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The preferential response to PARP inhibitors (PARPis) in BRCA-deficient and Schlafen 11 (SLFN11)-expressing ovarian cancers has been documented, yet the underlying molecular mechanisms remain unclear. As the accumulation of single-strand DNA (ssDNA) gaps behind replication forks is key for the lethality effect of PARPis, we investigated the combined effects of SLFN11 expression and BRCA deficiency on PARPi sensitivity and ssDNA gap formation in human cancer cells. PARPis increased chromatin-bound RPA2 and ssDNA gaps in SLFN11-expressing cells and even more in cells with BRCA1 or BRCA2 deficiency. SLFN11 was co-localized with chromatin-bound RPA2 under PARPis treatment, with enhanced recruitment in BRCA2-deficient cells. Notably, the chromatin-bound SLFN11 under PARPis did not block replication, contrary to its function under replication stress. SLFN11 recruitment was attenuated by the inactivation of MRE11. Hence, under PARPi treatment, MRE11 expression and BRCA deficiency lead to ssDNA gaps behind replication forks, where SLFN11 binds and increases their accumulation. As ovarian cancer patients who responded (progression-free survival >2 years) to olaparib maintenance therapy had a significantly higher SLFN11-positivity than short-responders (<6 months), our findings provide a mechanistic understanding of the favorable responses to PARPis in SLFN11-expressing and BRCA-deficient tumors. It highlight the clinical implications of SLFN11.

DOI： 10.1038/s41388-024-03094-1

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This study aimed to evaluate the associations of fasting plasma glucose (FPG) and glycosylated hemoglobin (HbA1c) levels at <24 weeks of gestation with hypertensive disorders of pregnancy (HDP) and compare the strengths of the associations of HDP with FPG and HbA1c levels. Totally, 1,178 participants were included in this prospective cohort study. HDP, FPG, HbA1c, and potential confounding factors were included in multiple logistic regression models. The number of HDP cases was 136 (11.5%). When FPG and HbA1c were included in the model separately, quartile 4 (Q4) of FPG (87-125 mg/dL) and HbA1c (5.2-6.3% [33-45 mmol/mol]) levels had higher odds of HDP than quartile 1. The odds ratios (ORs) were 1.334 (95% confidence interval [CI]: 1.002-1.775) for Q4 of FPG and 1.405 (95% CI: 1.051-1.878) for Q4 of HbA1c. When the participants were divided into two categories based on the cut-off value with the maximum Youden Index of FPG or HbA1c, the ORs for high FPG (≥84 mg/dL) or high HbA1c (≥5.2% [33 mmol/mol]) were 1.223 (95% CI: 1.000-1.496) and 1.392 (95% CI: 1.122-1.728), respectively. When both FPG and HbA1c were included in the model simultaneously, the statistical significance of Q4 of FPG disappeared, whereas that of HbA1c remained. In two-category models, the same results were obtained. High FPG and HbA1c levels at <24 weeks of gestation were risk factors for HDP in pregnant Japanese women. In addition, high HbA1c levels were more strongly associated with HDP than high FPG levels.

DOI： 10.1507/endocrj.EJ23-0568

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Publishing type：Research paper (scientific journal)   Publisher：Elsevier BV  

DOI： 10.1016/j.bcp.2024.116454

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Our aim is to investigate the obstetric practices in Japan regarding the screening and management of gestational diabetes mellitus (GDM) diagnosed before 20 weeks of gestation (early-GDM). A web-based questionnaire survey was administered to 991 teaching hospitals between November 2021 and February 2022, and 602 responses were received (a response rate of 61%). Screening tests for all pregnant women in the first trimester were conducted in 553 (92%) hospitals, and nearly all of these hospitals (535/553 [97%]) adhered to an individual protocol, predominantly relying on random plasma glucose measurements (488/535 [91%]). A quarter (139 [26%]) implemented a risk profile assessment for GDM screening, taking into account factors such as previous gestational diabetes, prior macrosomia, and family history of diabetes. A small number (23 [4%]) targeted only women at high risk of GDM using the risk profile assessment. The majority of hospitals (501 [94%]) employed a 75 g oral glucose tolerance test as a diagnostic measure, and glycemic control for early-GDM was established in most hospitals (429 [80%]). Of the 535 hospitals that maintained an individual management protocol, 356 [67%] facilitated dietary management, self-monitoring of blood glucose, and insulin administration if needed to meet glycemic targets. Our survey revealed a widespread adoption of universal screening and subsequent treatment for early-GDM in Japan.

DOI： 10.1007/s13340-024-00700-1

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AIM: Some concerns exist that diagnosis of gestational diabetes mellitus (GDM) may be missed when the simplified diagnostic criteria of the Japanese Society of Diabetes and Pregnancy (JSDP) for GDM (published during the COVID-19 pandemic) are used. Moreover, limited data is available regarding how widespread these diagnostic criteria are used when managing GDM during the COVID-19 pandemic. Therefore, this study aimed to determine how GDM diagnosis has changed during the COVID-19 pandemic in Japan. METHODS: The changes in GDM diagnosis during the COVID-19 pandemic were investigated using an online questionnaire to 2159 obstetric facilities in Japan. The questionnaire collected data on facility type, awareness of Japanese GDM diagnostic strategies, modifications to diagnostic methods for early and late GDM, and opinions on GDM management, with the pandemic divided into seven periods. RESULTS: We received responses from 593 facilities (27%). Approximately 90% of the facilities did not change their diagnostic process for early GDM or late GDM (occurring after 24 weeks gestation). However, during the COVID-19 pandemic, 19 facilities discontinued the use of 75-g oral glucose tolerance tests before 24 weeks of gestation, and 17 facilities discontinued it after 24 weeks of gestation, instead using the aforementioned Japanese GDM diagnostic strategy. CONCLUSIONS: Although a limited number of facilities modified their diagnostic method in response to the COVID-19 pandemic, this study demonstrated that those that adjusted their diagnostic method primarily used the Japanese COVID-19 GDM strategy by the JSDP.

DOI： 10.1111/jog.15929

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AIMS/INTRODUCTION: Gene-environment interactions are considered to critically influence type 2 diabetes mellitus development; however, the underlying mechanisms and specific interactions remain unclear. Given the increasing prevalence of low birthweight (LBW) influenced by the intrauterine environment, we sought to investigate genetic factors related to type 2 diabetes development in individuals with LBW. MATERIALS AND METHODS: The interaction between 20 reported type 2 diabetes susceptibility genes and the development of type 2 diabetes in LBW (<2,500 g) individuals in a population-based Japanese cohort (n = 1,021) was examined by logistic regression and stratified analyses. RESULTS: Logistic regression analyses showed that only the G/G genotype at the rs1862513 locus of the resistin gene (RETN), an established initiator of insulin resistance, was closely related to the prevalence of type 2 diabetes in individuals with LBW. Age, sex and current body mass index-adjusted stratified analyses showed a significant interaction effect of LBW and the RETN G/G genotype on fasting insulin, homeostatic model assessment 2-insulin resistance, Matsuda index and the prevalence of type 2 diabetes (all P-values for interaction <0.05). The adjusted odds ratio for type 2 diabetes in the LBW + G/G genotype group was 7.33 (95% confidence interval 2.43-22.11; P = 0.002) compared with the non-LBW + non-G/G genotype group. Similar results were obtained after excluding the influence of malnutrition due to World War II. CONCLUSIONS: Simultaneous assessment of LBW and the RETN G/G genotype can more accurately predict the risk of future type 2 diabetes than assessing each of these factors alone, and provide management strategies, including early lifestyle intervention in LBW population.

DOI： 10.1111/jdi.14163

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AIMS: This study aimed to investigate the association of maternal birth weight (MBW) with early and late gestational diabetes mellitus (GDM). METHODS: A total of 69318 pregnant Japanese women were included in this birth cohort study. The associations between maternal birth weight and early gestational diabetes mellitus (diagnosed at <24 gestational weeks) and late GDM (diagnosed at ≥24 gestational weeks) were investigated using a multinomial logistic regression model, with an maternal birth weight of 3000-3499 g as the reference category. RESULTS: Lower maternal birth weight was associated with higher odds of developing early and late gestational diabetes mellitus (P < 0.0001 and P < 0.0001, respectively). The adjusted odds ratios (aORs) for early gestational diabetes mellitus in participants with a MBW of <2500 g and 2500-2999 g were 1.345 (95% confidence interval [CI]: 0.912-1.984) and 1.338 (95% CI: 1.098-1.629), respectively. The aORs for late gestational diabetes mellitus in participants with a MBW of <2500 g and 2500-2999 g were, 1.657 (95% CI: 1.298-2.115) and 1.218 (95% CI: 1.058-1.402), respectively. CONCLUSIONS: Regardless of the gestational age when gestational diabetes mellitus was diagnosed, a lower maternal birth weight was associated with an increased risk of gestational diabetes mellitus. Furthermore, the association of a MBW <2500 g with late gestational diabetes mellitus tended to be stronger than that with early gestational diabetes mellitus.

DOI： 10.1111/jdi.14159

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BACKGROUND: Subclinical hypothyroidism, elevated thyroid-stimulating hormone (TSH) and normal free thyroxine (FT4) levels, is associated with multiple adverse pregnancy outcomes. Despite the uncertainty regarding the effectiveness of levothyroxine treatment on pregnancy outcomes in subclinical hypothyroidism, levothyroxine is widely administered with a threshold TSH level of 2.5 mU/L. The aim of this study is to investigate the efficacy of periconceptional levothyroxine treatment for subclinical hypothyroidism, including TSH levels >2.5 mU/L, and identify the characteristics of subclinical hypothyroidism that can benefit from levothyroxine treatment. METHODS: We conducted a systematic review and meta-analysis of randomized controlled trials from inception to February 2023. We analyzed the pooled effects of levothyroxine on subclinical hypothyroidism before and during pregnancy. The main outcomes before pregnancy were live birth, pregnancy, and miscarriage. The main outcomes during pregnancy were live birth, miscarriage, and preterm birth. We conducted subgroup analyses to compare the effects of levothyroxine on subclinical hypothyroidism with TSH levels of 2.5-4.0 mU/L and >4.0 mU/L. RESULTS: Of the 795 studies identified, 25 full-text articles were screened for eligibility. Finally, five studies on pre-conception treatment with 763 participants and seven studies on treatment during early pregnancy with 2,504 participants were analyzed. Pre-conception levothyroxine treatment showed no effect in improving live births and pregnancies, or decreasing miscarriages (risk ratio (RR):1.41; 95% confidence interval (CI):0.84-2.36, RR:1.73; 95%CI:0.88-3.39, and RR:0.46; 95%CI:0.11-2.00, respectively). Levothyroxine treatment during pregnancy showed no effect in improving live births (RR:1.03; 95%CI:0.98-1.09) or decreasing miscarriage rates (RR:0.99; 95%CI:0.65-1.51). The effect of levothyroxine treatment on preterm birth during pregnancy was significantly different depending on the TSH values (p=0.04); a positive effect was shown in the subclinical hypothyroidism subgroup with TSH >4.0 mU/L (RR:0.47; 95%CI:0.20-1.10), while no effect was shown in the subgroup with TSH 2.5-4.0 mU/L (RR:1.35; 95%CI:0.79-2.31). CONCLUSIONS: Pre-conceptional levothyroxine treatment does not improve fertility or decrease the incidence of miscarriages. However, further well-designed studies are needed for pre-conceptional treatment, especially in TSH >4.0 mU/L. Levothyroxine treatment during pregnancy had a positive effect on preterm birth; nevertheless, this was only applicable to subclinical hypothyroidism with TSH >4.0 mU/L.

DOI： 10.1089/thy.2023.0546

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Publishing type：Research paper (scientific journal)   Publisher：Elsevier BV  

DOI： 10.1016/j.lfs.2023.122214

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As 2 years have passed since the outbreak of coronavirus disease 2019 (COVID-19), we had an examination of the measures taken at the perinatal medical and child centers during this period at 42 National University Hospital. The first questionnaire survey was conducted during March 17-25, 2022 and the second questionnaire survey was conducted during April 4-30, 2022. For the treatment of pregnant women with COVID-19, a public health center-coordinated triage system had been created and implemented in each region and prefecture. The issues related to the hospital management of pregnant women with COVID-19 include the hindrances to the normal functioning of the center, the limited number of hospital beds and medical care systems as the beds were dedicated to patients with COVID-19, and the problems associated with the mode of delivery. There were no set rules regarding the management of mothers and babies at delivery and thereafter. Initially, cesarean delivery was allowed in almost all cases to reduce the risk of exposure to medical staff. Furthermore, many institutions did not permit expressed breast milk feeding and direct breastfeeding during the quarantine period. The COVID-19 pandemic has been created a shortage of healthcare delivery systems. It is expected that the emergence of new infectious diseases and pandemics will cause the same pressure on systems providing healthcare in the future.

DOI： 10.1111/jog.15650

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Pregnant women presumably gather information about the coronavirus disease 2019 (COVID-19) from various sources. However, it is difficult for pregnant women who are not medical professionals to source the appropriate information because of the infodemic related to the COVID-19 pandemic. Therefore, the objective of our study was to investigate how pregnant women gathered information about COVID-19 and COVID-19 vaccination. To address this issue, we conducted an online questionnaire survey between 5 October and 22 November 2021, which was approved by the Ethics Committee of Nihon University School of Medicine. We received 4962 responses after excluding 1179 insufficient answers. Our study found that age, occupation, and infection-risk anxiety influenced the selection of media for obtaining information. Pregnant women who were older, medical professionals, public servants, or educators tended to rely on specialized medical websites, whereas housewives tended to use mass media, social media, and sources with uncertain scientific evidence. Additionally, the number of weeks of gestation and the method of conception (natural or assisted reproductive conception) affected the selection of media. The accessibility of COVID-19 information for pregnant women was determined by their social background and pregnancy status. We need to continue making efforts to ensure that appropriate information is readily available to pregnant women and their families.

DOI： 10.3390/vaccines11040805

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Publishing type：Research paper (scientific journal)   Publisher：Wiley  

DOI： 10.1111/jdi.13977

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Other Link： https://onlinelibrary.wiley.com/doi/full-xml/10.1111/jdi.13977

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INTRODUCTION: The incidence of endometrial cancer (EC) has been increasing worldwide. However, because there are limited chemotherapeutic options for the treatment of EC, the prognosis of advanced-stage EC is poor. METHODS: Gene expression profile datasets for EC cases registered in The Cancer Genome Atlas (TCGA) was reanalyzed. Highly expressed genes in advanced-stage EC (110 cases) compared with early-stage EC (255 cases) were extracted and Gene Ontology (GO) enrichment analysis was performed. Among the enriched genes, Kaplan-Meier (KM) plotter analysis was performed. Candidate genes expression was analyzed in HEC50B cells and Ishikawa cells by RT-qPCR. In HEC50B cells, LIM homeobox1 (LIM1) was knocked down (KD) and cell proliferation, migration, and invasion ability of the cells were evaluated. Xenografts were generated using LIM1-KD cells and tumor growth was evaluated. Ingenuity Pathway Analysis (IPA) of RNA-seq data using LIM-KD cells was performed. Expression of phospho-CREB and CREB-related proteins were evaluated in LIM1-KD cells by western blotting and in xenograft tissue by immunofluorescent staining. Two different CREB inhibitors were treated in HEC50B and cell proliferation was evaluated by MTT assay. RESULTS: Reanalysis of TCGA followed by GO enrichment analysis revealed that homeobox genes were highly expressed in advanced-stage EC. Among the identified genes, KM plotter analysis showed that high LIM1 expression was associated with a significantly poorer prognosis in EC. Additionally, LIM1 expression was significantly higher in high-grade EC cell lines, HEC50B cells than Ishikawa cells. Knockdown of LIM1 showed reduced cell proliferation, migration and invasion in HEC50B cells. Xenograft experiments revealed that tumor growth was significantly suppressed in LIM1-KD cells. IPA of RNA-seq data using LIM-KD cells predicted that the mRNA expression of CREB signaling-related genes was suppressed. Indeed, phosphorylation of CREB was decreased in LIM1-KD cells and LIM1-KD cells derived tumors. HEC50B cells treated by CREB inhibitors showed suppression of cell proliferation. CONCLUSION AND DISCUSSION: Collectively, these results suggested that high LIM1 expression contributed to tumor growth via CREB signaling in EC. Inhibition of LIM1 or its downstream molecules would be new therapeutic strategies for EC.

DOI： 10.3389/fonc.2023.1082441

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OBJECTIVE: Female cancer survivors planning to become pregnant are concerned about the impact of cancer treatment on their ability to maintain normal pregnancy and the negative impact on their offspring. However, studies on the pregnancy outcomes of cancer survivors in Japan are limited. Therefore, this study aimed to investigate the pregnancy outcomes of female cancer survivors by comparing them with women without a history of malignant tumors in Japan. METHODS: This cross-sectional study included 3308 subjects, based on an internet-based questionnaire (self-reported) survey conducted in Japan. Differences in pregnancy outcomes, including multiple pregnancies, stillbirth, preterm birth (PTB), and infant birthweight, between cancer survivors and subjects without a history of malignant tumors, were evaluated using a generalized linear mixed-effects model with adjustment for possible confounding factors. RESULTS: Of 3308 subjects included in this study, 629 (19.0%) were cancer survivors, among whom cervical (40.4%), breast (19.1%), and thyroid (7.0%) malignancies were most frequent. 71 (2.2%) and 53 (1.6%) participants had a history of multiple pregnancies and stillbirth, respectively; 385 (11.8%), 179 (5.5%), and 137 (4.2%) participants, respectively, had histories of PTB at less than 37, 34, and 32 weeks of gestation. Further, 302 (10.7%), 326 (11.6%), and 330 (11.7%) participants delivered to low birthweight (LBW), small-for-gestational-age (SGA), and large-for-gestational-age (LGA) infants, respectively. Subjects with a history of cervical or breast cancers had significantly higher odds of PTB at <37 weeks of gestation (adjusted odds ratios [ORs], 1.87 [95% CI: 1.25-2.81] and 2.61 [95% CI: 1.77-3.86], respectively), preterm LBW infants (adjusted ORs, 2.70 [95% CI: 1.39-5.24] and 2.76 [95% CI: 1.03-7.38], respectively), and LGA infants (1.98 [95% CI: 1.36-2.89] and 1.99 [95% CI: 1.14-3.49], respectively), compared to those without a history of a malignant tumor. Subjects with a history of thyroid cancer had significantly higher odds of stillbirth (adjusted OR, 5.11 [95% CI: 1.11-23.5]). CONCLUSION: Cancer survivors had a higher risk of adverse pregnancy outcomes than those without a history of malignant tumors in Japan. Healthcare providers should consider the high likelihood of adverse pregnancy outcomes during preconception counseling for cancer survivors.

DOI： 10.1080/14767058.2022.2155037

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This study aimed to investigate the relationship between gestational diabetes mellitus (GDM) screening methods and GDM incidences. In 2018, a national questionnaire was administered at 231 institutions (56.6%) of all 408 perinatal medical centers in Japan. Of 100,485 women, 2,982 (3.0%) were diagnosed with GDM during their first pregnancy period (FPP) and 7,289 (7.3%) were diagnosed with GDM during their middle pregnancy period (MPP). The proportion of women diagnosed with GDM during FPP and MPP using 95 mg/dL as the cutoff value (CV) for random plasma glucose (PG) at FPP (4.3% and 9.2%) was significantly higher than that of women diagnosed with GDM using 100 mg/dL as the CV for random PG (2.7% and 6.9%, p < 0.0001, respectively). Compared with women screened for GDM using "random PG and random PG," women who were screened for GDM using "random PG and 50-g glucose challenge test (GCT)" had a significantly higher incidence of GDM (6.6% versus 8.9%, p < 0.0001). Using random PG and 50-g GCT, the incidence of GDM among women diagnosed at MPP using a CV of 95 mg/dL at FPP was significantly higher than that of women diagnosed using a CV of 100 mg/dL (16.5% versus 7.8%: p < 0.0001). While, using "random PG and random PG," the incidences of GDM among women were similar between institutions using a CV of 100 mg/dL and those using a CV of 95 mg/dL at FPP (6.7% versus 6.9%: p = 0.3581). This study showed random PG as a first-step screening method in MPP may overlook women with GDM.

DOI： 10.1507/endocrj.EJ22-0072

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We conducted two-year seroprevalence surveys of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies among outpatients and healthcare workers (HCWs) at Ehime University Hospital. Data were collected for outpatients and HCWs in June 2020 (1st survey), December 2020 (2nd survey), July 2021 (3rd survey), and December 2021 (4th survey), focusing on demographics, occupation, and the seroprevalence of anti-SARS-CoV-2 antibodies. Blood samples were obtained from randomly selected outpatients who visited our hospital for medical care and HCWs undergoing regular medical checks with opt-out informed consent. SARS-CoV-2 antibody positivity was evaluated using two laboratory-based quantitative tests. The total number of participants enrolled was 6,369 (1st survey: 1,000 outpatients and 743 HCWs, 2nd survey: 1,000 outpatients and 407 HCWs, 3rd survey: 1,000 outpatients and 804 HCWs, 4th survey: 1,000 outpatients and 415 HCWs). The prevalence of SARS-CoV-2 antibodies among outpatients and HCWs was 0-0.1% and 0-0.124% during the research period, respectively, and changed little over time. These findings suggest that the magnitude of COVID-19 infection during the pandemic among outpatients and HCWs in this rural hospital might have been small.

DOI： 10.7883/yoken.JJID.2022.155

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Large-scale data on maternal and neonatal outcomes of pregnancy-associated cervical cancer in Japan are scarce, and treatment strategies have not been established. This multicenter retrospective observational study investigated clinical features and trends in pregnancy-associated cervical cancer treatments at 523 hospitals in Japan. We included cervical cancer cases that were histologically diagnosed (between 1 January 2012, and 31 December 2017), and their clinical information was retrospectively collected. Of 40 patients diagnosed with pregnancy-associated cervical cancer at ≥22 gestational weeks, 34 (85.0%) were carefully followed until delivery without intervention. Of 163 diagnosed at <22 gestational weeks, 111 continued and 52 terminated their pregnancy. Ninety patients with stage IB1 disease had various treatment options, including termination of pregnancy. The 59 stage IB1 patients who continued their pregnancy were categorized by the primary treatment into strict follow-up, conization, trachelectomy, and neoadjuvant chemotherapy groups, with no significant differences in progression-free or overall survival. The birth weight percentile at delivery was smaller in the neoadjuvant chemotherapy group than in the strict follow-up group (p = 0.029). Full-term delivery rate was relatively higher in the trachelectomy group (35%) than in the other groups. Treatment decisions for pregnancy-associated cervical cancer are needed after estimating the stage, considering both maternal and fetal benefits.

DOI： 10.3390/cancers14133072

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To investigate the vaccination status and adverse reactions to the COVID-19 vaccine among pregnant women in Japan, we conducted an online questionnaire survey from October 5 to November 22, 2021. The number of participants in the online survey was 6576. Of the participants, 4840 (73.6%) were vaccinated twice, and 557 (8.5%) were vaccinated once. A total of 1179 (17.9%) responders had never been vaccinated against COVID-19. The most frequent adverse reaction was local pain at the injection site. The incidence of local adverse reactions was almost identical after the first and the second vaccinations, while systemic reactions, such as fever and fatigue/malaise, and adverse reactions outside the vaccination site such as headache and arthralgia, were more frequent after the second vaccination than after the first vaccination. Regarding the obstetrical complications, uterine tension and/or contraction was observed in 1.65% of the pregnant women after the first vaccination and in 2.98% after the second vaccination, and uterine pain appeared in 1.06% of the pregnant women after the second vaccination. However, serious symptoms, such as hemorrhage, decreased fetal movement, edema, increased blood pressure, and amniorrhexis, were seen in less than 1% of vaccinated women after both the first and second vaccinations. This study clarified the characteristics of vaccination, adverse reactions, and obstetrical symptoms in pregnant women in Japan who had the COVID-19 vaccine up to the second dose. As a booster vaccination is currently underway, further study is needed to improve the management of pregnant women during the current pandemic.

DOI： 10.1111/jog.15285

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The long-term effect of changes in maternal dietary composition during pregnancy on the offspring's metabolic homeostasis is uncertain. We aimed to investigate the long-term effects of maternal balanced low-fat interventions on metabolic homeostasis of the offspring using a mouse model of gestational obesity induced by a high-fat diet (HFD). Male newborns in the balanced low-fat intervention group had significantly lower serum insulin and higher serum adiponectin levels than those in the HFD group. Changes in maternal dietary composition improved glucose tolerance in pups at 3 and 12 weeks of age. We also performed transcriptomic analysis of the liver in neonatal and 3-week-old pups. Genes in the peroxisome proliferator-activated receptor signaling pathway were significantly down-regulated in neonates in the balanced low-fat intervention group compared with the HFD group. A maternal balanced low-fat diet fully compensated for the detrimental effects of a maternal HFD on glucose metabolism, insulin tolerance, circulating insulin, dyslipidemia, and body weight gain in male offspring by changing the gene expression profile. These data suggest that maternal balanced low-fat intervention is critical for improving the metabolic health of future generations.

DOI： 10.1016/j.jnutbio.2022.108971

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Aim: Diabetes confers a high risk of developing poor health in later life in women. Based on the Developmental Origins of Health and Disease theory, the present study was undertaken to investigate the efficacy of perinatal fat restriction in maternal high-fat-exposed female offspring to maintain glucose homeostasis in later life between adulthood and aging. Methods: Low-fat dietary intervention during either gestation or lactation was performed using a high-fat diet-induced maternal obesity mouse model (HFD mice). Physiological metabolic parameters, including body weight and serum levels of total cholesterol and triglycerides, were monitored. Glucose tolerance test and insulin sensitivity test were performed in 12- and 70-week-old offspring. Insulin-positive islet cells were also observed using immunohistochemical staining. Results: HFD significantly induced abnormal weight gain, hyperlipidemia and impairment of both glucose tolerance and insulin sensitivity in offspring. Standard diet intake after weaning improved weight gain, serum total cholesterol level and glucose tolerance, but not insulin sensitivity, in 70-week-old offspring. Only perinatal fat restriction during both gestation and lactation, followed by standard food intake for the rest of their life, provided adequate efficacy to restore insulin sensitivity in aging female progeny. Conclusions: Perinatal low-fat intervention may prevent deterioration of glucose metabolism. To improve the health status over a female's lifespan, appropriate nutritional intervention during the early developmental stage may reset the disease trajectory and prevent the onset and development of diabetes. Geriatr Gerontol Int 2022; 22: 441–448.

