Mortality and morbidity of extremely low birth weight infants in Japan, 2015.

BACKGROUND: In Japan, the mortality rate of extremely low birth weight (ELBW) infants is notably low in comparison with other developed countries, but the prevalence of chronic lung disease (CLD) and retinopathy of prematurity (ROP) is relatively high. This study aimed to estimate the mortality and morbidity of ELBW infants born in 2015 who were admitted to neonatal intensive care units (NICUs) in Japan and to examine the factors that affected the short-term outcomes of these infants. We also compared the mortality of ELBW infants born in 2005, 2010, and 2015. METHODS: We analyzed the mortality, morbidity, and factors related to short-term outcomes of ELBW infants, using data from 2782 infants born in 2015 and registered at NICUs in Japan. RESULTS: The mortality rates during NICU stays were 17.0%, 12.0%, and 9.8% for ELBW infants born in 2005, 2010, and 2015, respectively. Among ELBW infants born in 2015, multiple logistic regression analysis showed that short gestational age and low birthweight Z-score contributed to the increased risk of death. Births by cesarean section and antenatal corticosteroid administration were significantly associated with a reduced risk of death. Among infants who survived, CLD was observed in 53.1% and ROP requiring treatment was observed in 30.4%. CONCLUSIONS: Mortality in ELBW infants decreased significantly from 2005 to 2015. As CLD and ROP may affect quality of life and long-term outcomes of infants who survived, prevention strategies and management for these complications are critical issues in neonatal care in Japan.

An International Aircraft Transport of a Neonate From Georgia to Japan.

International air transport over long distances necessitates considerable effort. It is even more challenging when the patient is a neonate and has a congenital disease. We hereby report a case of an international aircraft transport of a neonate from Tbilisi, Georgia to Osaka, Japan. The patient was transported to Osaka University Hospital after being diagnosed with a double outlet right ventricle (DORV), requiring surgical intervention. This unique experience has raised four issues: 1) language issues for referral and consultation; 2) medical equipment and healthcare professionals required to accompany the transport for adequate care; 3) scheduling of the international flight; and 4) the administrative procedures such as birth certificate, passport, and healthcare insurance. In this report, we describe how the patient was successfully transported, received treatment, and discharged home.

Development of information dissemination methods that contribute to improving maternal and child healthcare using social networking sites: a community-based cross-sectional study in Japan.

BACKGROUND: In recent years, feelings of isolation among mothers caring for small children has become a significant social issue in Japan. The purpose of this study is to develop a message to alleviate their loneliness, to evaluate the impact of social networking sites (SNS) for delivering such messages, and to propose means of more effective information transmission to promote health for mothers raising small children. METHODS: Our study was conducted in two stages, first an interview and then a cross-sectional study of the mothers involving a questionnaire survey. The interview was targeted two public-health nurses caring for mothers. Based on these interviews, we developed six messages intended to alleviate the mothers' sense of loneliness, which were vetted by seven mothers. The second stage was to conduct a questionnaire survey of mothers both before and after our selected message as advertisement on Instagram and analyzed the effect. The surveys were collected during routine child health check-ups in the City of Takatsuki, Japan. RESULTS: From the six draft messages created based on interviews with public health nurses, we selected the message that most relieves the feeling of loneliness of the mothers who are raising small children. The survey questionnaire was taken by 494 mothers prior to our posting of Instagram advertisements (ads), and afterwards by 419 mothers. The percentage of mothers feeling loneliness tended to decrease after reading the messages (before ads.:8.1%, after ads.:5.8%). 8.6% of the mothers (36/419) remembered seeing the Instagram ads. Mothers with financial anxiety were significantly more likely to have remembered seeing the Instagram ads (p < 0.01). CONCLUSIONS: Our results indicate that usefulness of SNS messaging for mothers raising small children may reduce their feeling of loneliness. Among the SNS, disseminating child-rearing information on Instagram may be more effective for people with financial instability.

A questionnaire survey on a feeling of loneliness of the mothers raising children.

