHING GROUP, 2006年02月, GYNECOLOGICAL ENDOCRINOLOGY, 22 (2), 87 - 91, 英語[査読有り]
研究論文(学術雑誌)
研究論文(国際会議プロシーディングス)
[査読有り]
研究論文(学術雑誌)
研究論文(国際会議プロシーディングス)
研究論文(国際会議プロシーディングス)
研究論文(国際会議プロシーディングス)
研究論文(国際会議プロシーディングス)
研究論文(国際会議プロシーディングス)
研究論文(国際会議プロシーディングス)
[査読有り]
研究論文(学術雑誌)
研究論文(国際会議プロシーディングス)
Some children with profound and long-standing hypothyroidism present with signs of paradoxical sexual maturation. In females, it is characterized by breast development, vaginal bleeding, lack of pubic hair, and delayed bone age. A case of multiple ovarian cysts in a prepubertal girl with severe hypothyroidism due to autoimmune thyroiditis is reported. A 7-year, 8-month-old girl presented with precocious puberty and vaginal bleeding. A pelvic ultrasound revealed markedly enlarged ovaries with numerous cysts which disappeared dramatically after thyroid replacement. When large multiple ovarian cysts with vaginal bleeding are found in a prepubertal girl who has a retarded bone age, the possibility of associated hypothyroidism should be considered. Health care providers should keep this in mind because this constellation of symptoms can be completely reversed with the initiation of thyroid replacement.
BLACKWELL PUBLISHING INC, 2004年05月, INTERNATIONAL JOURNAL OF GYNECOLOGICAL CANCER, 14 (3), 543 - 545, 英語[査読有り]
研究論文(学術雑誌)
研究論文(国際会議プロシーディングス)
研究論文(国際会議プロシーディングス)
研究論文(国際会議プロシーディングス)
研究論文(国際会議プロシーディングス)
[査読有り]
研究論文(学術雑誌)
研究論文(国際会議プロシーディングス)
[査読有り]
研究論文(学術雑誌)
[査読有り]
研究論文(学術雑誌)
研究論文(国際会議プロシーディングス)
研究論文(国際会議プロシーディングス)
近年の医療では抗生物質,抗腫瘍剤,免疫抑制剤やカテーテル類の多用による易感染性宿主(compromised host)が増加するなかで,深在性真菌症に対する対応が重要視されてきている.深在性真菌症は患者の死因に直接結びつく場合があるので,その予防,診断,治療と管理は重要である.
今回,われわれは産婦人科入院患者で有効抗生物質投与にもかかわらず37.0℃以上の発熱を示す109症例について,血中真菌抗原検出法のカンジテック(CAND-TEC)とファンギテック(FUNGI-TEC)を施行し,CAND-TECが(4+)以上,またはFUNGI-TECが11.0 pg/ml 以上の陽性を深在性真菌症発生の指標としてとらえ,本症の病態把握と適正な管理法について検討した.検討項目として,血中真菌抗原陽性群と血中真菌抗原陰性群において,基礎疾患の良・悪性別,カテーテル類使用の有無,白血球数,CRP(C-reactive protein)値を比較検討した.血中真菌抗原陽性群での良性疾患の割合は8.7%と血中真菌抗原陰性群での32.5%に比較して有意に低率であった.血中真菌抗原陽性群では4500/mm3以下の白血球減少が52.1%と血中真菌抗原陰性群での12.5%に比べ有意に高率であった.また血中真菌抗原陽性と判定された時点から1ヵ月以内の死亡について調査したところ,血中真菌抗原陽性群での死亡率は39.1%であり,同時期の血中真菌抗原陰性群での死亡率15.0%に比較して有意に高率であった.さらに当科作成の真菌血症管理指針に基づき行った血中真菌抗原陽性患者に対する治療効果の検討では,有効率は68.0%と従来報告の35~50%に比して改善傾向が認められた.〔産婦の進歩55(2):161-166, 2003(平成15年5月)〕
研究論文(国際会議プロシーディングス)
Purpose: beta-catenin plays dual important roles in epithelial cell-cell adhesion in cytoplasm as well as in the nuclear T-cell factor (TCF)/lymphoid enhancing factor-1 (LEF-1) signaling pathway. Abnormal nuclear accumulation of beta-catenin promotes colorectal carcinogenesis by triggering the expression of cyclin D1 gene through the TCF/LEF-1 pathway. The purpose of this study was to investigate the possible involvement of the TCF/LEF-1 pathway in endometrial carcinbgenesis. Methods: Immunohistochemical localization of beta-catenin and cyclin D1 in normal endometrium, hyperplastic endometrium and endometrial carcinoma were assessed on serial tissue sections. Results: Nuclear accumulation of beta-catenin was observed in endometrial carcinomas compared with normal endometria. Cyclin D1-positive endometrial cancer cases were beta-catenin-positive in the nuclei, especially in 70% (7/10) of G1 and 55.6% (5/9) of G2 differentiated endometrial carcinomas, but never in G3 undifferentiated ones. Conclusions: These results imply that the simultaneous nuclear accumulation of beta-catenin and cyclin D1 - suggesting the activation of the TCF/LEF-1 pathway - may be a potential marker for the progression of Type 1 endometrial carcinogenesis.
