Kazuhiro Minegishi

Expression of Ovary-Specific Acidic Protein in Steroidogenic Tissues: A Possible Role in Steroidogenesis

Ovary-specific acidic protein (OSAP) is a novel molecule discovered from a genomic project designed to identify ovary-selective genes in mice. Whereas public databases suggest extraovarian expression of OSAP, its tissue distribution has not yet been well documented. Thus, the expression profile of mouse and human OSAP was determined by quantitative real-time RT-PCR using RNAs isolated from various tissues. The results demonstrate that the human and mouse OSAP expression profiles are similar; OSAP is prominently expressed in steroidogenic tissues with the highest level of expression observed in the adrenal gland. Placenta served as an exception and possessed minimal level of OSAP mRNA. Immunohistochemical studies show that mouse OSAP localizes almost exclusively to the steroid-producing cells of the ovary, adrenal gland, and testis. Consistent with predictions made by several subcellular localization algorithms, dual labeling studies in Y-1 mouse adrenocortical cells indicate OSAP resides in the mitochondria. Because of its abundant expression in steroidogenic cells and mitochondrial localization, a role for OSAP in steroidogenesis was determined. OSAP silencing by specific small interfering RNAs significantly inhibits 8-bromoadenosine-cAMP-induced progesterone production in Y-1 cells. Reduction in OSAP levels results in mitochondrial fragmentation and a decrease in the cellular content of mitochondrial DNA, indicative of decreased mitochondrial abundance. Lastly, 8-bromoadenosine-cAMP does not regulate OSAP protein expression in Y-1 cells as is the case for other steroidogenic components known to be induced by cAMP. Collectively these results suggest that OSAP is involved in steroidogenesis, potentially through its ability to maintain mitochondrial abundance and morphology.

Pregnancy Outcomes After Abdominal Radical Trachelectomy for Early-Stage Cervical Cancer: A 13-Year Experience in a Single Tertiary-Care Center.

Objective To investigate pregnancy outcomes in women after abdominal radical trachelectomy (RT) for early-stage cervical cancer. Methods The patients’ background, fertility, and pregnancy outcomes were reviewed in a total of 61 pregnancies in 48 of 172 women who underwent abdominal RT at Keio University Hospital between September 2002 and December 2013. Results There were 5 women with stage IA1, 2 with stage IA2, and 41 with stage IB1. Histological types were as follows: squamous cell carcinoma (n = 36), adenocarcinoma (n = 10), and adenosquamous cell carcinoma (n = 2). The pregnancy rate of women attempting to conceive after abdominal RT was 44% (48/109). The mean ± SD duration from abdominal RT to conception was 3.1 ± 1.9 years. Of 61 pregnancies, 42 pregnancies were achieved by fertility treatment (in vitro fertilization-embryo transfer, 39; intrauterine insemination, 3). After excluding one pregnancy without detailed clinical information, there were 42 live births (5 in 22–27 weeks, 11 in 28–33weeks, 20 in 34–36 weeks, and 6 in 37–38 weeks), 13 miscarriages, and 5 ongoing pregnancies. While there were 10 first trimester miscarriages, 3 pregnancies ended in the second trimester owing to chorioamnionitis. The mean gestational age at birth was 33 weeks of pregnancy. Thirty-seven neonates were appropriate-for-date, and one was small-for-date. Six pregnancies exhibited massive bleeding from the residual cervix in the late pregnancy. Preterm birth less than 34 weeks of pregnancy was related to premature rupture of the membrane (P < 0.05). Chorioamnionitis was evident in 9 of 11 pregnancies with preterm premature rupture of the membrane followed by birth at less than 34 weeks of pregnancy. No parturients exhibited lochiometra and endometritis postpartum. Conclusions Abdominal RT provided favorable pregnancy outcomes, and fertility treatment could be advantageous to conception. Massive bleeding from the residual cervix as well as ascending infection might be characteristic features during pregnancy after abdominal RT.