AIM: A feeling of isolation childcare mothers' face is a serious social problem in Japan because the relationships with mothers and local communities have grown sparser. The purpose of this study was to clarify the feelings of isolation of mothers during childcare and the factors related to it. METHODS: We conducted a questionnaire survey in Yao City, Osaka. We mailed out a questionnaire survey of 1293 mothers with infants who had either a 4-month or 42-month routine health checkup during the period from September to December of 2018. RESULTS: There was no association between "feeling lonely while raising my child" and the absence of "people who helped raise my children." On the other hand, it was found that the mothers' inner feelings, such as "I wasn't satisfied with my childcare environment" (OR: 2.55, 95% CI: 1.32-4.91, p = 0.0052) or "I lacked confidence in my own childcare abilities" (OR: 6.21, 95% CI: 4.31-8.95, p < 0.0001), were associated with their sense of loneliness. CONCLUSIONS: Mothers' "sense of loneliness" was shown to be best correlated with their dissatisfaction with the environment of their childcare and with their lack of confidence in raising their own children.

A human isogenic iPSC-derived cell line panel identifies major regulators of aberrant astrocyte proliferation in Down syndrome.

Astrocytes exert adverse effects on the brains of individuals with Down syndrome (DS). Although a neurogenic-to-gliogenic shift in the fate-specification step has been reported, the mechanisms and key regulators underlying the accelerated proliferation of astrocyte precursor cells (APCs) in DS remain elusive. Here, we established a human isogenic cell line panel based on DS-specific induced pluripotent stem cells, the XIST-mediated transcriptional silencing system in trisomic chromosome 21, and genome/chromosome-editing technologies to eliminate phenotypic fluctuations caused by genetic variation. The transcriptional responses of genes observed upon XIST induction and/or downregulation are not uniform, and only a small subset of genes show a characteristic expression pattern, which is consistent with the proliferative phenotypes of DS APCs. Comparative analysis and experimental verification using gene modification reveal dose-dependent proliferation-promoting activity of DYRK1A and PIGP on DS APCs. Our collection of human isogenic cell lines provides a comprehensive set of cellular models for further DS investigations.

4-Phenylbutyrate ameliorates apoptotic neural cell death in Down syndrome by reducing protein aggregates.

Individuals with Down syndrome (DS) commonly show unique pathological phenotypes throughout their life span. Besides the specific effects of dosage-sensitive genes on chromosome 21, recent studies have demonstrated that the gain of a chromosome exerts an adverse impact on cell physiology, regardless of the karyotype. Although dysregulated transcription and perturbed protein homeostasis are observed in common in human fibroblasts with trisomy 21, 18, and 13, whether and how this aneuploidy-associated stress acts on other cell lineages and affects the pathophysiology are unknown. Here, we investigated cellular stress responses in human trisomy 21 and 13 neurons differentiated from patient-derived induced pluripotent stem cells. Neurons of both trisomies showed increased vulnerability to apoptotic cell death, accompanied by dysregulated protein homeostasis and upregulation of the endoplasmic reticulum stress pathway. In addition, misfolded protein aggregates, comprising various types of neurodegenerative disease-related proteins, were abnormally accumulated in trisomic neurons. Intriguingly, treatment with sodium 4-phenylbutyrate, a chemical chaperone, successfully decreased the formation of protein aggregates and prevented the progression of cell apoptosis in trisomic neurons. These results suggest that aneuploidy-associated stress might be a therapeutic target for the neurodegenerative phenotypes in DS.

Elimination of protein aggregates prevents premature senescence in human trisomy 21 fibroblasts.

