Kei Miyakoshi

Absent inner dynein arms in a fetus with familial hydrocephalus-situs abnormality

We report a family in which a healthy, unrelated couple had a male fetus with bilateral ventriculomegaly, a normal liveborn girl, a hydatidiform molar pregnancy, a female fetus with ventriculomegaly and situs abnormalities, and a male fetus with hydrocephalus, a three‐lobed left lung, and defective tracheal cilia with absent inner dynein arms and a single centriole. A mutation analysis of FOXJ1 and POLL in the last fetus with ciliary defect revealed no mutation within their coding regions. The presence of three affected fetuses of both sexes in a family with phenotypically normal parents suggests that the condition was inherited as an autosomal recessive trait. A thorough evaluation of the thoracic and abdominal situs is recommended before counseling a family of a child with hydrocephalus, because the recognition of situs defects may point to the diagnosis of primary ciliary defect and recurrence risk of 25% for siblings. This figure is much higher than the general risk of 1–2% for siblings of a patient with isolated hydrocephalus.

Cutoff value of 1 h, 50 g glucose challenge test for screening of gestational diabetes mellitus in a Japanese population.

A total of 2651 consecutive native Japanese women who underwent a glucose challenge test (GCT) were retrospectively investigated. GCT was performed between 24 and 27 weeks of gestation; each subject received a 50 g oral glucose load without regard to the fasting or fed state, followed by a determination of 1 h venous plasma glucose level. Women demonstrating GCT exceeding 130 mg/dl received a 75 g, 2 h oral glucose tolerance test to determine whether or not they had gestational diabetes mellitus (GDM). All women with GDM were treated with a strict diabetic protocol including insulin therapy. Forty-nine (1.8%) women were diagnosed to have GDM. The receiver-operator characteristic curve identified a GCT finding above 140 mg/dl as the cutoff value for detecting GDM, which showed a sensitivity and specificity of 96 and 76%, respectively. Our results suggest that the cutoff value of a 50 g GCT is 140 mg/dl to identify pregnancies with GDM in a Japanese population.

Prenatal ultrasound diagnosis of small-bowel torsion

Background We report a case of congenital small-bowel torsion detected by prenatal ultrasonographic examination. Case A 27-year-old primigravida was found to have a fetus with a small-bowel obstruction by ultrasound examination during the third trimester. At 35 weeks of gestation, she complained of absence of fetal activity. A nonstress test showed a nonreactive pattern with reduced baseline variability. Sonographic examination revealed heterogeneous echogenicity within the dilated bowel, and loss of peristalsis. Also noted was a small amount of fetal ascites. After birth, torsion of the dilated small bowel associated with ileal atresia was found at exploratory laparotomy. Conclusion Serial sonographic examinations with special attention to changes in the dilated bowel are useful in the management of prenatally diagnosed small-bowel obstruction.

Prenatal diagnosis of hemifacial microsomia by magnetic resonance imaging.

Abstract We present a case of hemifacial microsomia, first detected by prenatal sonography and confirmed by ultrafast magnetic resonance (MR) imaging. A 26-year-old patient was referred to our hospital at 20 weeks of gestation because of unilateral right-sided ventriculomegaly and of a possible ventriculoseptal defect (VSD). Our sonographic examination suggested a right orbital hypoplasia and a hemiatrophy of the nose. The ultrafast T2-weighted single-shot fast-spin echo MR imaging, demonstrated a right ear hypoplasia (microtia), a right orbital hypoplasia, and a right renal hypoplasia. Epibulbar dermoid or conjunctival lipodermoid were not recognized. The fetus was prenatally diagnosed as hemifacial microsomia. Termination of pregnancy was performed at 21 weeks gestation, and a male baby weighing 342g was stillborn. The baby showed facial asymmetry, including hemiatrophy of the right nose, and right ear hypoplasia. Autopsy revealed a 2mm area of VSD, agenesis of the right kidney and ureter, pancreatic and renal aberration into right adrenal gland, thymus hypoplasia and an unfixed ascending colon without intestinal malrotation. To the best of our knowledge, this is the first report of prenatal diagnosis for hemifacial microsomia using fetal MR imaging. In our case, fetal MR imaging has evolved into a powerful diagnostic tool, for the accurate prenatal diagnosis.

Role of β1 Integrins in Human Endometrium and Decidua during Implantation

The present study was undertaken to investigate the expression and function of β₁ integrins in human endometrium and decidua. Fluorescence-activated flow cytometry demonstrated the greater expression of the β₁, α₁, α₂, and α₅ subunits of the β₁ integrin family in cultured stromal cells from the midsecretory phase than in those of the early proliferative phase. The addition of estradiol (E₂) and progesterone (P) to cultured stromal cells in the early proliferative phase increased the expression of β₁ integrins in vitro. The immunohistochemical distribution of β₁ integrins demonstrated predominantly glandular epithelial staining in the proliferative phase, and stromal and glandular staining in the midsecretory phase. Flow cytometry also demonstrated the expression of β₁, α₁, α₂, α₃, α₅, and α₆ subunits of β₁ integrin family in cultured decidual cells. Immunohistochemistry confirmed the β₁ integrin cell surface phenotypes in cultured decidual cells observed by flow cytometry. In the subsequent experiment, the effects of antibodies against specific β₁ integrin heterodimers on mouse embryo attachment and spreading were tested to identify the role of β₁ integrins in early implantation. We developed assays for the attachment of mouse embryos and for trophoblastic spreading on cultured human decidual cells. The addition of antibodies directed against β₁ and α integrin subunits to cultured decidual cells did not affect the rates of hatching or attachment of the blastocysts, whereas the outgrowth of embryos on the decidual cells was inhibited by their antibodies in a dose-dependent manner. Thus, β₁ integrin in human endometrium and decidua may be important in mediating the organization of extracellular matrix proteins derived from embryos during the early stage of implantation.

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.

Fetal goitrous hypothyroidism followed by neonatal transient hyperthyroidism: A case report

We report a case of fetal goitrous hypothyroidism followed by neonatal transient hyperthyroidism. A fetal goiter (26 × 38 mm) was detected by ultrasound and magnetic resonance imaging at 29 weeks of gestation. Hypothyroidism was confirmed by cordocentesis, which revealed an elevated TSH (255 µIU/ml) and a low free T4 (0.4 ng/dl). The fetal goiter decreased in size after treatment with four 240-microgram intra-amniotic administrations of levothyroxine. A 2,829-gram male neonate was delivered vaginally at 37 weeks of gestation, showing an euthyroid status at birth. On day 3, free T3 was 6.9 pg/ml and free T4 was 6.4 ng/dl, indicating hyperthyroidism. This persisted for 4 months. His thyroid functions reverted to normal at 4 months of age and have been within normal range since. Undetermined factors might be involved in the development of thyroid dysfunction in the perinatal period.

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.