[show abstract][hide abstract] ABSTRACT: The present study examined the association between food intake and endometrial cancer restricted to endometrial endometrioid adenocarcinoma (EEA) using a case-control study in Japanese women. One hundred sixty-one cases and 380 controls who completed a questionnaire regarding demographic, lifestyle, and food frequency questionnaire were analyzed. Odds ratio (OR) between selected food intakes and EEA were calculated by logistic regression analysis. After adjustment putative confounding factors, the higher intakes of vegetables [odds ratio (OR) = 0.47, 95% confidence interval (CI) = 0.26-0.83], peanuts (OR = 0.48, CI = 0.27-0.86), fish (OR = 0.52, CI = 0.29-0.93), boiled egg (OR = 0.24, CI = 0.33-0.92), instant noodles (OR = 1.94, CI = 1.12-3.34), instant food items (OR = 2.21, CI = 1.31-3.74), and deep-fried foods (OR = 2.87, CI = 1.58-5.21) were associated with a risk for EEA. The inverse association with a risk of EEA was also seen in higher intakes (g/1000 kcal) for vegetables (0.45, CI = 0.25-0.81) and fish (0.53, CI = 0.30-0.94) as compare to lower intake. Higher intake of vegetables, peanuts, fish, and boiled egg was associated with a reduced risk for EEA, whereas instant noodles, instant food items, and deep-fried foods was associated with an increased risk for EAA as compared to lower levels of intake.
Nutrition and Cancer 09/2013; · 2.70 Impact Factor
[show abstract][hide abstract] ABSTRACT: Although there are some reports that low plasma volume or increased cardiac output is associated with developing preeclampsia, there are few reports of daily serial hemodynamic data during pregnancy. A total of 37,092 home blood pressure (BP) and heart rate (HR) measurements were obtained from 425 normal pregnant women. Heart rate and shock index (SI) gradually increased by gestational week 32 and then decreased, whereas double product (DP) increased linearly during pregnancy. Although systolic BP and DP were consistently and negatively correlated with daily minimum outside temperature, HR and SI were positively correlated with minimum outside temperature in summer.
Clinical and Experimental Hypertension 05/2012; 34(4):290-6. · 1.28 Impact Factor
[show abstract][hide abstract] ABSTRACT: Objective: To investigate the efficacy of recombinant human soluble thrombomodulin (rTM) in disseminated intravascular coagulation (DIC) associated with severe postpartum hemorrhage (PPH). Patients and Methods: We conducted a retrospective review of 36 patients with severe PPH complicated by DIC admitted to a single tertiary center. The first 26 patients were treated without rTM (control group), and the next 10 consecutive patients were treated with rTM. Clinical parameters including bleeding symptoms and coagulation indices were evaluated. Results: Baseline characteristics, total blood loss, and transfusion requirements were similar between the 2 groups. On day 2, there was a significant difference between the 2 groups in the decrease in d -dimer level from baseline. The incidence of bleeding symptoms was decreased in the rTM group compared with the control group. No adverse events were observed in the rTM group. Conclusion: Recombinant human thrombomodulin may be an effective adjunctive therapy in the management of DIC related to PPH.
Clinical and Applied Thrombosis/Hemostasis 04/2012; · 1.02 Impact Factor
[show abstract][hide abstract] ABSTRACT: 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.
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.
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.
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.
Gynecologic and Obstetric Investigation 03/2012; 74(1):35-40. · 1.10 Impact Factor
[show abstract][hide abstract] ABSTRACT: Aberrant DNA methylation leads to loss of heterozygosity (LOH) or loss of imprinting (LOI) as the first hit during human carcinogenesis. Recently we developed a new high-throughput, high-resolution DNA methylation analysis method, bisulphite PCR-Luminex (BPL), using sperm DNA and demonstrated the effectiveness of this novel approach in rapidly identifying methylation errors.