Chromosome abnormalities induces profound alterations in gene expression, leading to various disease phenotypes. Recent studies on yeast and mammalian cells have demonstrated that aneuploidy exerts detrimental effects on organismal growth and development, regardless of the karyotype, suggesting that aneuploidy-associated stress plays an important role in disease pathogenesis. However, whether and how this effect alters cellular homeostasis and long-term features of human disease are not fully understood. Here, we aimed to investigate cellular stress responses in human trisomy syndromes, using fibroblasts and induced pluripotent stem cells (iPSCs). Dermal fibroblasts derived from patients with trisomy 21, 18 and 13 showed a severe impairment of cell proliferation and enhanced premature senescence. These phenomena were accompanied by perturbation of protein homeostasis, leading to the accumulation of protein aggregates. We found that treatment with sodium 4-phenylbutyrate (4-PBA), a chemical chaperone, decreased the protein aggregates in trisomy fibroblasts. Notably, 4-PBA treatment successfully prevented the progression of premature senescence in secondary fibroblasts derived from trisomy 21 iPSCs. Our study reveals aneuploidy-associated stress as a potential therapeutic target for human trisomies, including Down syndrome.

A Pair of Maternal Chromosomes Derived from Meiotic Nondisjunction in Trisomy 21 Affects Nuclear Architecture and Transcriptional Regulation.

Eukaryotic genomes are organised into complex higher-order structures within the nucleus, and the three-dimensional arrangement of chromosomes is functionally important for global gene regulation. The existence of supernumerary chromosome 21 in Down syndrome may perturb the nuclear architecture at different levels, which is normally optimised to maintain the physiological balance of gene expression. However, it has not been clearly elucidated whether and how aberrant configuration of chromosomes affects gene activities. To investigate the effects of trisomy 21 on nuclear organisation and gene expression, we performed three-dimensional fluorescent imaging analysis of chromosome-edited human induced pluripotent stem cells (iPSCs), which enabled identification of the parental origin of the three copies of chromosome 21. We found that two copies of maternal chromosomes resulting from meiotic nondisjunction had a higher tendency to form an adjacent pair and were located relatively distant from the nuclear membrane, suggesting the conserved interaction between these homologous chromosomes. Transcriptional profiling of parental-origin-specific corrected disomy 21 iPSC lines indicated upregulated expression of the maternal alleles for a group of genes, which was accompanied by a fluctuating expression pattern. These results suggest the unique effects of a pair of maternal chromosomes in trisomy 21, which may contribute to the pathological phenotype.

Systematic Cellular Disease Models Reveal Synergistic Interaction of Trisomy 21 and GATA1 Mutations in Hematopoietic Abnormalities.

Chromosomal aneuploidy and specific gene mutations are recognized early hallmarks of many oncogenic processes. However, the net effect of these abnormalities has generally not been explored. We focused on transient myeloproliferative disorder (TMD) in Down syndrome, which is characteristically associated with somatic mutations in GATA1. To better understand functional interplay between trisomy 21 and GATA1 mutations in hematopoiesis, we constructed cellular disease models using human induced pluripotent stem cells (iPSCs) and genome-editing technologies. Comparative analysis of these engineered iPSCs demonstrated that trisomy 21 perturbed hematopoietic development through the enhanced production of early hematopoietic progenitors and the upregulation of mutated GATA1, resulting in the accelerated production of aberrantly differentiated cells. These effects were mediated by dosage alterations of RUNX1, ETS2, and ERG, which are located in a critical 4-Mb region of chromosome 21. Our study provides insight into the genetic synergy that contributes to multi-step leukemogenesis.

Serum concentrations of bevacizumab (avastin) and vascular endothelial growth factor in infants with retinopathy of prematurity.