DOI： 10.1111/ggi.14378

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Perioperative management of pregnant women with heart failure is difficult. Management of anesthesia in pregnant women is especially difficult because all of the currently available choices present challenges. We report a patient with peripartum cardiomyopathy (PPCM) who required an emergent cesarean section and discuss the possible tactics for managing anesthesia. A 40-year-old primipara with severe cardiac and respiratory failure required an emergent cesarean section at 39+1 gestational weeks. Her left ventricular ejection fraction was between 10% and 15%, and she had orthopnea. General anesthesia was planned after inserting sheaths for percutaneous cardiopulmonary support from the femoral artery and vein. However, when the patient was asked to lie down on the operation bed, she panicked and resisted because of labor pain and dyspnea. Therefore, anesthesia was induced instead of the initial plan. Finally, we successfully managed the anesthesia and delivered the newborn. There are no alternatives to general anesthesia in patients with PPCM presenting with orthopnea. Anesthesia induction in the supine position is impossible in such patients owing to dyspnea. Anesthesia should be started with light sedation in the sitting position, and ketamine or low-dose remifentanil may be an option to maintain maternal hemodynamics and prevent neonatal asphyxia.

DOI： 10.1177/03000605211063077

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Leo Chu, Takashi Sugiyama, and Ronald Ma provide their perspective on recent updates on research in gestational diabetes mellitus, including updates on the epidemiology, diagnosis, and long-term follow-up of women with gestational diabetes mellitus. They also provide a summary of current challenges and a perspective on research gaps on this important clinical and public health problem.

DOI： 10.1111/jdi.13670

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AIM: Recent advances in cancer treatment have improved the prognosis of child, adolescent, and young adult (CAYA) cancer survivors. This study aimed to examine the current status of pregnancy outcomes among female cancer survivors in Japan. METHODS: The first questionnaire was sent to 633 major tertiary institutions certified by the Japan Society of Obstetrics and Gynecology to identify institutions managing cases of pregnant cancer survivors between January 2011 and December 2015. The second questionnaire was sent only to institutions with pregnant cancer survivors during the study period. RESULTS: We analyzed 2242 singleton deliveries of cancer survivors based on the responses received in the second questionnaire (199/255 responses; 78.0%). The three most frequent types of malignant tumors were uterine cervical (23.4%), breast (17.6%), and thyroid cancers (17.5%). Conception was aided by the use of assisted reproductive technology in 17.0% of the patients. The proportions of mothers aged 35-39.9 and ≥ 40 years were 36.5% and 11.8%, respectively. The prevalence of preterm birth (PTB) at <37, <34, and < 32 weeks' gestation were 16.7%, 6.8%, and 4.3%, respectively. The proportion of infants with low birth weight (LBW) was 18.9%. CONCLUSION: The present study findings suggest that advanced maternal age was common among pregnant cancer survivors and these survivors often gave birth to PTB and LBW infants in Japan. The likelihood of adverse pregnancy outcomes should be considered by healthcare providers when planning counseling and perinatal care for cancer survivors.

DOI： 10.1111/jog.14909

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BACKGROUND: Obese pregnant women are known to experience poorer pregnancy outcomes and are at higher risk of postnatal arteriosclerosis. Hence, weight control during and after pregnancy is important for reducing these risks. The objective of our planned randomized controlled trial is to evaluate whether the rate of change in body weight in obese women before pregnancy to 12 months postpartum would be lower with the use of an intervention consisting of Internet of Things (IoT) devices and mobile applications during pregnancy to 1 year postpartum compared to a non-intervention group. METHODS: Women will be recruited during outpatient maternity checkups at four perinatal care institutions in Japan. We will recruit women at less than 30 weeks of gestation with a pre-pregnancy body mass index ≥ 25 kg/m2. The women will be randomly assigned to an intervention or non-intervention group. The intervention will involve using data (weight, body composition, activity, sleep) measured with IoT devices (weight and body composition monitor, activity, and sleep tracker), meal records, and photographs acquired using a mobile application to automatically generate advice, alongside the use of a mobile application to provide articles and videos related to obesity and pregnancy. The primary outcome will be the ratio of change in body weight (%) from pre-pregnancy to 12 months postpartum compared to before pregnancy. DISCUSSION: This study will examine whether behavioral changes occurring during pregnancy, a period that provides a good opportunity to reexamine one's habits, lead to lifestyle improvements during the busy postpartum period. We aim to determine whether a lifestyle intervention that is initiated during pregnancy can suppress weight gain during pregnancy and encourage weight loss after delivery. TRIAL REGISTRATION: UMIN: UMIN (University hospital Medical Information Network) 000,041,460. Resisted on 18th August 2020. https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000047278.

DOI： 10.1186/s12884-021-03998-w

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Preeclampsia (PE) is a serious disease that can be fatal for the mother and fetus. The two-stage theory has been proposed as its cause, with the first stage comprising poor placentation associated with the failure of fertilized egg implantation. Successful implantation and placentation require maternal immunotolerance of the fertilized egg as a semi-allograft and appropriate extravillous trophoblast (EVT) invasion of the decidua and myometrium. The disturbance of EVT invasion during implantation in PE results in impaired spiral artery remodeling. PE is thought to be caused by hypoxia during remodeling failure-derived poor placentation, which results in chronic inflammation. High-mobility group protein A (HMGA) is involved in the growth and invasion of cancer cells and likely in the growth and invasion of trophoblasts. Its mechanism of action is associated with immunotolerance. Thus, HMGA is thought to play a pivotal role in successful pregnancy, and its dysfunction may be related to the pathogenesis of PE. The evaluation of HMGA function and its changes in PE might confirm that it is a reliable biomarker of PE and provide prospects for PE treatment through the induction of EVT proliferation and invasion during the implantation.

DOI： 10.3390/biom11060822

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The pathogenesis of preeclampsia begins when a fertilized egg infiltrates the decidua, resulting in implantation failure (e.g., due to extravillous trophoblast infiltration disturbance and abnormal spiral artery remodeling). Thereafter, large amounts of serum factors (e.g., soluble fms-like tyrosine kinase 1 and soluble endoglin) are released into the blood from the hypoplastic placenta, and preeclampsia characterized by multiorgan disorder caused by vascular disorders develops. Successful implantation and placentation require immune tolerance to the fertilized egg as a semi-allograft and the stimulation of extravillous trophoblast infiltration. Recently, exosomes with diameters of 50-100 nm have been recognized to be involved in cell-cell communication. Exosomes affect cell functions in autocrine and paracrine manners via their encapsulating microRNA/DNA and membrane-bound proteins. The microRNA profiles of blood exosomes have been demonstrated to be useful for the evaluation of preeclampsia pathophysiology and prediction of the disease. In addition, exosomes derived from mesenchymal stem cells have been found to have cancer-suppressing effects. These exosomes may repair the pathophysiology of preeclampsia through the suppression of extravillous trophoblast apoptosis and promotion of these cells' invasive ability. Exosomes secreted by various cells have received much recent attention and may be involved in the maintenance of pregnancy and pathogenesis of preeclampsia.

DOI： 10.3390/ijms22052572

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BACKGROUND: The association between cesarean section and the risk of postpartum depressive symptoms remains controversial. The present prebirth cohort study examined this issue in Japan. METHODS: Study subjects were 1310 women. Information under study was obtained using a self-administered questionnaire. Postpartum depressive symptoms were defined as a total Edinburgh Postnatal Depression Scale score of nine or higher between three and four months postpartum. Multivariate logistic regression analysis was used to adjust for age, body mass index, gestational weeks at baseline, gestational weeks at delivery, number of children at baseline, previous miscarriage or stillbirth, previous abortion, history of depression, family history of depression, region of residence, employment status, educational level, household income, family structure, breastfeeding status, smoking during pregnancy, infant's birthweight, and infant's sex. RESULTS: Postpartum depressive symptoms were identified in 8.2%. After adjustment for the confounding factors, compared with vaginal delivery, cesarean section was independently associated with an increased risk of postpartum depressive symptoms: the adjusted odds ratio (OR) was 1.95 (95% confidence interval [CI]: 1.16-3.23). This positive association was more apparent among those who had no other children at baseline than among those who already had one or more children: the adjusted ORs were 2.94 (95% CI: 1.35-6.26) and 1.45 (95% CI: 0.68-2.92), respectively; however, this interaction was not significant. LIMITATIONS: Information on whether each cesarean section was emergency or elective and other obstetric complications was not available. CONCLUSIONS: Cesarean section may be associated with an increased risk of postpartum depressive symptoms, especially among women without children at baseline.

DOI： 10.1016/j.jad.2020.09.106

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AIMS: To investigate the associations between glycosylated hemoglobin (HbA1c) levels at less than 24 weeks of gestation and adverse pregnancy outcomes in Japan. METHODS: This was a prospective nationwide birth cohort study of 77,526 subjects with an HbA1c level of <6.5% (<48 mmol/mol) at less than 24 weeks of gestation. Associations of HbA1c level with adverse pregnancy outcomes were evaluated using multivariate analyses. RESULTS: The adjusted odds ratios per 1% (11 mmol/mol) increase in HbA1c level were 1.77 (95% confidence interval [CI]: 1.48-2.12) for hypertensive disorders of pregnancy; 1.78 (95% CI: 1.12-2.83) for placental abruption; 1.30 (95% CI: 1.12-1.50) for preterm birth; 2.11 (95% CI: 1.41-3.16) for very preterm birth; 1.49 (95% CI: 1.33-1.68) for low birth weight infants; 1.95 (95% CI: 1.42-2.70) for macrosomia; 1.23 (95% CI: 1.09-1.39) for small for gestational age; 1.15 (95% CI: 1.04-1.28) for large for gestational age; and 1.29 (95% CI: 1.20-1.39) for the composite adverse pregnancy outcome. CONCLUSIONS: The higher the HbA1c level, the higher the risk of adverse pregnancy outcomes in Japan. Further studies will be needed to determine prenatal management based on the HbA1c level in pregnant women with HbA1c <6.5% (<48 mmol/mol) at less than 24 weeks of gestation.

DOI： 10.1016/j.diabres.2020.108377

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Objective: The authors investigated the relationship between the usefulness of CPT-11 + PLD combination therapy and the UGT1A1 genotype. Materials and Methods: Forty-one patients who provided informed consent were divided into the following two groups according to UGT1A1 genotypes: wild type and non-wild type. Adverse events, antitumor effect, and outcomes were compared between these two groups. Results: Twenty-three patients were wild type and 18 were non-wild type for UGT1A1. A total of 94 and 73 treatment cycles were prescribed to the wild-type and non-wild-type groups, respectively. No significant differences in the incidence of any grade 3 or higher adverse events were observed between the two groups. However, the next treatment cycle was postponed in 9.6% of the wildtype group and 12.3% of the non-wild-type group (p = 0.891). The antitumor effects as assessed by response rate were 26.1% in the wildtype group and 55.6% in the non-wild-type group (p = 0.054). The median observation period was 13 months. The median progression-free survival was three months in the wild-type group vs. five months in non-wild-type group (p = 0.913), while the median overall survival was 24 vs. 22 months (p = 0.535). Conclusions: This study did not demonstrate a statistically significant difference in the usefulness of CPT-11 + PLD combination therapy for recurrent ovarian cancer between the two groups of UGT1A1 genotypes. This study was considered to have significance as the first study conducted in Japan to prospectively evaluate the relationship between the usefulness of CPT-11-based chemotherapy and the UGT1A1 genotype for recurrent ovarian cancer.

DOI： 10.31083/J.EJGO.2020.03.5156

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OBJECTIVE: This study aimed to evaluate whether the Edinburgh Postnatal Depression Scale (EPDS) score predicts the occurrence of premenstrual syndrome (PMS) and premenstrual dysphoric disorder (PMDD) after delivery. MATERIALS AND METHODS: The women in this study were registered at 35-36 weeks of pregnancy at Mie University Hospital from 2013 to 2015. We prospectively divided the puerperants into those with an EPDS score ≥9 (the high-EPDS group) and those with an EPDS score <9 (the low-EPDS group) at 1 month postpartum. We compared the incidence rate of severe PMS and PMDD between both groups at 1 year after delivery. RESULTS: Of 200 registered cases, 178 (89.0%) did not experience severe PMS or PMDD before pregnancy. Among them, 21 were in the high-EPDS group, and 89 in the low-EPDS group. Four of the 21 women (19.0%) in the high-EPDS group and five of the 89 (5.6%) in the low-EPDS group had severe PMS or PMDD at 1 year after delivery. The incidence rate of severe PMS or PMDD in the high-EPDS group was higher than that in the low-EPDS group (p = 0.07). CONCLUSIONS: The novel finding of this study is that the EPDS may predict the occurrence of severe PMS/PMDD after delivery. The EPDS will contribute to the early detection of these diseases and to improving the quality of life of the patients by allowing treatment initiation at an early stage.

DOI： 10.1016/j.tjog.2020.03.003

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OBJECTIVE: Mycoplasma hominis usually colonizes the lower urogenital tract and has been occasionally associated with pelvic inflammatory disease, postpartum fever, preterm labor in pregnant females. The aim of this study was to investigate the incidence and antimicrobial susceptibilities of M. hominis isolated from the urogenital tracts of pregnant females. METHODS: Specimens were obtained from the urogenital tract of pregnant females at Department of Obstetrics and Gynecology, Ehime University Hospital, between November 2014 and December 2017. The identification of M. hominis was confirmed by the polymerase chain reaction (PCR) methods. The minimum inhibitory concentrations (MICs) of antibiotics were measured using a broth microdilution assay. RESULTS: Of the 1074 specimens tested, 63 (5.9%) were positive for M. hominis. The M. hominis-positive rate was highest at 21.3% between 18 and 24 years old. The 21 (25.6%) of 82 patients with bacterial vaginosis were positive for M. hominis. The 17 (40.5%) of 42 patients delivered by cesarean section that occurred infections including of intrauterine infection and pelvic abscess were positive for M. hominis. They were all administered β-lactam antibiotics before and after cesarean section. All patients recovered immediately following administration of clindamycin (CLDM). β-lactam antibiotics, macrolides and fosfomycin (FOM) were all resistant against M. hominis strains. In contrast, M. hominis strains were susceptible to CLDM, minocycline (MINO) and quinolones. CONCLUSIONS: Our data suggests that the prevalence of genital M. hominis in pregnant females is high at younger age, bacterial vaginosis and infections after cesarean section with β-lactam antibiotics administration. CLDM, MINO and quinolones may be recommended against M. hominis infection. Especially, CLDM can be used as the adequate agent for pregnant females because tetracycline and quinolones are undesirable during pregnancy and lactation.

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AIMS/INTRODUCTION: Low birthweight is reportedly associated with type 2 diabetes mellitus; however, this association has not been confirmed in the Japanese population, and whether high birthweight is associated with type 2 diabetes mellitus is controversial. We aimed to investigate the association between birthweight and type 2 diabetes mellitus among a general Japanese population. MATERIALS AND METHODS: Overall 1,135 middle- to old-aged Japanese men and women were enrolled in the Toon Health Study. A 75-g oral glucose tolerance test was used to diagnose type 2 diabetes mellitus, and a questionnaire survey about birthweight was administered. The association between birthweight and the prevalence of type 2 diabetes mellitus in later life of the participants was examined using multivariable logistic regression analysis. Stratified analysis by current body mass index was also carried out. RESULTS: The mean age was 56.5 ± 12.2 years. Type 2 diabetes mellitus was observed in 9.3% of the participants in this study. Compared with the reference group (2,500-3,999 g), the adjusted odds ratio of the low-birthweight group (<2,500 g) for type 2 diabetes mellitus was 2.46 (95% confidence interval 1.48-4.10). The association between the high-birthweight group (≥4000 g) and type 2 diabetes mellitus was not significant after including family history of diabetes in the multivariable model. The odds ratio of the low-birthweight group for type 2 diabetes mellitus was higher in the overweight/obese group than in the non-overweight group. CONCLUSIONS: Low birthweight was associated with an increased risk of type 2 diabetes mellitus in a Japanese population, especially in overweight/obese individuals.

DOI： 10.1111/jdi.13274

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AIMS/INTRODUCTION: To compare pregnancy outcomes between women with gestational diabetes mellitus (GDM) diagnosed early and late in pregnancy in Japan. MATERIALS AND METHODS: We examined women diagnosed with GDM in this multi-institutional retrospective study. Women were divided into two groups by gestational age at diagnosis: <24 weeks of gestation (early group, 14.4 ± 4.2 weeks) and ≥24 weeks of gestation (late group, 29.6 ± 3.4 weeks). Dietary counseling with self-monitoring of blood glucose with or without insulin therapy was initiated for both groups. Pregnancy outcomes were compared between the groups. RESULTS: Data from 600 early and 881 late group participants from 40 institutions were included. Although pre-pregnancy body mass index was higher in the early group than in the late group, gestational weight gain was lower in the early group. Hypertensive disorders of pregnancy and cesarean section were more prevalent in the early than in the late group (9.3% vs 4.8%, P < 0.001; 34.2% vs 32.0%, P < 0.001, respectively). The prevalence of large-for-gestational-age infants was higher in the late than in the early group (24.6% vs 19.7%, respectively, P = 0.025). There was no significant difference in other neonatal adverse outcomes between the groups. Multiple logistic regression analysis showed that early group, nulliparity and pre-pregnancy body mass index were associated with hypertensive disorders of pregnancy. CONCLUSIONS: These results suggest that maternal complications, including hypertensive disorders of pregnancy and cesarean delivery, were higher in the early group than in the late group. Earlier intervention for GDM might be associated with a reduction in large-for-gestational-age infants.

DOI： 10.1111/jdi.13101

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As one of the main antimicrobial peptides, human β-defensin 2 (HBD2) plays multiple roles in the lower genital tract. Based on the Nugent score as a diagnostic criterion for bacterial vaginosis, we sought to clarify the correlations among the Nugent score and Interleukin-6 (IL-6) and HBD2 levels in vaginal secretions in association with various types of infection. Ninety-eight women were recruited for this study. Levels of HBD2 and IL-6 in the vaginal wash were measured by enzyme-linked immunosorbent assays. According to the Nugent method, the number of Lactobacillus morphotypes per field of view was well correlated with the HBD2 level. The amount of HBD2 was also well correlated with the presence of Candida spp.(p<0.01). In vitro experiments revealed that the expression of HBD2 from the human vaginal epithelial cell line, VK2/E6E7, was induced by the addition of heat-killed Candida albicans (HKCA). The addition of HKCA induced the expression of Dectin-1 mRNA, and a luciferase assay for NF-kB responsive elements showed that HKCA activated NF-kB signaling. These results suggested that Candida albicans would be induced the activation of Dectin-1 and NF-kB signaling, resulting in HBD2 expression. In conclusion, the expression of HBD2 was positively correlated with the presence of Lactobacillus and Candida spp..

DOI： 10.7883/yoken.JJID.2019.190

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AIMS/INTRODUCTION: To evaluate the differences in the results of 75-g oral glucose tolerance tests (OGTTs) according to gestational age in Japan. MATERIALS AND METHODS: In this prospective cohort study, 2,578 pregnant women were divided into three categories based on their gestational age during the 75-g OGTT: <14 weeks' gestation, 14-23 weeks' gestation and 24-32 weeks' gestation. The association between gestational age and the results of the 75-g OGTT were evaluated using multivariable analysis. RESULTS: Early gestational age was associated with high fasting plasma glucose levels at the time of the 75-g OGTT, and low corresponding 1-h and 2-h plasma glucose levels. Compared with women with a gestational age of 24-32 weeks, women who had undergone the 75-g OGTT at <14 weeks' gestation had significantly higher odds of gestational diabetes mellitus diagnosis based on the currently used criteria in Japan (adjusted odds ratio 1.42, 95% confidence interval 1.07-1.90). CONCLUSIONS: The results of the 75-g OGTT varied by gestational age. The use of the same 75-g OGTT cut-off values for the diagnosis of gestational diabetes mellitus, regardless of gestational age, might lead to increases in the prevalence of gestational diabetes mellitus diagnosis in Japan.

DOI： 10.1111/jdi.13044

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To ensure that experiences and lessons learned from the unprecedented 2011 Great East Japan Earthquake are used to improve future disaster planning, the Japan Diabetes Society (JDS) launched the "Research and Survey Committee for Establishing Disaster Diabetes Care Systems Based on Relevant Findings from the Great East Japan Earthquake" under the supervision of the Chairman of the JDS. The Committee conducted a questionnaire survey among patients with diabetes, physicians, disaster medical assistance teams (DMATs), nurses, pharmacists, and nutritionists in disaster areas about the events they saw happening, the situations they found difficult to handle, and the needs that they felt required to be met during the 2011 Great East Japan Earthquake. A total of 3,481 completed questionnaires were received. Based on these and other experiences and lessons reported following the 2011 Great East Japan Earthquake and the 2004 Niigata-Chuetsu Earthquakes, the current "Manual for Disaster Diabetes Care" has been developed by the members of the Committee and other invited authors from relevant specialties. To our knowledge, the current Manual is the world's first to focus on emergency diabetes care, with this digest English version translated from the Japanese original. It is sincerely hoped that patients with diabetes and healthcare providers around the world will find this manual helpful in promoting disaster preparedness and implementing disaster relief.

DOI： 10.1111/jdi.13053

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To ensure that experiences and lessons learned from the unprecedented 2011 Great East Japan Earthquake are used to improve future disaster planning, the Japan Diabetes Society (JDS) launched the "Research and Survey Committee for Establishing Disaster Diabetes Care Systems Based on Relevant Findings from the Great East Japan Earthquake" under the supervision of the Chairman of the JDS. The Committee conducted a questionnaire survey among patients with diabetes, physicians, disaster medical assistance teams (DMATs), nurses, pharmacists, and nutritionists in disaster areas about the events they saw happening, the situations they found difficult to handle, and the needs that they felt required to be met during the 2011 Great East Japan Earthquake. A total of 3,481 completed questionnaires were received. Based on these and other experiences and lessons reported following the 2011 Great East Japan Earthquake and the 2004 Niigata-Chuetsu Earthquakes, the current "Manual for Disaster Diabetes Care" has been developed by the members of the Committee and other invited authors from relevant specialties. To our knowledge, the current Manual is the world's first to focus on emergency diabetes care, with this digest English version translated from the Japanese original. It is sincerely hoped that patients with diabetes and healthcare providers around the world will find this manual helpful in promoting disaster preparedness and implementing disaster relief.

DOI： 10.1007/s13340-019-00397-7

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© 2018 The Authors. The Journal of Gene Medicine Published by John Wiley & Sons, Ltd. Background: A549 carrier cells infected with oncolytic adenovirus can induce complete tumor reduction of subcutaneous ovarian tumors but not intraperitoneal disseminated ovarian tumors. This appears to be a result of the insufficient antitumor effect of A549 carrier cells. Therefore, in the present study, we cloned a novel carrier cell with the aim of improving the antitumor effects. Methods: Carrier cells infected with oncolytic adenovirus AdE3-midkine with a midkine promoter were cloned by limiting dilution. We examined the antitumor effects of these cells on subcutaneous and intraperitoneal OVHM ovarian tumors in a syngeneic mouse model. Biosafety tests were conducted in beagle dogs and rabbits. Results: We cloned EHMK-51-35 carrier cells with 10-fold higher antitumor effects compared to A549 carrier cells in vitro. EHMK-51-35 carrier cells co-infected with AdE3-midkine and Ad-mGM-CSF induced a 100% complete tumor reduction in subcutaneous tumors and a 60% reduction of intraperitoneal disseminated tumors. Single-dose acute toxicity test on beagle dogs with EHMK-51-35 carrier cells co-infected with AdE3-midkine and Ad-cGM-CSF showed no serious side effects. Biologically active adenoviruses were not detected in the blood, saliva, feces, urine or whole organs. In a chronic toxicity test, VX2 tumors in rabbits were injected five times with EHMK-51-35 carrier cells infected with AdE3-midkine and these rabbits showed no serious side effects. Conclusions: Significant antitumor effects and safety of cloned EHMK-51-35 carrier cells were confirmed in intraperitoneal ovarian tumors and toxicity tests, respectively. These findings will be extended to preclinical efficacy studies using dogs and cats, with the aim of conducting human clinical trials on refractory solid tumors.

DOI： 10.1002/jgm.3064

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© Cambridge University Press and the International Society for Developmental Origins of Health and Disease 2019 This is an Open Access article, distributed under the terms of the Creative Commons Attribution licence (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted re-use, distribution, and reproduction in any medium, provided the original work is properly cited. This study examines the relationship between paternal height or body mass index (BMI) and birth weight of their offspring in a Japanese general population. The sample included 33,448 pregnant Japanese women and used fixed data, including maternal, paternal and infant characteristics, from the Japan Environment and Children&#039;s Study (JECS), an ongoing nationwide birth cohort study. Relationships between paternal height or BMI and infant birth weight [i.e., small for gestational age (SGA) and large for gestational age (LGA)] were examined using a multinomial logistic regression model. Since fetal programming may be a sex-specific process, male and female infants were analyzed separately. Multivariate analysis showed that the higher the paternal height, the higher the odds of LGA and the lower the odds of SGA in both male and female infants. The effects of paternal BMI on the odds of both SGA and LGA in male infants were similar to those of paternal height; however, paternal height had a stronger impact than BMI on the odds of male LGA. In addition, paternal BMI showed no association with the odds of SGA and only a weak association with the odds of LGA in female infants. This cohort study showed that paternal height was associated with birth weight of their offspring and had stronger effects than paternal BMI, suggesting that the impact of paternal height on infant birth weight could be explained by genetic factors. The sex-dependent effect of paternal BMI on infant birth weight may be due to epigenetic effects.