In the current study, we applied the BPL method to the analysis of DNA methylation for identification of prognostic panels of DNA methylation cancer biomarkers of imprinted genes. We found that the BPL method precisely quantified the methylation status of specific DNA regions in somatic cells. We found a higher frequency of LOI than LOH. LOI at IGF2, PEG1 and H19 were frequent alterations, with a tendency to show a more hypermethylated state. We detected changes in DNA methylation as an early event in ovarian cancer. The degree of LOI (LOH) was associated with altered DNA methylation at IGF2/H19 and PEG1.
The relative ease of BPL method provides a practical method for use within a clinical setting. We suggest that DNA methylation of H19 and PEG1 differentially methylated regions (DMRs) may provide novel biomarkers useful for screening, diagnosis and, potentially, for improving the clinical management of women with human ovarian cancer.
BMC Medical Genomics 03/2012; 5:8. · 3.47 Impact Factor
[show abstract][hide abstract] ABSTRACT: 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.
The Tohoku Journal of Experimental Medicine 01/2012; 226(1):37-44. · 1.37 Impact Factor
[show abstract][hide abstract] ABSTRACT: Since the first observations of Cremer in 1906, fetal electrocardiogram (ECG) measurements via the maternal abdominal wall have remained a formidable challenge for clinical technicians and engineers in the cutting-edge field of information theory.
Previous obstacles in extracting fetal ECG still complicate their acquisition at the present. These include three main difficulties for non-invasive measurement of fetal ECG: first, the low signal to noise ratio; second, the lack of a standard lead system for fetal ECG on the maternal abdomen; and third, the factor of fetal movement or non-stationarity during recording. A new extraction system based on blind source separation with reference signals (BSSR) was utilized and our detection rates, both off-line (91%) and on-line (60%), in pregnancies of 20 to 41 weeks of gestation have shown a marked improvement from earlier attempts. With this development, we discuss the potentials and limitations of this new system.
[show abstract][hide abstract] ABSTRACT: 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.
The Tohoku Journal of Experimental Medicine 01/2011; 225(2):89-94. · 1.37 Impact Factor
[show abstract][hide abstract] ABSTRACT: 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.
The Tohoku Journal of Experimental Medicine 01/2011; 224(3):163-71. · 1.37 Impact Factor
[show abstract][hide abstract] ABSTRACT: Both a decrease in endovascular trophoblastic invasion and impaired vascular remodeling of spiral arteries have been cited as possible pathogenetic factors in preeclampsia. The resultant reduction in uteroplacental perfusion consequent to shallow implantation could lead to an hypoxic placenta that releases cytokines and reactive oxygen species, initiating vascular and endothelial dysfunction. Endothelial progenitor cells (EPCs) have been identified in the maternal circulation and, once recruited and mobilized from the bone marrow, are able to restore an intact endothelial lining. There are reports of fewer and less functional EPCs in patients having other disorders, including cardiovascular disease and diabetes.
The investigators counted circulating EPCs and assessed their senescence in 8 women with preeclampsia, defined as the development of a blood pressure of 140/90 mm Hg or higher and proteinuria exceeding 300 mg/24 hour after 20 weeks gestation. EPCs were counted by the colony-forming unit (CFU) method, and cellular senescence was estimated by measuring endogenous β-galactosidase activity. In addition, serum levels of the inflammatory marker C-reactive protein (CRP) were determined.
EPCs were identified as spindle-shaped cells sprouting from colonies of cultured peripheral blood mononuclear cells. Preeclamptic women, compared with normal control women, had decreased numbers of circulating EPCs (median, 10 vs 34 CFU, P < .01). In addition, the rate of cellular senescence was significantly enhanced in the preeclamptic group (33.9% vs 22.9%). EPC CFU counts were markedly decreased in women whose serum CRP levels were 0.l mg/dL or higher than in CRP-negative patients (5 vs 25 CFU). Median values for cellular senescence were greater in the CRP-positive group but not to a significant degree.
These findings clearly point to reduced numbers of EPCs in preeclamptic women and indicate that those cells that are present tend to be more senescent than those without this disorder. These abnormalities are associated with elevated circulating levels of CRP, a marker of systemic inflammation.
