Aryl Hydrocarbon Receptor and Dioxin-Related Health Hazards-Lessons from Yusho.

Poisoning by high concentrations of dioxin and its related compounds manifests variable toxic symptoms such as general malaise, chloracne, hyperpigmentation, sputum and cough, paresthesia or numbness of the extremities, hypertriglyceridemia, perinatal abnormalities, and elevated risks of cancer-related mortality. Such health hazards are observed in patients with Yusho (oil disease in Japanese) who had consumed rice bran oil highly contaminated with 2,3,4,7,8-pentachlorodibenzofuran, polychlorinated biphenyls, and polychlorinated quaterphenyls in 1968. The blood concentrations of these congeners in patients with Yusho remain extremely elevated 50 years after onset.

A rare association of left pulmonary artery sling with right pulmonary hypoplasia and total anomalous pulmonary venous connection.

We present the second reported case of left pulmonary artery sling with dextrocardia, right pulmonary hypoplasia, and total pulmonary venous connection in a fetus. This case highlights the importance of the determination of pulmonary artery arrangement by fetal echocardiography if right pulmonary hypoplasia and/or congenital heart disease is suspected.

Prenatal Sonographic Image of Sirenomelia with Anencephaly and Craniorachischisis Totalis.

Sirenomelia is a rare congenital malformation characterized by varying degrees of fusion of the lower extremities. It is commonly associated with severe urogenital and gastrointestinal malformations; however, the association of sirenomelia with anencephaly and rachischisis totalis is extremely rare. To our knowledge, the prenatal sonographic images of this association have not been previously published.

Prenatal Diagnosis of Criss-Cross Heart Using 4-Dimensional Color Doppler Rendering.

Criss-cross heart is a rare congenital cardiac anomaly characterized by the crossing of two ventricular inflow streams. We have demonstrated the utility of 4-dimensional color Doppler rendering in diagnosing the criss-cross heart in a fetus. Four-dimensional color Doppler rendering can demonstrate the relative direction of intracardiac blood flows and facilitate recognition of the crossover of inflow streams in the same plane, confirming the criss-cross heart diagnosis in the fetus.

Current state of yusho and prospects for therapeutic strategies.

The mass food poisoning incident yusho occurred in Japan in 1968. It was caused by the ingestion of rice bran oil contaminated with polychlorinated biphenyls and various dioxins and dioxin-like compounds including polychlorinated dibenzo-p-dioxins and polychlorinated dibenzofurans (PCDFs). Notably, PCDFs were found to contribute to approximately 65% of the total toxicity equivalent in the blood of yusho patients.

The Vernix Caseosa is the Main Site of Dioxin Excretion in the Human Foetus.

Dioxins are highly toxic to foetuses and prenatal exposure leads to adverse health effects; however, the metabolic pathways involved in dioxin excretion are poorly understood. We determined the dynamics of maternal-to-foetal dioxin transfer during normal pregnancy and how foetuses eliminate polychlorinated dibenzo-p-dioxins, polychlorinated dibenzofurans, and non-ortho polychlorinated biphenyls. Dioxin levels in maternal blood, cord blood, placenta, vernix caseosa, meconium, and amniotic fluid were analysed by high-resolution gas chromatography/mass spectrometry.

Analysis of antenatal-onset cerebral palsy secondary to transient ischemia in utero using a national database in Japan.

Aim: We conducted a retrospective analysis of summary medical reports of children diagnosed with cerebral palsy (CP) to identify clinical features of antenatal onset of CP secondary to transient ischemia in utero.

Methods: The 658 brief summary reports available in the Japan Obstetric Compensation System for Cerebral Palsy were screened, and we identified cases of singleton pregnancy, delivered at gestational age ≥ 33 weeks and those with cord blood gas pH ≥ 7.20.

[Relationships between Half-Lives of Dioxins and SNPs in AhR among Yusho Patients].

Half-lives of blood levels of 2,3,4,7,8-Pentachlorodibenzofuran (PeCDF) are varied in Yusho patients. The objective was to evaluate a relationship between half-lives of PeCDF levels and types of SNP rs10249788 of aryl hydrocarbon receptor (AHR) gene in 93 Yusho patients. Based on physical symptoms, age, sex, body mass index and other factors, we set up suitable calculation formulas to fit the actual PeCDF levels thorough rates of change in PeCDF.

Yusho and its latest findings-A review in studies conducted by the Yusho Group.

The Yusho incident is an unprecedented mass food poisoning that occurred in Japan in 1968. It was caused by the ingestion of rice bran oil contaminated with polychlorinated biphenyls (PCBs) and various dioxins and dioxin-like compounds, such as polychlorinated dibenzo-p-dioxins (PCDDs) and polychlorinated dibenzofurans (PCDFs). The victims of Yusho have suffered from characteristic skin manifestations associated with systemic, ophthalmological, and mucosal symptoms for a long period of time.

Aryl hydrocarbon receptor SNP -130 C/T associates with dioxins susceptibility through regulating its receptor activity and downstream effectors including interleukin 24.