DOI： 10.1017/S2040174418001162

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OBJECTIVES: Although a twin pregnancy is a risk factor for hypertensive disorders of pregnancy, studies investigating longitudinal blood pressure changes during twin pregnancies are uncommon. The aims of this study were to evaluate the longitudinal blood pressure changes during twin pregnancies and to compare blood pressure levels between twin and singleton pregnancies. METHODS: Five hundred dichorionic diamniotic twin, 240 monochorionic diamniotic twin, and 80 775 singleton pregnancies were included in this Japanese prospective birth cohort study. A marginal model was applied to evaluate the SBP, DBP, and mean arterial pressure levels during early gestation, mid-gestation, and late gestation. RESULTS: The blood pressure levels fell from early-to-mid-gestation and rose after mid-gestation in the dichorionic and monochorionic diamniotic twin pregnancies. The SBP and mean arterial pressure levels during early gestation and the DBP and mean arterial pressure levels during late gestation were higher in the dichorionic diamniotic twin pregnancies than those in the singleton pregnancies. The blood pressure levels in the monochorionic diamniotic twin pregnancies were higher than those in the singleton pregnancies at each gestational stage, except for the SBP during late gestation. CONCLUSION: Although the longitudinal blood pressure changes during twin pregnancies were similar to those during singleton pregnancies, the blood pressure levels during twin pregnancies were higher. Further studies that examine the associations between the longitudinal blood pressure changes during pregnancy and the perinatal outcomes in twin pregnancies are necessary.

DOI： 10.1097/HJH.0000000000001846

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This study examined the association between maternal alcohol consumption during pregnancy and hypertensive disorders of pregnancy in the Japan Environment and Children's Study, a nationwide birth cohort study. A total of 76 940 pregnant women were included in the analysis. Information about alcohol consumption during pregnancy was obtained using two questionnaires: T1 and T2. The mean (standard deviation) gestational age in the T1 and T2 questionnaires were 16.5 (5.8) and 27.9 (3.7) weeks, respectively. Alcohol consumption was considered as an exposure, hypertensive disorders of pregnancy as an outcome, and possible confounding factors were included in a generalized linear mixed-effects model with a logit link function. Among the study subjects, 2 348 (3.1%) women developed hypertensive disorders of pregnancy. Compared with 25 300 women who never drank alcohol, 43 women who drank alcohol according to the T1 questionnaire and continued to drink ≥150 g ethanol/week according to the T2 questionnaire had significantly higher odds of hypertensive disorders of pregnancy. The adjusted odds ratio was 3.98 (95% confidence interval [CI], 1.33-11.9). In conclusion, alcohol consumption of ≥150 g ethanol/week during pregnancy is better avoided because of the high odds of developing hypertensive disorders of pregnancy. It may be meaningful that healthcare providers confirm information about alcohol consumption during pregnancy. Moreover, discontinuation of alcohol consumption is recommended to prevent the onset of hypertensive disorders of pregnancy in Japan.

DOI： 10.1038/s41440-018-0124-3

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The introduction of laparoscopic surgery has also been beneficial for patients with gynecological malignancies. In this respect, surgeons should receive related training in the context of human resource development. Hands-on training was introduced using Thiel-embalmed human cadavers (THCs) in 2014. To determine the usefulness of THCs, they were evaluated in terms of tissue color, consistency and operative tactility, among others, compared with in vivo laparoscopic training for gynecological malignancies. Hands-on training sessions using THCs were held for a total of 11 times at Ehime University Graduate School of Medicine between March 2014 and October 2017. Training on THCs included advanced laparoscopic procedures for radical hysterectomy type III. At the end of each training session, data were collected using a standardized, anonymous questionnaire termed the Likert scale. THCs ensured flexibility and plasticity of tissues and organs; therefore, the working space was similar to that in the living body under pneumoperitoneum. After analyzing the quality and consistency of tissue and organ color compared with in vivo conditions, most of the participants agreed or strongly agreed regarding the uterus, adnexa and ureter, but not regarding the large blood vessels. The highest scores were observed in the authenticity of the anatomical condition of each organ. Most participants strongly agreed that training using THCs would help improve their laparoscopic skills with a high level of satisfaction. Furthermore, most participants reported that they would recommend this training to other obstetrician-gynecologists. Laparoscopic training for gynecological malignancies using THCs was comparable to the in vivo conditions in terms of surgical view and operative tactility. Therefore, THCs may be an excellent training tool for improving laparoscopic surgical skills for gynecological malignancies.

DOI： 10.3892/mco.2018.1715

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PURPOSE: We evaluated the associations between gestational age (GA) and lung-to-liver signal intensity ratio (LLSIR) and fetal lung volume (FLV) using magnetic resonance imaging (MRI). Moreover, we evaluated the reproducibility of these measurements. MATERIALS AND METHODS: LLSIR and FLV were measured using single-shot fast spin-echo MRI in 88 consecutive fetuses. The Spearman test was used to assess the relationships between (1) LLSIR and GA, and (2) FLV and GA in 81 fetuses without lung abnormalities. Intra- and inter-observer reliabilities were assessed using intra-class correlation coefficients (ICCs). RESULTS: Overall, GA and LLSIR were significantly correlated (r = 0.62, p < 0.001). However, GA and LLSIR were only significantly correlated during the third trimester (before third trimester: r = 0.39, p = 0.08; during third trimester: r = 0.46, p < 0.001). Overall, GA and FLV were significantly correlated (r = 0.72, p < 0.001). FLV was significantly correlated with GA before (r = 0.86, p < 0.001) and during the third trimester (r = 0.47, p < 0.001). All ICCs were above 0.90. CONCLUSIONS: LLSIR and FLV are useful for the assessment of fetal lung maturity and are highly reproducible. Before the third trimester, FLV is more suitable than LLSIR for the evaluation of fetal lung maturity.

DOI： 10.1007/s11604-018-0745-0

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Korean Society of Gynecologic Oncology and Colposcopy  

Objective: To examine the surgical-pathological predictors of para-aortic lymph node (PAN) metastasis at radical hysterectomy, and for PAN recurrence among women who did not undergo PAN dissection at radical hysterectomy. Methods: This is a retrospective analysis of a nation-wide cohort study of surgically-treated stage IB–IIB cervical cancer (n=5,620). Multivariate models were used to identify independent surgical-pathological predictors for PAN metastasis/recurrence. Results: There were 120 (2.1%) cases of PAN metastasis at surgery with parametrial involvement (adjusted odds ratio [aOR]=1.65), deep stromal invasion (aOR=2.61), ovarian metastasis (aOR=3.10), and pelvic nodal metastasis (single-node aOR=5.39 and multiple-node aOR=33.5, respectively) being independent risk factors (all, p&lt
0.05). Without any risk factors, the incidence of PAN metastasis was 0.9%, while women exhibiting certain risk factor patterns (&gt
20% of the study population) had PAN metastasis incidences of ≥4%. Among 4,663 clinically PAN-negative cases at surgery, PAN recurrence was seen in 195 (4.2%) cases that was significantly higher than histologically PAN-negative cases (2.5%, p=0.046). In clinically PAN-negative cases, parametrial involvement (adjusted hazard ratio [aHR]=1.67), lympho-vascular space invasion (aHR=1.95), ovarian metastasis (aHR=2.60), and pelvic lymph node metastasis (single-node aHR=2.49 and multiple-node aHR=8.11, respectively) were independently associated with increased risk of PAN recurrence (all, p&lt
0.05). Without any risk factors, 5-year PAN recurrence risk was 0.8%
however, women demonstrating certain risk factor patterns (&gt
15% of the clinically PAN-negative population) had 5-year PAN recurrence risks being ≥8%. Conclusion: Surgical-pathological risk factors proposed in this study will be useful to identify women with increased risk of PAN metastasis/recurrence.

DOI： 10.3802/jgo.2018.29.e11

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Objective: High-mobility group A1 (HMGA1) protein is known to express in trophoblast; however, the role of migration has not been reported to date. In this study, we investigated the role of HMGA1 on the pathogenesis of preeclampsia using immortalized human trophoblast cell (HTR-8/SVneo).
Materials and Methods: We investigated HMGA1 expression in cytotrophoblasts derived from our preeclampsia model mouse, the CD40L mouse, using immunofluorescence. Wound healing and transwell migration assays were also performed using HTR-8/SVneo (extravillous trophoblast) cells transfected with DNA or siRNA of HMGA1. The effect of extranuclear translocation of HMGA1 on the migration of extravillous trophoblastic cells was evaluated using deoxycholic acid (DCA).
Results: HMGA1 was expressed exclusively in the nuclei of trophoblasts derived from control mice; cytoplasmic expression was observed only in CD40L mice with preeclampsia. Furthermore, overexpression of HMGA1 in the nuclei of HTR-8/SVneo cells stimulated cell proliferation and migration. Translocation of nuclear HMGA1 to cytoplasm treated with DCA reduced cell migration.
Conclusions: Collectively, these findings demonstrate that proper subcellular localization of HMGA1 is important for its function in trophoblast cells, and suggest that aberrant cytoplasmic expression of HMGA1 contributes to the pathogenesis of preeclampsia through impairment of trophoblast migration.

DOI： 10.1177/1933719117697254

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AimsThe objective of this study was to determine how many pregnant Japanese women with diabetes mellitus (DM)/gestational diabetes mellitus (GDM) experience perinatal mortality in the presence of fetal anomalies.
MethodsOur investigation included data from 205 secondary/tertiary obstetric facilities located widely in Japan. The Japan Ministry of Health, Labour and Welfare Vital Statistics of Japan was used for comparison.
ResultsOf 237 941 women giving birth at 205 hospitals, 1796 (0.8%) and 13 037 (5.5%) had DM and GDM, respectively. The perinatal mortality rates (per 1000 births) were 10.6 (19/1796) for women with DM, 5.2 (68/13037) for women with GDM, and 3.7 (7612/2039504) for the general Japanese population. Detailed information was available for 63 (72%) of the 87 perinatal deaths occurring in women with diabetes including DM and GDM; fetal anomalies were associated with 40% (25/63) of perinatal deaths, exceeding 16% (1211/7612) in the general Japanese population (P &lt; 0.0001). The leading four fetal anomalies associated with perinatal mortality in women with diabetes were fetal trisomy (6 cases: 1 of trisomy-13 and 5 of trisomy-18), non-immune hydrops fetalis (5 cases), cardiac deformities (3 cases) and holoprosencephaly (2 cases).
ConclusionsPerinatal mortality was more likely to occur in women with glucose intolerance. In the Japanese infants that succumbed to perinatal mortality, fetal anomaly was more prevalent in those born to women with a glucose intolerance than in those born to the general population.

DOI： 10.1111/jog.13431

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AIMS: There is no previous study comparing the predictive ability of maternal pre-pregnancy body mass index (BMI) versus a 75-g oral glucose tolerance test (OGTT) in early pregnancy for large-for-gestational-age (LGA) infants. METHODS: This multi-institutional prospective cohort study included 966 pregnant Japanese women. A multiple logistic regression model was applied to compare the effect size of pre-pregnancy BMI, fasting plasma glucose (PG), and 1- and 2-h PG levels after a 75-g OGTT performed before 22weeks gestation for LGA. After these variables were included separately into the model as per continuous variables 1 standard deviation (SD) increase, they were included simultaneously. RESULTS: When pre-pregnancy BMI, fasting PG, and 1- and 2-h PG after a 75-g OGTT were separately included in the model, the adjusted odds ratios (ORs) for LGA per 1 SD increase in pre-pregnancy BMI, fasting, and 1- and 2-h PG were 1.55 (95% confidence interval [CI]: 1.26-1.91), 1.26 (95% CI: 1.03-1.54), 0.99 (95% CI: 0.78-1.25), and 1.17 (95% CI: 0.93-1.49), respectively. When these variables were included simultaneously, the adjusted ORs per 1 SD increase in pre-pregnancy BMI, fasting, and 1- and 2-h PG were 1.52 (95% CI: 1.23-1.88), 1.19 (95% CI: 0.96-1.46), 0.77 (95% CI: 0.57-1.03), and 1.30 (95% CI: 0.96-1.76), respectively. CONCLUSIONS: Maternal pre-pregnancy BMI was more strongly associated with LGA compared with a 75-g OGTT in early pregnancy. Health-care providers should recognize that women with a higher pre-pregnancy BMI carry a higher risk for having LGA infants regardless of the results of a 75-g OGTT.

DOI： 10.1016/j.diabres.2017.07.017

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Background: To prepare for a future clinical trial for improving the long-term prognosis of patients with uterine leiomyosarcoma (ULMS), we conducted a multi-institutional survey in the Tohoku region of Japan. Methods: We conducted a retrospective cohort study between 2011 and 2014 in member institutions of the Tohoku Translational Research Center Development Network. Results: A total of 53 patients with ULMS were registered in 31 institutions for the present survey. The median patient age was 56 years, 67.9% of the patients were postmenopausal, 88.7% had a performance status of 0 or 1, and only 6 patients (11.3%) showed preoperative evidence of malignancy. Although retroperitoneal lymphadenectomy was performed in only 26.4% of patients, 64.2% patients were identified as having FIGO stage 1 disease
73.6% were eligible to undergo complete surgery. Among 36 patients who were treated with postoperative chemotherapy, 28 (77.8%) received docetaxel and gemcitabine combination therapy. The most frequent recurrence site was the lungs, and the median progression-free survival of all enrolled patients was 11.7 months. However, the median progression-free survival and the median overall survival in patients with stages III and IV disease were 3.4 and 11.4 months, respectively. Conclusion: Although ULMS was associated with a high rate of complete or optimal surgery, the long-term prognosis was poor. Effective postoperative therapy should be developed to improve the long-term prognosis of patients with ULMS.

DOI： 10.1007/s10147-017-1097-y

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Purpose
Innovative laser speckle flowgraphy (LSFG) enables noninvasive evaluation of retinal microcirculation and the usefulness has been reported in the field of ophthalmology. LSFG has allowed us to measure the real time changes of retinal blood flow without pupillary dilatations and contrast media. Herein, we investigated the change of retinal blood flow in normal pregnant women during gestation using LSFG.
Methods
A prospective cohort study was conducted in 53 pregnant women who visited our institution between January, 2013 and July, 2014. Finally, a total of 41 participants without any obstetric complications were available for evaluation. Retinal blood flow was measured with LSFG in a total of 4 times during pregnancy (T1. 11-13 weeks, T2. 19-21 weeks, T3. 28-30 weeks, T4. 34-36 weeks) and mean blur rate (MBR), blowout score (BOS), flow acceleration index (FAI), and resistive index (RI) are analyzed from these measurements. Relations between LSFG parameters and mean arterial blood pressure (MAP) are determined throughout pregnancy.
Results
MBR showed no significant changes throughout pregnancy. BOS showed a tendency to increase in the 3rd trimester. FAI values showed a slight increase from the 1st to 2nd trimester while a significant decrease was noted in the 3rd trimester. RI exhibited no changes between the 1st and 2nd trimesters, values decreased significantly after the 3rd trimester. MAP was positively correlated with BOS, and negatively correlated with FAI and RI.
Conclusion
The present study clearly demonstrated that profiles of LSFG parameters demonstrated a decrease of resistance in retinal blood vessels. These changes in indices provide a highly sensitive reflection of physiological changes in vascular resistance due to pregnancy. Thus, LSFG may be useful, as a non-invasive, diagnostic tool to detect pregnancy related disorders such as preeclampsia.

DOI： 10.1371/journal.pone.0173127

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We analyzed a cohort of 36 females with pregnancy loss. In addition to 11 patients with antiphospholipid antibody syndrome and 2 patients with congenital antithrombin (AT) or protein C deficiency, we identified 5 patients with low fibrinogen levels (median 110 mg/dL) prior to 10 weeks of gestation. Four of these 5 patients underwent a fibrinogen gene analysis, and all 4 were found to be heterozygotes for the -fibrinogen (FGA) Thr321Ala polymorphism. One female without hypofibrinogenemia with a history of 8 pregnancy losses was found to be homozygous for the same polymorphism, and she also showed hypercoagulability without thrombosis. In conclusion, there was a relatively high frequency of pregnancy loss in the setting of hypofibrinogenemia and/or the FGA Thr312Ala polymorphism, and this may be an important risk factor for pregnancy loss and a hypercoagulable state in later pregnancy.

DOI： 10.1177/1076029615594003

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We analyzed a cohort of 36 females with pregnancy loss. In addition to 11 patients with antiphospholipid antibody syndrome and 2 patients with congenital antithrombin (AT) or protein C deficiency, we identified 5 patients with low fibrinogen levels (median 110 mg/dL) prior to 10 weeks of gestation. Four of these 5 patients underwent a fibrinogen gene analysis, and all 4 were found to be heterozygotes for the -fibrinogen (FGA) Thr321Ala polymorphism. One female without hypofibrinogenemia with a history of 8 pregnancy losses was found to be homozygous for the same polymorphism, and she also showed hypercoagulability without thrombosis. In conclusion, there was a relatively high frequency of pregnancy loss in the setting of hypofibrinogenemia and/or the FGA Thr312Ala polymorphism, and this may be an important risk factor for pregnancy loss and a hypercoagulable state in later pregnancy.

DOI： 10.1177/1076029615594003

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Health benefits of fermented foods are attracting attention worldwide, and they have been traditionally eaten in Japan. Moreover, a recent study showed the association between the higher intake of yogurt and lower prevalence of depressive symptoms during pregnancy. Psychological problems, such as anxiety and depression, during pregnancy are serious health concerns and may increase the risk of adverse outcomes in children. In this study, we explored the association between fermented food consumption and psychological distress in 10,129 pregnant Japanese women, using the fixed data of the Japan Environment and Children's Study (JECS), an ongoing nation-wide birth cohort study. Food consumption was assessed with a semi-quantitative food frequency questionnaire (FFQ), and the Kessler 6-item psychological distress scale (K6) was administered to eligible women during their second or third trimester to eliminate overlap with the period of hyperemesis gravidarum. The mean median gestation in the subjects was 24.8 weeks. In total, 9,030 subjects completed the K6 questionnaire and FFQ. Importantly, the prevalence of the K6 score of 13 was 3.1% (280 subjects). This value was lower compared to precedent studies, which may reflect that cooperative and health conscious subject participated in the survey. The multivariate logistic regression analysis indicates that the intake of yogurt, lactic acid beverages, cheese, Japanese pickles, miso soup, or fermented soybeans was not significantly associated with a K6 score of &gt;= 13. In conclusion, the present cohort study shows no association between fermented food consumption and psychological distress symptoms during the second or third trimester of pregnancy.

DOI： 10.1620/tjem.240.309

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Background: Social capital is generally defined as the quality and frequency of social interactions with relatives, neighbors, and society. Social capital refers to broad concepts of social interactions and structures in individuals, communities and societies such as trust (e.g., neighborhood trust, which is social cohesion with neighbors) and social support (e.g., emotional support, which is the level of the feeling of being loved). Studies during the last few decades have shown that there is a significant inverse association between social capital and the prevalences of diseases such as depression and acute coronary syndrome. Significant inverse associations between trust, social support and the prevalence of diabetes have also been shown. However, associations between social capital and the prevalence of gestational diabetes mellitus (GDM) are less clear.
Methods: We used the primary dataset of the Japan Environment and Children's Study (JECS), including 10,228 mothers with recorded obstetric outcomes from January to December 2011. In this study, we included 8874 the 10,228 participants. Diagnosis of GDM was determined using the criteria of the Japan Diabetes Society (JDS). The quality and quantity of social capital were measured with nine questions on a self-administered questionnaire during the second or third trimester. Using principal component analysis (PCA), we distinguished the following three components (indices) of social capital: (A) index of all nine questions about social capital, (B) index of emotional support and neighborhood trust and (C) index of generalized trust. The high factor loading variants of indices were as follows; (A) all nine variants, (B) five variants about emotional support and neighborhood trust and (C) two variants about generalized trust. Multivariate random effect modeling was used to calculate the odd ratios (ORs) for evaluating the association between these indices of social capital and the prevalence of GDM. This model was adjusted for baseline characteristics such as family income, BMI before pregnancy and smoking during pregnancy.
Results: Of the 8874 participants, 204 women developed GDM (2.30%). Multivariable logistic regression analysis showed that index B, the index of emotional support and neighborhood trust (adjusted OR: 0.651, 95% CI: 0.429, 0.987) was significantly and independently associated with the prevalence of GDM.
Conclusions: We found that the 5-question index of emotional support and neighborhood trust is significantly associated with the prevalence of GDM during pregnancy. (C) 2016 Elsevier Ireland Ltd. All rights reserved.

DOI： 10.1016/j.diabres.2016.07.020

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：AMER ASSOC CANCER RESEARCH  

Purpose: Mogamulizumab (Mog), a humanized anti-CC chemokine receptor 4 (CCR4) mAb that mediates antibody-dependent cellular cytotoxicity (ADCC) using Fc gamma R IIIa (CD16)-expressing effector cells, has recently been approved for treatment of CCR4-positive adult T-cell leukemia (ATL) in Japan. However, Mog failure has sometimes been observed in patients who have accompanying chemotherapy-associated lymphocytopenia. In this study, we examined whether adoptive transfer of artificial ADCC effector cells combined with Mog would overcome this drawback.
Experimental Design: We lentivirally gene-modified peripheral blood T cells from healthy volunteers and ATL patients expressing the affinity-increased chimeric CD16-CD3 zeta receptor (cCD16 zeta-T cells). Subsequently, we examined the ADCC effect mediated by those cCD16 zeta-T cells in the presence of Mog against ATL tumor cells both in vitro and in vivo.
Results: cCD16 zeta-T cells derived from healthy donors killed in vitro Mog-opsonized ATL cell line cells (n = 7) and primary ATL cells (n = 4) depending on both the number of effector cells and the dose of the antibody. cCD16 zeta-T cells generated from ATL patients (n = 3) also exerted cytocidal activity in vitro against Mogopsonized autologous ATL cells. Using both intravenously disseminated model (n = 5) and subcutaneously inoculated model (n = 4), coadministration of Mog and human cCD16 zeta-T cells successfully suppressed tumor growth in xenografted immunodeficient mice, and significantly prolonged their survival (P &lt; 0.01 and P = 0.02, respectively).
Conclusions: These data strongly suggest clinical feasibility of the novel combined adoptive immunotherapy using cCD16 zeta-T cells and Mog for treatment of aggressive ATL, particularly in patients who are ineligible for allogeneic hematopoietic stem cell transplantation. (C) 2016 AACR.

DOI： 10.1158/1078-0432.CCR-15-2714

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OBJECTIVE: The aim of this study was to compare the efficacy of nedaplatin-based concurrent chemoradiotherapy (CCRT) with that of cisplatin-based CCRT in patients with cervical cancer. METHODS: The medical records of patients with cervical cancer who had undergone CCRT between 2003 and 2007 were retrospectively reviewed. Of these, 129 patients were treated postoperatively with CCRT (n = 52) or primary CCRT (n = 77). A total of 29 patients were treated with nedaplatin-based postoperative CCRT and 23 patients were treated with cisplatin-based postoperative CCRT. A total of 28 patients were treated with nedaplatin-based postoperative CCRT, and 49 patients were treated with cisplatin-based postoperative CCRT. Progression-free survival (PFS) and overall survival (OS) were compared between the treatment groups. RESULTS: With postoperative CCRT, there were no significant differences in recurrence rate (P = 1.0000), PFS (log-rank: P = 0.8503), and OS (log-rank: P = 0.8926) between the two treatment groups. With primary CCRT, there were no significant differences in PFS (log-rank: P = 0.7845) and OS (log-rank: P = 0.3659). The frequency of acute toxicity was not significantly different between the cisplatin-based postoperative CCRT group and the nedaplatin-based postoperative CCRT group. CONCLUSIONS: Nedaplatin-based postoperative CCRT is an effective and well-tolerated regimen for both early-stage and advanced-stage cervical cancer patients.

DOI： 10.1007/s10147-016-0946-4

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：NATURE PUBLISHING GROUP  

This prospective cohort study compared measurements of maternal home blood pressure (HBP) with clinic blood pressure (CBP) before 20 weeks' gestation to determine associations with the risk of delivering a lower birth weight infant. A total of 605 Japanese women were included. Exposures were initial CBP, made between 10 weeks 0 days and 19 weeks 0 days, and HBP for comparison made within 1 week of CBP. Outcome was infant's birth weight, categorized and ranked as follows: &gt;= 3500 g, 3000-3499 g, 2500-2999 g and &lt;2500 g. The proportional odds model with possible confounding factors was applied to compare the associations between CBP and HBP on infant birth weight. When both CBP and HBP were included simultaneously, the adjusted odds ratios (ORs) per 1 standard deviation (1s.d.) increase in clinic and home diastolic BP (DBP) were 1.06 (95% confidence interval (CI): 0.87-1.30) and 1.28 (95% CI: 1.04-1.58), respectively. The adjusted ORs per 1s.d. increase in clinic and home mean arterial pressure (MAP) were 1.02 (95% CI: 0.83-1.24) and 1.29 (95% CI: 1.04-1.59), respectively. Systolic BP measurement was not associated with infant birth weight. In conclusion, high maternal home DBP and MAP before 20 weeks' gestation was associated with a higher risk of lower infant birth weight than clinic DBP and MAP. Therefore, in addition to CBP, it may be worth having pregnant women measure HBP to determine the risk of lower infant birth weight.

DOI： 10.1038/hr.2015.108

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DOI： 10.14740/jocmr2371w

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This multi-institutional study was conducted to clarify the clinicopathological features of squamous cell carcinomas of the vulva.
The medical records of vulvar cancer patients treated between 2002 and 2012 were retrospectively reviewed following approval by the Institutional Review Board of each institution.
One hundred and eleven patients with vulvar malignancies were included. Of these, 63 patients had squamous cell carcinoma (57 %). Initial treatment was surgery, radiation therapy (RT), and concurrent chemoradiotherapy (CCRT) in 34 (54 %), 15 (24 %), and 11 (17 %) patients, respectively. Nineteen, 11, 26, and 7 patients had stage I, II, III, and IV disease, respectively. Of the 34 patients who had surgical treatment, 50 % had stage I disease, while 74 % of those who received CCRT had stage III or IV disease. Complete response (CR) rates for the surgery, RT, and CCRT groups were 73, 60, and 64 %, respectively. The 5-year survival rates for stage I/II and III/IV disease were 64 and 39 %, respectively (P = 0.019). The 5-year survival rates for the surgery, RT, and CCRT groups were 53, 38, and 50 %, respectively, and the prognosis of patients treated with surgery or CCRT was significantly better than that of patients who received RT (P &lt; 0.05). In multivariate analysis, clinical response to initial treatment was an independent prognostic factor (P &lt; 0.001).
Although many patients had advanced-stage disease in the CCRT group, the therapeutic outcome for the surgery and CCRT groups was similar. Thus, CCRT may be a promising treatment for squamous cell carcinoma of the vulva.