Obstetrical and Gynecological Survey 06/2006; 61(7):460-461. · 2.51 Impact Factor
[show abstract][hide abstract] ABSTRACT: A frequent cause of fetal acidemia, which sometimes results in hypoxic-ischemic encephalopathy, is umbilical cord compression associated with uterine contraction. Using a sheep model of fetal acidemia, we examined the changes in electrocorticogram (ECoG), carotid artery blood flow, arterial blood pressure and fetal heart rate during cord compression. A characteristic burst of ECoG spikes emerged during cord compression at fetal arterial pH 7.18 even before the pH went down to severe fetal acidemia (less than 7.10). The administration of a neuromuscular blocking agent to the fetus did not abolish the appearance of the spikes. These results suggest that cord compression may cause abnormal brain excitement even in the absence of severe fetal acidemia and that this abnormal excitement can lead to fetal brain dysfunction, if cord compression is repeated or prolonged.
The Tohoku Journal of Experimental Medicine 02/2006; 208(1):9-17. · 1.37 Impact Factor
[show abstract][hide abstract] ABSTRACT: To evaluate fetal myocardial movement by using newly developed ultrasonic technique.
We analyzed 50 normal fetuses between 25 and 41 weeks' gestation for changes in thickness of fetal myocardium using the phased-tracking method, a technique with high vertical distance resolution and the potential to evaluate fine ventricular wall movements. We analyzed differences in the rate of change in ventricular wall thickness and in changes in the inner and outer wall layers with advancing gestation. We also analyzed myocardial thickening period and evaluated the ratio of increasing thickness period to stroke interval.
Mean thickness changing rate was significantly higher in the right (1.18 +/- 0.34 m/s/m) than in the left ventricular wall (0.86 +/-0.31 m/s/m) (p < 0.001). Mean ratio of increasing thickness period to stroke interval was significantly higher in the right (0.57 +/- 0.064) than in the left ventricle (0.46 +/- 0.075) (p < 0.001), indicating that myocardial contraction in the fetal right ventricle predominates. The thickness-changing rate of the bilateral ventricular walls was positively and linearly correlated with gestational age. The myocardial-wall thickness-changing rate was higher in the outer layer than in the inner layer in late gestation.
We conclude that measurement of the thickness-changing rate of fetal ventricular walls using the phased-tracking method might be useful for evaluation of fetal cardiac function.
Fetal Diagnosis and Therapy 01/2006; 21(5):458-65. · 1.90 Impact Factor
[show abstract][hide abstract] ABSTRACT: In preeclampsia, the precise mechanism of impaired vascular function is still unclear. We hypothesized that cellular function of circulating endothelial progenitor cells (EPCs) might be impaired in patients with preeclampsia.
The objective of this study was to investigate the number and status of cellular senescence of EPCs in the circulation of women with preeclampsia.
Circulating EPCs were cultured from patients with preeclampsia (n = 8) and normotensive pregnant women (n = 7). EPC numbers were assessed by colony-forming unit (CFU) methodology as previously reported. In addition, to assess cellular senescence, we measured endogenous beta-galactosidase activity. Moreover, we assessed whether the serum level of C-reactive protein (CRP), a marker for systemic inflammation, was associated with cellular impairment of EPCs.
The number of circulating EPCs was decreased in women with preeclampsia controls (median, 10.0 vs. 34.0 CFU; P < 0.01). The rate of cellular senescence was significantly increased in patients with preeclampsia (33.9%) compared with that in controls (22.9%; P < 0.05). Patients with preeclampsia were divided into two subgroups: the CRP-negative group (CRP, <0.1 mg/dl; n = 4) and the CRP-positive group (CRP, > or =0.1 mg/dl; n = 4). Interestingly, EPC CFU counts were markedly decreased in CRP-positive patients compared with those in CRP-negative patients (5.0 and 25.0 CFU, respectively; P < 0.05). Median values for cellular senescence were greater in the CRP-positive group than in the CRP-negative group, although this did not achieve statistical significance (43.5% and 33.3%, respectively; P = 0.12).
Depletion and cellular aging of EPCs in patients with preeclampsia might be associated with endothelial dysfunction and could be affected by systemic inflammation.
