Surveys of postpartum depression in Miyagi, Japan, after the Great East Japan Earthquake.

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 ≥9 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 ≥9. 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.

The SRA protein Np95 mediates epigenetic inheritance by recruiting Dnmt1 to methylated DNA.

DNA methyltransferase (cytosine-5) 1 (Dnmt1) is the principal enzyme responsible for maintenance of CpG methylation and is essential for the regulation of gene expression, silencing of parasitic DNA elements, genomic imprinting and embryogenesis. Dnmt1 is needed in S phase to methylate newly replicated CpGs occurring opposite methylated ones on the mother strand of the DNA, which is essential for the epigenetic inheritance of methylation patterns in the genome. Despite an intrinsic affinity of Dnmt1 for such hemi-methylated DNA, the molecular mechanisms that ensure the correct loading of Dnmt1 onto newly replicated DNA in vivo are not understood. The Np95 (also known as Uhrf1 and ICBP90) protein binds methylated CpG through its SET and RING finger-associated (SRA) domain. Here we show that localization of mouse Np95 to replicating heterochromatin is dependent on the presence of hemi-methylated DNA. Np95 forms complexes with Dnmt1 and mediates the loading of Dnmt1 to replicating heterochromatic regions. By using Np95-deficient embryonic stem cells and embryos, we show that Np95 is essential in vivo to maintain global and local DNA methylation and to repress transcription of retrotransposons and imprinted genes. The link between hemi-methylated DNA, Np95 and Dnmt1 thus establishes key steps of the mechanism for epigenetic inheritance of DNA methylation.

Maternal undernutrition induces the expression of hypoxia-related genes in the fetal brain.

Maternal undernutrition during pregnancy is a risk factor for cerebrovascular and cardiovascular diseases in adulthood. Hypoxia-inducible factor 1 alpha (HIF1α) plays an essential role in cellular hypoxic responses, and its increased expression is associated with cerebrovascular and cardiovascular diseases. However, it is not known whether maternal undernutrition influences HIF1α expression in the fetal brain. We therefore analyzed the expression levels of HIF1α and its downstream genes in the fetal brain (day 17.5 of gestation, 1-2 days before birth). Maternal undernutrition did not noticeably affect the fetal body and brain weights. Both HIF1α mRNA and protein levels were increased in the brain under maternal undernutrition, despite the absence of hypoxia, as judged by the staining profile with hypoxyprobe-1 that identifies hypoxic cells. Importantly, maternal undernutrition caused the accumulation of HIF1α protein in oligodendrocyte precursor cells at the subventricular zone, a site of neurogenesis in the fetal brain. Maternal undernutrition also increased the mRNA level of mammalian target of rapamycin (mTOR), which could increase the level of HIF1α protein under normoxia. Furthermore, microarray analysis revealed that expression levels of mRNAs for 10 HIF1α downstream targets, including enolase 1 and hexokinase 1, were increased in the fetal brain under maternal undernutrition. Thus, the biochemical consequence of maternal undernutrition is similar to that of mild hypoxia. In conclusion, maternal undernutrition induces the expression of HIF1α in oligodendrocyte precursor cells at the subventricular zone, and it also induces the expression of hypoxia-related genes in the fetal brain probably via activation of the mTOR pathway.

Assessment of maternal heart-rate variability during labor using wavelet-based power spectral analysis.

OBJECTIVE: Changes in the maternal cardiac autonomic nervous system were assessed in the presence and absence of uterine contractions by analyzing maternal heart-rate variability during labor using wavelet-based power spectral analysis. METHODS: We assessed the heart-rate variability in 20 pregnant women during labor and in 15 pregnant women with threatened premature labor with the use of wavelet-based power spectral analysis. RESULTS: There was no significant difference in high-frequency components between the uterine contraction and non-contraction periods. The intensities of the low-frequency and very-low-frequency components during uterine contractions were significantly stronger than the corresponding intensities between uterine contractions. CONCLUSION: Maternal sympathetic activity was upregulated during uterine contractions, and influenced the very-low-frequency components. This method of analysis may represent a novel means of identifying uterine contractions.