I R O G CANADA, INC, 2003年, EUROPEAN JOURNAL OF GYNAECOLOGICAL ONCOLOGY, 24 (2), 129 - 134, 英語[査読有り]
研究論文(学術雑誌)
研究論文(学術雑誌)
2020年2月12日の『Lancet』に、武漢市内で妊娠後期に新型コロナウイルスに感染した妊婦9例が報告されて以来、妊婦のCOVID-19に関する情報が数多く発表されている。これまでの報告によれば、早産リスクは高いが、胎児異常、流産、死産のリスクは高くはない。母子感染率は2〜4%であるが、胎児感染はまれである。妊婦はCOVID-19への不安を強く感じており、産後うつ病のリスクが高いことが指摘されている。妊娠が重症化リスクであり、日本でも妊娠後期の感染で急激に悪化した症例が報告されているため、妊娠中は感染予防を常に心がける。ワクチンを接種することのメリットが、デメリットを上回ると考えられるので、特に感染の多い地域や感染リスクの高い医療従事者等、および糖尿病、高血圧、気管支喘息などの基礎疾患を合併している方は、接種を検討する。(著者抄録)
(株)ライフメディコム, 2021年11月, カレントテラピー, 39 (11), 1081 - 1086, 日本語2020年2月12日Lancetに、武漢市内で妊娠後期に新型コロナウイルスに感染した妊婦9例が報告されて以来、妊婦の新型コロナウイルス感染に関する論文が多数発表された。これまでの報告によれば、早産リスクは高いが、胎児異常、流産、死産のリスクは高くはない。母子感染率は2〜4%と推定されるが、胎児感染は稀である。世界的に妊婦の症状は非妊婦と変わらないとの報告が多いが、11月に米国疾病予防センターは、妊娠は重症化リスクであると発表した。母乳を介した感染リスクは極めて低い。ワクチンは、現時点で妊婦、胎児や出生児への安全性は確立していないが、ワクチン接種対象からは除外しない。感染リスクが高い医療従事者、重症化リスクの肥満や糖尿病などを合併している方は、ワクチン接種を考慮する。(著者抄録)
(公社)日本母性衛生学会, 2021年07月, 母性衛生, 62 (2), 学8 - 学17, 日本語<文献概要>●産科医師は母子感染予防をかねて日頃より妊婦に感染予防策を啓発していくことがパンデミック時の妊婦の感染予防に役立つ.●産科医師自身も平時から分娩介助時の職業感染予防に関心をもち,標準予防策を実施していくことがシミュレーショントレーニングになる.●産科に特化した国内の感染情報収集とその情報の発信体制の確立が望まれる.●移動の制限を伴うパンデミックは妊婦のみならず,褥婦の精神環境の悪化にもつながり,適切なサポートが必要である.