[show abstract][hide abstract] ABSTRACT: Ectopic pregnancy developing in a previous Cesarean section scar is rare and is associated with catastrophic complications, such as uterine rupture and uncontrollable bleeding, which may lead to loss of the uterus. The operative treatments that have been reported for cesarean scar pregnancy are dilatation and curettage and excision of trophoblastic tissues using either laparotomy or laparoscopy. Recently, conservative treatment of scar pregnancy with locally and/or systemically administered methotrexate (MTX) has been reported. However, recent reports demonstrated that cases treated with MTX sometimes required laparotomy later because of excessive bleeding. In this series of cases we have demonstrated that viable cesarean scar pregnancies can be treated safely by selective transarterial embolization in combination with subsequent dilatation and curettage and local or systemic injections of MTX. In these three cases, uterine artery embolization proved to be a useful procedure for preventing uncontrollable bleeding and unnecessary uterine loss.
The Tohoku Journal of Experimental Medicine 08/2005; 206(3):261-5. · 1.37 Impact Factor
[show abstract][hide abstract] ABSTRACT: The precise molecular and cellular mechanisms that regulate maternal vascular development during gestation are largely unknown. Endothelial progenitor cells (EPCs), which play an important role in vascular homeostasis, have been discovered in the circulation. We examined the level of circulating EPCs throughout uncomplicated pregnancies (n = 20) and assessed the correlation between serum estradiol levels and the number of EPCs. The number of circulating EPCs increased gradually and paralleled the progression of gestational age. In addition, the number of EPCs correlated significantly with the level of serum estradiol. The present study suggests that EPCs may play an important role in the regulation and maintenance of the placental development and vascular integrity during pregnancy.
[show abstract][hide abstract] ABSTRACT: The physiological significance of spectral and fractal components of spontaneous heart rate (HR) variability in the fetus remains unclear. To examine the relationship between circadian rhythms in different measures of HR variability, R-R interval time series obtained by fetal ECGs were recorded continuously over 24 h in five pregnant sheep at 116-125 days gestation. Conventional measures of short-term (STV) and long-term variability (LTV), low-frequency (LF; 0.025-0.15 cycles/beat) and high-frequency (HF; 0.2-0.5 cycles/beat) spectral powers, the LF-to-HF ratio, and fractal dimension values were calculated from 24-h ECG recordings and quantified every 60 min. STV, LTV, and LF and HF spectral powers were minimal during the day but increased significantly to their highest values at night. We found a significant positive correlation between these measures, whereas the cosinor method showed significant similarity between their circadian rhythm patterns. Fetal R-R intervals also exhibited fractal structures. Fetal HR variability had a fractal structure, which was similar between day and night. These results suggested that the circadian rhythms exhibited by STV and LTV during the day were mainly due to changes in frequency components rather than to fractal components of fetal HR fluctuation.
[show abstract][hide abstract] ABSTRACT: The objective of this study was to examine whether the fetal baroreceptor reflex contributed to the low frequency component (LF: 0.025-0.125 cycles/beat) of fetal heart rate fluctuations.
Sheep fetuses in late gestation with normoxemia were used. The baroreceptor function was expressed as the baroreceptor reflex sensitivity (BRS) based on the change of the R-R interval in response to the elevation of blood pressure by noradrenaline (Nor-Ad). A frequency analysis was conducted by the autoregression method on heart rate fluctuations and blood pressure fluctuations in 300 stable heart beats immediately before the Nor-Ad test. The gain and the coherence from blood pressure LF to heart rate LF were calculated. The correlations between the BRS and the power values of heart rate LF, blood pressure LF, and the gain or the coherence were examined.
The BRS and the gain showed a positive correlation (p < 0.01). There was a negative correlation between the heart rate LF and the BRS, and between the blood pressure LF and the BRS (p < 0.01, p < 0.005).
This study showed that fetal BRS was involved in the change of LF in fetal heart rate fluctuation. Baroreceptor function should be considered when examining the change of LF domain in fetal heart beat fluctuation.
Gynecologic and Obstetric Investigation 01/2003; 55(3):156-61. · 1.10 Impact Factor