PURPOSE: To determine the serum concentrations of bevacizumab and vascular endothelial growth factor (VEGF) in infants with retinopathy of prematurity (ROP) who received intravitreal bevacizumab; and to determine whether the changes in the serum concentration of bevacizumab were significantly correlated with the serum concentration of VEGF after intravitreal bevacizumab. DESIGN: Case series. METHODS: Eleven infants (4 girls and 7 boys) with ROP were studied. They received 0.25 mg or 0.5 mg of intravitreal bevacizumab to either 1 eye (unilateral cases) or both eyes (bilateral cases) with vascularly active ROP. Serum samples were collected before and 1 day, 1 week, and 2 weeks after the intravitreal bevacizumab. The serum concentrations of bevacizumab and VEGF were measured by enzyme-linked immunosorbent assay, and the correlation in the serum levels between the 2 was determined. RESULTS: The serum concentration of bevacizumab before and 1 day, 1week, and 2 weeks after a total of 0.5 mg of intravitreal bevacizumab was 0 ng/mL, 195 ± 324 ng/mL, 946 ± 680 ng/mL, and 1214 ± 351 ng/mL, respectively. The serum bevacizumab level before and 1 day and 1 week after a total 1.0 mg of intravitreal bevacizumab was 0 ng/mL, 248 ± 174 ng/mL, and 548 ± 89 ng/mL, respectively. The serum concentration of VEGF before and 1 day, 1 week, and 2 weeks after a total of 0.5 mg intravitreal bevacizumab was 1628 ± 929 pg/mL, 427 ± 140 pg/mL, 246 ± 110 pg/mL, and 269 ± 157 pg/mL, respectively. There was a significant negative correlation (r = -0.575, P = .0125) between the serum concentration of bevacizumab and VEGF when a total of 0.25 mg or 0.5 mg of bevacizumab was injected. CONCLUSIONS: These results indicate that bevacizumab can escape from the eye into the systemic circulation and reduce the serum level of VEGF in infants with ROP. Continued extensive evaluations of infants are warranted for possible effects after intravitreal bevacizumab in ROP patients.

Fetal and neonatal anemia associated with anti-Jr(a) : a case report showing a poorly hemolytic mechanism.

Although recently published case reports suggest the significance of Jr(a) alloimmunization in the obstetric setting, the involved mechanism still remains unclear. Here we report a case of severe fetal and neonatal anemia associated with anti-Jr(a) alloimmunization, which was successfully managed using Doppler assessment of peak systolic velocity of the fetal middle cerebral artery (MCA-PSV). A Japanese woman with anti-Jr(a) (titer 1024) was referred to our department at 20 weeks' gestation. As fetal MCA-PSV exceeded 1.5 multiple of median, labor was induced and a female neonate of 1998 g was delivered vaginally at 33 weeks and 5 days of gestation. The infant's hematocrit and hemoglobin levels were 25.4% and 82 g/L, respectively, but her total bilirubin level (15 µmol/L; 0.9 mg/dL) and reticulocyte counts (4.5%) were low. During the course, the infant showed no apparent signs of hemolysis. Jr(a) alloimmunization should be recognized as a possible cause of fetal anemia with no direct hemolytic process.

Circulating levels of soluble alpha-Klotho are markedly elevated in human umbilical cord blood.

CONTEXT: Fetal serum levels of calcium and phosphate are higher than those in the maternal levels. Although α-Klotho is known to participate in calcium and phosphate metabolism in adults, its role in the perinatal period remains unknown. OBJECTIVE: This study aimed to determine the baseline levels of soluble α-Klotho in fetuses and compare them with those in neonates, mothers, and adults to clarify whether α-Klotho is involved in the fetal-specific regulation of calcium and phosphate metabolism. DESIGN AND SETTING: We conducted a cross-sectional evaluation of healthy babies (at birth and/or at 4 d after birth), their mothers, and adult volunteers at one hospital. PARTICIPANTS: Twenty-one healthy mothers, their babies (23 in total, including two pairs of twins), and 25 adult volunteers participated in the study. MAIN OUTCOME MEASURES: We measured the serum levels of soluble α-Klotho and fibroblast growth factor 23 (FGF23). RESULTS: In cord blood, the level of α-Klotho was markedly higher (3243 ± 1899 pg/ml) than levels in neonates at d 4 (582 ± 90 pg/ml), mothers (768 ± 261 pg/ml), and adult volunteers (681 ± 140 pg/ml) (P < 0.001), whereas the fetal level of FGF23 was lower than levels in the other subjects. The levels of soluble α-Klotho were negatively correlated with those of FGF23 in cord blood. Immunohistochemistry demonstrated that α-Klotho was predominantly expressed in syncytiotrophoblasts in normal term placenta. CONCLUSION: Levels of soluble α-Klotho are markedly elevated in cord blood and might be useful as a biomarker for mineral metabolism in the fetus.

The prognostic factors and the outcome of primary isolated fetal ascites.