Dioxins are persistent environmental pollutants that cause multiple adverse health effects in humans, mainly through binding to the ligand-activated transcription factor, aryl hydrocarbon receptor (AhR). Genetic variation in AhR may modulate the susceptibility to dioxins. In this study, we aimed to evaluate the effects of the single nucleotide polymorphism (SNP) -130 C/T in the AhR promoter on dioxin-inducible gene transcription, and to investigate interleukin-24 (IL-24) and interleukin-1β (IL-1β) as proxies for 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) exposure.

2,3,4,7,8-Pentachlorodibenzofuran is far less potent than 2,3,7,8-tetrachlorodibenzo-p-dioxin in disrupting the pituitary-gonad axis of the rat fetus.

The effect of 2,3,4,7,8-pentachlorodibenzofuran (PnCDF) on the fetal pituitary-gonad axis was compared with that produced by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in Wistar rats. Maternal treatment at gestational day (GD) 15 with PnCDF and TCDD reduced the fetal expression at GD20 of pituitary luteinizing hormone (LH) and the testicular proteins necessary for steroidogenesis. The relative potencies of PnCDF ranged from 1/42nd to 1/63rd of the TCDD effect.

Selenium-binding protein 1: its physiological function, dependence on aryl hydrocarbon receptors, and role in wasting syndrome by 2,3,7,8-tetrachlorodibenzo-p-dioxin.

Background: Selenium-binding protein 1 (Selenbp1) is suggested to play a role in tumor suppression, and may be involved in the toxicity produced by dioxin, an activator of aryl hydrocarbon receptors (AhR). However, the mechanism or likelihood is largely unknown because of the limited information available about the physiological role of Selenbp1.

Methods: To address this issue, we generated Selenbp1-null [Selenbp1 (-/-)] mice, and examined the toxic effect of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in this mouse model.

Blood levels of PCDDs, PCDFs, and coplanar PCBs in Yusho mothers and their descendants: association with fetal Yusho disease.

Maternal exposure to polychlorinated dibenzo-p-dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs), and polychlorinated biphenyls (PCBs) may result in adverse health effects in their children. In Japan in 1968, an accidental human exposure to rice oil contaminated with PCDDs, PCDFs, and PCBs, led to the development of Yusho disease. Yusho mothers delivered descendants with low birth weights and hyperpigmented skin and mucosa, which are characteristic of fetal Yusho disease (FYD).

A retrospective chart review of the perinatal period in 22 pregnancies of 16 women with Moyamoya disease.

Moyamoya disease (MMD) is characterized by severe stenoses of the arteries in the circle of Willis, which predispose the patient to brain ischemia and intracranial hemorrhage. We performed a retrospective chart review of 22 pregnancies in 16 patients with MMD at the Kyushu University Hospital. An uncomplicated Cesarean delivery was performed in nearly all patients.

Restoration of dioxin-induced damage to fetal steroidogenesis and gonadotropin formation by maternal co-treatment with α-lipoic acid.

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD), an endocrine disruptor, causes reproductive and developmental toxic effects in pups following maternal exposure in a number of animal models. Our previous studies have demonstrated that TCDD imprints sexual immaturity by suppressing the expression of fetal pituitary gonadotropins, the regulators of gonadal steroidogenesis. In the present study, we discovered that all TCDD-produced damage to fetal production of pituitary gonadotropins as well as testicular steroidogenesis can be repaired by co-treating pregnant rats with α-lipoic acid (LA), an obligate co-factor for intermediary metabolism including energy production.

Characterization of placental transfer of polychlorinated dibenzo-p-dioxins, dibenzofurans and polychlorinated biphenyls in normal pregnancy.

Aim: Prenatal exposure to dioxins may result in many adverse health effects. However, the mechanisms by which dioxins are transferred from mother to fetus through the placenta are not well understood. The aim of this study was to investigate the differences in dioxin concentrations between maternal blood, the placenta, and cord blood in normal pregnant women, and to identify which individual congeners of these compounds are transferred from mother to fetus through the placenta.

Aortic regurgitation associated with critical aortic stenosis in a fetus.

Aortic regurgitation in association with aortic stenosis is rare in the fetus. Findings have shown that severe aortic regurgitation is worsened by the increase in systemic vascular resistance after birth, resulting in low cardiac output, hypoxemia, and neonatal death. This report describes a unique case of aortic regurgitation with aortic stenosis, severe mitral regurgitation, retrograde flow in the aortic arch, and an enormous left atrium with a restrictive foramen ovale in a fetus.

Ultrasound evaluation of fetal brain dysfunction based on behavioral patterns.

To identify fetuses at high risk of poor neurological outcomes using a novel ultrasound evaluation system. We assessed an ultrasound evaluation system based on our previous findings, consisting of screening for decreased or lack of fetal movements, abnormal patterns of fetal heart rate, congenital CNS malformations, polyhydramnios of unknown cause, and a "brief ultrasound evaluation" of fetal brain functions, including movement of extremities, breathing movements, ultradian rhythm, REM period, and NREM period. We then assessed the correlation between fetal brain functions and neurological outcomes in infancy (MR, CP, and low Developmental Quotient).