Maternal undernutrition with vaginal inflammation impairs the neonatal oligodendrogenesis in mice.

Maternal undernutrition and infection during pregnancy may impair development of oligodendrocytes, thereby increasing risks of neuropsychiatric disorders of their children. We analyzed the effects of those risk factors on oligodendrogenesis in fetal and neonatal brains. Female mice were given low-protein or regular food for 2 weeks before their pregnancy. On the 14th day of pregnancy, they received a transvaginal injection of lipopolysaccharide to induce inflammation or control solution, consisting of four groups, depending on nutritional conditions with or without vaginal inflammation. We collected fetal brains on embryonic day (E) 17 for evaluating oligodendrocyte precursor cells (OPCs) and neonatal brains on postnatal day (P) 7 for evaluating mature oligodendrocytes. OPCs and mature oligodendrocytes were identified as positive immunostaining for oligodendrocyte-lineage transcription factor 2 and myelin basic protein, respectively. There was no difference in the number of OPCs in E17 brains among the four groups, suggesting that nutritional restriction with or without inflammation exerts no noticeable influence on the differentiation of OPCs. However, the number of mature oligodendrocytes was decreased in P7 brains obtained from nutrient-restricted mice with inflammation, suggesting that their combination impairs oligodendrogenesis in the neonatal brain. We also analyzed reactive astrocytes that express both glial fibrillary acidic protein and nestin for evaluating brain inflammation. The population of reactive astrocytes was increased in P7 brains derived from mice with LPS injection, irrespective of nutritional restriction, indicating that maternal vaginal inflammation induces neonatal brain inflammation. The maternal management of both nutrition and infection is crucial to prevent neuropsychiatric disorders of the children.

Successful detection of the fetal electrocardiogram waveform changes during various states of singletons.

Accurate assessment of fetal well-being is one of the most important tasks for obstetricians. It is still difficult to measure fetal electrocardiogram (ECG) during fetal movements. Recently, a new method, blind source separation with reference signals, was proposed for stable measurements. This method distinguishes weak signals from noisy mixed signals with little information about the sources. The aim of this study is to estimate the ability of this method for fetal ECG monitoring and to establish standard fetal ECG electrocardiogram values of normal singletons including during fetal movement. The subjects enrolled were 167 pregnant women with normal single pregnancy from 18- to 41-week gestation, who regularly visited Tohoku University Hospital, and 12 pregnant women with fetal abnormality. Fetal signals were successfully separated in 163 of 179 subjects at 91.1% success rate regardless of fetal movements. Time intervals of ECG (P, PR and QRS intervals and QTc) were measured. The standard curves of each interval through the gestational period were obtained. The data in active phase were compared to that in rest phase and the data obtained from normal and abnormal fetuses were investigated. PR intervals in the rest phase were prolonged compared to those in the active phase. Fetal ECG showed anomalous values such as PR interval or QTc prolongation in the abnormal fetuses. The fetal ECG was measured by the new method with or without fetal movements, and the standard fetal ECG values have been established. This study provides a foundation for further detailed clinical studies.

Aberrant expression of hypoxia-inducible factor 1α in the fetal heart is associated with maternal undernutrition.

Maternal undernutrition during pregnancy is a risk factor that impairs fetal growth and causes cardiovascular diseases. However, the underlying mechanism is still unknown. In this study, we evaluated the effect of maternal undernutrition on the expression levels of transcription factors in the fetal heart. Female mice were given low protein or regular food from 2 weeks before mating and during their pregnancy. The fetal hearts were collected on day 17.5 of gestation, about 1-2 days before birth. Maternal undernutrition resulted in a significant increase in the relative heart weight (heart weight/body weight) in female fetuses, but not in male fetuses. Microarray analysis revealed that expression levels of mRNAs for 133 transcription factors were changed in the fetal heart under maternal undernutrition. Among them, we focused on hypoxia-inducible factor 1 alpha (HIF1α) that is involved in the pathogenesis of cardiovascular diseases on adulthood. Quantitative real-time PCR analysis showed that the expression level of HIF1α mRNA was increased about 1.3-fold in male fetal heart under maternal undernutrition, but remained unchanged in female heart. Moreover, maternal undernutrition increased the mRNA level of prolyl hydroxylase 1 (PHD1), which contributes to degradation of HIF1α, in male heart but not in female heart. Immunohistochemical analysis showed the accumulation of HIF1α protein in the fetal heart of both sexes under maternal undernutrition, without the induction of HIF1α mRNA expression in female heart. These results suggest that maternal undernutrition may induce HIF1α expression in the fetal heart through the distinct mechanisms depending on the sex.