(株)医学書院, 2021年06月, 臨床婦人科産科, 75 (6), 573 - 578, 日本語国内での新型コロナウイルス(COVID-19)妊婦症例の蓄積と解析が必要と考え、2020年9月よりレジストリー研究を開始した。2021年4月20日までに401名のCOVID-19感染妊婦が報告され61名のレジストリー登録が完了した。1)新型コロナウイルス感染妊婦の疾患登録システム(患者レジストリー)、2)新型コロナウイルス感染妊婦61名の概要、3)妊婦でのCOVID中等症・重症の危険因子、4)胎児感染、5)COVID感染妊婦からの出生児の管理、について述べた。
(一社)日本産婦人科感染症学会, 2021年05月, 日本産婦人科感染症学会誌, 5 (1), 8 - 15, 日本語症例は70歳代女性で、帯下、不正性器出血を主訴に受診し、子宮に腫瘤性病変を指摘された。MRIでは子宮体部に91×73×78mm大の腫瘤を認めた。画像所見からは子宮肉腫が疑われたが、由来部位が同定困難であり、非類内膜腺癌なども鑑別に挙げられた。腫瘤は複数の成分からなっており、T2強調像では腹側部は低信号、背頭部は比較的高信号、背尾側部は中程度の高信号を呈していた。18F-FDG PETでは腹側部はFDG集積が弱く、背頭部には軽度の集積、背尾部に強い集積を認めた。肉眼所見では子宮内腔に腫瘤が充満していた。画像所見にみられた腫瘍の各成分についての病理学的な特徴は以下のとおりであった。腫瘤腹側部には、異型の乏しい腺管構造が散見され、大小不同の核を呈する紡錘形細胞が認められた。腫瘤背頭部には、典型性の強い紡錘形細胞が多数認められ、正常な腺構造は認められなかった。腫瘤背頭部では、異型性の強い紡錘形細胞や壊死組織、炎症細胞が多数認められた。細胞密度は高く、正常な腺構造は認められなかった。根治的手術(子宮全摘術および両側付属器切除)が実施され、病理学的に腺肉腫の診断がなされた。子宮筋層の深部浸潤があり、pT1c FIGO IC期相当と判断された。術後特に問題なく退院となったが、術後2年3ヵ月で多発肺転移が生じた。全身状態良好であり、転移病変の増大が遅い点から経過観察の方針となり、術後3年9ヵ月時点では無症状で生存している。
金原出版(株), 2021年04月, 臨床放射線, 66 (4), 381 - 385, 日本語研究発表ペーパー・要旨(国際会議)
進行卵巣癌・原発性腹膜癌に対して術前化学療法(NAC)を行う際の主な診断方法として腹腔鏡下生検(LB)と体腔液の穿刺吸引細胞診がある。このうちLBは開腹手術に比べて低侵襲であり、診断の確実性からも有用な方法であるが、全身状態不良などの理由で腹腔鏡手術ですら躊躇する症例も少なくない。一方、穿刺吸引細胞診は全身状態不良な患者でも比較的安全に施行できるが、組織型の診断が困難という欠点がある。そこで、組織型の再現がしやすいcell block法(CB法)を穿刺吸引細胞診に取り入れている。今回、当院で2008〜2018年に進行卵巣癌もしくは原発性腹膜癌が疑われ治療された患者のうち、NAC施行時の診断目的にLBもしくはCB法を行い、根治手術時に病理診断が可能であった53例を対象とし、LB群(18例)とCB群(35例)に分け、「診断精度」「診断までに要した日数」「検査に伴う合併症」などについて群間比較した。結果、診断精度はLB群の全例で生検による診断と最終的な病理診断が一致していた。CB群では、漿液性癌の診断精度は高かったが、粘液性癌や癌肉腫では診断困難なケースが多かった。診断までに要した日数はLB群が平均8.9日、CB群が平均7.0日で、CB群ほうが有意に短かった。合併症の発生率に有意差は認めなかった。