DOI： 10.1007/s10147-015-0803-x

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Venous thromboembolism (VTE) occurs frequently in pregnant women and is a significant cause of maternal death. Hemostatic abnormalities were examined in 18 pregnant women with thrombosis. We studied five families with congenital antithrombin (AT) deficiency, and two families with congenital protein C (PC) deficiency. One woman with PC deficiency showed protein S (PS) Tokushima. The AT activity levels were significantly lower at the onset of thrombosis in the pregnant women than during the stable state. The PS activity and antigen levels were also significantly lower at the onset of thrombosis. In the patients with congenital AT deficiency, AT activity was significantly low in the stable state and decreased further at the onset of thrombosis. Although AT levels were normal before pregnancy, they subsequently decreased and in two cases the patients required the administration of AT after pregnancy. Gene analysis revealed one family with AT Budapest, one family with AT Toyama, and three families with AT Glasgow. Additionally, there were one family with PC Tochigi and one family with combined heterozygous of PC deficiency and PS Tokushima. In conclusion, the deficiency of natural anticoagulants, especially AT, is an important cause of pregnancy-related VTE.

DOI： 10.1007/s12185-015-1822-0

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Background This study aimed to evaluate surgical, pregnancy, and prognostic outcomes of radical abdominal trachelectomy (RAT) for Japanese patients with early-stage cervical cancer.
Methods This was a multicenter prospective cohort study conducted in member facilities of Tohoku Gynecologic Cancer Unit. Patients with FIGO 1A-1B1 squamous cell carcinoma were included.
Results A total of 42 patients were registered in this study, and all patients underwent planned RAT. The median stromal invasion and median horizontal spread of resected specimens were 4.6 (range 1.0-10.0) and 12.4 mm (range 3.0-28.0), respectively. The median surgical time and median blood loss were 304 min (range 233-611) and 848 mL (range 250-3984), respectively. Five patients (11.9 %) received blood transfusion. Five of 18 (27.8 %) patients who attempted to conceive achieved pregnancy, and 3 patients had healthy babies. However, all pregnancies required assisted reproductive technology with in-vitro fertilization and embryo transfer. Four patients (9.5 %) received postoperative adjuvant therapy, and 3 patients (7.1 %) developed disease recurrence.
Conclusions RAT may be safely performed for Japanese patients with FIGO 1A-1B1 squamous cell carcinoma of the cervix, even in educational medical facilities. However, less-invasive surgery should be considered more often to improve pregnancy outcomes.

DOI： 10.1007/s10147-014-0763-6

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Background This study aimed to evaluate surgical, pregnancy, and prognostic outcomes of radical abdominal trachelectomy (RAT) for Japanese patients with early-stage cervical cancer.
Methods This was a multicenter prospective cohort study conducted in member facilities of Tohoku Gynecologic Cancer Unit. Patients with FIGO 1A-1B1 squamous cell carcinoma were included.
Results A total of 42 patients were registered in this study, and all patients underwent planned RAT. The median stromal invasion and median horizontal spread of resected specimens were 4.6 (range 1.0-10.0) and 12.4 mm (range 3.0-28.0), respectively. The median surgical time and median blood loss were 304 min (range 233-611) and 848 mL (range 250-3984), respectively. Five patients (11.9 %) received blood transfusion. Five of 18 (27.8 %) patients who attempted to conceive achieved pregnancy, and 3 patients had healthy babies. However, all pregnancies required assisted reproductive technology with in-vitro fertilization and embryo transfer. Four patients (9.5 %) received postoperative adjuvant therapy, and 3 patients (7.1 %) developed disease recurrence.
Conclusions RAT may be safely performed for Japanese patients with FIGO 1A-1B1 squamous cell carcinoma of the cervix, even in educational medical facilities. However, less-invasive surgery should be considered more often to improve pregnancy outcomes.

DOI： 10.1007/s10147-014-0763-6

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The aim of this study was to evaluate prognostic factors including efficacy of postoperative chemotherapy in Japanese patients with uterine carcinosarcoma.
We conducted a retrospective survey of seven medical facilities in the Tohoku Gynecologic Cancer Unit.
A total of 45 patients who had undergone hysterectomy and bilateral salpingo-oophorectomy were enrolled. No significant difference was observed in overall survival according to patient age (a parts per thousand currency sign50 years vs &gt; 50 years) or retroperitoneal lymphadenectomy (performed vs. not performed). However, the International Federation of Gynecology and Obstetrics stage (stage I/II vs stage III/IV) and postoperative chemotherapy (provided vs not provided) were significant prognostic factors in both univariate and multivariate analyses for the 25-month median follow-up period.
Our results revealed that postoperative chemotherapy should be considered for all uterine carcinosarcoma stages in Japanese patients.

DOI： 10.1007/s10147-014-0732-0

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AimThe aim of this study was to investigate the long-term fertility prognosis after B-Lynch sutures for post-partum hemorrhage (PPH).
MethodsA retrospective observational study was conducted on patients who underwent B-Lynch sutures in our hospital between 2005 and 2010. Patient data was collected from hospital records. Information regarding subsequent pregnancies and menstrual complications were obtained by posted questionnaires and telephone interviews with patients who avoided hysterectomy.
ResultsA total of 28 B-Lynch sutures were performed in 3976 deliveries, all in patients that underwent cesarean section. Twenty-two of the 26 patients who avoided hysterectomy answered our questionnaire or took part in an interview. All patients recovered regular menstruation with no severe complications. Of the 19 patients who wanted another child, 12 patients (63.2%) had 14 subsequent pregnancies in a mean follow-up period of 52.1 months. The results of pregnancies were nine uncomplicated term pregnancies, all delivered by elective cesarean section, two artificial abortions and three miscarriages. A significant difference was observed in the age of patients with subsequent pregnancies and those without pregnancies (30.8 vs 34.6 years, P=0.04).
ConclusionB-Lynch sutures for PPH do not appear to jeopardize fecundity. An older age was a risk factor for achieving subsequent pregnancies.

DOI： 10.1111/jog.12590

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The impact of an increase in maternal fat consumption on fetal metabolic programming separately from maternal obesity remains unclear. The purpose of this study was to document the effect of in utero high-fat diet exposure on the development of metabolic syndrome characteristics in offspring. C57BL/6 female mice were fed either a control diet (10% fat) or a moderately high-fat (MHF) diet (45% fat) until delivery. All pups were fostered to mothers fed with the control diet. Pups were raised on the control diet and assessed until 35 weeks of age. The caloric intake from fat was significantly increased in the MHF dams compared with the control dams. There were no significant differences in the maternal weight at mating or at gestational Day 18 between the two groups. The MHF offspring did not become obese, but they developed hypertension and glucose intolerance. Moreover, the MHF offspring had significantly higher serum non-esterified fatty acid and triglyceride levels during the refeeding state following fasting as compared with the control offspring. Serum adiponectin levels were significantly lower, and the cell size of the mesenteric adipose tissue was significantly larger in the MHF offspring than in the control offspring. The mRNA levels of the proinflammatory macrophage markers in the mesenteric adipose tissue were significantly higher in the MHF offspring than those of the control offspring. These results suggest that in utero high-fat diet exposure causes hypertension and glucose intolerance resulting from mesenteric adipose tissue dysfunction in offspring, independently of maternal obesity. (C) 2015 Elsevier Inc. All rights reserved.

DOI： 10.1016/j.jnutbio.2014.10.012

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This study explores the correlation between the impact of the Great East Japan Earthquake and the incidence of postpartum depression in Miyagi prefecture, Japan. The design used was a cross-sectional study with self-administered questionnaires, 6-9 months after the disaster. The results showed the prevalence of postnatal women with Edinburgh Postnatal Depression Scale (EPDS) score of a parts per thousand yen9 to be 21.3 %. Multivariate analysis showed that exposure to tsunami (odds ratio, 1.80; 95 % confidence interval, 1.16-2.78) was significantly and independently associated with an EPDS score of a parts per thousand yen9. Postnatal women and their children should be treated as a vulnerable population, and a protective framework must be established to prepare for future devastating disasters.

DOI： 10.1007/s00737-014-0459-y

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BACKGROUND: Paclitaxel and carboplatin (PC) have shown antitumor activity in carcinosarcoma of the uterus (CS). The purpose of this prospective multi-institutional study was to determine the response rate (RR), progression-free survival (PFS) and overall survival (OS) and to assess the toxicity of paclitaxel and carboplatin in patients with CS. METHODS: We conducted a phase II study in which patients were administered paclitaxel 175 mg/m(2) over a 3-h period followed by carboplatin (area under the serum concentration-time curve = 6) intravenously over a 30-min period on day 1 of each treatment cycle (3 weeks) until disease progression or adverse effects prohibited further therapy. Eligible patients had histologically confirmed, advanced stage (III or IV), persistent or recurrent measurable disease, and no prior chemotherapy. RESULTS: Six patients were enrolled between February 2006 and April 2009. The median age of the patients was 61 (range 48-77) years; one patient was stage IIIC (17 %) and five were stage IVB (83 %). Three patients (50 %) (1 at stage IIIC and 2 at stage IVB) received total abdominal hysterectomy plus bilateral salpingo-oophorectomy as part of the initial treatment; five (83 %) had homologous tumors and one (17 %) had a heterologous tumor. The median cycle number administered was 4.8 (range 2-7). The RR was 66.7 % (complete response, 2; partial response, 2); the PFS was 9.1 months and OS was not reached. The frequently observed Grade 4 toxicities were neutropenia (3 patients, 50 %). Manageable neutropenic sepsis developed in one patient. CONCLUSION: This is the first prospective multi-institutional study in Asia showing that PC may be effective and tolerable for the treatment of advanced or recurrent CS.

DOI： 10.1007/s10147-013-0658-y

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

The present study was performed to evaluate pregnancy outcomes in women with type 1 and type 2 diabetes mellitus (DM) in Japan. This multi-institutional retrospective study was conducted in 40 general hospitals in Japan during 2003-2009. We evaluated 369 and 579 pregnant women with type 1 and type 2 DM, respectively, and compared pregnancy outcomes between the two groups. Glycosylated hemoglobin levels in the first trimester did not differ significantly between the studied groups. Gestational weight gain was lower in type 2 DM than in type 1 DM. Although there were no significant differences in perinatal outcomes between the groups, the primary cesarean section rate was higher in type 2 DM than in type 1 DM. Multiple logistic regression analysis revealed that primigravida status, pre-gestational body mass index (BMI), gestational weight gain, chronic hypertension, and microvascular disease including diabetic retinopathy or nephropathy were associated with onset of pregnancy-induced hypertension. Further, pre-gestational BMI was associated with the need for primary cesarean section. This study demonstrated that no differences were observed in the rates of perinatal mortality and congenital malformation between pregnant women with type 1 DM and type 2 DM; however, women with type 2 DM displayed a higher risk of primary cesarean section.

DOI： 10.1507/endocrj.EJ14-0140

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The aim of this study was to determine the effects of pre-gestational body mass index on pregnancy outcomes of women with gestational diabetes in Japan. A multi-institutional retrospective study was performed. We examined pregnant women who met the former criteria for gestational diabetes in Japan, receiving dietary intervention with self-monitoring of blood glucose with or without insulin therapy. Women with gestational diabetes were divided into three groups according to pre-gestational body mass index: body mass index &lt;25 (control group), 25 &lt;= body mass index &lt;30 (overweight group), body mass index &gt;= 30 (obese group). Data from a total of 1,758 eligible women were collected from 40 institutions. Participants included 960 controls, 426 overweight women, and 372 obese women with gestational diabetes. Gestational weight gain was highest in the control and lowest in the obese group. The prevalences of chronic hypertension and pregnancy induced hypertension were higher in the overweight and obese groups than in the control group. Multiple logistic regression analysis revealed pre-gestational body mass index, gestational weight gain, chronic hypertension, and nulliparity to be associated with the onset of pregnancy induced hypertension, while the 75-g OGTT results were unrelated to pregnancy induced hypertension. The prevalence of large-for-gestational age was lower in infants born to obese women than in those born to overweight or control women. The present results suggest that medical interventions for obese women with gestational diabetes may contribute to reducing the prevalence of large-for-gestational age but would not achieve marked reductions in maternal complications.

DOI： 10.1507/endocrj.EJ13-0541

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Language：English   Publisher：SAGE PUBLICATIONS INC  

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The standard postoperative chemotherapy for epithelial ovarian cancer is a combination therapy including platinum and taxanes. The aim this study was to investigate the degree of platinum sensitivity in patients with relapsed epithelial ovarian cancer according to the treatment-free interval (TFI) and the histological tumor type. The medical records of 405 patients diagnosed with stage III/IV ovarian cancer, including 107 patients who relapsed after attaining a clinical complete response with first-line treatment, were retrospectively reviewed. The degree of platinum sensitivity was assessed by comparing the progression-free survival (PFS) following the second-line treatment. In patients with serous/endometrioid adenocarcinoma who were treated with platinum following relapse, there were significant differences in the PFS between the following groups of patients: those who relapsed within 6 months and those who relapsed between 6 and 12 months; those who relapsed between 6 and 12 months and those who relapsed between 12 and 18 months; and those who relapsed between 12 and 18 months and those who relapsed after 18 months. By contrast, in patients with clear cell/mucinous adenocarcinoma who were treated with platinum following a relapse, there were no significant differences in the PFS between patients who relapsed within 6 months and those who relapsed between 6 and 12 months, while there were significant differences in the PFS between those who relapsed between 6 and 12 months and those who relapsed after 12 months. With regard to the patients who relapsed after 12 months, the PFS of those with clear cell/mucinous adenocarcinoma was significantly shorter compared with the PFS of those with serous/endometrioid adenocarcinoma. Therefore, we considered it justified to classify patients with clear cell/mucinous adenocarcinoma who relapsed within 12 months as platinum-resistant and those who relapsed after 12 months as platinum-sensitive.

DOI： 10.3892/mco.2013.223

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：ELSEVIER IRELAND LTD  

Aims: To determine whether treating mild gestational diabetes mellitus (GDM) is associated with improvement of pregnancy outcomes in Japan.
Methods: In a multi-institutional retrospective study, we examined pregnant women meeting the criteria for mild GDM (i.e., only one abnormal value [OAV] for 75-g OGTT; fasting glucose &gt;= 100 mg/dL, 1-h postprandial glucose &gt;= 180 mg/dL, and 2-h postprandial glucose &gt;= 150 mg/dL), receiving either routine prenatal care (non-treatment group) or dietary intervention alone or dietary intervention with self-monitoring of blood glucose and/or insulin therapy, if necessary (treatment group). Pregnancy outcomes were compared between these groups.
Results: Data from 893 eligible women were collected from 30 institutions. Participants included 542 untreated and 351 treated women. Although there were no significant differences in baseline clinical characteristics or maternal and perinatal outcomes between these groups, the incidence of large-for-gestational-age (LGA) infants was lower in the treatment group (P = 0.07). Multiple logistic regression analysis (MLRA) revealed that pre-pregnancy BMI and gestational weight gain were associated with LGA infants, while 75-g OGTT results were unrelated to LGA. When overweight and obese women were the subjects, the number of LGA infants was significantly lower in the intervention than in the control group, and gestational weight gain was significantly lower in the treatment than in the control group. MLRA showed that intervention was significantly related to a lower incidence of LGA infants.
Conclusions: Our study suggests that maternal BMI impacts fetal growth and that treatment for overweight or obese mothers with OAV is associated with a lower frequency of LGA infants. (C) 2013 Elsevier Ireland Ltd. All rights reserved.

DOI： 10.1016/j.diabres.2013.12.017

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Language：English   Publisher：SAGE PUBLICATIONS INC  

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Aims: To determine differences in pregnancy outcomes including diabetic complications, maternal and perinatal complications between gestational diabetes mellitus and overt diabetes in pregnancy in Japan. Methods: A multi-institutional retrospective study compared pregnancy outcomes between gestational diabetes mellitus and overt diabetes in pregnancy. We examined pregnant women who met the former criteria for gestational diabetes mellitus and received dietary intervention with self-monitoring of blood glucose with or without insulin. Overt diabetes in pregnancy was defined as ≥2 abnormal values on 75-g oral glucose tolerance test, fasting glucose ≥126 mg/dl (7.0 mmol/l) and 2-h postprandial glucose ≥200. mg/dl (11.1 mmol/l), or glycated hemoglobin levels ≥6.5% (48. mmol/mol). Results: Data were collected on 1267 women with gestational diabetes and 348 with overt diabetes in pregnancy. Pregestational body mass index was higher (26.2 ± 6.1 vs. 24.9 ± 5.7 kg, P&lt
0.05) and gestational age at delivery was earlier (37.8 ± 2.5 weeks vs. 38.1 ± 2.1 weeks, P&lt
0.05) in overt diabetes than in gestational diabetes. Glycated hemoglobin (6.8 ± 1.1% [51. mmol/mol] vs. 5.8 ± 0.5% [40. mmol/mol], P&lt
0.05) and glucose on 75-g oral glucose tolerance test and prevalence of retinopathy (1.2% vs. 0%, P&lt
0.05) and pregnancy-induced hypertension (10.1% vs. 6.1%, P&lt
0.05) were higher in overt diabetes than in gestational diabetes. Pregnancy-induced hypertension was associated with pregestational body mass index, gestational weight gain, chronic hypertension, and nulliparity but not with 75-g oral glucose tolerance test. Conclusions: Overt diabetes in pregnancy is significantly associated with maternal complications such as retinopathy and pregnancy-induced hypertension. © 2013 Elsevier Ireland Ltd.

DOI： 10.1016/j.diabres.2013.10.020

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The effects of low thyroid hormone level during embryogenesis on MRI of the brain and social behaviors of hatchlings were examined using "fertilized hen's egg-embryo-chick" system.
Control and hatchlings treated with methimazole (20 mu mol/egg), which hatched 3 days later than controls were examined. The results are as follows:
1. The MRI examination of the midsagittal section of the brain on hatch day showed that the sizes, by T1- and ADC values by diffusion-weighted images, of the optic lobe and cerebellum of the MMI-hatchlings were significantly bigger than those of the controls.
2. The social behaviors o post-hatch day 3 were based on the following tests:
(a) Aggregation test: The speed of four chicks, individually isolated by cardboard barriers in a box, to make a group upon the removal of barriers.
(b) Belongingness tests: The speed of a chick isolated at a corner to join the group of three chicks placed at the opposite corner.
(c) Vocalization test: The number of decibel produced by a chick isolated at a corner using a sound meter. These tests demonstrated that MMI-hatchlings took longer times and had weaker vocalization than the controls, significantly.
Upregulation of THR beta mRNA after MMI treatment suggested that THR was necessary for cerebellum development.
The MMI exposure during the last week of embryogenesis possibly delayed the myelination of certain brain regions and impaired the social behaviors of hatchlings. The chick embryos can be easily induced with hypothyroidism without maternal influences, and the hatchling's behaviors were analyzed using a video camera. The present method will be useful for assessing the effects of unfavorable influences during embryogenesis on social behaviors in later life.

DOI： 10.1007/s00213-013-3229-z

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

Purpose: A phase I clinical study was conducted to determine the maximum tolerated dose (MTD) and the recommended dose (RD) of irinotecan hydrochloride (CPT-11) in CPT-11/pegylated liposomal doxorubicin (PLD) combination therapy, a novel treatment regimen for platinum- and taxane-resistant recurrent ovarian cancer. Methods: Pegylated liposomal doxorubicin was administered intravenously on day 3 at a fixed dose of 30 mg/m2. CPT-11 was administered intravenously on days 1 and 15, at a dose of 50 mg/m2 on both days. One course of chemotherapy was 28 days, and patients were given a maximum of six courses, with the CPT-11 dose being increased in increments of 10 mg/m 2 (level 1, 50 mg/m2
level 2, 60 mg/m2
level 3, 70 mg/m2
level 4, 80 mg/m2) to determine MTD and RD. Results: During the period from April 2010 to March 2013, three patients were enrolled for each level. In the first course, no dose-limiting toxicity occurred in any of the patients. Grade 4 neutropenia was observed in two of three patients at level 4. At level 4, the antitumor effect was a partial response (PR) in two of the three patients and stable disease (SD) in one. At level 3, one of the three patients showed PR and two had SD. At level 4, the start of the next course was postponed in two of three patients. In addition, one patient at level 4 experienced hemotoxicity that met the criteria for dose reduction in the next course. The above results suggested that administration of CPT-11 at dose level 5 (90 mg/m2) would result in more patients with severe neutropenia and in more patients requiring postponement of the next course or a dose reduction. Based on the above, the RD of CPT-11 was determined to be 80 mg/m2. Conclusions: The results suggest that CPT-11/PLD combination therapy for recurrent ovarian cancer is a useful treatment method with a high response rate and manageable adverse reactions. In the future phase II study, the safety and efficacy of this therapy will be assessed at 80 mg/m2 of CPT-11 and 30 mg/m2 of PLD. © 2014 The Author(s).

DOI： 10.1007/s00280-014-2418-8

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UNLABELLED: Diabetic ketoacidosis (DKA) during pregnancy is a serious complication in both mother and fetus. Most incidences occur during late pregnancy in women with type 1 diabetes mellitus. We report the rare case of a woman with type 1 diabetes mellitus who had normal glucose tolerance during the first trimester but developed DKA during late pregnancy. Although she had initially tested positive for screening of gestational diabetes mellitus during the first trimester, subsequent diagnostic 75-g oral glucose tolerance tests showed normal glucose tolerance. She developed DKA with severe general fatigue in late pregnancy. The patient's general condition improved after treatment for ketoacidosis, and she vaginally delivered a healthy infant at term. The presence of DKA caused by the onset of diabetes should be considered, even if the patient shows normal glucose tolerance during the first trimester. LEARNING POINTS: The presence of DKA caused by the onset of diabetes should be considered, even if the patient shows normal glucose tolerance during the first trimester.Symptoms including severe general fatigue, nausea, and weight loss are important signs to suspect DKA. Findings such as Kussmaul breathing with ketotic odor are also typical.Urinary test, atrial gas analysis, and anion gap are important. If pH shows normal value, calculation of anion gap is important. If the value of anion gap is more than 12, a practitioner should consider the presence of metabolic acidosis.

DOI： 10.1530/EDM-13-0085

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

Uterine papillary serous carcinoma (UPSC) morphologically resembles ovarian serous carcinoma and is categorized as a type II endometrial cancer. UPSC comprises about 10% of all types of endometrial cancer and has an aggressive clinical course and a poor prognosis. The 14-3-3 sigma gene was originally discovered as a p53-inducible gene; its expression is induced by DNA damage in a p53-dependent manner, which leads to G2 arrest and repair of damaged DNA. Moreover, it has been reported that expression of 14-3-3 sigma is frequently lost in various types of human cancer, including ovarian cancer. We therefore examined the association between 14-3-3 sigma expression determined by immunohistochemistry and clinical outcomes of 51 patients with UPSC. UPSC was considered positive for 14-3-3 sigma when &gt; 30% of tumor cells were stained with a specific antibody. Of these patients, 29 (58.7%) showed positive immunoreactivity for 14-3-3 sigma and 22 (41.3%) had decreased 14-3-3 sigma staining. Decreased immunoreactivity for 14-3-3 sigma was associated with stage (P = 0.001) and lymphovascular space involvement (P = 0.005). Moreover, decreased 14-3-3 sigma expression was an independent risk factor for reduced overall survival (P = 0.0416) in multivariate analysis. Direct bisulfite sequencing was performed to evaluate the methylation status of the 27 CpG islands in the promoter region and first exon of the 14-3-3 sigma gene. These CpG islands were hypermethylated in 30% of 14-3-3 sigma-positive UPSC and 80% of 14-3-3 sigma-negative UPSC, although the difference was not statistically significant. These findings suggest that decreased expression of immunoreactive 14-3-3 sigma may be a predictor of poor prognosis in patients with UPSC.

DOI： 10.1620/tjem.231.193

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

Yolk sac tumor (YST) of the ovary is a rare germ cell tumor comprising about 1% of all ovarian malignancies. YST usually occurs as a rapidly growing unilateral tumor in young women. With the introduction of cisplatin, YST has been changed from a fatal tumor to a curable tumor. The standard treatment of YST consists of fertility-preserving surgery and 3 or 4 courses of adjuvant combination chemotherapy with bleomycin, etoposide, and cisplatin (BEP). However, the long-term prognosis of BEP-treated YST patients has not been well studied. We therefore conducted a retrospective multicenter study to investigate the prognostic factors of 33 YST patients, including 25 patients treated with BEP. The median age at initial treatment was 20 years (range 10-53). There were 15 patients (at stage l), one (stage II), 16 (stage III), and one (stage IV). Nominal and grouped numerical values were analyzed by the Kaplan-Meier method. All patients had unilateral tumor, with right-side predominance (23 patients; P = 0.02). Eighteen patients had pure YST, 13 had mixed germ cell tumor with YST component, and other 2 patients were not specified. Twenty-eight patients received fertility-preserving surgery. Twenty-seven patients had optimal surgery with less than 1 cm residual tumor diameter. Median number of chemotherapy courses was 5. Median follow-up period was 49 months. The cumulative 5-year survival rate was 87%. Univariate analysis revealed the following significant prognostic factors (P &lt; 0.05): stage, tumor diameter, and residual tumor. Extensive debulking surgery to minimize residual tumor would improve the prognosis.