Understanding congenital heart defects through abdominal fetal electrocardiography: case reports and clinical implications.

AIMS: Congenital heart defects are the most common fetal structural anomalies of which a significant number remain unrecognized during postnatal life. Fetal electrocardiography (FECG) is an ideal clinical tool to complement ultrasonography for the screening and management of these cases where early and accurate diagnoses would allow definite rather than palliative treatment. The objective of this report was to correlate the particular FECG results found with the different types of congenital heart defects involved and to further demonstrate the usefulness of FECG in clinical settings. MATERIAL & METHODS: This is a report of four cases of prenatally diagnosed congenital heart defects seen at a university hospital in Sendai, Japan. Their complete and thorough evaluation included, among other tests, abdominal FECG analysis. RESULTS: The presence of premature ventricular contractions, a prolonged pre-ejection period (PEP > 75 msec), and prolonged QTc intervals (QTc > 440 msec) served as markers of hemodynamic alteration but were unlikely determinants of disease severity precluding further investigation. CONCLUSIONS: In practice, similar findings found on FECG should raise the index of suspicion for the presence of congenital heart disease and prompt a targeted ultrasound scan.

Neurobehavioral effects of prenatal exposure to methylmercury and PCBs, and seafood intake: neonatal behavioral assessment scale results of Tohoku study of child development.

As factors affecting neonatal neurodevelopment, methylmercury, polychlorinated biphenyls (PCBs), and maternal seafood intake reflecting n-3 polyunsaturated fatty acids (PUFAs) are believed to have adverse or beneficial effects, but there are a few reports addressing such factors simultaneously. We carried out a birth cohort study to clarify the effects of these three factors on the Neonatal Behavioral Assessment Scale (NBAS), administered 3 days after birth. In a total of 498 mother-neonate pairs, the total mercury level (median, 1.96microg/g) in maternal hair at parturition and the summation operatorPCB level (45.5ng/g-lipid) in cord blood were analyzed, and maternal seafood intake was estimated using a semi-quantitative food frequency questionnaire. A negative relationship between the hair mercury level and the motor cluster of NBAS was observed, even after adjusting for PCBs, maternal seafood intake, and possible confounders such as maternal age, birth weight, and parity. The summation operatorPCB level was negatively correlated with the motor cluster, but this association was attenuated after adjusting for mercury and the confounders. There was seen to be a positive association between maternal seafood intake and the motor cluster when considering the effects of mercury and PCBs. In conclusion, our data suggest that prenatal exposure to methylmercury adversely affects neonatal neurobehavioral function; in contrast, maternal seafood intake appears to be beneficial. The neurobehavioral effect of prenatal exposure to PCBs remains unclear in our study. Further research is necessary to elucidate interactive effects of methylmercury, PCBs, and n-3 PUFAs, originating from fish, on child neurodevelopment.

Steroid and Xenobiotic Receptor (SXR) as a possible prognostic marker in epithelial ovarian cancer.

We examined the expression of the steroid and xenobiotic receptor (SXR) and evaluated its clinical significance in human epithelial ovarian carcinoma. One hundred forty-one cases were examined using immunohistochemistry for SXR with archival specimens. All cases were scored using a semi-quantitative histological scoring (HSCORE) method. Specimens with an HSCORE > 60 were regarded as SXR-positive. Various clinicopathologic variables were examined. SXR showed significant differences in age, histology, grade, ER alpha and PR. SXR was detected in 35 of 141 (24.8%) ovarian cancer tissues. There was a statistically significant negative correlation between SXR-positive status and both disease-free survival and overall survival (P= 0.0415 and 0.0316, respectively), independent of stage (P= 0.0167 and 0.021, respectively). In multivariate analysis, SXR was a statistically independent risk factor for both disease-free survival and overall survival (P= 0.049 and 0.0354). Our results support an association of SXR between ER alpha and PR in epithelial ovarian cancers. Our data suggest that SXR is a prognostic factor in epithelial ovarian cancer and may represent a useful marker to identify patients at risk of recurrence or death.