「産婦人科の進歩」編集室, 2020年08月, 産婦人科の進歩, 72 (3), 211 - 215, 日本語<Key Points>(1)最近では、先天性CMV感染児の症候性/無症候性の割合や後遺症リスクは、母体の妊娠中のCMV初感染/非初感染の別にかかわらず同程度とされる。(2)全妊婦を対象とした抗体スクリーニングでは、半数以上を占める母体CMV非初感染(非活性化ないし再感染)による先天性感染児を見逃す。(3)妊婦ターゲットスクリーニングとして、リスク因子の症状や所見を認めた場合、母体血CMV IgGとIgMを測定する。IgG陽性であれば、保険適用で新生児尿CMV核酸検査を行う。(4)新生児聴覚スクリーニングでリファー(要再検)の新生児には、保険適用で新生児尿CMV核酸検査を生後3週以内にその分娩施設で行う。(5)トキソプラズマIgM陽性妊婦からの出生児は、症状や所見がなくても生後12ヵ月までフォローアップし、血液検査を行う。(6)出生前羊水でトキソプラズマDNA陰性であっても、分娩時羊水や新生児血液でDNA陽性となって先天性感染と診断されることがある。(著者抄録)
(株)東京医学社, 2020年01月, 小児内科, 52 (1), 23 - 29, 日本語<Key Points>(1)最近では、先天性CMV感染児の症候性/無症候性の割合や後遺症リスクは、母体の妊娠中のCMV初感染/非初感染の別にかかわらず同程度とされる。(2)全妊婦を対象とした抗体スクリーニングでは、半数以上を占める母体CMV非初感染(非活性化ないし再感染)による先天性感染児を見逃す。(3)妊婦ターゲットスクリーニングとして、リスク因子の症状や所見を認めた場合、母体血CMV IgGとIgMを測定する。IgG陽性であれば、保険適用で新生児尿CMV核酸検査を行う。(4)新生児聴覚スクリーニングでリファー(要再検)の新生児には、保険適用で新生児尿CMV核酸検査を生後3週以内にその分娩施設で行う。(5)トキソプラズマIgM陽性妊婦からの出生児は、症状や所見がなくても生後12ヵ月までフォローアップし、血液検査を行う。(6)出生前羊水でトキソプラズマDNA陰性であっても、分娩時羊水や新生児血液でDNA陽性となって先天性感染と診断されることがある。(著者抄録)
(株)東京医学社, 2020年01月, 小児内科, 52 (1), 23 - 29, 日本語妊娠は凝固系を含む母体の恒常性に劇的な変化をもたらす。多くの凝固因子が増加する一方、プロテインS(PS)は妊娠8〜13週には既に低下し、その低値は妊娠末期まで継続し過凝固となる。抗リン脂質抗体(aPL)が不育症の原因とされたのち、他の血栓性素因と不育症の関連も検討されたが、原因とするまでの根拠がなく「リスク因子」と考えられている。1)抗リン脂質抗体症候群は妊娠高血圧症候群、胎児発育不全等の原因となる。aPLによる産科異常は血栓だけでなく、胎盤絨毛傷害が関与する。妊娠前からの低用量アスピリン(LDA)と妊娠後のヘパリン(Hep)が妊娠予後を改善するが、さらなる妊娠予後改善のため、プレドニゾロンや免疫グロブリン、最近ではヒドロキシクロロキンの投与が試みられている。2)PS低下は不育症や産科異常の「リスク因子」とされる。我々の妊娠コホートの中間解析では、妊娠初期PS低値と産科異常の関連は認めなかったが、過去の死産歴と関係した。治療はaPL陰性の場合、LDA単独で十分かもしれない。3)凝固第XII因子低下と不育症の関連では、第XII因子やPSのEGF like domainに対する抗体が注目されている。自己抗体によるEGF系抑制による胎盤形成障害が不育症に関連しているのかもしれない。凝固カスケードは止血以外にも、炎症や細胞増殖など多くの作用がある。産婦人科には凝固が関わる生理現象が多くあり、その機能調節と凝固の関連についての研究が今後進んでいくことを期待したい。(著者抄録)
(一社)日本検査血液学会, 2019年11月, 日本検査血液学会雑誌, 20 (3), 455 - 463, 日本語研究発表ペーパー・要旨(国際会議)
妊娠中に維持透析療法を要した慢性腎不全(CRF)合併妊娠3症例の臨床経過を調べ、周産期管理の問題点を検討した。症例1(43歳、G3P2)は腎血管性高血圧によるCRF患者で、妊娠26週に透析導入したが、高血圧が持続するため、Dry Weight(DW)を漸減したところ、羊水過少傾向を示し、胎児発育不全(FGR)となった。症例2(40歳、G1P0)は、IgA腎症によるCRFにて38歳時に透析導入となり、妊娠中期からDWを漸増したところ、羊水過多症を合併した。症例3(37歳、G1P0)は、膀胱尿管逆流症によるCRFにて18歳時に透析導入となり、血圧コントロールの目的でDWを漸減したところ、羊水過少傾向となったが、重篤なFGRは認めなかった。3例とも早産で、2例が極低出生体重児であった。維持透析を要する妊婦の管理には産科、新生児科、腎臓内科の綿密な連携が必須であることが示唆された。