DOI： 10.1620/tjem.230.211

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：SPANDIDOS PUBL LTD  

The present study investigated the clinicopathological features of fallopian tube malignancy (FTM) and elucidated the biological behavior of this disorder. Data were compiled concerning FTM from 68 patients from 7 institutes. The patients included 60 cases with fallopian tube carcinoma and 8 cases with fallopian tube carcinosarcoma. The clinical stage was stage III or higher in 72% of the cases. A complete response or partial response was achieved in 56 and 10 of the 68 patients with FTM, respectively, indicating a response rate of 97.1%. The median observation period for FTM was 41 months (3 to 126 months). Three of the 19 patients with stage I/II disease (16%) and 31 of the 49 patients with stage III/IV disease (63%) experienced recurrence, with a median progression-free survival of 17.5 months, and a 3-year overall survival of 77.2%. Regarding the site of recurrence, local intraperitoneal recurrence (26.2%) and solitary recurrences in lymph nodes (19.0%) and in the liver (16.7%) were relatively frequent. Secondary debulking surgery (SDS) was performed in 15 patients (44%) out of the 34 recurrent FTMs. Conversely, recurrence was associated with ascites (carcinomatous peritonitis) in 4 of the 34 recurrent patients, but all 4 patients died. The median survival period after recurrence was 28 months: 7.5 and 30 months with and without ascites, respectively (P&lt;0.001). A univariate analysis showed that prognosis was significantly correlated only with whether SDS could be performed. These results suggest that since FTM frequently results in solitary recurrence, aggressive recurrence treatment including SDS could improve prognosis.

DOI： 10.3892/or.2013.2439

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

Objectives: Epidemiological and animal studies have shown that maternal obesity predisposes the offspring to obesity and the metabolic syndrome, possibly via late-onset metabolic programming of the fetus. Little is known, however, about the metabolic effect of maternal obesity on the fetus. This study investigated the effect of a maternal high-fat diet (HFD) on fetal growth and glucose metabolism using a diet-induced obesity mouse model.
Study design: Female mice (6 weeks old; C57BL/6N) were fed either a normal chow diet (NCD, 10 kcal% fat) or an HFD (60 kcal% fat) for 4 weeks before mating and throughout pregnancy. At 17 days of gestation, gene expression of inflammatory markers and adipokines in fetal subcutaneous adipose tissue was analyzed by quantitative real-time polymerase chain reaction.
Results: HFD mice were overweight, glucose intolerant and insulin resistant compared with NCD mice of the same gestational age. Although fetal body weight was not significantly different, fetal plasma glucose and insulin levels were higher in the HFD group than the NCD group. Furthermore, examination of fetal subcutaneous adipose tissue in the HFD group revealed hypertrophy with an increase in the levels of cluster of differentiation-68, chemokine receptor-2 and tumor necrosis factor-os mRNA, but a decrease in the level of glucose transporter-4 mRNA.
Conclusion: Maternal HFD causes inflammatory changes in the adipose tissue of offspring. (c) 2013 Elsevier Ireland Ltd. All rights reserved.

DOI： 10.1016/j.ejogrb.2013.02.003

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Proteins form the most important structural component of cells that constitute the various types of tissue, such as muscle, skin, and bone. Proteins also function as enzymes and hormones to regulate various metabolic processes in the body. The estimated average requirement (EAR) of protein for both men and women who habitually consume mixed protein was evaluated as 0.72 g/kg body weight/d by nitrogen balance studies as the value to maintain nitrogen equilibrium with high quality protein, revised with digestibility of mixed protein in habitual food intake. The recommended intake of protein for infants is normally based on the adequate intake (AI) standard, which reflects the observed mean protein intake of infants fed principally with breast milk for up to 6 mo of age. The EAR of children aged 1-17 y was estimated by the factorial method, which adds the amount required for protein storage because of growth and protein requirement for maintenance. The EAR of protein in the elderly was calculated by meta-analysis, employing 144 data sets obtained from 5 published reports, with 60 subjects, and was found to be 0.85 g of habitual mixed protein/kg body weight/d. The tolerable upper intake level (UL) of protein must be established based on the health risk caused by excessive protein intake. However, no clear evidence to establish this value is available at present, and therefore, the UL of protein cannot be determined.

DOI： 10.3177/jnsv.59.S36

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The Dietary Reference Intakes for Japanese 2010 (DRIs-J 2010) included a new chapter for lifestage. In this chapter, important characteristics of the nutritional status and the special considerations in applying for DRIs in each lifestage-infants and children, pregnant and lactating women, and the elderly-were described. In infants, the references of nutrient requirement are mostly presented by adequate intake (AI) because of the impossibility of human experiments to determine the estimated average requirement (EAR). The quality and quantity of breast milk is assumed to be nutritionally desirable for every infant. Therefore, AI was determined on the basis value obtained by nutritional concentration and average amount of breast milk consumed by healthy infants. In addition, the anthropo-metric references for 4 periods based on the 50th percentiles in growth curves were newly demonstrated. The nutrient requirement increased in the pregnant and lactating stage. Increments were estimated based on the fetal growth during whole pregnancy period in pregnant women and on the daily milk production of 780 mL/d in lactating women. In the elderly stage, the scarcity of nutritional studies regarding the Japanese elderly makes it difficult to determine the appropriate DRI values for the elderly. Furthermore, the changes in nutritional status and physical function with aging have been influenced by not only the chronological age but also various other factors, which complicates the establishment of DRIs for the elderly. In light of these facts, the promotion of further and more comprehensive studies of the elderly is desirable.

DOI： 10.3177/jnsv.59.S103

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Language：English   Publishing type：Part of collection (book)   Publisher：Nova Science Publishers, Inc.  

Weight gain management before and during pregnancy may be a key factor influencing the health of women during pregnancy and the development of the fetus. Adequate gestational weight gain contributes to better pregnancy outcomes in both mothers and infants, in short- and long-term. The Institute of Medicine (IOM) released gestational weight guidelines for optimal pregnancy outcomes. The guideline will be used in clinical practices for effective weight management aiming at improving fetal and maternal outcomes. Evidences from human and animal studies of pre-pregnancy body mass index and gestational weight gain showed that altering the environment of utero could lead to lifelong health consequences, such as high adiposity, sarcopenia, insulin resistance, glucose intolerance, and high blood pressure. Population-based prospective cohort studies starting from different geographical regions in the pre-conceptional period or in early fetal life, in which the offspring is followed from early fetal life until young adulthood. All women of reproductive age are encouraged to follow the IOM recommendations and maintain a well-balanced diet. To improve birth outcomes, it is critical for women to modify their health behaviors for a better nutritional status before, during, and after conception. © 2013 Nova Science Publishers, Inc.

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Postnatal depression and bonding failure after childbirth are major mental health issues. We investigated 99 pregnant women on three occasions (late in pregnancy and 5 days and 1 month postnatally). Anxiety during pregnancy predicted postnatal depression and bonding failure, whereas negative attitudes towards pregnancy predicted bonding failure. The effect of negative attitudes towards pregnancy on postnatal depression was possibly mediated by bonding failure. Postnatal depression and bonding failure are correlated with different risk factors and run rather independently over the course of the puerperium. Postnatal depression may be predicted by bonding failure.

DOI： 10.1007/s00737-012-0279-x

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DOI： 10.1111/j.1447-0756.2011.01573.x

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The infiltration of classically activated macrophages (M1) and alternatively activated macrophages (M2) in subcutaneous adipose tissue (SAT) and parametrial adipose tissue (PAT) was analyzed to investigate whether local inflammatory change in adipose tissue occurs in late pregnancy. C57BL/6N female mice at 6 weeks of age were fed a normal chow diet for 4 weeks prior to mating at 10 weeks of age and were sampled on day 17 of pregnancy. The serum levels of adipokines and biochemical markers were measured using ELISA and enzymatic methods. The identification of M1 and M2 was analyzed by double immunofluorescence with anti-F4/80 and anti-CD11c antibodies. The gene expression of adipokines in adipose tissues was analyzed by quantitative RT-PCR. The pregnant group showed adipocyte hypertrophy, higher macrophage infiltration, and higher M1/M2 in both SAT and PAT compared with the non-pregnant (NP) group. Serum levels of free fatty acids, tumor necrosis factor alpha (TNF alpha), interleukin 6 (IL6), and IL10 were higher, and serum levels of adiponectin were lower in the pregnant group than those in the NP group. The gene expressions of CD68, Itgax, CCR2, TNF alpha, and PAI1 in SAT during pregnancy were significantly higher than those in the NP group, as were the gene expressions of CD68, Emrl, Itgax, MCP1, TNF alpha, IL6, PAI1, adiponectin, and IL10 in PAT. These results suggest that the low-grade inflammation of adipose tissue indicated by increased macrophage infiltration occurs in late normal pregnancy. Journal of Molecular Endocrinology (2011) 47, 157-165

DOI： 10.1530/JME-11-0030

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Aim: The aim of this study was to survey early preterm (prior to 32 weeks' gestation) singleton live births in Iwate Prefecture as a provincial model of the medical situation in Japan. Materials and Methods: Data from 177 early preterm singleton live births, and 31 445 total live births (January 2005-December 2007) in Iwate Prefecture Japan were used to analyze the incidence of early preterm singleton live birth in each medical service area. Results: The incidence of spontaneous early preterm singleton live birth did not differ between the coastal and inland medical service areas (3.35 vs 3.57 per 1000 live births). In the Morioka medical service area (radius about 40 km), the incidence of spontaneous early preterm singleton live birth in municipalities without obstetric care facilities was significantly higher than that in municipalities with obstetric care facilities (6.62 vs 2.65 per 1000 live births, P &lt
0.005). The incidence of early preterm singleton live birth due to pregnancyinduced hypertension in the coastal medical service areas was higher than that in the inland areas (1.67 vs 0.71 per 1000 live births, P &lt
0.05). Conclusions: In Iwate Prefecture, Japan, the incidence of singleton preterm live birth before 32 weeks of pregnancy varies among its constituent medical service areas according to geographic factors as well as the availability of obstetric care facilities. © 2011 The Authors.

DOI： 10.1111/j.1447-0756.2010.01456.x

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

Aim:
Greater antenatal weight or body mass index (BMI) gains may lead to larger fetuses and thus increase the risk for operative deliveries, such as cesarean deliveries. In order to examine the effect of weekly maternal weight and BMI changes on large-for-gestational-age (LGA) infants and cesarean delivery, delivery records from overall healthy women were analyzed.
Materials and Methods:
Singleton, term delivery records from January to December 2003, at three obstetric departments (urban, suburban, rural) in Japan (1617 records) were analyzed. Multivariate logistic regression analyses were applied in order to estimate the effect of maternal pre-pregnancy body size, higher maternal weight or BMI gains by calculating the odds ratios for LGA infants and cesarean deliveries.
Results:
Maternal pre-pregnancy overweight, primiparity, and BMI gains of more than 0.13 per week were independent factors positively related to LGA, and maternal underweight was negatively related. Urban hospital setting, maternal age 35 years or older, primiparity, and BMI gains of more than 0.13 per week independently increased the odds ratios for cesarean delivery. Weight or BMI gains between two-week intervals (26-28 weeks, 32-34 weeks) were not useful for predicting either LGA or cesarean delivery. LGA was unrelated to cesarean delivery risk.
Conclusions:
Applying BMI gains per week enables target weight gains to be set according to the mother&apos;s height, which may be useful in reducing risks for LGA and cesarean delivery, especially in shorter women. Further investigation may be needed to explore the practicality and effectiveness of advising women to gain weight according to their body height.

DOI： 10.1111/j.1447-0756.2010.01396.x

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：SCHATTAUER GMBH-VERLAG MEDIZIN NATURWISSENSCHAFTEN  

There are three different diagnostic score systems for disseminated intravascular coagulation (DIC) established by the Japanese Ministry Health and Welfare (JMHW), the International Society on Thrombosis and Haemostasis (ISTH) and the Japanese Association for Acute Medicine (JAAM). The JMHW criteria are still used in Japan. In the present study, all three diagnostic criteria were used to prospectively evaluate 413 patients with different underlying diseases of DIC who were; treated at the Mie University Hospital (JMHW, n=166; ISTH, n=143; JAAM, n=291). The odds ratio (95% confidence interval) for death was 1.88 (1.22 - 2.90) in JMHW, 2.55 (1.65 - 3.95) in ISHT and 1.99 (1.19 - 3.32)in JAAM. The platelet count, prothrombin time, fibrin and fibrinogen degradation products and fibrinogen were significantly important for diagnosis of DIC by all three diagnostic criteria. Haemostatic molecular markers were significantly high in all patients and were useful for the diagnosis of DIC. The JAAM diagnostic criteria displayed a high sensitivity for DIC and the ISTH overt-DIC diagnostic criteria displayed a high specificity for DIC. All three diagnostic criteria for DIC were related to a poor patient outcome.

DOI： 10.1160/TH10-05-0293

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DOI： 10.5402/2011/919816

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Pseudomyxoma peritonei (PMP) is a rare condition of mucinous ascites associated mainly with mucinous tumors of appendix or ovary. PMP often recurs after treatment and may eventually cause death by abdominal visceral dysfunction via compression with mucinous ascites. Although radical peritonectomy and hyperthermic intra-peritoneal chemotherapy are becoming popular globally, the optimal treatment of PMP has not been established in Japan. We conducted a retrospective multicenter study to clarify the optimal treatment and the prognostic factors of PMP. A total of 23 patients with PMP were analyzed in the Tohoku Gynecologic Cancer Unit (TGCU). Clinical and follow-up data were retrieved and a central pathology review was performed. The median follow-up period was 46 months. Eleven patients underwent complete resection. There were 7 deaths out of 13 recurrences/progressions in this period. All the recurrence/ progression was confined to the abdomen. Unexpectedly, neither radical peritonectomy nor hyperthermic intra-peritoneal chemotherapy had been performed, indicating that both radical peritonectomy and hyperthermic intra-peritoneal chemotherapy are not yet popular in Japan. The medians of overall survival and disease-free period were 166 months and 30 months, respectively. Univariate and multivariate analyses revealed that the only prognostic factor was macroscopic residual tumor (P = 0.022). Although chemotherapy was not a prognostic factor (P = 0.16), those who received intra-peritoneal chemotherapy tended to have a better prognosis than those who received systemic or no chemotherapy (P = 0.064). In conclusion, the macroscopic residual tumor is an important prognostic factor in Japanese patients with PMP. © 2011 Tohoku University Medical Press.

DOI： 10.1620/tjem.223.91

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

Aims/hypothesis Experimental studies have suggested that apoptosis is involved in diabetic embryopathy through oxidative stress. However, the precise mechanism of diabetic embryopathy is not yet clear. Thioredoxin (TRX) is a small, ubiquitous, multifunctional protein, which has recently been shown to protect cells from oxidative stress and apoptosis. Using transgenic mice that overproduce human TRX-1 (TRX-Tg mice), we examined whether oxidative stress is involved in fetal dysmorphogenesis in diabetic pregnancies.
Methods Non-diabetic and streptozotocin-induced diabetic (DM) female mice were mated with male TRX-Tg mice. Pregnant mice were killed either at day 10 or day 17 of gestation, and viable fetuses and their placentas were recovered, weighed and assessed for gross and histological morphology, biochemical markers and gene expression.
Results In both wild-type (WT) and transgenic (Tg) groups, fetal and placental weights in the diabetic group were significantly decreased compared with the non-diabetic group. The incidence of malformation was higher in the diabetic group, and was significantly decreased in the TRX-Tg group (DM-WT vs DM-Tg; 28.6% vs 10.4%). Oxidative stress markers such as thiobarbituric acid reactive substances and 8-hydroxy-2&apos;-deoxyguanosine were increased in DM-WT group fetuses but were decreased in fetuses from the DM-Tg group. Furthermore, immunohistochemically assayed apoptosis and cleaved caspase-3 production in embryonic neuroepithelial cells was significantly increased in the DM-WT group, and was significantly decreased in the DM-Tg group.
Conclusions/interpretation These results indicate that oxidative stress is involved in diabetic embryopathy, and that the antioxidative protein TRX at least partially prevents diabetic embryopathy via suppression of apoptosis.

DOI： 10.1007/s00125-010-1784-y

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

Group-A-streptococcus-(GAS)-induced toxic shock syndrome (TSS) is uncommon, but carries a high risk of maternal mortality during pregnancy. The onset of gravidic GAS-TSS has been reported mostly during the puerperium.
A 16-year-old woman, who was at 37 weeks of gestation, and without obstetrical care during the last 30 weeks, was referred to our hospital. She complained of fever for one day with headache and abdominal pain after the fever developed. On admission, her consciousness was drowsy, intrauterine fetal death was recognized, and she rapidly developed shock status with coma and hypotension, hemolysis, disseminated intravascular coagulation (DIC), and multi-organ failure. Although we had not obtained the results of a bacterial culture, we suspected sepsis with DIC with homolysis and multi-organ failure resulting from an infection. The patient was treated with antibiotics and intubation because of respiratory insufficiency. Twelve hours after admission to the intensive care unit in our hospital, she died. Cultures from blood, subcutaneous tissue, vaginal discharge, and pharynx all revealed GAS bacteria, and therefore she was diagnosed as having GAS-TSS.
GAS-TSS in pregnancy is rare. However, once the infection occurs in a pregnant woman, it rapidly develops into sepsis with multi-organ failure. Therefore, early recognition and intensive treatment for GAS during pregnancy is recommended in women with high fever, muscular pain, hemolysis and DIC during pregnancy.

DOI： 10.1111/j.1447-0756.2010.01259.x

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

Background: Most patients with malignant diseases are frequently complicated with some type of thrombosis, such as disseminated intravascular coagulation (DIC) or deep vein thrombosis (DVT)/pulmonary embolism (PE). Objective: The cohort and retrospective study was designed to examine the frequency of thrombosis in patients with malignant diseases and to evaluate the efficacy of D-dimer and soluble fibrin (SF) for the diagnosis of thrombosis. Patients/Methods: The plasma concentrations of D-dimer and SF were measured in patients with malignant diseases suspected of having thrombosis. D-dimer and SF were measured using a latex aggregation assay. Results: Thrombosis was observed in 23.3% of the patients with malignant diseases. Disseminated intravascular coagulation was frequently observed in patients with hepatoma, and DVT/PE was frequently observed in patients with colon cancer, lung cancer, and uterine cancer. The plasma levels of D-dimer and SF were increased in malignant diseases, especially hepatoma. Plasma levels of D-dimer and SF were significantly higher in patients with thrombosis in comparison to patients without thrombosis. A receiver operating characteristic (ROC) analysis showed the D-dimer and SF levels to be useful in the diagnosis of thrombosis. Conclusion: Elevated D-dimer and SF levels might indicate a high risk of thrombosis in patients with malignant disease; however, these assays still need to be standardized.

DOI： 10.1177/1076029609340901

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

Aim:
Fetal exposure to excessive or deficient glucocorticoids may alter the programming in differentiation and maturation of various tissues including the brain and nervous system, leading to dysfunctions later in life. For further exploration of this possibility, we established an animal model using developing chick embryos.
Methods:
(i) Reverse-transcription polymerase chain reaction was used to determine the expression of glucocorticoid receptor mRNA in the brain of chick embryos. (ii) Embryos on day 15 were administered betamethasone or mifepristone and their cerebrum, cerebellum and optic lobe were investigated to determine the activity of acetylcholinesterase.
Results:
(i) Glucocorticoid receptor mRNA was shown to be present in the cerebrum, cerebellum and optic lobe. (ii) After the administration of betamethasone, acetylcholinesterase activities in the cerebrum, cerebellum and optic lobe on day 19 were 1.5- to 2-fold higher than those of untreated control. Weights of body and brain parts were 0.65-0.75-fold relative to control values. However, these differences were less noticeable on day 22. (iii) Administration of mifepristone before treatment with betamethasone prevented high-dose betamethasone-induced changes in acetylcholinesterase activity and bodyweights on day 19. Administration of mifepristone alone did not induce differences from the control.
Conclusions:
The cerebrum, cerebellum and optic lobe of chick embryos could be influenced by glucocorticoids because of the presence of glucocorticoid receptor mRNA. Although the effects observed after treatment with excess glucocorticoids (even no effects after mifepristone treatment) were transitory, they may alter the developmental program in ways that could result in lasting change and influence behavioral activities after hatching.

DOI： 10.1111/j.1447-0756.2009.01091.x

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

Fulminant type 1 diabetes associated with pregnancy is very rare. However if it occurs, the rapid onset is associated with an extremely high risk of fetal death. Therefore, it is important for physicians to make an appropriate diagnosis as early as possible and to begin immediate treatment of both the mother and the fetus. We report a case of fulminant type 1 diabetes associated with pregnancy in which a good outcome was achieved for both the mother and the fetus.

DOI： 10.1111/j.1447-0756.2009.01068.x

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Congenital diaphragmatic hernia (CDH) occurs in multiple malformation syndromes and associations, and has been associated with cytogenetic aberrations on almost every chromosome arm. However, CDH with a duplication of chromosome 1q is very rare in the literature, and all previously reported cases with detailed clinical courses died soon after birth. We present the first surviving case of CDH with a duplication of 1q12-q23, who had arthrogryposis multiplex congenita and hypertrophic cardiomyopathy. CDH patients with a proximal duplication of chromosome 1q may have a chance for survival, and CDH with a duplication of chromosome 1q is not necessarily a lethal association.

DOI： 10.1007/s00383-009-2421-z

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Maternal pregravid obesity is associated with adverse outcomes in pregnancy. There are many complications by maternal obesity during pregnancy, such as spontaneous abortion, congenital malformations, gestational hypertention, preeclampsia, gestational diabetes mellitus, fetal macrosomia, and so on. Also, at parturition, the prevalence of cesarean section and associated complications such as deep vein thrombosis, wound disruption, and infection increase. Furthermore, offspring of obese women increases the risk of adolescent components of the metabolic syndrome. To improve short- and long-term adverse outcome associated with obese pregnant women, we need to encourage obese women to lose body weight before pregnancy. During pregnancy, weight gain should be limited to Institute of Medicine guidelines. © 2009 Bentham Science Publishers Ltd.

DOI： 10.2174/157340409790069970

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

The fibrin-related markers (FRMs), including soluble fibrin (SF), d-dimer and fibrin and fibrinogen degradation products (FDP) are considered to be useful for the diagnosis of thrombosis; however, evidence for the diagnosis of thrombosis by SF is still not well established. The present study was designed to evaluate the usefulness of SF in the diagnosis of venous thromboembolism (VTE). The plasma concentrations of FRMs were measured in 551 in-patients suspected to have a VTE. The plasma levels of SF, Td-dimer and FDP were significantly higher in patients with VTE than patients without VTE and those were significantly higher in patients without VTE than in healthy volunteers. In a receiver operating characteristic analysis for the diagnosis of VTE, the area under the curve was 0.950 for SF, 0.933 for FDP and 0.805 for d-dimer. The appropriate cut-off values for the diagnosis were as follows SF 5.9 mu g/ml, FDP 2.1 mu g/ml and d-dimer 4.8 mu g/ml. To obtain a 100% negative predictive value for the diagnosis of VTE, the SF was less than 5.2 mu g/ml, FDP was less than 1.3 mu g/ml, and d-dimer was less than 0.5 mu g/ml. Our findings suggest that the SF assay is useful for the diagnosis and exclusion of VTE.

DOI： 10.1007/s12185-008-0173-5

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

Background Inadequate folate status has been associated with many negative reproductive outcomes, such as neural tube defects (NTD), low birth weight and placental abruption. Aim of the study The objectives of this study were to evaluate the levels of dietary folate intake during pregnancy in Japanese women and the subsequent birth weight of their babies. Methods A longitudinal prospective study was conducted with 197 women with a singleton pregnancy in 2005. Dietary folate was investigated 3 times: in the first trimester at 12 weeks, in the second trimester at 20 weeks and in third trimester at 32 weeks using a diet history questionnaire (DHQ). Non fasting blood samples were collected from the women for measurement of homocysteine, hemoglobin, ferritin, unbound iron-binding capacity (UIBC) and total iron-binding capacity (TIBC). Results Energy intake increased as pregnancy advanced, but not significantly. The daily intake of folate increased from 248.5 +/- 113.1 mu g/d in the first trimester to 275.4 +/- 100.2 mu g/d in the third trimester (P = 0.04). This was well below the recommended level of 440 mu g/d and only 10% of mothers were above the levels. In the third trimester, plasma homocysteine concentration was significantly higher in the low folate group of less than 250 mu g/d (P = 0.02), but not the first and second trimesters. Dietary folate intake and plasma homocysteine concentrations were not likely to be predictors of birth weight in our subjects. Conclusions Our study shows that Japanese women&apos;s energy and folate intakes do not meet their energy needs during pregnancy and are at an extremely low recommended dietary allowance level throughout pregnancy.

DOI： 10.1007/s00394-008-0733-8

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

Oxidative stress occurs where there is an imbalance between the production and scavenging of free radicals. Pregnancy per se is a state of oxidative stress due to the increased metabolic activity of placental mitochondria and reduced scavenging ability of antioxidant systems. Overproduction of reactive oxygen species may be associated with impaired fetal growth. However, the physiological influence of antioxidant systems on fetal growth is not well understood. In this study we assessed the effects of antioxidant systems on fetal growth using human thioredoxin (hTRX)-1 overexpressing transgenic (Tg) mice. Tg or C57BL/6 [wild-type (WT)] male mice were mated with WT female mice, and dams were killed to obtain the fetuses and placentas on gestational d 15. Tg fetuses were significantly heavier than WT fetuses, whereas placental weight did not differ significantly between the two groups. Immunohistochemically, hTRX-1 was localized to the nuclei of labyrinthine trophoblasts in Tg mice. In addition, placental expression of 8-hydroxy-2&apos;-deoxyguanosine, which reflects DNA damage caused by oxidative stress, was reduced in Tg mice compared with WT mice. Placental expression of glucose transporter-1 mRNA and protein was significantly higher in Tg mice than WT mice, whereas no significant differences were observed for glucose transporter-3, IGF, and IGF-binding protein mRNA expression. These results suggest that placental and/or systemic antioxidant systems can influence fetal growth. In particular, increased hTRX-1 activity and the resulting modified placental redox state may play an important role in fetal growth by increasing the availability of glucose.

DOI： 10.1210/en.2007-1682

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We experienced a case of fetal overgrowth probably due to maternal hyperglycemia following the interruption of insulin therapy in a woman with gestational diabetes mellitus (GDM), probably undiagnosed type 2 diabetes mellitus. A 27-year-old Japanese woman was referred to our center because of GDM at 15 weeks of gestation. During the course of her educational admission, diet control and insulin therapy resulted in favorable blood sugar levels and she was discharged at 17 weeks of gestation. During these periods, fetal growth remained below average at between -1 and -1.5 S.D. After a check-up in the 29th week, she failed to appear for any further appointments. After the onset of labor, at 38 weeks of gestation, she suddenly consulted her former physician who delivered a baby weighing 4852 g by cesarean section on the 38th week. A noteworthy point in this case is the growth curve of the fetus. Even if rapid overgrowth is assumed, starting after the time of interruption of insulin at 30 weeks of gestation, fetal weight gain appears to be about 400 g per week, suggesting a weight increase at twice the normal rate. This case prompted us to keep in mind that rigid glycemic control will prevent the development of fetal macrosomia in diabetic pregnant women. © 2008 Elsevier Ireland Ltd. All rights reserved.