The uterus sustains stable biological clock during pregnancy.

Maternal circadian information has been reported to play an important role in fetal physiology and development. Hormones and nutrition have been mainly investigated as circadian cues from mother to fetus. However, the influences of circadian properties of the pregnant reproductive organs on fetuses have not been fully investigated. To gain an insight on the circadian functions of the reproductive organs, we examined molecular clocks in the pregnant rat uterus and placenta. By using a Period1-luciferase (Per1-luc) rat, whose tissues express luciferase corresponding to activation of Period1, a "key clock gene", we examined the uterus clock during non-pregnancy, on embryonic day 12 (E12), and on E22 (the end of pregnancy) in a light-dark (LD) cycle and constant darkness (DD). By in situ hybridization we further explored Per1 mRNA rhythms in the placenta on E12 and E22. The uterus in vitro showed clear circadian Per1-luc rhythms both in and out of pregnancy, having peaks at around the time corresponding to dusk in LD. Likewise, in DD, the uterus in vitro had the same Per1-luc rhythms. The decidua in LD showed circadian Per1 mRNA rhythms, peaking during night 6 h after dusk, while the decidua in DD showed the same Per1 mRNA rhythms only on E22. In contrast, the labyrinth showed no circadian Per1 mRNA rhythms in LD or DD during pregnancy. These results suggest that the uterus and decidua, a maternally-originated tissue of the placenta, but not the labyrinth, a fetus-originated tissue of the placenta, can provide the fetus with circadian information.

Effects of antenatal steroid therapy on neurodevelopment in an IUGR mouse model.

BACKGROUND/OBJECTIVE: To investigate the neurodevelopmental response in postnatal mice secondary to antenatal steroid treatment in association with maternal protein restriction. METHODS: C57BL/6N pregnant mice (n = 24; 4 per treatment group) were administered control (C) or protein-restricted (PR) diets and subjected to daily subcutaneous injection stress during late gestation (E10-E17) with either 100 microl/kg of dexamethasone sodium phosphate in normosaline (C-D/S, PR-D/S) or normosaline alone (C-S, PR-S). Non-treatment groups were also included (C, PR). Brain samples of pups were collected on postnatal day 7 and analyzed by immunohistochemistry and qRT-PCR. RESULTS: Neonatal weights in the treatment groups were smaller than their counterparts in the C group, but there were no significant differences in brain size. Immunohistochemical evaluation of neuroglial cells revealed a pronounced effect of protein restriction on oligodendrocytes and oligodendrocyte precursor cells with distinct fetal responses to stress and dexamethasone. Further evaluation using quantitative RNA analysis showed significant activation of Galr1, Galr2, Igfbp-1, Igfbp-3, Igfbp-6, and Fgf2 by 1- to 2.5-fold in the PR-D/S group and by much higher increments, 1- to 10.5-fold, in the PR-S group. CONCLUSION: This preliminary investigation revealed the possible role of dexamethasone in further increasing vulnerability to cell damage in injury-prone neuroglial cells. The distribution of key glial markers and the overexpression of several neurotrophic factors depicted ongoing cellular adaptation.

Functional assessment of centrosomes of spermatozoa and spermatids microinjected into rabbit oocytes.