Pancreatic β-cell function and fetal growth in gestational impaired glucose tolerance

Objective. To investigate the metabolic phenotype and pregnancy outcomes of gestational impaired glucose tolerance (IGT) defined by isolated hyperglycemia during an oral glucose tolerance test (OGTT). Design. Retrospective cohort study. Setting. University referral hospital. Population. A total of 4,789 women were screened for gestational diabetes mellitus (GDM) between 1996 and 2008 with a glucose challenge test (GCT), followed by a 2‐hour 75‐g OGTT if the GCT result was abnormal; in addition, measurement of plasma insulin concentration during the OGTT was implemented from 2004. Methods. The insulin sensitivity (ISOGTT) and β‐cell function (insulinogenic index/homeostasis model assessment for insulin resistance) were calculated for 283 women who underwent a diagnostic OGTT between 2004 and 2008. Perinatal complications were examined in 4,789 women who were screened for GDM between 1996 and 2008. Main outcome measures. Comparison of outcomes among women stratified by glucose tolerance status using the GCT and OGTT profiles. Results. Insulin sensitivity and β‐cell function significantly decreased from normal OGTT to 2‐hour IGT (single hyperglycemia at 2 hours) to 1‐hour IGT (single hyperglycemia at 1 hour) to GDM, with significant differences between normal OGTT and 1‐hour IGT or GDM. The occurrence of large‐for‐gestational age (LGA) neonates was significantly increased in women with GDM or 1‐hour IGT (adjusted odds ratio: 2.15, 2.22; 95% confidence interval 1.23–3.75 and 1.04–4.35, respectively) compared to those with normal GCT or normal diagnostic OGTT results. Conclusions. Like GDM, isolated 1‐hour hyperglycemia on the OGTT is associated with β‐cell dysfunction and an increased risk for LGA neonates.

Comparison of the right and left ventricular performance during the fetal development using velocity vector imaging

BACKGROUND Studies on myocardial characteristics examined by speckle-tracking echocardiography are limited. AIMS To compare myocardial performance between the right and left ventricles during the fetal development using velocity vector imaging (VVI). SUBJECTS AND STUDY DESIGN Echocardiograms of 95 uncomplicated singleton fetuses (19-36 weeks pregnancy) were retrospectively analyzed by VVI to measure global longitudinal peak velocity, strain, and strain rate of both the right ventricle (RV) and left ventricle (LV). The regional values were calculated for three segments (base, mid, and apex) of the ventricular free wall and segment. OUTCOME MEASURES The VVI-derived measurements were examined for gestational age and compared between ventricles. RESULTS The global peak systolic and diastolic velocity values of both ventricles significantly increased over gestation examined, whereas the global systolic strain and strain rate were stable (RV: strain -22.6 ± 5.0%, strain rate -2.6 ± 0.7/s; LV: strain -21.5 ± 5.6%, strain rate -2.5 ± 0.7/s). Compared to the LV, the RV showed significantly higher global velocity in systole and diastole (P = 0.001 for systole, P < 0.001 for diastole). The global systolic velocity of the LV increased close to the RV toward term, whereas the RV was dominant in diastole throughout the examined gestation. Basal strain and strain rate in the RV were significantly greater than that of the LV, although there were no significant differences in the middle and apical values between ventricles. CONCLUSION Our findings suggest the RV predominance of longitudinal contraction and dilatation, compared to the LV in uncomplicated fetuses.

The Periphery of the Human Fetal Adrenal Gland Is a Site of Angiogenesis: Zonal Differential Expression and Regulation of Angiogenic Factors