DOI： 10.1016/j.diabres.2008.01.020

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Language：Japanese   Publishing type：Research paper (scientific journal)   Publisher：Societas Neurologica Japonica  

We report a rare case of multiple cranial nerve palsy associated with pregnancy, the cause of which remained to be clarified despite of extensive inspections. A 28-year-old woman with type 1 diabetes on insulin therapy developed left oculomotor nerve palsy in the fourth month of pregnancy. Her symptoms improved after one month's administration of vitamins B1 and B12. Numbness appeared in the left side of the face in the 8th month of pregnancy, and then moved to the right side in two weeks. Dysarthria and dysphagia occurred one month later. Bulbar symptoms were worsened, and she became unable to eat or drink. Neurological examination revealed disturbance of sensation in the right side of the face, soft palate paresis, and bilateral atrophy and fasciculation of the tongue. Extensive laboratory examinations including immunological and endocrinological studies, cerebrospinal fluid examination and brain magnetic resonance imaging were unremarkable. These symptoms remitted spontaneously after delivery, and the methylprednisolone pulse therapy accelerated the improvement. Neurological examination done one year after delivery showed complete recovery of the symptoms except for persistent tongue atrophy.

DOI： 10.5692/clinicalneurol.48.579

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：JOHN WILEY & SONS LTD  

DOI： 10.1002/pd.1754

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

Purpose To elucidate the promoter region of human decidual prolactin (dPRL) gene in the human endometrial stromal cells (ESC).
Methods Various segments of the human dPRL promoter that direct the expression of the secreted alkaline phosphatase (SEAP) reporter gene were transfected into human ESC decidualized by estrogen (E) + progesterone (P) or cyclic AMP (cAMP) to identify E + P or cAMP responsive elements.
Results The region between nucleotides -2038 and -1605 relative to the transcriptional initiation site includes two activator protein-1 (AP-1) sites, which both provided maximal response to E + P or cAMP in decidualized cells. When either AP-1 site was mutated, response in the promoter activity to both E + P or cAMP response showed a decrease compared with control. The region between -310 and -285 that contains consensus-binding sequences for transcription factors of CCAAT/Enhancer-binding proteins (C/EBP) contributed to E + P and cAMP response in decidualized cells. Also, the 5'-flanking region that extends 79 base pairs upstream, including an imperfect cAMP response element (CRE), contributed to E + P and cAMP response. In cells treated with E + P or cAMP for 10 days, mutant of C/EBP-binding site showed an increase in promoter activity comparing to dPRL-2038. In contrast, treatment with PKI showed a decrease in promoter activity in cells treated with E + P or cAMP alone.
Conclusions These results suggest that cAMP-induced region of the human dPRL promoter resides between -1862 and -1856, -1703 and -1697, -310 and -285, and that the sequences between -1862 and -1856, -1703 and -1697 of the promoter display E + P-induced promoter activity. Furthermore, the current study indicates that E + P or cAMP cooperatively regulate the dPRL gene transcription through some transcriptional factors such as C/EBP, CREB, and other cofactor(s), and that some repressor(s) or corepressor(s) may be involved in the C/EBP-binding site of the human dPRL promoter.

DOI： 10.1007/s11010-006-9388-z

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

Purpose To elucidate the promoter region of human decidual prolactin (dPRL) gene in the human endometrial stromal cells (ESC).
Methods Various segments of the human dPRL promoter that direct the expression of the secreted alkaline phosphatase (SEAP) reporter gene were transfected into human ESC decidualized by estrogen (E) + progesterone (P) or cyclic AMP (cAMP) to identify E + P or cAMP responsive elements.
Results The region between nucleotides -2038 and -1605 relative to the transcriptional initiation site includes two activator protein-1 (AP-1) sites, which both provided maximal response to E + P or cAMP in decidualized cells. When either AP-1 site was mutated, response in the promoter activity to both E + P or cAMP response showed a decrease compared with control. The region between -310 and -285 that contains consensus-binding sequences for transcription factors of CCAAT/Enhancer-binding proteins (C/EBP) contributed to E + P and cAMP response in decidualized cells. Also, the 5'-flanking region that extends 79 base pairs upstream, including an imperfect cAMP response element (CRE), contributed to E + P and cAMP response. In cells treated with E + P or cAMP for 10 days, mutant of C/EBP-binding site showed an increase in promoter activity comparing to dPRL-2038. In contrast, treatment with PKI showed a decrease in promoter activity in cells treated with E + P or cAMP alone.
Conclusions These results suggest that cAMP-induced region of the human dPRL promoter resides between -1862 and -1856, -1703 and -1697, -310 and -285, and that the sequences between -1862 and -1856, -1703 and -1697 of the promoter display E + P-induced promoter activity. Furthermore, the current study indicates that E + P or cAMP cooperatively regulate the dPRL gene transcription through some transcriptional factors such as C/EBP, CREB, and other cofactor(s), and that some repressor(s) or corepressor(s) may be involved in the C/EBP-binding site of the human dPRL promoter.

DOI： 10.1007/s11010-006-9388-z

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

The progress of a fetal severe pleural effusion at mid- trimester is extremely poor. We encountered a fetus that developed a severe left pleural effusion at 21 weeks of gestation. The pleural effusion was removed by thoracocentesis at 22 weeks. Cytology revealed abundant lymphocytes, suggesting chylothorax. However, a reaccumulation of pleural effusion with hydrops was subsequently noted, and a thoracoamniotic shunt with double- basket catheters was installed at 23 weeks. The pleural effusion decreased after 24 weeks and completely disappeared at 26 weeks. At 40 weeks of gestation, a female infant was born by vaginal delivery, with no evidence of pleural effusion. We would like to stress that thoracoamniotic shunt with double- basket catheters in the second trimester is effective for pleural effusion with hydrops.
Copyright (C) 2007 S. Karger AG, Basel

DOI： 10.1159/000106347

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

Immunoregulatory CD4(+)CD25(+) T cells play an important rote in the induction and maintenance of peripheral self-tolerance. These professional regulatory cells prevent the activation and proliferation of potentially autoreactive T cells that have escaped thymic deletion. Therefore, CD4(+)CD25(+) T cells are believed to possibly play an important role in pathogenic autoimmune diseases. We measured the count of CD4(+)CD25(+) T cells in 44 patients with idiopathic thrombocytopenic purpura (ITP), and the number of CD4(+)CD25(+) T cells and clinical features were then analyzed. By using a flow cytometric analysis, the number of CD4(+)CD25(+) T cells in the patients with ITP showed a very wide distribution in comparison to healthy volunteers. The number of CD4(+)CD25(+) T cells was significantly tower in the ITP patients in the severe phase, and in patients positive for anti-glycoprotein IIb-IIIa antibody. However, the number of those cells increased in the patients at the complete remission phase, especially after a splenectomy. The Foxp3 mRNA levels of peripheral blood mononuclear cells (PBMC) of ITP patients were higher with an improved platelet count than in those with a low platelet count. In addition, the Foxp3 mRNA levels closely correlated with the number of CD4(+)CD25(+) cells. These mechanisms remain to be fully elucidated, however, the count of CD4(+)CD25(+) T cells is considered to possibly be related to the severity of ITP. (C) 2006 Elsevier Ltd. All rights reserved.

DOI： 10.1016/j.thromres.2006.09.008

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Language：English   Publishing type：Research paper (international conference proceedings)  

The usefulness of the vascular ultrasound in the field of obstetrics is now well recognized. Intima-media thickness (IMT) and elastic property of the common carotid artery are affected by pregnancy and vary with complications. Flow-mediated vasodilation (FMD) of the brachial artery reflects the vascular endothelial function and is reported to be useful in the management of complicated pregnancy, especially pre-eclampsia. For the screening of deep vein thrombosis of the lower extremities in the perinatal period, compression ultrasonography (CUS) is useful.

DOI： 10.1080/14722240600787154

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：TAYLOR & FRANCIS AS  

Background. To analyze the association of pregnancy complications with prepregnant body mass index and weight gain during pregnancy in Japanese women. Methods. A retrospective cohort study was conducted with 21,718 Japanese women with a singleton pregnancy. Pregnant women were grouped by prepregnant body mass index and evaluated for association with pregnancy complications using multivariate logistic regression analysis. The women in each body mass index group were then divided into groups by weight gain during pregnancy using intervals of 0.05 kg/week to analyze the relationship between the weight gain and pregnancy complications by multivariate logistic regression association analysis. Results. In both nulliparous and parous women, the least pregnancy complications were found among women with medium prepregnant body mass indexes (18-23.9). Significant risks of pregnancy complications were associated with low (&lt;18) and high (&gt;= 24) prepregnant body mass indexes, particularly high prepregnant body mass indexes. In nulliparous; women, the optimal weight gain was 0.25-0.4 kg/week for low (&lt;18) prepregnant body mass index, 0.20-0.30 kg/week for medium (18-23.9) prepregnant body mass index, and &gt;= 0.05 kg/week for high (&gt;= 24) prepregnant body mass index. In parous women, the corresponding values were &gt;= 0.20, 0.20-0.30, and 0.05-0.30 kg/week. Conclusions. Japanese women with prepregnant body mass indexes from 18 to 23.9 are least associated with pregnancy complications, although there is a broad range of prepregnant body mass indexes associated with few pregnancy complications. Optimal weight gain is roughly inversely related to prepregnant body mass index.

DOI： 10.1080/00016340500502044

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Giant fetal neck masses can cause airway obstructions with potential poor fetal prognosis after delivery. The relationship between the fetal neck mass and airway structure can be defined prenatally with ultrasound and magnetic resonance imaging (MRI). The ex utero intrapartum treatment (EXIT) procedure is an available technique to obtain a fetal airway while feto-maternal circulation is preserved. We present a case in which prenatally a giant fetal neck mass was diagnosed on ultrasound and MRI, and a successful EXIT procedure could be performed. Copyright (C) 2005 S. Karger AG, Basel.

DOI： 10.1159/000083908

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：GEORG THIEME VERLAG KG  

Adiponectin, a fat-derived factor, is downregulated in insulin resistance and obesity; insulin resistance has been demonstrated during late pregnancy in both humans and in rodents. The present study examines the physiological change of adiponectin gene expression as well as the circulating levels of adiponectin during pregnancy. We examined the relative quantity of adiponectin mRNA produced in the adipose tissues of pregnant compared to virgin mice. We also measured serum adiponectin levels and parametrial adipocyte size in mice throughout pregnancy. Adiponectin mRNA was significantly reduced by 74 +/- 8% and 63 +/- 4 % at days 15 and 18 of pregnancy, respectively, compared to virgin mice. Serum adiponectin concentration decreased on days 15 (30.7 +/- 8.5 mug/ml) and 18 (27.9 +/- 8.7 mug/ml) of pregnancy, and the values were significantly lower than that of virgin mice (56.8 +/- 6.6 pg/ml). Parametrial adipocytes from mice on days 15 and 18 of pregnancy were significantly larger than in virgin mice or during early pregnancy. Fat-cell size was closely correlated to degradation of adiponectin gene expression and serum adiponectin levels. These results suggest that changes of adiponectin expression affect metabolic status in pregnant mice.

DOI： 10.1055/s-2004-825726

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Language：Japanese   Publisher：(株)診断と治療社  

インスリン抵抗性は2型糖尿病の重要な病態であるが,PCOSにおいても主病態であり,インスリン抵抗性を基盤に糖代謝異常およびステロイド合成異常をきたす症候群である.そこで,このPCOSと糖代謝の関連について解説をおこなった

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：ELSEVIER SCI IRELAND LTD  

The objective of this study was to investigate the utility and characteristics of various screening procedures for gestational diabetes mellitus (GDM) in Japan during the first trimester and between 24 and 28 weeks of pregnancy. The subjects were 749 pregnant women who came to our hospitals. A 50-g oral glucose challenge test (GCT), casual plasma glucose measurements, fasting blood glucose measurements, and glycosylated hemoglobin measurements were performed in the first trimester. Subjects with no abnormalities were tested again at 24-28 weeks of gestation. Of the 749 subjects, 22 (2.9%) tested positive for GDM. Of those 22 patients, 14 were diagnosed with GDM in the first trimester (63.6%) and eight in the second trimester (36.4%). This finding suggests the importance of screening for glucose intolerance in the first trimester. Furthermore, it appears that the GCT has the most utility for GDM screening; the other screening methods tested were not as useful because of their low sensitivity, particularly in the second trimester. (C) 2003 Elsevier Ireland Ltd. All rights reserved.

DOI： 10.1016/S0168-8227(03)00146-3

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Language：Japanese   Publisher：(一社)日本周産期・新生児医学会  

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Language：Japanese   Publisher：(一社)日本糖尿病学会  

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

Dramatic alternations in maternal metabolism occur during gestation and lactation, especially glucose and fat metabolism. For example, in rats, the amount of body fat mass increases during gestation, then decreases just prior to delivery, and remains low after parturition. To investigate the factors involved in such changes in maternal fat mass, messenger ribonucleic acid (mRNA) levels of adipocytokines, peroxisome proliferator-activated receptor-gamma (PPAR-gamma) and tumor necrosis factor-alpha (TNF-alpha), were examined in the intraabdominal adipose tissue of non-pregnant rats, pregnant rats and postpartum rats. We also examined the issue of whether apoptosis, which could be promoted by PPAR-alpha and TNF-alpha, is involved in any of the changes in maternal fat mass The activity of lipoprotein lipase (LPL) and hormone sensitive lipase (HSL) in adipose tissue was also measured. PPAR-gamma and TNF-alpha mRNA levels remained constant during the gestational and postpartum periods. Apoptosis was not detected at any time as evidenced by DNA laddering and in situ staining. LPL activity was significantly increased at day 5 and remained elevated until day 14 of gestation. HSL activity was significantly increased at day 10 of gestation and then decreased after delivery, at day 10 of lactation. In conclusion, during the gestational and postpartum period of rats, changes in maternal fat mass did not directly correlate with the levels of expression of PPAR-gamma and TNF-alpha mRNA. Apoptosis also does not appear to influence on fat mass change. The changes in LPL and HSL activities during gestation suggest that these enzymes might be regulators of maternal adipose tissue level. (C) 2002 Elsevier Science Inc. All rights reserved.

DOI： 10.1016/S0024-3205(02)02445-1

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We reviewed reports on first-trimester sonographical screening for fetal abnormalities and fetal aneuploidies. Higher incidences of spontaneous abortion or placenta previa are reported to exist in cases where the gestational sac is detected in the middle or lower portion of the uterine corpus. In multiple pregnancies, the determination of chorionicity and amnionicity must be accurately made during the first trimester of pregnancy. Reports on the usefulness of nuchal translucency measurements for screening of aneuploidies have been presented, but some investigators have reported on the very limited usefulness, especially for the low-risk population. Some of the major structural abnormalities are detectable in the first trimester and are considered to be related to aneuploidies. It is reported that early growth restriction of the fetus is related to trisomies 18 and 13. In trisomies 21, 13 and Turner syndrome, it is reported that the fetal heart rate in early pregnancy is significantly higher. Doppler velocimetry in the umbilical artery, umbilical vein, ductus venosus and maternal uterine artery is helpful for the prediction of fetal abnormalities. First-trimester sonography is very important for the early detection of fetal aneuploidies and other abnormalities.

DOI： 10.3109/14722240208500471

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：BLACKWELL PUBLISHING LTD  

A case of fetal goitrous hypothyroidism associated with high-output cardiac failure is presented. At 32 weeks of gestation, the antenatal diagnosis of goiter was made based on ultrasound examination, and the fetal thyroid function was examined by amniocentesis and cordocentesis. Color and pulsed Doppler examinations demonstrated a high vascular flow Pattern in the goiter and marked elevation of the maximum velocity in the common carotid artery at the level of the neck. It was suspected that arteriovenous shunting through the large goiter resulted in high-output cardiac failure with cardiomegaly and pleural effusion. The fetus was treated by injection of levothyroxine sodium into the amniotic fluid at 33 weeks of gestation and the goiter thereafter decreased in size, with subsequent improvement of the high-output cardiac failure. The maximum velocity in the common carotid artery fell rapidly before the shrinkage of the fetal goiter and in parallel with the fetal level of thyroid-stimulating hormone.

DOI： 10.1046/j.1469-0705.2002.00680.x

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

Twin-to-twin transfusion syndrome (TTTS) is a severe complication of monochorionic twin pregnancies, with high perinatal loss and significant morbidity. The etiology of this syndrome remains unclear. Hyperreactio luteinalis is a rare benign condition characterized by maternal ovarian enlargement due to theca lutein cysts. We present 4 cases of hyperreactio luteinalis associated with severe TTTS. We detected maternal ovarian enlargement by prenatal ultrasonography in 2 cases, at the cesarean section in 1 case, and postpartum in 1 case. Three cases showed hydrops fetalis and all cases showed congestive cardiac failure. Serial amnioreduction was performed in all cases, and regression of hydrops fetalis and maternal ovarian enlargement occurred in 1 case. These cases suggest that the pathophysiology of TTTS is closely related to the etiology of hyperreactio luteinalis. Copyright (C) 2002 S. Karger AG, Basel.

DOI： 10.1159/000064566

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

The effect of twin gestation on carbohydrate metabolism was evaluated using a 75 g oral glucose tolerance test (75 g OGTT). A 75 g OGTT was performed in 63 twin gestations and 3 791 single-ton gestations during the third trimester. Plasma glucose concentrations were measured in the pregnant women under fasting conditions as well as 30 min, 1 h, and 2 h after ingestion of glucose (75 g oral load), and serum insulin concentrations were measured in fasting and 30 min post-ingestion samples. Women with twin gestations showed significantly lower plasma glucose concentrations during fasting and 30 min after the glucose load in the samples taken than those with singleton gestations. No significant difference in serum glucose concentrations was found in the other specimens. There were no cases of gestational diabetes mellitus in our study. Although women with twin gestations demonstrated lower plasma glucose concentrations than women with singleton gestations, the difference observed was subtle. We could not find any significant differences in these plasma glucose values as used to define a pathologic OGTT between twin and singleton pregnancies, with the exception of the fasting value.

DOI： 10.1055/s-2002-33263

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：ELSEVIER SCI IRELAND LTD  

Data for 416 Japanese pregnant women who received a 75g oral glucose tolerance test (OGTT) for determination of gestational diabetes mellitus (GDM) in 13 hospitals in Japan were analyzed retrospectively. Comparison of the diagnostic criteria of the World Health Organization (WHO) and the Japan Society of Obstetrics and Gynecology (JSOG) revealed pregnant women who met the latter criteria for GDM to have significantly higher incidences of low Apgar scores, respiratory problems, neonatal hypoglycemia, preterm delivery and requirements for insulin therapy and cesarean section. The women who met the WHO criteria but not the JSOG criteria had minor complications. These observations suggest that the GDM criteria of the JSOG are more appropriate than the WHO criteria from the standpoint of therapeutic intervention for pregnant women. (C) 2000 Elsevier Science Ireland Ltd. All rights reserved.

DOI： 10.1016/S0168-8227(00)00135-2

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

Chicken ovalbumin upstream promoter-transcription factors (COUP-TFs), orphan members of the nuclear receptor superfamily, play a key role in the regulation of organogenesis, neurogenesis, and cellular differentiation during embryogenic development. COUP-TFs are also involved in the regulation of several genes that encode metabolic enzymes. Although COUP-TFs function as potent transcription repressors, there are at least three different molecular mechanisms of activation of gene expression by COUP-TFs, First, as we have previously shown, COUP-TF is required as an accessory factor for the complete induction of phosphoenolpyruvate carboxykinase gene transcription by glucocorticoids, This action is mediated by the binding of COUP-TF to the glucocorticoid accessory factor 1 (gAF1) and 3 (gAF3) elements in the phosphoenolpyruvate carboxykinase gene glucocorticoid response unit. In addition, COUP-TF1 binds to DNA elements in certain genes and transactivates directly. Finally, COUP-TF1 serves as a coactivator through DNA-bound hepatic nuclear factor 4, Here we show that the same region of COUP-TFI, located between amino acids 184 and 423, is involved in these three mechanisms of transactivation by COUP-TFI, Furthermore, we show that GRIP1 and SRC-1 potentiate the activity of COUP-TFI and that COUP-TFI associates with these coactivators in vivo using the same region required for transcription activation. Finally, overexpression of GRIP1 or SRC-1 does not convert COUP-TFI from a transcriptional repressor into a transcriptional activator in HeLa cells.

DOI： 10.1074/jbc.275.5.3446

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Japan Endocrine Society  

The patient was a 32-year-old obese woman with a history of type 2 diabetes and hypertension for 6 years. Although she was treated with antihypertensive agents and intensive insulin therapy, her hyperglycemia was difficult to control. She wanted to have a baby but pregnancy was not recommended because her diabetes was under poor control and the use of antihypertensive medication. To achieve good control of obesity, diabetes and hypertension, she was admitted to our clinical department for weight reduction using very low calorie diet (VLCD). During VLCD she had a 19.8 kg reduction in body weight and her blood glucose and blood pressure were in good control without the use of drugs. Five months later, she became pregnant after the fourth trial of intrauterine insemination (IUI) and gave birth to a female baby under insulin therapy. This is the first report that showed the usefulness of VLCD for prepregnant control of glucose metabolism and blood pressure in an obese hypertensive patient with type 2 diabetes mellitus.

DOI： 10.1507/endocrj.47.787

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

The effects of 17 beta-estradiol (E) and/or progesterone (P) on; glucose transporter 4 (GLUT4) expression in the adipose tissue and skeletal muscle of ovariectomized female rats were studied. The Sprague-Dawley rats received daily subcutaneous injections of various doses of E and/or P for 7 days (n=5-6 per dose). The expression of GLUT4 mRNA was assessed by performing ribonuclease protection assays. GLUT4 protein levels were assessed by Western blotting assays. The adipose tissue levels of GLUT4 mRNA were reduced by the administration of 50 mu g E, which resulted in unphysiologically high serum E concentrations. Although the GLUT4 mRNA levels did not change after the administration of 10 mu g E or 5 mg P, they were reduced significantly to approximately half the control group level by the administration of both hormones (p &lt;0.01). The skeletal muscle GLUT4 mRNA levels were not changed significantly by hormone treatment. These findings suggest that E and P may be involved in the regulation of GLUT4 mRNA expression in adipose tissue.

DOI： 10.1016/S0024-3205(99)00636-0

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Language：Japanese   Publisher：(一社)日本糖尿病学会  

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

Complete induction of hepatic phosphoenolpyruvate carboxykinase (PEPCK) gene transcription by glucocorticoids requires a complex glucocorticoid response unit (GRU). The GRU is comprised of two glucocorticoid receptor (GR)-binding sites (GR1 and GR2) and four accessory factor-binding sites [AF1, AF2, AF3, and cAMP response element (CRE)] that bind distinct transcription factors. Hepatic nuclear factor 4 (HNF4) and chicken ovalbumin upstream promoter transcription factor (COUP-TF) bind to the AF1 element and account for AF1 activity. Members of the hepatic nuclear factor 3 (HNF3) family bind to the AF2 element and provide AF2 activity. In this report, we show that the functions of AF1 and AF2 are dependent on their positions in the promoter, since they cannot substitute for each other nor can they be exchanged without a reduction in the response to glucocorticoids. We also identified the domains of HNF4 and HNF3 beta that are required for the AF1 and AF2 activities, respectively. The carboxy-terminal transactivation domain of HNF4 (amino acids 128-374) confers most of the AF1 activity, while the carboxyterminal transactivation domain of HNF3 beta (amino acids 361-458) mediates AF2 activity. These domains of HNF4 and HNF3 beta appear to have distinct roles in the response to glucocorticoids, as there are unique structural requirements for each, as judged by the failure of most other classes of transactivation domains to serve as accessory factors. These results suggest that the regulation of the PEPCK gene by glucocorticoids requires specific interactions between GR, accessory factors, and coactivators, and that the transactivation domains of AF1 and AF2 are of fundamental importance in the assembly of this multiprotein complex.

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Georg Thieme Verlag  

Depletion of GLUT4, the primary glucose transporter protein in adipose tissue and skeletal muscle, is reported to contribute to insulin resistance in pregnancy or diabetes. To examine this phenomenon, the expression of GLUT4 protein was assessed by Western blotting in streptozotocin-induced diabetic pregnant rats. In adipose tissue, relative to control, it was decreased by 30% in the normal pregnant group (p&lt
0.001), by 37% in the diabetic nonpregnant group (p&lt
0.01) and by 65% in the diabetic pregnant group (p &lt
0.001). On the other hand, no significant variation was evident among the groups in skeletal muscle. To assess the mechanisms responsible for depletion of GLUT4 protein in adipose tissue, we quantitated levels of GLUT4 mRNA with a RNase protection assay. It was decreased by 44% in the normal pregnant group (p &lt
0.05) and by 55% in the diabetic pregnant group (p &lt
0.05), but not altered in the diabetic nonpregnant group. These results suggest that the depletion of GLUT4 protein in adipose tissue is a factor contributing to insulin resistance in pregnancy or diabetes, especially when the two states exist in combination.

DOI： 10.1055/s-2007-978785

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

The weight of the uteri of ovariectomized(OVX) rats was drastically increased by about 5 times at 1 week after one subcutaneous (s.c.) injection of oestradiol, but not changed by hydroxyprogesterone administration. The activities of ornithine decarboxylase (ODC) and spermidine/spermine N-1-acetyltransferase (SAT) in the uterus of OVX rats were controlled by exogenous administrations of the sex steroid hormones, oestradiol and/or hydroxyprogesterone to the OVX rats. ODC activity in the uterus of OVX rats was drastically increased by one s.c. injection of oestrdiol, but not changed by one s.c. injection of hydroxyprogesterone. On the other hand, SAT activity in the uterus of OVX rats was reduced to one-third by oestradiol administration, while by the hydroxyprogesterone administration the enzyme activity was not changed,keeping the control level of SAT activity in the uteri of OVX rats treated with the vehicle(sesame oil). It is noteworthy that the patterns of changes in ODC activity by these hormone treatments are the reverse of the patterns of changes in SAT activity in the uteri of OVX rats. Patterns of ODC activity alteration by these sex hormones were very similar to the patterns of the organ weight alteration, demonstrating that ODC activity correlates to the growth of the organ.