Although intracytoplasmic sperm injection (ICSI) is a widely used assisted reproductive technique, the fertilization rates and pregnancy rates of immature spermatids especially in round spermatid injection (ROSI) remain very low. During mammalian fertilization, the sperm typically introduces its own centrosome which then acts as a microtubule organizing center (MTOC) and is essential for the male and female genome union. In order to evaluate the function of immature germ cell centrosomes, we used the rabbit gamete model because rabbit fertilization follows paternal pattern of centrosome inheritance. First, rabbit spermatids and spermatozoa were injected into oocytes using a piezo-micromanipulator. Next, the centrosomal function to form a sperm aster was determined. Furthermore, two functional centrosome proteins (gamma-tubulin and centrin) of the rabbit spermatogenic cells were examined. Our results show that the oocyte activation rates by spermatozoa, elongated spermatids, and round spermatids were 86% (30/35), 30% (11/36), and 5% (1/22), respectively. Sperm aster formation rates after spermatozoa, elongated spermatids, and round spermatids injections were 47% (14/30), 27% (3/11), and 0% (0/1), respectively. The aster formation rate of the injected elongating/elongated spermatids was significantly lower than that of the mature spermatozoa (P = 0.0242). Moreover, sperm asters were not observed in round spermatid injection even after artificial activation. These data suggest that poor centrosomal function, as measured by diminished aster formation rates, is related to the poor fertilization rates when immature spermatogenic cells are injected.

Effect of intrauterine inflammation on fetal cerebral hemodynamics and white-matter injury in chronically instrumented fetal sheep.

OBJECTIVE: The purpose of this study was to analyze the effects of intrauterine inflammation on cerebral hemodynamics and white-matter injury in premature fetal sheep. STUDY DESIGN: Fetuses were given an intravenous infusion of granulocyte colony-stimulating factor and an intraamniotic infusion of endotoxin; the fetuses were then assigned randomly to an acute hemorrhage group, an exchange transfusion group, or a control group. During each insult, the cerebral hemodynamics were assessed with near-infrared spectroscopy. Finally, the fetuses were processed for neuropathologic analysis and compared statistically. RESULTS: Necrotizing funisitis and chorioamnionitis were induced in all the fetuses. A significant decrease in the blood oxygen content and an increase in the brain total hemoglobin level were observed after the endotoxin infusion. Soon after hemodynamic insult, the fetuses in both the acute hemorrhage and the exchange transfusion groups showed an abrupt decrease in the total brain hemoglobin level; 4 of the 5 fetuses in each treatment group, but none of the fetuses in the control group, exhibited periventricular leukomalacia. CONCLUSION: Hemorrhagic hypotension or anemic hypoxemia might induce a sudden cessation of fetal brain-sparing effects through progressive inflammatory hypoxemia, which results in focal white-matter injuries.

Seasonal trends of blood pressure during pregnancy in Japan: the babies and their parents' longitudinal observation in Suzuki Memorial Hospital in Intrauterine Period study.

OBJECTIVE: Blood pressure (BP) increases both in winter and in the last trimester of pregnancy. Some interaction seems to exist between season and gestational age. The present study observed home BP values during pregnancy with adjustment for seasonal variation and gestational age. METHODS: We observed 10353 home BP measurements from 101 normal pregnant women attending a maternity hospital in Japan. Home BP values were examined by mixed linear model adjusting for meteorological data and gestational age. RESULTS: The lowest home BP values were observed in the second trimester [mean (+/-standard deviation) systolic/diastolic BP, 101.8 +/- 7.9/59.8 +/- 5.8 mmHg at gestational week 20]. In the last trimester, home BP values gradually increased and the values after gestational week 26 were significantly higher than those at gestational week 20 (110.1 +/- 9.7/66.8 +/- 7.7 mmHg at gestational week 40). A 10 degrees C increase in daily minimum outdoor temperature was associated with a mean reduction of 2.5/2.5 mmHg (Delta systolic BP/Delta diastolic BP: 95% confidence interval, 2.3/2.4 to 2.6/2.7 mmHg) in home BP with adjustment for gestational age. The largest and smallest estimated home BP changes during pregnancy were 12.8/12.5 and 3.1/3.0 mmHg in pregnant woman who delivered in January and July, respectively. CONCLUSION: Interactions among BP, season and gestational age should be considered when evaluating BP in pregnant women. Risks associated with high BP might be underestimated in pregnant woman in summer who will deliver in winter.

A phase II multicenter trial of concurrent chemoradiotherapy with weekly nedaplatin in advanced uterine cervical carcinoma: Tohoku Gynecologic Cancer Unit Study.