CONTEXT Although the inner fetal zone (FZ) of the mid-gestation human fetal adrenal (HFA) produces dehydroepiandrosterone sulfate, the function of the outer definitive zone (DZ) remains less clear. We have proposed that the DZ phenotype is that of a pool of progenitor cells, many of which are mitotically active. Recently, we studied HFA expression of a family of vascular endothelial cell-specific angiogenic factors, the angiopoietins (Angs), and demonstrated that Ang2 was localized predominantly in the periphery of the gland. Ang1 stabilizes, whereas Ang2 destabilizes, vessels, increasing responsiveness to angiogenic stimuli such as vascular endothelial growth factor (VEGF)-A and fibroblast growth factor (FGF)-2. OBJECTIVE Our objective was to test the hypothesis that the periphery of the HFA is a site of angiogenesis. DESIGN Studies were conducted involving RNA, frozen sections, and primary cell cultures from midgestation HFAs. MAIN OUTCOME MEASURES Immunofluorescence, laser capture microdissection, and real-time quantitative RT-PCR were used. RESULTS Double immunostaining demonstrated that proliferating endothelial cells were limited to the DZ and DZ/FZ border. Ang2 mRNA was primarily expressed in the DZ, whereas Ang1 mRNA was primarily in the FZ. VEGF-A and FGF-2 mRNA levels were higher in the DZ. FGF-2 (10 ng/ml) induced Ang2 mRNA by 4-fold in both zones of cells (P < 0.01, at 24 h), but not Ang1 or VEGF-A mRNA. CONCLUSION Data suggest that angiogenesis occurs at the periphery of the HFA. The DZ-predominant expression of Ang2 may be explained, in part, by the parallel pattern of FGF-2 expression.

Occipital scalp hemangioma: prenatal sonographic and magnetic resonance images.

Fetal scalp hemangioma in the occipital region is extremely rare and its accurate diagnosis is essential for perinatal management. We present a case of occipital scalp hemangioma diagnosed by prenatal sonography and magnetic resonance imaging (MRI). An echogenic mass measuring 29 mm × 23 mm × 30 mm was found in the occipital region by sonography at 20 weeks of gestation. Color‐flow Doppler sonography depicted vascularity only at the periphery of the mass. The MRI results indicated that the extracranial mass exhibited a heterogeneous appearance of predominantly hyperintensity on T1‐ and hypointensity on T2‐weighted images without evidence of fat signals, suggesting a soft tissue lesion containing blood products. Based on sonographic and MRI findings, the fetus was diagnosed to have occipital scalp hemangioma. Postmortem examination revealed cavernous hemangioma with hemorrhage. The MRI was a valuable adjunct to sonography for prenatal evaluation of an occipital lesion.

Perinatal outcomes: Intravenous patient‐controlled fentanyl versus no analgesia in labor

To investigate perinatal outcomes, the analgesic efficacy and maternal satisfaction in nulliparous women receiving fentanyl intravenous patient‐controlled analgesia (i.v.‐PCA).

Prenatal diagnosis of retroperitoneal teratoma: a case report and review of the literature.

We report a case of retroperitoneal teratoma diagnosed prenatally by serial sonographic examinations in the third trimester. A 29-year-old woman was referred for sonographic evaluation at 33 weeks’ gestation because of a fetal intra-abdominal mass. Our initial sonographic image suggested a neuroblastoma. Repeat ultrasound images demonstrated an increase in size of the tumor, while the content of the tumor became predominantly solid with areas of calcification. Teratoma should be considered on detection of any cystic or mixed semisolid mass, especially when calcification is present. The fetus was prenatally diagnosed with retroperitoneal teratoma. After birth at 39 weeks, the tumor was removed and histological analysis revealed an immature retroperitoneal teratoma. Intensive monitoring of the changes in ultrasound images of the tumor should provide ground for a precise antenatal diagnosis.

Antepartum oral disposition index as a predictor of glucose intolerance postpartum.

Although women with gestational diabetes mellitus (GDM) have an increased subsequent risk for diabetes, the diabetic risk might be heterogeneous because the degree of abnormal glucose metabolism varies. The glucose tolerance status in pregnancy is related with postpartum prediabetes or diabetes, whereas studies on the antepartum factors associated with dysglycemia postpartum are limited (1,2). Women with GDM should be screened for diabetes postpartum; however, some miss the follow-up for the glucose surveillance. β-Cell function contributes to the development of glucose intolerance, and the oral glucose tolerance test (OGTT)-derived measures for β-cell function (i.e., oral disposition index [DIo]) seem to be predictive of developing diabetes (3). Likewise, the DIo during pregnancy might have potential to predict glucose intolerance postpartum. Therefore, we investigated the relation …

Mid‐trimester residual cervical length and the risk of preterm birth in pregnancies after abdominal radical trachelectomy: a retrospective analysis

To investigate the association between mid‐trimester residual cervical length (CL) and the risk of preterm birth in pregnancies after abdominal radical trachelectomy (RT).