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：University of Tokyo Press  

Objective: To investigate the effects of 17β-estradiol and progesterone on the expression of glucose transporter 4 (GLUT4) in the adipose tissue and skeletal-muscle tissue of ovariectomized rats. Methods: Female Sprague-Dawley rats (n = 63) received a daily subcutaneous injection of 10 μg, 50 μg, or 250 μg of 17β-estradiol (Group E) or of 1 mg, 5 mg or 25 mg of progesterone (Group P) for 3 days, 7 days, or 10 days (n = 3, at each dose). The expression of GLUT4 mRNA was assessed by performing ribonuclease protection assays. Results: The levels of GLUT4 mRNA in adipose tissue was significantly reduced by treatment with estradiol, 50 μg or 250 μg, relative to findings in control rats (p &lt
0.01). No such reductions were seen regarding the progesterone treatment. The level of GLUT4 mRNA in skeletal-muscle tissue did not change, regardless of treatment. Conclusion: In ovariectomized rats, higher than physiologic dosages of 17β-estradiol can suppress the expression of GLUT4 mRNA in adipose tissue.

DOI： 10.1111/j.1447-0756.1999.tb01115.x

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The phosphoenolpyruvate carboxykinase (PEPCK) gene promoter contains a glucocorticoid response unit (GRU) that includes three accessory factor-binding sites (AF1, AF2, and AF3), two glucocorticoid receptor-binding sites (GR1 and GR2), and a cAMP response element. All of these elements, and the proteins that bind to them, are required for a complete glucocorticoid response. The PEPCK promoter also contains a retinoic acid response unit (RARU) that consists of two retinoic acid response elements (RARE1 and RARE2) that bind retinoic acid receptor/9-cis-retinoic acid receptor heterodimers. The sequences of RARE1 and RARE2 coincide with those for AF1 and AF3, respectively. Thus, the PEPCK promoter can mediate different hormone responses through hormone response units that utilize common elements, but that bind different sets of proteins. We reasoned that each response might require a unique structural assembly and therefore tested how various arrangements of the PEPCK promoter affect the actions of either glucocorticoids or retinoic acid. The activation of the PEPCK gene in response to glucocorticoids requires a specific set of cis-acting elements that must be precisely positioned within the GRU. The distance between AF2 and GR1 is critical for the glucocorticoid response, and since the AF2 factor, HNF3, interacts with GR in vitro, this protein-protein interaction may be important for the glucocorticoid response. By contrast, the distance and orientation requirements of AF1 and AF3 with respect to GR1 are more flexible. In the case of the RARU, although the relative positions of RARE1 and RARE2 are important for the retinoic acid response, more tolerance for distance and stereospecific alignment between RARE1 and RARE2 is allowed. In addition, we show that the GRU and the RARU can act as a module, within a restricted region, in the context of the PEPCK promoter and in limited contexts of a heterologous promoter. These observations suggest that the structural requirements of the GRU and the RARU are different, and this may have important implications for how multiple hormonal signals are integrated through this promoter.

DOI： 10.1210/mend.12.10.0187

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

OBJECTIVE: Our purpose was to investigate the influence of pregnancy and lactation on hexokinase II activity and gene expression in adipose tissue and skeletal muscle of rats. STUDY DESIGN: Intraabdominal adipose tissue and femoral quadriceps muscle were removed from Sprague-Dawley rats at various times (6 to 10 animals per group) during pregnancy and lactation. Hexokinase II messenger ribonucleic acid was assayed by quantitative ribonuclease protection analysis, and hexokinase activity was measured with the glucose- 6-phosphate-coupled assay. RESULTS: The amount of hexokinase II messenger ribonucleic acid in adipose tissue on day 20 of pregnancy was 55.4% ± 8.4% (p &lt
0.01, unpaired Student t test) of the value for nonpregnant control rats
hexokinase II activity was also decreased in this tissue at this time (39.34 ± 3.05 vs 27.81 ± 3.61 mU · min-1 · mg protein-1, p &lt
0.05). Hexokinase II activity and messenger ribonucleic acid abundance in skeletal muscle were unaffected by pregnancy and lactation. CONCLUSION: Both hexokinase II messenger ribonucleic acid abundance and enzyme activity are reduced in adipose tissue of pregnant rats near term, possibly contributing to the insulin resistance associated with late pregnancy.

DOI： 10.1016/S0002-9378(97)70564-7

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

The purpose of this study is to investigate the risks of delivery of malformed infants in diabetic mothers in comparison with those in non- diabetic mothers and to clarify risk factors for malformation due to maternal diabetes. The delivery records available at the Department of Obstetrics and Gynecology, Mie University School of Medicine between 1979 and 1992 showed 103 mothers with diabetes mellitus among 4,353 pregnancies. The incidence of malformation in infants born to diabetic mothers was 9.7% and it was 2.5% overall. By logistic regression analysis of all mothers in this series, diabetes as well as maternal age, and fetal age were shown to be significant risk factors for malformation. A further logistic model for diabetic mothers revealed that a younger age of the mother at the time of labour, low fetal age, older age at onset of diabetes, previous history of pregnancies, and an Hemoglobin A1 (HbA1) level higher than 9% were independent risk factors, among which HbA1 (&gt
9%) showed the highest odds ratio of 24. Careful management is therefore needed to reduce the risk of malformation in pregnancy of diabetic mothers.

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：BioScientifica Ltd.  

Prolactin receptor (PRL-R) mRNA expression levels in the female rat brain (cerebrum) during pup contact stimulation were determined by the reverse transcription-PCR method. The high expression levels of long form PRL-R mRNA found in the brain of lactating rats were markedly reduced by removal of pups, and long form PRL-R mRNA levels were recovered by resumption of pup contact. Interestingly, pup contact stimuli of nulliparous virgin rats also markedly induced long form but not short form PRL-R mRNA expression in the brain in 1.3 days, together with the expression of maternal behaviour. In ovariectomized (OVX) or hypophysectomized (HYPOX) virgin rats, or in OVX plus HYPOX virgin rats, however, brain long form PRL-R mRNA was not significantly induced by pup contact stimuli for as long as 7 days, while maternal behaviour was finally expressed in these rats after 7 days of pup contact. The in situ hybridization experiments revealed that the long form PRL-R mRNA induced in virgin rats in contact with pups or in lactating rats was localized in the epithelial cells of the choroid plexus. No significant increase in mRNA was detected in other regions of the brain, such as the hypothalamus or cortex, in these maternal female rats. These results suggest that pup contact induces the expression of long form PRL-R mRNA in the choroid plexus of the brain in the presence of female sex steroid and pituitary hormones for the rapid expression of maternal behaviour. Our studies also suggested that maternal behaviour can be expressed in OVX or HYPOX rats after exposure to pups for 7 days without any significant increase in brain PRL-R mRNA expression.

DOI： 10.1677/joe.0.1490335

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

A case is reported of a 51‐year‐old woman who had a hysterectomy and bilateral salpingo‐oophorectomy in the same year, following a radical mastoidectomy for breast cancer with metastases to the axillary lymph nodes. Histological examination showed breast cancer metastatic to uterine leiomyoma. The literature about metastasis of extragenital cancer to a leiomyoma is reviewed, and the possible mechanism involved is discussed. © 1995 Japan Society of Obstetrics and Gynecology

DOI： 10.1111/j.1447-0756.1995.tb01022.x

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：BioScientifica Ltd.  

Prolactin (PRL) exerts a wide variety of physiological effects on mammalian tissues through its receptor (PRL-R) on the target cells. PRL-R in rat tissue consists of two isoforms, the long and the short form, and the regulatory mechanisms of their mRNA expression in tissues are complex and diverse. The present study reports the differential regulation of PRL-R mRNA expression in rat liver and kidney by testosterone and oestradiol. Using Northern blot analysis, short form PRL-R mRNA was clearly detected in female rat liver and male rat kidney, and long form PRL-R mRNA was faintly observed only in female rat liver. However, the reverse transcription-polymerase chain reaction method enabled efficient analysis of mRNA levels in short and long forms of PRL-R in the liver and kidney of both male and female rats. The mRNA levels for the long and short forms of PRL-R were depressed in the liver of male rats but not in that from female rats during sexual maturation. Castration of male rats resulted in the induction of the mRNAs for these two forms of PRL-R in the liver. Testosterone, but not oestradiol, completely blocked the induction by castration of Liver PRL-R gene expression. In kidney, in contrast, mRNA levels for both forms of PRL-R were depressed in female rats but not in male rats after sexual maturation. Administration of oestradiol, but not of testosterone, caused marked repression of short form PRL-R mRNA, particularly in the kidney of male rats. The levels of long form PRL-R mRNA in the kidney was less affected by the administration of oestradiol. These results have suggested that the expression of PRL-R mRNAs in rat liver and kidney is differentially regulated by testosterone and oestrogen.

DOI： 10.1677/joe.0.1430383

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：BioScientifica Ltd.  

The mRNA species for prolactin receptor (PRL-R) isoforms, long and short form PRL-Rs, were estimated by the reverse transcription-polymerase chain reaction method in the rat brain (cerebrum) during the oestrous cycle, pregnancy and lactation. The levels of long form PRL-R mRNA increased at pro- oestrus and oestrus, at the same time as serum prolactin levels increased, whereas the mRNA level of short form PRL-R was relatively unchanged. Long form PRL-R mRNA expression was also markedly increased in the brain at mid- and late gestation, and this elevated mRNA level was maintained during the period of lactation. In contrast, basal levels of short form PRL-R mRNA were also maintained throughout these periods of gestation and lactation. Ovariectomy moderately reduced brain mRNA levels of both long and short form PRL-R from the levels of those in control dioestrous rats, and hypophysectomy further suppressed them to the lowest levels. Administration of oestradiol valerate (E2V) or 17α-hydroxyprogesterone caproate (17OHPC) to ovariectomized rats resulted in dramatic increases in long form PRL-R mRNA levels in the brain, whereas no significant increase in short form PRL-R mRNA was observed. In rats which were ovariectomized and hypophysectomized, the administration of 17OHPC, rat prolactin or rat GH partially restored the brain level of long form PRL-R mRNA but not short form PRL-R mRNA. E2V, on the other hand, had no effect on the expression of brain PRL-R mRNAs in these hypophysectomized rats, suggesting that the stimulatory effect of E2V on long form PRL-R mRNA expression in ovariectomized rats was mediated by an enhanced secretion of a pituitary hormone, prolactin. These results suggest that the expression of long form PRL-R mRNA in the rat brain is directly induced by progesterone, prolactin or GH during the oestrous cycle, pregnancy and lactation.

DOI： 10.1677/joe.0.1410325

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Language：Japanese   Publisher：(一社)日本周産期・新生児医学会  

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Language：Japanese   Publisher：(公社)日本糖尿病協会  

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Language：Japanese   Publisher：(一社)日本糖尿病学会  

妊娠糖尿病(gestational diabetes mellitus;GDM)の臨床的意義として,(1)妊娠合併症の増加,(2)母体の将来の2型糖尿病発症を含めた疾患発症の増加,(3)次世代の耐糖能低下や肥満を含めた疾患発症の増加といった短期・中期・長期にわたる問題点があげられる.すなわちGDMは,母児共に妊娠中のみならず長期的な合併症の発症とも関連する点より診断を含めた管理は重要であるといえる.GDMは妊娠時に初めて発見された耐糖能低下である.GDMの診断基準は,heavy-for date(HFD)児といったGDMの望ましくない妊娠アウトカムと関連する血糖値のカットオフ値を求めることにより設定するが,当然,GDMの診断を行い,治療介入することにより望ましくない妊娠アウトカムの発生率を下げることができれば望ましい.本稿では,GDMの診断に関する現在の運用法と問題点につき概説する.(著者抄録)

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Language：Japanese   Publisher：(公社)日本母性衛生学会  

本研究目的は,産院退院後から1ヵ月の母親の産後ケアニーズを構成する因子を明らかにし,属性ごとに比較することである。A病院において1ヵ月健診を受診した母親200名に対し,属性,育児支援チェックリスト,エジンバラ産後うつ病質問票(EPDS),赤ちゃんへの気持ち質問票(MIBS-J),産後ケアニーズ質問票を用いて質問紙調査を実施した。195名から得られた回答を最尤法・プロマックス回転の因子分析,記述統計,t検定を用いて分析した。因子分析より,第1因子:心身の負担を軽減することへのニーズ,第2因子:児の成長を確認し自分なりの育児を習得することへのニーズ,第3因子:母乳育児の継続に向けたニーズ,第4因子:育児支援に関する社会資源活用へのニーズが抽出された(α係数:全体0.96,各因子0.85～0.93)。第1因子は精神疾患既往・現病あり,MIBS-J高得点,第2および第3因子は児の要求の理解困難,第3因子は職業あり,入院中に混合または人工栄養,全ての因子では初産婦においてそれぞれ得点が有意に高かった。母親の属性により異なる専門職への産後ケアニーズを考慮し,支援方法を検討していく必要がある。(著者抄録)

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Language：Japanese   Publisher：(株)東京医学社  

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Other Link： https://search.jamas.or.jp/default/link?pub_year=2023&ichushi_jid=J00621&link_issn=&doc_id=20240215030008&doc_link_id=10.24479%2Fperi.0000001228&url=https%3A%2F%2Fdoi.org%2F10.24479%2Fperi.0000001228&type=%E5%8C%BB%E6%9B%B8.jp_%E3%82%AA%E3%83%BC%E3%83%AB%E3%82%A2%E3%82%AF%E3%82%BB%E3%82%B9&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00024_2.gif

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

症例は53歳,子宮体癌疑いにて単純子宮全摘術+両側付属器摘出術を施行し,術後の病理検査にて絨毛癌と診断された。転移所見は無く経過観察していたが,術後2ヵ月でhCGが上昇し,肺転移を認めた。EMA/CO(etoposide,methotrexate,actinomycin-D,cyclophosphamide,vincristine)療法を施行し寛解したが,その後hCGの上昇と肺転移を認めた。EMA/EP(etoposide,methotrexate,actinomycin-D,cisplatin)療法を施行し寛解したが,再度hCGの上昇を認め,PET-CTにて肺転移を指摘された。肺病変に対して胸腔鏡下肺部分切除を施行した後MEA(methotrexate,etoposide,actinomycin-D)療法を施行したが,2サイクル目以降はhCGの低下が得られず,また末梢神経障害と口内炎の副作用が高度にて5サイクルで終了した。本症例が将来有効とされる化学療法に抵抗性であることと腫瘍組織のPD-L1が高発現であり,免疫チェックポイント阻害薬の有効性が期待できる可能性を検討し,院内の倫理審査委員会の承認と患者の同意を得てpembrolizumabの投与を行った。4サイクル施行したがhCGの低下が得られず,肺転移に加え腹膜播種病変も出現し全身状態が悪化のため,治療を終了した。絨毛癌は化学療法の感受性は高いが,10%程度は化学療法抵抗性を示し予後不良である。化学療法抵抗性の絨毛癌に対しては有効な治療法がない。腫瘍細胞のPD-L1発現のある症例での免疫チェックポイント阻害薬の有効性について報告されており,今後の治療開発が望まれる。(著者抄録)

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Other Link： https://search.jamas.or.jp/default/link?pub_year=2023&ichushi_jid=J05038&link_issn=&doc_id=20231221330003&doc_link_id=%2Fcv0mtrob%2F2023%2F007201%2F003%2F0013-0018%26dl%3D0&url=https%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fcv0mtrob%2F2023%2F007201%2F003%2F0013-0018%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

Language：Japanese   Publisher：(一社)日本糖尿病・妊娠学会  

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

【緒言】Wunderlich症候群は,1976年にWunderlichによって報告されたMuller管の発生異常が引き起こす先天性子宮形態異常の1つで,重複子宮に子宮頸部の閉鎖腔を伴う症候群である。稀な疾患であり,その妊娠・出産に関する報告は少なく,周産期予後は不明であるため,妊娠管理について確立されていない。今回我々は,子宮頸部嚢胞開窓術後に患側子宮に自然妊娠し生児を得たWunderlich症候群の2例を経験したので報告する。【症例1】22歳,G1P0。初経11歳,月経痛あり。12歳時に左子宮頸部嚢胞開窓術施行した。左側(患側)子宮に自然妊娠成立し,妊娠管理を行っていたが,妊娠34週5日切迫早産のため入院管理とし,妊娠38週0日選択的帝王切開を施行した。【症例2】32歳,G1P0。初経12歳,月経痛あり。16歳頃から膿性帯下を認めていた。18歳時に左子宮頸部嚢胞開窓術施行した。左側(患側)子宮に自然妊娠成立し,近医で妊娠管理を受けていたが,妊娠29週4日大量出血と子宮収縮を認めたため,当院に緊急母体搬送となった。切迫早産の診断で,リトドリン塩酸塩持続点滴を開始した。妊娠30週0日に呼吸苦が出現し,薬剤性肺水腫が疑われたため,リトドリン塩酸塩を中止した。子宮収縮増強し,同日緊急帝王切開を施行した。【考案】Wunderlich症候群では思春期女性に症状を認めた場合,早期に正しく診断・治療を行えば,妊孕性は保たれると考えられているが,感染や子宮内膜症などが生じると不妊となる可能性もある。また妊娠・出産のリスクは,子宮頸部の形態,瘻孔の位置など病態が様々であるため,一律に論ずることはできない。それぞれの疾患での詳細な妊娠・出産率は不明であり,周産期管理についても確立されていない。個々の症例での厳重な妊娠管理が必要である。(著者抄録)

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Language：Japanese   Publisher：(株)医学書院  

＜文献概要＞●糖尿病性ケトアシドーシス(DKA)は,母児の生命にかかわる疾患であり,早期診断と早期治療が重要である.●妊婦の場合,1型糖尿病のみならず,2型糖尿病や妊娠糖尿病でさえ生じうることを念頭に置く.●劇症1型糖尿病が妊娠と関連するので,本疾患が妊娠中に発症する可能性も念頭に置く.●DKAの治療を先行するか緊急帝王切開するかは,妊娠時期,DKAの程度などにより,総合的に,糖尿病専門医や小児科と相談のうえ決定する.

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Language：Japanese   Publisher：金原出版(株)  

＜文献概要＞挙児希望女性における代謝内分泌疾患の合併症については,適切な時期に適切な情報を女性やカップルへ提供し,将来妊娠のためのヘルスケアを行うことが重要である。甲状腺疾患や糖尿病を合併した女性では妊娠前から既存疾患に対する厳重な管理をすることで,周産期予後の改善が期待できる。これら疾患に対するプレコンセプションケアは,他科との連携が不可欠であり,自らの健康のみならず次世代への影響も考慮した管理が必要である。

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Language：Japanese   Publisher：(株)診断と治療社  

＜文献概要＞Point 妊娠中の糖・脂質代謝では,妊娠後半期における生理的なインスリン抵抗性増大による食後高血糖,高インスリン血症,および脂肪分解亢進による遊離脂肪酸の増加が特徴的である.これは本来妊娠に伴う母児双方のエネルギー需要の増大に対応するための合目的的な変化だが,糖尿病合併妊娠では血糖コントロール悪化や糖尿病合併症の増悪,糖尿病ケトアシドーシス発症をまねく恐れがある.また,非妊娠時にはみつからない軽度の耐糖能異常が,この妊娠による代謝ストレスに対し代償性にインスリン分泌を増加させることができない(膵β細胞機能不全)場合,妊娠糖尿病を発症すると考えられている.

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Other Link： https://search.jamas.or.jp/default/link?pub_year=2023&ichushi_jid=J00525&link_issn=&doc_id=20230405130021&doc_link_id=10.34433%2Fog.0000000141&url=https%3A%2F%2Fdoi.org%2F10.34433%2Fog.0000000141&type=%E5%8C%BB%E6%9B%B8.jp_%E3%82%AA%E3%83%BC%E3%83%AB%E3%82%A2%E3%82%AF%E3%82%BB%E3%82%B9&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00024_2.gif

Language：Japanese   Publisher：(株)日本医事新報社  

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Language：Japanese   Publisher：東京 : 医学出版  

CiNii Books

CiNii Research

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Other Link： https://ndlsearch.ndl.go.jp/books/R000000004-I033018872

Language：Japanese   Publisher：(株)メディカ出版  

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Publisher：東京医学社  

DOI： 10.24479/peri.0000000443

CiNii Research

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Publisher：東京医学社  

DOI： 10.24479/peri.0000000523

CiNii Research

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Language：Japanese   Publisher：(株)東京医学社  

＜ポイント＞・プレコンセプションケアとして,肥満の合併がある場合,妊娠前の生活習慣の介入により減量を図る。・すべての妊婦に推奨されるが,糖尿病女性の場合,特に葉酸摂取が望まれる。(著者抄録)

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Language：Japanese   Publisher：(株)東京医学社  

＜ポイント＞・妊娠初期の母体高血糖は胎児形態異常や流産と関連するため,妊娠前から厳格な血糖管理を行い,良好な血糖コントロール下に計画妊娠を行うことが重要である。・妊娠前の血糖管理はHbA1c値6.5%未満を目標とする。・糖尿病合併症は妊娠中に悪化する恐れがあるため,妊娠前に網膜症や腎症などの評価と治療を行う。・経口血糖降下薬やアンジオテンシン変換酵素阻害薬など,妊娠前に変更・中止が望ましい薬剤について確認し,代替療法への切り替えを行う。(著者抄録)

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Language：Japanese   Publisher：さいたま : 埼玉産科婦人科学会  

CiNii Books

CiNii Research

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Other Link： https://ndlsearch.ndl.go.jp/books/R000000004-I032460077

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

我が国では骨盤臓器脱に対する腹腔鏡下仙骨腟固定術(Laparoscopic sacral colpopexy:LSC)は2016年に保険収載され、当科でも2018年9月より導入している。LSC群の手術成績・中期的予後について検討する目的で、LSC群と腟式子宮全摘術・前後腟壁形成術・肛門挙筋縫縮術・膀胱底縫縮術(total vaginal hysterectomy:TVH)群の手術成績を比較検討した。また、LSC群の術後合併症を経験し改善するための考察をおこなった。対象は2018年9月から2020年4月までにLSCを施行した13例と、TVHを施行した14例であり、診療録をもとに手術時間、術中出血量、術後当日の鎮痛剤使用の有無を抽出した。患者の年齢は2群間に差はなく、BMIも2群間に差を認めなかった。平均手術時間はLSC群で有意に長かったが、術後当日の疼痛に対する鎮痛薬使用はLSC群で有意に少なかった。また、今回導入したLSC術後の経過では、排尿障害が13例中11例において改善したが、再発が1例、投薬を必要とする尿失禁が1例、便秘が2例に認められた。しかし、いずれも1年以内に治癒した。今後、LSC術後の長期的な再発率や、LSC特有の術後合併症ともいえる尿失禁や便秘についてはより多くの症例での長期間の追跡検討を行う必要があると考える。(著者抄録)

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Language：Japanese   Publisher：金原出版(株)  

＜文献概要＞妊娠高血圧症候群患者は分娩後もしばらくの間大きなリスクのなかにいる。妊娠高血圧症候群関連疾患である子癇・HELLP症候群・肺水腫・周産期心筋症などの発症率は分娩後も高く,厳格な血圧管理や尿量測定が必要である。しかし,必ずしも関連疾患が高血圧患者のみに発症するわけではなく,検査所見だけでなく患者が訴える臨床症状にもしっかり耳を傾ける必要がある。

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Language：Japanese   Publisher：東京 : 東京医学社  

CiNii Books

CiNii Research

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Other Link： https://ndlsearch.ndl.go.jp/books/R000000004-I032169059

Language：Japanese   Publisher：(一社)日本周産期・新生児医学会  

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Language：Japanese   Publisher：(株)東京医学社  

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Other Link： https://search.jamas.or.jp/default/link?pub_year=2022&ichushi_jid=J00621&link_issn=&doc_id=20220309080036&doc_link_id=10.24479%2Fperi.0000000066&url=https%3A%2F%2Fdoi.org%2F10.24479%2Fperi.0000000066&type=%E5%8C%BB%E6%9B%B8.jp_%E3%82%AA%E3%83%BC%E3%83%AB%E3%82%A2%E3%82%AF%E3%82%BB%E3%82%B9&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00024_2.gif

Language：Japanese   Publisher：東京 : 日本糖尿病・妊娠学会  

CiNii Books

CiNii Research

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Other Link： https://ndlsearch.ndl.go.jp/books/R000000004-I032012326

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

腟原発悪性黒色腫は稀な疾患とされており、悪性黒色腫全体のうち腟由来は0.3～0.8%であり、腟悪性腫瘍の2.4～2.8%程度を占めると言われている。また、予後不良な疾患であり5年生存率は0～25%と報告されている。今回、我々は腟原発悪性黒色腫に対して手術療法及び術後補助療法としてnivolumabを投与した1例を経験したので報告する。症例は61歳女性。未産婦。不正性器出血のため前医を受診したところ、腟入口部前壁に黒色の隆起性病変を認めた。生検の結果、悪性黒色腫と診断され当科に紹介された。骨盤部造影MRI検査及びPET-CT検査では、明らかな腟壁外浸潤は否定的であった。膀胱鏡では外尿道口から約1cm離れた尿道粘膜に黒色変化を伴う隆起性病変を認め、生検結果は悪性黒色腫であった。泌尿器科及び消化器外科と合同で腹腔鏡補助下前方骨盤内臓全摘術、回腸導管造設術を施行した。術後は会陰縫合部より浸出液の漏出を認めたが、その後改善し術後38日目に退院となった。術後病理診断にて悪性黒色腫IIB期(pT4aNxM0)と診断した。術後補助療法としてnivolumabを12ヵ月投与した。術後13ヵ月目に会陰部に局所再発を認め、消化器外科及び形成外科が合同で、直腸・肛門切除、人工肛門造設、外陰部皮膚軟部組織摘出、皮膚再建(筋膜移植、右臀溝皮弁)を施行した。切除断端は一部陽性であり、現在はpembrolizumabによる維持療法を行っている。今回、腟原発悪性黒色腫に対し手術療法及び術後補助療法としてnivolumabを投与した1例を経験した。腟原発悪性黒色腫は稀な疾患であり、今後は症例を蓄積し治療方針を確立することが必要である。(著者抄録)