The purpose of this study was to evaluate the effectiveness and safety of concurrent chemoradiotherapy using weekly nedaplatin for the treatment of locally advanced squamous cell carcinoma of the uterine cervix. Nedaplatin at 30 mg/m(2) was administered weekly 6 times with a concurrent external beam and intracavity radiotherapy. External beam radiation was delivered with a fraction dose of 2 Gy per day for 5 days a week during a 5-week period and intracavitary brachytherapy, of which the fraction size is 6 Gy to point A, was given once a week for a total of 4 times using a remote after-loading system. Forty-five patients were enrolled in this trial between April 2003 and December 2006. Of the 45 patients, 40 (88.9%) completed the scheduled treatment and were evaluated for efficacy and safety. Of these, 4 were stage Ib2, 12 were stage IIb, 18 were stage IIIb and 6 were stage IVa. The age distribution ranged from 27 to 79 years with a median age of 58. The 40 patients achieved an objective response, 36 (90%) a complete response and 4 (10%) a partial response. At a median follow-up of 29 months (range, 8-52), the 3-year progression-free and overall survival were 58.7% (95% confidence interval, 42-75%) and 78.0% (95% confidence interval, 56-90.0%), respectively. Acute toxicities were transient and rendered non-lethal. Of the 45 patients enrolled for the trial, only 3 (6.7%) had grade 4 leukopenia and neutropenia, respectively. Grade 3 diarrhea and nausea/ vomiting were observed in 2 (4.4%) and 1 (2.2%), respectively. These results indicate that weekly nedaplatin of 30 mg/m(2) with concurrent radiotherapy is an effective and well-tolerated regimen for advanced squamous cell carcinoma of the uterine cervix.

Intramanchette transport during primate spermiogenesis: expression of dynein, myosin Va, motor recruiter myosin Va, VIIa-Rab27a/b interacting protein, and Rab27b in the manchette during human and monkey spermiogenesis.

AIM: To show whether molecular motor dynein on a microtubule track, molecular motor myosin Va, motor recruiter myosin Va, VIIa-Rab27a/b interacting protein (MyRIP), and vesicle receptor Rab27b on an F-actin track were present during human and monkey spermiogenesis involving intramanchette transport (IMT). METHODS: Spermiogenic cells were obtained from three men with obstructive azoospermia and normal adult cynomolgus monkey (Macaca fascicularis). Immunocytochemical detection and reverse transcription-polymerase chain reaction (RT-PCR) analysis of the proteins were carried out. Samples were analyzed by light microscope. RESULTS: Using RT-PCR, we found that dynein, myosin Va, MyRIP and Rab27b were expressed in monkey testis. These proteins were localized to the manchette, as shown by immunofluorescence, particularly during human and monkey spermiogenesis. CONCLUSION: We speculate that during primate spermiogenesis, those proteins that compose microtubule-based and actin-based vesicle transport systems are actually present in the manchette and might possibly be involved in intramanchette transport.

Regional Birth Outcomes after the 2011 Great East Japan Earthquake and Tsunami in Miyagi Prefecture.

OBJECTIVES: This study was aimed to analyze post-disaster birth outcomes in coastal and inland regions of Miyagi Prefecture, Japan. METHODS: Primary data sets were compiled from birth records of obstetric facilities and 12,808 patients were analyzed for baseline birth outcomes by region. Regional risk analysis of the low-birth-weight rate and premature birth rate were conducted using multi-level logistic regression analysis. RESULTS: From overall baseline birth outcomes, a preterm birth rate was 4.6% and low-birth-weight rate was 8.8%. Regional analysis revealed that a preterm birth rate was 3.2% (coastal) and 5.0% (inland), respectively, and the rate of low birth weight was 6.5% in the coastal and 8.5% in the inland region. In the risk analysis of low-birth-weight rate and preterm birth rate, the risk in the coastal region could not be considered any higher than in the inland region (adjusted odds ratio 0.91 [0.73-1.14] and 0.85 [0.46-1.59], respectively). CONCLUSIONS: The incidence of preterm birth and low birth weight were not adversely affected by the disaster. Early transfer and intensive medical intervention may have led to those findings. Further survey will be necessary to determine the long-term effects in both mothers and children. Sugawara J , Iwama N , Hoshiai T , Tokunaga H , Nishigori H , Metoki H , Okamura K , Yaegashi N . Regional birth outcomes after the 2011 Great East Japan Earthquake and tsunami in Miyagi Prefecture. Prehosp Disaster Med. 2018;33(2):215-219.