PURPOSE: The purpose of the present study was to evaluate the prognostic factors and review the outcome of primary isolated fetal ascites. METHODS: A retrospective cohort study was conducted for fetuses with primary isolated ascites with a prenatal diagnosis between 1994 and 2009. The patients were divided into the favorable group (Group I) whose ascites were resolved by medical treatment alone and an unfavorable group (Group II) who required surgical intervention after birth due to refractory ascites. RESULTS: There were seven patients in Group I and five patients in Group II. Six of seven patients who developed ascites after 30 weeks' gestation were categorized in Group I, and four of five infants who developed ascites before 30 weeks' gestation were categorized in Group II. There was a negative correlation between the gestational age at diagnosis and the severity of the fetal abdominal distention. In Group II, the ascites resolved in two cases and was reaccommodated in another two cases after surgery. An infant with trisomy 21 received continuous drainage and eventually died of infection. CONCLUSIONS: The prognosis of primary isolated fetal ascites can be predicted based on the gestational age at diagnosis and the severity of the fetal abdominal distention.

Valor predictivo del puntaje de Apgar en neonatos prematuros y de bajo peso al nacer: [revisión] / Predictive value of the Apgar score in low birth weight and preterm infants: [review]

Introducción: Dado que en algunas investigaciones se demuestra que la puntuación de Apgar no es lo suficientemente precisa para estimar el pronóstico neonatal, en especial en los niños prematuros, se debate la posibilidad de discontinuar su utilización. Métodos: Este es un análisis poblacional transversal de los registros disponibles de todos los neonatos internados en 37 unidades neonatales en la Prefectura de Osaka, Japón. Mediante la estratificación en función del peso al nacer y de la edad gestacional, se calculó, para la puntuación de Apgar, el valor predictivo, la sensibilidad, la especificidad y los cocientes positivo y negativo de probabilidad para determinar la mortalidad neonatal para cada umbral de puntaje entre 0 y 9 puntos. Resultados: En los neonatos prematuros y de bajo peso al nacer, el área bajo la curva (ABC) se incrementó con el aumento de la edad gestacional y del peso al momento del nacimiento. La puntuación de Apgar a los 5 minutos siempre se asoció con mayores valores de ABC y de cociente positivo de probabilidad que la puntuación calculada en el primer minuto. El ABC de la puntuación de Apgar a los 5 minutos para los niños con un peso al nacer comprendido entre 1 500 y 2 499 g y para edades gestacionales de entre 32 y 36 semanas fue de 0.89 y 0.91, respectivamente. Conclusión: El valor predictivo de la puntuación de Apgar no fue similar a lo largo del tiempo y los grupos poblacionales. En Osaka, Japón, la puntuación de Apgar es una variable predictiva para los neonatos con un peso al nacer de entre 1 500 y 2499 g o con una edad gestacional de 32 a 36 semanas. Para estratificar la precisión del valor predictivo de la puntuación de Apgar, la edad gestacional es un parámetro más adecuado que el peso al nacer.

Valor predictivo del puntaje de Apgar en neonatos prematuros y de bajo peso al nacer: [revisión] / Predictive value of the Apgar score in low birth weight and preterm infants: [review]

Introducción: Dado que en algunas investigaciones se demuestra que la puntuación de Apgar no es lo suficientemente precisa para estimar el pronóstico neonatal, en especial en los niños prematuros, se debate la posibilidad de discontinuar su utilización. Métodos: Este es un análisis poblacional transversal de los registros disponibles de todos los neonatos internados en 37 unidades neonatales en la Prefectura de Osaka, Japón. Mediante la estratificación en función del peso al nacer y de la edad gestacional, se calculó, para la puntuación de Apgar, el valor predictivo, la sensibilidad, la especificidad y los cocientes positivo y negativo de probabilidad para determinar la mortalidad neonatal para cada umbral de puntaje entre 0 y 9 puntos. Resultados: En los neonatos prematuros y de bajo peso al nacer, el área bajo la curva (ABC) se incrementó con el aumento de la edad gestacional y del peso al momento del nacimiento. La puntuación de Apgar a los 5 minutos siempre se asoció con mayores valores de ABC y de cociente positivo de probabilidad que la puntuación calculada en el primer minuto. El ABC de la puntuación de Apgar a los 5 minutos para los niños con un peso al nacer comprendido entre 1 500 y 2 499 g y para edades gestacionales de entre 32 y 36 semanas fue de 0.89 y 0.91, respectivamente. Conclusión: El valor predictivo de la puntuación de Apgar no fue similar a lo largo del tiempo y los grupos poblacionales. En Osaka, Japón, la puntuación de Apgar es una variable predictiva para los neonatos con un peso al nacer de entre 1 500 y 2499 g o con una edad gestacional de 32 a 36 semanas. Para estratificar la precisión del valor predictivo de la puntuación de Apgar, la edad gestacional es un parámetro más adecuado que el peso al nacer.(AU)