「産婦人科の進歩」編集室, 2019年05月, 産婦人科の進歩, 71 (2), 103 - 108, 日本語妊娠中に維持透析療法を要した慢性腎不全(CRF)合併妊娠3症例の臨床経過を調べ、周産期管理の問題点を検討した。症例1(43歳、G3P2)は腎血管性高血圧によるCRF患者で、妊娠26週に透析導入したが、高血圧が持続するため、Dry Weight(DW)を漸減したところ、羊水過少傾向を示し、胎児発育不全(FGR)となった。症例2(40歳、G1P0)は、IgA腎症によるCRFにて38歳時に透析導入となり、妊娠中期からDWを漸増したところ、羊水過多症を合併した。症例3(37歳、G1P0)は、膀胱尿管逆流症によるCRFにて18歳時に透析導入となり、血圧コントロールの目的でDWを漸減したところ、羊水過少傾向となったが、重篤なFGRは認めなかった。3例とも早産で、2例が極低出生体重児であった。維持透析を要する妊婦の管理には産科、新生児科、腎臓内科の綿密な連携が必須であることが示唆された。
「産婦人科の進歩」編集室, 2019年05月, 産婦人科の進歩, 71 (2), 103 - 108, 日本語過去10年間に当科で経験した正常胎児と全奇胎の双胎(CHMCF)3例について報告した。CHMCFの診断週数は12〜14週で、2例は排卵誘発による妊娠であった。母体合併症は妊娠悪阻が1例、性器出血が3例であった。診断後、妊娠継続に関するリスクについて十分な説明を行ったところ、2例は妊娠中絶を希望したが、残りの1例は希望により妊娠継続をしていた。だが、臨床的侵入奇胎のため妊娠21週1日目で人工妊娠中絶となった。3例中2例では続発性疾患(奇胎後hCG存続症1例、臨床的侵入奇胎1例)を認め、化学療法にて寛解が得られた。
「産婦人科の進歩」編集室, 2019年02月, 産婦人科の進歩, 71 (1), 9 - 16, 日本語研究発表ペーパー・要旨(国際会議)
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Angiosarcoma of the vagina is an extremely rare neoplasm and is characterized by frequent recurrence and early metastatic spread. Although previous reports emphasized the poor prognosis of this disease, effective treatment strategies have not been adequately stated. We report a case of angiosarcoma of the vagina, in which the diagnosis was made 9 years after intrapelvic irradiation, and recombinant interleukin-2 (rIL-2) therapy could be effective to suppress the development of distant metastasis. We recommend rIL-2 therapy in combination with irradiation as a palliative therapeutic option for vaginal angiosarcoma when the tumor is inoperable or the patient refuses to undergo surgery. Although vaginal angiosarcoma is an extremely rare condition, its possibility should be borne in mind when finding a vaginal mass in a previously irradiated patient.