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Language：Japanese   Publisher：(株)診断と治療社  

妊娠や出産はおめでたいことである一方、妊産婦にとってこの時期は身体的および精神的に負荷がかかり変調をきたしやすい時期である。産後のQOL(quality of life)を考えるうえで、身体的・精神的・社会的・経済的、すべてを含めた生活の質の向上を考えなくてはならない。特にQOLが低下した産後うつ病などのハイリスク症例は自殺企図や虐待へのリスクが高い。しかし、どの産後の女性にも起こり得る可能性があるため、産後2～4週にエジンバラ産後うつ病質問票を中心とした自記式質問票を実施し、その後の丁寧な聞き取りを行い、医療機関を含む多職種で介入できる体制を整え、将来的な自殺や虐待のない社会へつなげていくことが重要である。(著者抄録)

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Other Link： https://search.jamas.or.jp/default/link?pub_year=2021&ichushi_jid=J00525&link_issn=&doc_id=20210224050011&doc_link_id=%2Fae4sanke%2F2021%2F008803%2F012%2F0330-0336%26dl%3D0&url=https%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fae4sanke%2F2021%2F008803%2F012%2F0330-0336%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

Language：Japanese   Publisher：医歯薬出版(株)  

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Language：Japanese   Publisher：医歯薬出版(株)  

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Language：Japanese   Publisher：(一社)日本がん・生殖医療学会  

40歳(1妊0経産婦)。悪性リンパ腫に対するR-CHOP療法終了から5年後に自然妊娠した。妊娠38週5日より呼吸困難が出現し、症状増悪のため緊急帝王切開術目的で妊娠39週1日に当院へ搬送となった。搬送時、重症心不全を呈し、全身麻酔、気管内挿管、PCPSシース・中心静脈カテーテル挿入下に帝王切開術が行われ、2602gの男児を娩出した。術後は心不全の治療を開始することで心機能は改善し、母児ともに経過良好であった。尚、本症例は過去のアントラサイクリン系薬剤の投与が周産期心筋症の発症に寄与した可能性が考えられた。

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Language：Japanese   Publisher：(公社)日本婦人科腫瘍学会  

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Language：Japanese   Publisher：東京 : 日本糖尿病・妊娠学会  

CiNii Books

CiNii Research

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Other Link： https://ndlsearch.ndl.go.jp/books/R000000004-I031297545

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

異所性妊娠の90%以上は卵管膨大部妊娠であり、卵管間質部妊娠は2-4%と稀であるが、卵管切除後の同側間質部妊娠の発症頻度はさらに稀である。卵管膨大部妊娠に対し腹腔鏡下卵管切除術を行った後、同側卵管間質部妊娠をきたした2例を経験したので報告する。症例1は30歳、3妊1産、1年前に左卵管膨大部妊娠で腹腔鏡下卵管切除術の既往があった。妊娠5週0日、超音波検査で胎嚢様所見を認めたものの、2日後に左下腹部痛を自覚し再受診した。血中hCGは1,415mIU/ml、経腟超音波検査で子宮腔内に胎嚢を認めず、左卵巣周囲に2-3cm大の血腫様の腫瘤とダグラス窩にecho free spaceを認めた。その後、echo free spaceの増大と左下腹痛が持続したため、腹腔鏡手術を施行した。術中所見は、左卵管間質部が暗赤色に腫脹し、ダグラス窩には中等量の血液貯留を認めた。同部を切除し、子宮筋層は吸収糸を用いて2層に連続縫合を行なった。術後2日目、血中hCGは580mIU/mlと低下し、術後30日目に陰性化を確認した。症例2は37歳、3妊0産、1年前に右卵管膨大部妊娠で腹腔鏡下右卵管切除術の既往があった。妊娠5週1日、経腟超音波検査で子宮内に胎嚢を認めず、翌日に下腹痛が出現したため再受診した。経腟超音波検査で径5cmの右卵巣嚢胞に隣接した2cm大の腫瘤性病変を認め、異所性妊娠の疑いで当院へ紹介された。血中hCGは2,328mIU/mlで、ダグラス窩穿刺を行い血液を吸引した。腹腔鏡下手術では右卵管間質部が腫大しており、線状切開で絨毛様の内容物を排出し、同切除術を行った。術後3日目、血中hCGは280mIU/mlに低下し、術後32日目に陰性化を確認した。これら2例の経験を踏まえ、卵管切除後の妊娠では、切除同側の間質部妊娠の可能性も考慮に入れて管理する必要があると考えられた。(著者抄録)

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Other Link： https://search.jamas.or.jp/default/link?pub_year=2020&ichushi_jid=J05038&link_issn=&doc_id=20201214470027&doc_link_id=%2Fcv0mtrob%2F2020%2F006901%2F027%2F0151-0155%26dl%3D0&url=https%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fcv0mtrob%2F2020%2F006901%2F027%2F0151-0155%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

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

QT延長症候群は、心電図においてQT延長を認め、torsade de pointesと呼ばれる特異な心室頻拍あるいは心室細動などの重症心室性不整脈によって、脳虚血症状や突然死を来たし得る重篤な疾患である。QT延長症候群では妊娠や分娩などのストレスが致死的な不整脈の誘因となることが知られており、内科と共診の上、母体の心機能を厳重に管理していくことが大切である。また、胎児に遺伝すると子宮内胎児死亡や乳幼児死亡の原因となる為、早期発見が求められる。我々は遺伝子型が判明している先天性QT延長症候群患者4例の妊娠・分娩管理を経験した。先天性QT延長症候群は、遺伝子型の違いによって病態や臨床症状が異なるため、それぞれの型に合わせた生活指導や治療が良好な周産期予後を得るために必要である。(著者抄録)

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Language：Japanese   Publisher：金原出版(株)  

＜文献概要＞胎児期や乳幼児期などの生涯の早い段階における環境は,将来の健康状態に影響を与える。また将来の生活習慣病のみならず,精神神経系などのあらゆる発達に対する影響も含めた非感染性疾患(NCDs)の発症のリスクと関連することが明らかになっており,DOHaDという概念として提唱されている。そのなかで低出生体重児は,循環器系疾患,2型糖尿病,慢性閉塞性肺疾患,精神発達異常など将来のNCDsの発症のリスクが高いことが明らかになってきており,出生体重はNCDs発症の重要因子の1つであると考えられる。出生体重を規定する要因としては,遺伝因子のみならず子宮内環境などによるエピジェネティクスを介することが報告されている。両親の体格に関しては,母親の体格が出生体重に与える影響はよく知られているが,父親の体格が出生体重に与える影響については,一致した見解はない。子どもの健康と環境に関する全国調査「エコチル調査(JECS)」は,環境省の事業として2010年度から開始された環境化学物質の健康影響に主眼をおいた出生コホート研究である。われわれは,わが国において最大規模の疫学調査である「エコチル調査」のデータを用いて,全国15ヶ所の地域における約10万組の親子の出生体重と父親の体格に関する関連性を検討した。

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Language：Japanese   Publisher：金原出版(株)  

＜文献概要＞再発婦人科がんの多くは化学療法抵抗性を示し,現在のところ確固たる治療法は確立されていない。当科では局所的な再発病変に関して他臓器切除を含めた手術療法を積極的に行っており,2013年以降に当科にて再発と診断し手術療法を行った9例の婦人科がん症例について後方視的検討を行った。再発手術は全例肉眼的残存なく完遂しており,術後3例で再発を認めた。再発からの生存期間は中央値39ヵ月(8〜68ヵ月)であった。再発婦人科がんであっても,局所的な再発でとどまり,手術までの期間他臓器への転移をきたさなければ,消化管・尿路合併切除も含めて積極的な手術療法を行うことで比較的良好な予後が得られた。

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Language：Japanese   Publisher：(株)東京医学社  

＜回答のポイント＞1)母子健康手帳は、妊娠期から乳幼児期までの健康に関する情報が管理されている成長を記録する手帳である。2)全国共通の母子健康手帳であり、地域と母子、母と子をつなぐ手帳でもある。3)妊娠が判明した時点で住んでいる地域の保健センター・市区役所・町村役場で母子健康手帳を受け取る。医師からの妊娠届が必要な場合もある。(著者抄録)

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Language：Japanese   Publisher：(株)東京医学社  

＜回答のポイント＞1)最終月経開始日から分娩予定日を決定するが、排卵日や胚移植が特定できる場合は後者を採用する。2)最終月経開始日からの分娩予定日と胎児頭臀長(CRL)が14〜44mmから予測される分娩予定日に7日以上のずれがある場合はCRLを採用する。3)妊娠12週以上で20週未満、もしくはCRL>50mmである場合は、児頭大横径(BPD)、大腿骨長(FL)を参考にし、分娩予定日に10日以上ずれがある場合は超音波計測を採用する。4)妊娠20週以降も上記に準じて決定するが、誤差が大きい場合があるので慎重に妊娠管理する。予定日決定困難な場合は、出生後にDubowitz法で決定する。(著者抄録)

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Language：Japanese   Publisher：(株)東京医学社  

＜回答のポイント＞1)産科超音波検査は「広義の出生前検査のひとつ」であり、妊婦健診時に行われる「通常超音波検査」と胎児形態異常診断を目的とした「胎児超音波検査」の二つがある。2)妊娠中の超音波検査で胎児形態異常の有無を知ることで、今後の治療方針や心構えができる。(著者抄録)

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Language：Japanese   Publisher：(株)東京医学社  

＜回答のポイント＞1)妊娠が判明した場合、まずかかりつけ医や近い産婦人科を受診し、担当医をつくる。2)地域により周産期医療体制は異なるため、担当医に相談し出産する場所を決定する。3)合併症妊娠や妊娠による合併症、特定妊婦など周産期にかかわる高度医療を必要とする際は、総合・地域周産期母子医療センターと連携体制をとる。(著者抄録)

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Language：Japanese   Publisher：(株)医学書院  

＜文献概要＞●帝王切開術は,産科医療の基本的な手術であり,通常の術式は理解のうえ,執刀医として完遂できることが望ましい.●児と胎盤娩出後の筋層縫合は丁寧に行うことが肝要であり,その後の短期的のみならず長期的合併症と関連することに留意するべきである.●早産時や,前置胎盤,さらには前置癒着胎盤が疑われる症例は,帝王切開術の"応用編"であり,また出血量が多い際は,適宜,圧迫縫合術などを行えるように,日頃よりシミュレーションすることが望ましい.

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Language：Japanese   Publisher：(一社)日本糖尿病・妊娠学会  

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Language：Japanese   Publisher：(一社)日本糖尿病・妊娠学会  

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Language：Japanese   Publisher：(一社)日本糖尿病・妊娠学会  

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Language：Japanese   Publisher：医歯薬出版(株)  

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

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

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

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

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Language：Japanese   Publisher：(株)東京医学社  

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

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

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

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

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Language：Japanese   Publisher：日本妊娠高血圧学会  

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Language：Japanese   Publisher：愛媛医学会  

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Language：Japanese   Publisher：メディカルフロントインターナショナル(有)  

愛媛大学医学部附属病院・産科外来を妊婦健診のために受診した妊婦58名(平均年齢34.2歳、妊娠初期31名、中期24名、後期3名)を対象に、妊娠期に経験される睡眠の問題と情報通信機器使用の実態について質問紙調査を実施した。調査には睡眠問診票とメディア使用状況調査票を用いた。対象者のうち、就労している者は25名、主婦は30名であった。平日の平均就寝時刻は23時12分、平均起床時刻は7時7分、夜間の平均睡眠時間は7時間13分であった。午睡を取るのは平均週2.7日、平均昼寝時間は61分/日であった。1日あたりの情報通信機器への平均接触時間は、テレビが5時間52分、スマートフォン3時間18分、パソコン1時間6分であった。テレビに毎日平均10時間以上接触している妊婦は23.9%、スマートフォンに1日平均10時間以上接触している妊婦は2.0%であった。対象者52名は、平均的なオンラインユーザーであったが、5名にはインターネットによる問題があり、生活に影響を与えている可能性が示された。

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

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Language：Japanese   Publisher：(一社)日本糖尿病・妊娠学会  

妊娠糖尿病と診断された女性のうち、2型糖尿病発症高リスク群((1)妊娠前肥満、または(2)妊娠前非肥満かつ妊娠糖尿病診断時の糖負荷試験での異常ポイント数が2ポイント以上)を対象に、妊娠中から食事・運動・母乳推進・教育介入を組み合わせた包括的な強化介入を行うことによる産後の糖尿病予防効果を明らかにする研究を開始した。現在、産後3ヵ月時点の耐糖能異常率および母乳栄養率をアウトカムとしたパイロット試験が、多施設共同オープンランダム化比較試験(デイジーマムスタディ)として進行中である。今後、パイロット試験における介入プログラムの実行可能性およびその効果を探索的に評価して本試験のデザインを決定する。(著者抄録)

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Language：Japanese   Publisher：(一社)日本糖尿病・妊娠学会  

妊娠糖尿病と診断された女性のうち、2型糖尿病発症高リスク群((1)妊娠前肥満、または(2)妊娠前非肥満かつ妊娠糖尿病診断時の糖負荷試験での異常ポイント数が2ポイント以上)を対象に、妊娠中から食事・運動・母乳推進・教育介入を組み合わせた包括的な強化介入を行うことによる産後の糖尿病予防効果を明らかにする研究を開始した。現在、産後3ヵ月時点の耐糖能異常率および母乳栄養率をアウトカムとしたパイロット試験が、多施設共同オープンランダム化比較試験(デイジーマムスタディ)として進行中である。今後、パイロット試験における介入プログラムの実行可能性およびその効果を探索的に評価して本試験のデザインを決定する。(著者抄録)

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

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

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

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Language：Japanese   Publisher：(一社)日本糖尿病・妊娠学会  

子宮内環境が低栄養の場合、一般に胎児の発育は抑制され、small for gestational age(SGA)として出生するが、多くの症例において新生児期にcatch-up growthが認められ、発育の抑制を取り戻す。しかし、近年の疫学研究や基礎研究により、生後のcatch-up growthを呈したSGA児は、将来の肥満や耐糖能低下といった非感染性疾患(non-communicable diseases;NCDs)の発症と関連することが明らかとなった。一方、子宮内の過栄養状態も児の将来のNCDs発症と関連することも明らかとなってきた。(著者抄録)

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

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

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Language：Japanese   Publisher：(株)医学出版  

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Language：Japanese   Publisher：(株)東京医学社  

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

手術不能な再発子宮体がんに対する治療は、化学療法や放射線治療を中心に行われるが、患者の予後や全身状態を勘案し症例ごとの検討が必要である。今回、左臼蓋骨転移および多発肺転移を来した再発子宮体がんに対し、化学療法と放射線治療を行なった後、酢酸メドロキシプロゲステロン(medroxyprogesterone acetate:MPA)療法および骨修飾薬によって3年以上再発病巣の進行を抑制できた症例を経験したので報告する。症例は57歳(初発時)、未妊、既往歴に特記すべき事なし。初回治療として準広汎子宮全摘術、骨盤リンパ節郭清術、傍大動脈リンパ節生検を施行し、pT1bN0M0、類内膜腺がんgrade 1と診断した。術後補助化学療法としてDC療法(ドセタキセル+カルボプラチン)を3サイクル施行したが、10ヵ月後に左臼蓋骨転移を来したため放射線治療を施行した。その後はDC療法3サイクル及びゾレドロン酸の投与を施行したが、1年後には多発肺転移を来した。DC療法を行うと多発肺転移病巣は縮小するも休薬すると再燃する、という経過を辿っていた。病理組織の免疫組織化学染色では、エストロゲン受容体、プロゲステロン受容体陽性であり、再発から5年後にMPA療法、RANKL阻害剤の投与に治療を変更した。その1年後には左腸骨、左中臀筋、大臀筋の再発腫瘤が増大し、同部位に放射線治療を施行したが、その後3年以上再発巣は増大なく経過している。MPA療法は再発子宮体がんにおける有用な治療選択肢と考えられる。(著者抄録)

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

本邦では近年の晩婚化や出産年齢の高齢化など、女性のライフスタイルの変化に伴い若年性子宮体がんの患者が増加している。子宮体がんの根治のためには妊孕性を失うこととなるが、妊孕性温存治療としての高用量酢酸メドロキシプロゲステロン(medroxyprogesterone acetate:MPA)療法が行われその有効性が現在までに示されている。2008年1月から2018年6月の期間、当院において妊孕性温存を希望したIA期かつ類内膜腺がんG1(以下EMG1)の子宮体がん:13例、子宮内膜異型増殖症(以下AEH):9例の合計21例を対象として、高用量MPA療法(600mg/日)を施行した症例について、後方視的に検討した。初回治療時の年齢の中央値は34.8歳(25-46歳)、BMIの中央値は30.3kg/m2(15-57kg/m2)で、全例で未妊であった。21例のうち、16例(76.2%)で病変消失を認めた。病理組織別の内訳は、EMG1は13例のうち9例(69.2%)で病変消失を認め、そのうち3例(33.3%)に再発した。AEHの8例では7例(87.5%)で病変消失を認め、そのうち2例(28.6%)で再発を認めた。再発例3例、病変残存例5例、分娩後1例に対して子宮摘出を行った。術後の病理組織はEMG1:7例、AEH:1例であった。また、病変残存例のEMG1:2例、AEH:1例、再発のEMG1:1例において、反復して高用量MPA療法を施行した結果、病変は消失している。他臓器への転移再発、重篤な血栓症の併発および死亡症例は認めなかった。また、子宮温存例のうち8例(38.1%)が妊娠に至り、5例が分娩に至り生児を得ている。妊娠例のうち、自然妊娠:1例、排卵誘発:2例、AIH:1例、IVF:4例であった。高用量MPA療法は妊孕性温存希望のEMG1、AEHにとって、本邦で施行可能な唯一の治療法である。当院においても分娩まで至る症例を経験しているが、その一方で再発率も高く、慎重かつ長期間の経過観察が必要である。(著者抄録)

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Language：Japanese   Publisher：(一社)日本周産期・新生児医学会  

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Language：Japanese   Publisher：(一社)日本周産期・新生児医学会  

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Language：Japanese   Publisher：(一社)日本周産期・新生児医学会  

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Language：Japanese   Publisher：(一社)日本周産期・新生児医学会  

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Language：Japanese   Publisher：(公社)日本婦人科腫瘍学会  

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Language：Japanese   Publisher：(公社)日本婦人科腫瘍学会  

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Language：Japanese   Publisher：(公社)日本婦人科腫瘍学会  

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Language：Japanese   Publisher：(一社)日本周産期・新生児医学会  

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

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Language：Japanese   Publisher：(公社)日本婦人科腫瘍学会  

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Language：Japanese   Publisher：「産婦人科の進歩」編集室  

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Language：Japanese   Publisher：産婦人科漢方研究会  

半夏白朮天麻湯が単独で月経前症候群(PMS)に著効した一例を経験した。一般的に、PMSは気血水のうち血の関与が大きいと考えられているが、脾胃虚を補い、水毒を捌く半夏白朮天麻湯の著効したPMSを経験したので報告する。症例は31歳の女性。月経前の頭痛、熱感、全身倦怠感を主訴に来院した。これらの症状は、月経前10日間ほど続き、月経後に消失することから、PMSと診断された。いくつかの方剤を試みたが、有効ではなく、最終的に半夏白朮天麻湯が著効した。気、血、水が複雑に関与する中で形成されたPMSでは、胃腸虚弱で疲れやすい脾胃虚および水毒の病態に対して半夏白朮天麻湯が方証一致したものと考えられる。(著者抄録)

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

22歳女性。妊娠11週の妊婦健診で充実性部分を含む左卵巣嚢腫を指摘された。MRIで骨盤腔の左側に4cm大の腫瘤を認め、内溶液は脂肪抑制され、DWIで高信号を示す壁在結節が見られた。左卵巣の成熟嚢胞奇形腫と診断し、分娩後に手術を予定した。分娩後も卵巣嚢腫の大きさは変わらず、腹腔鏡手術を施行した。手術は臍部にE・ Z-アクセスとラッププロテクターを留置した後、ViKY EPシステムを設置し、単孔式による腹腔鏡下卵巣嚢腫核出術を行った。完全なストレスフリーではなかったが、鉗子が当たってもカメラがぶれず、術者の手を邪魔する前立ちもないため、容易に手術を行うことができた。手術時間は2時間とやや長かったが、スムーズに手術を完遂できた。病理診断は成熟嚢胞奇形腫で、術後3日に軽快退院となった。ViKY EPシステムを用いることで、単孔式手術の応用性が広がり、ソロサージャリーに繋がると考えられた。

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

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

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

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

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

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

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

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Language：Japanese   Publisher：(NPO)日本がん・生殖医療学会  

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Language：Japanese   Publisher：(株)東京医学社  

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Language：Japanese   Publisher：(一社)千葉県産科婦人科医学会  

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Language：Japanese   Publisher：東京 : 日本糖尿病・妊娠学会  

CiNii Books

CiNii Research

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Other Link： https://ndlsearch.ndl.go.jp/books/R000000004-I029978114

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

卵巣静脈血栓症(postpartum ovarian vein thrombosis:POVT)は、全出産の0.02〜0.18%、帝王切開後の1〜2%に合併する周産期合併症で、13〜25%に肺塞栓症を合併するとされる。今回、経腟分娩後に右卵巣静血栓を合併した症例を経験したので、文献的考察を含めて報告する。症例は31歳女性、2妊2産。経腟分娩にて第2子出産後、産褥5日目に39度台の発熱と右下腹部に限局する圧痛を認め、虫垂炎の疑いで精査・管理目的のため前医より紹介された。経腟超音波検査では、腹痛の原因となり得る所見は得られなかった。造影CTを施行したところ、右卵巣静脈から下大静脈合流部および右腎静脈内の陰影欠損、右卵巣静脈壁の造影効果や周囲の液貯留を認めた。以上の所見より、右卵巣静脈血栓症、血栓性静脈炎と診断し、ヘパリン持続点滴・ワルファリン内服を開始すると共に抗菌薬の投与を行った。治療開始後2日目に解熱、症状は徐々に改善し、入院後16日目に退院となった。ワルファリン内服を継続し、発症1ヵ月後のCTでは血栓は消失した。(著者抄録)

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

【目的】肥満・非肥満女性間の良性腫瘍に対する全腹腔鏡下子宮摘出術(total laparoscopic hysterectomy:TLH)における周術期合併症に関する比較検討を行った。【方法】当院において2011年1月から2015年12月までに子宮良性疾患に対してTLHを施行した164例を対象とし、非肥満群(BMI<25)・肥満(BMI≧25)間の臨床背景や周術期合併症等について比較検討を行った【成績】非肥満群は129人(78.6%)、肥満群は35人(21.4%)であった。術前の基礎疾患合併症では、高血圧症、糖尿病、脂質代謝異常、血栓塞栓症を有する頻度が肥満群で有意に高かった。平均出血量は、両群間に有意差を認めなかった(非肥満群vs.肥満群:115.7±187.6g vs.163.9±221.6g、p=0.2)。平均手術時間は、肥満群において有意に長かった(非肥満群vs.非肥満群:200.7±70.7分vs.244.4±82.0分、p=0.002)。平均摘出組織の重量、入院日数は、両群間で差を認めなかった。周術期合併症では、創部感染、臓器損傷、血栓塞栓症、腟断端部血腫の発生率のいずれも両群間で差を認めなかった。手術時間に関連する因子を多変量解析により解析した結果、肥満の存在と出血量が手術時間に関連する因子であることが判明した。【結論】肥満症例においても術前・術中の管理を適切に行えば、非肥満症例と同様にTLHを安全に施行できる可能性が示唆された。(著者抄録)

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Language：Japanese   Publisher：(株)メディカルレビュー社  

わが国の若年女性は、やせの増加、肥満をはじめ脂質エネルギー比率の高い食事やカルシウム、鉄、葉酸などの必要な栄養素の摂取不足などさまざまな問題を抱えている。やせ、肥満はいずれも妊娠中の合併症を増加させ、次世代への影響も生じることが知られており、健やかな母子の視点から若年女性の妊娠前からの栄養問題の改善が望まれる。本稿ではわが国における若年女性の栄養を取り巻く諸問題について概説する。(著者抄録)

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Language：Japanese   Publisher：滋賀医科大学産科学婦人科学講座  

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Language：Japanese   Publisher：(一社)日本糖尿病・妊娠学会  

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Language：Japanese   Publisher：日本妊娠高血圧学会  

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Language：Japanese   Publisher：(公社)日本糖尿病協会  

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

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Language：Japanese   Publisher：(一社)日本IVF学会  

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

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Language：English   Publisher：(一社)日本癌治療学会  

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Language：English   Publisher：(一社)日本癌治療学会  

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Language：Japanese   Publisher：(株)医学書院  

＜文献概要＞●妊娠糖尿病に対する食事療法は推奨されるが,その具体的内容に関する根拠に乏しいのが現状である.●胎児の適切な発育を考慮に入れ,血糖コントロールを図る必要がある.●胎児の過剰発育予防の視点から,母体の肥満は特にハイリスク群として管理する必要がある.

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Language：Japanese   Publisher：(一社)日本糖尿病学会  

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

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

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

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

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

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

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

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

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Language：Japanese   Publisher：愛媛県産婦人科医会  

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Language：Japanese   Publisher：愛媛県産婦人科医会  

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Language：Japanese   Publisher：愛媛県産婦人科医会  

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Language：Japanese   Publisher：愛媛県産婦人科医会  

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Language：Japanese   Publisher：愛媛県産婦人科医会  

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Language：Japanese   Publisher：愛媛県産婦人科医会  

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Language：Japanese   Publisher：愛媛県産婦人科医会  

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

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

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Language：Japanese   Publisher：(株)メディカ出版  

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Language：Japanese   Publisher：日本医師会  

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Language：Japanese   Publisher：(一社)日本周産期・新生児医学会  

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Language：Japanese   Publisher：(一社)日本周産期・新生児医学会  

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