Peroxisome proliferator-activated receptor gamma and growth inhibition by its ligands in uterine endometrial carcinoma.

PURPOSE: In this study, we evaluated the correlation between endometrial carcinoma and peroxisome proliferator-activated receptor gamma (PPARgamma) expression and assessed whether PPARgamma ligands influence carcinoma growth. EXPERIMENTAL DESIGN: We examined the presence and cellular distribution of PPARgamma protein in 42 normal endometria, 32 endometria with hyperplasia, and 103 endometria with endometrial carcinoma by immunohistochemistry. We then compared PPARgamma mRNA expression in endometrial carcinoma with that in normal endometria using real-time reverse transcription-PCR. We subsequently confirmed expression of PPARgamma mRNA by real-time reverse transcription-PCR and PPARgamma protein by immunoblotting in endometrial carcinoma cell lines (Ishikawa, Sawano, and RL95-2 cells). We further examined the effects of PPARgamma agonist 15-deoxy-Delta12,14-prostaglandin J2 (15d-PGJ2), a naturally occurring PPARgamma ligand, to these endometrial carcinoma cell lines. We also examined the status of apoptosis and p21 mRNA expression of these endometrial carcinoma cell lines following addition of 15d-PGJ2. RESULTS: PPARgamma immunoreactivity was detected in 11 of 23 (48%) of proliferative-phase endometrium, 14 of 19 (74%) of secretory-phase endometrium, 27 of 32 (84%) of endometrial hyperplasia, and 67 of 103 (65%) of carcinoma cases. PPARgamma immunoreactivity was significantly lower in endometrial carcinoma than in secretory-phase endometrium (P = 0.012) and endometrial hyperplasia (P = 0.006). There was a significant positive association between the status of PPARgamma and p21 expression in endometrial carcinoma (P < 0.0001). There was a significant negative association between the body mass index and PPARgamma labeling index of carcinoma tissue in the patients with endometrial carcinoma (P < 0.0001). PPARgamma mRNA was expressed abundantly in normal endometria but not in endometrial carcinoma. We showed that PPARgamma agonist 15d-PGJ2 inhibited cell proliferation and induced p21 mRNA of endometrial carcinoma cell lines. CONCLUSION: We showed the expression of PPARgamma in human endometrial carcinoma and the effects of PPARgamma ligand in endometrial carcinoma cells. These findings suggest that a PPARgamma ligand, 15d-PGJ2, has antiproliferative activity against endometrial carcinoma.

A novel extraction method of fetal electrocardiogram from the composite abdominal signal.

In contrast to the ultrasonic measurement of fetal heart motion, the fetal electrocardiogram (ECG) provides clinically significant information concerning the electrophysiological state of a fetus. In this paper, a novel method for extracting the fetal ECG from abdominal composite signals is proposed. This method consists of the cancellation of the mother's ECG and blind source separation with the reference signal (BSSR). The cancellation of the mother's ECG component was performed by subtracting the linear combination of mutually orthogonal projections of the heart vector. The BSSR is a fixed-point algorithm, the Lagrange function of which includes the higher order cross-correlation between the extracted signal and the reference signal as the cost term rather than a constraint. This realizes the convexity of the Lagrange function in a simple form, which guarantees the convergence of the algorithm. By practical application, the proposed method has been shown to be able to extract the P and T waves in addition to the R wave. The reliability and accuracy of the proposed method was confirmed by comparing the extracted signals with the directly recorded ECG at the second stage of labor. The gestational age-dependency of the physiological parameters of the extracted fetal ECG also coincided well with that of the magnetocardiogram, which proves the clinical applicability of the proposed method.