BLACKWELL PUBLISHING, 2005年11月, INTERNATIONAL JOURNAL OF GYNECOLOGICAL CANCER, 15 (6), 1163 - 1165, 英語[査読有り]
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A case of a 30-year-old primiparous woman with pulmonary lymphangioleiomyomatosis is described. The patient had experienced six episodes of spontaneous pneumothorax at the age of 27 years and had been diagnosed as having pulmonary lymphangioleiomyomatosis based on histological findings of specimens obtained by transbronchial biopsy. She had undertaken open lung surgery and thoracoscopy. Thereafter, she became pregnant spontaneously. Her antenatal course was uneventful with no exacerbation of respiratory status. At 38 weeks of gestation, she underwent a selective cesarean section and myomectomy under combined spinal and epidural anesthesia. Her postoperative course was uneventful. No remarkable changes in computed tomographic findings of the lung were noted on the 20th day of postoperation compared with those before pregnancy. She has been followed-up in the pulmonary outpatient clinic with no deterioration of the disease.
2005年, Clinical and Experimental Obstetrics and Gynecology, 32 (3), 199 - 200, 英語[査読有り]
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A 83-year-old woman received bilateral salpingo-oophorectomy and hysterectomy due to a provisional diagnosis of ovarian cystic tumor. The tumor had a unilocular cystic cavity demonstrating serous cystadenoma and a solid mural nodule representing a biphasic pattern with mesenchyrnal and glandular components. The glandular elements were composed of benign serous cells, whereas the niesenchymal components consisted of an admixture of fibroinatous stromal cells without atypia and sarcomatous overgrowth. The area of transition from a fibromatous component to sarcomatous overgrowth was identified. After a 2-year follow-up, there were no signs of tumor recurrence or systemic disease. To the authors' knowledge, this is the first reported case of adenofibrosarconia originating from a mural nodule of ovarian serous cystadenoma.
I R O G CANADA, INC, 2005年, EUROPEAN JOURNAL OF GYNAECOLOGICAL ONCOLOGY, 26 (5), 511 - 513, 英語[査読有り]
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口頭発表(一般)
口頭発表(一般)
口頭発表(基調)
口頭発表(一般)
口頭発表(一般)
口頭発表(一般)
口頭発表(一般)
口頭発表(一般)
口頭発表(一般)
口頭発表(一般)
口頭発表(一般)
ポスター発表
ポスター発表
口頭発表(一般)
口頭発表(一般)
口頭発表(一般)
口頭発表(一般)
[招待有り]
シンポジウム・ワークショップパネル(指名)
ポスター発表
口頭発表(一般)
口頭発表(一般)
口頭発表(一般)
口頭発表(一般)
口頭発表(一般)
口頭発表(一般)
口頭発表(一般)
口頭発表(一般)
口頭発表(一般)
口頭発表(一般)
口頭発表(一般)
口頭発表(一般)
口頭発表(一般)
口頭発表(一般)
口頭発表(一般)
ポスター発表
ポスター発表
口頭発表(一般)
ポスター発表
シンポジウム・ワークショップパネル(公募)
口頭発表(一般)
口頭発表(一般)
その他
ポスター発表
ポスター発表
ポスター発表
シンポジウム・ワークショップパネル(公募)
ポスター発表
ポスター発表
ポスター発表
ポスター発表
ポスター発表
ポスター発表
ポスター発表
ポスター発表
シンポジウム・ワークショップパネル(公募)
ポスター発表
ポスター発表
その他
その他
口頭発表(一般)
口頭発表(一般)
口頭発表(一般)
口頭発表(一般)
口頭発表(一般)
口頭発表(一般)
口頭発表(一般)
口頭発表(一般)
[招待有り]
口頭発表(招待・特別)
口頭発表(一般)
口頭発表(一般)
口頭発表(一般)
口頭発表(一般)
口頭発表(一般)
口頭発表(一般)
口頭発表(一般)
口頭発表(一般)
ポスター発表
ポスター発表
口頭発表(一般)
ポスター発表
ポスター発表
ポスター発表
口頭発表(一般)
口頭発表(一般)
口頭発表(一般)
[招待有り]
口頭発表(招待・特別)
口頭発表(一般)
口頭発表(一般)
口頭発表(一般)
口頭発表(一般)
口頭発表(一般)
口頭発表(一般)
口頭発表(一般)
口頭発表(一般)
口頭発表(一般)
[招待有り]
口頭発表(招待・特別)
口頭発表(一般)
競争的資金
競争的資金
競争的資金
競争的資金
競争的資金
競争的資金