Sonographic femur length to trunk cross area ratio: prediction of fetal outcome in 30 cases in which micromelia was suspected.

AIM: The purpose of the present study was to investigate the potential value of fetal routine sonographic biometry in evaluating micromelias. METHODS: Thirty fetuses had a presumptive diagnosis of micromelia from antepartum ultrasound examinations during the period between 1 April 1996 and 31 March 2005. The postnatal clinical features, final diagnoses and outcomes were examined to retrospectively compare these cases with biometric parameters obtained from routine antepartum ultrasound examinations. RESULTS: Final diagnoses included skeletal dysplasia (16), small-for-dates (SFD) infant without any abnormalities (seven), chromosomal abnormality (three), pyruvate dehydrogenase complex deficiency (one), Marden-Walker syndrome (one), and suspected Freeman-Sheldon syndrome (one). One turned out to be a healthy infant. All cases were divided on the basis of the final diagnoses into three groups: skeletal dysplasia (16 fetuses), SFD and healthy infant (eight fetuses) and others (six fetuses). The ratios of femur length (FL) to mean FL at a given gestational age (%FL) and of FL to biparietal diameter (FL/BPD) were significantly lower in the skeletal dysplasia group than those in the other groups. Moreover, in the skeletal dysplasia group, when the lethal cases were excluded, the ratio of FL to fetal trunk cross area (FL/FTA) was significantly lower than that in the other groups. CONCLUSIONS: FL/FTA appears to be a useful parameter to help differentiate fetuses with non-lethal skeletal dysplasia from anatomically normal fetuses either with constitutionally short limbs or with intrauterine growth restriction (IUGR).

Early induction of neuronal lipocalin-type prostaglandin D synthase after hypoxic-ischemic injury in developing brains.

Lipocalin-type prostaglandin (PG) D synthase (L-PGDS) is up-regulated in oligodendrocytes (OLs) in mouse models for genetic neurological disorders including globoid cell leukodystrophy (twitcher) and GM1 and GM2 gangliosidoses and in the brain of patients with multiple sclerosis. Since L-PGDS-deficient twitcher mice undergo extensive neuronal death, we concluded that L-PGDS functions protectively against neuronal degeneration. In this study, we investigated whether L-PGDS is also up-regulated in acute and massive brain injury resulting from neonatal hypoxic-ischemic encephalopathy (HIE). Analysis of brains from human neonates who had died from HIE disclosed that the surviving neurons in the infarcted lesions expressed L-PGDS. Mouse models for neonatal HIE were made on postnatal day (PND) 7. Global infarction in the ipsilateral hemisphere was evident at 24h after reoxygenation in this model. Intense L-PGDS immunoreactivity was already observed at 10 min after reoxygenation in apparently normal neurons in the cortex, and thereafter, in neurons adjacent to the infarcted area. Quantitative RT-PCR revealed that the L-PGDS mRNA level of the infarcted hemisphere was 33-fold higher than that of the sham-operated mouse brains at 1h after reoxygenation and that it decreased to the normal level by 24h thereafter. Furthermore, in both human and mouse brains, many of L-PGDS-positive cells were also immunoreactive for p53; and some of these expressed cleaved caspase-3. The expression of L-PGDS in degenerating neurons implies that L-PGDS functions as an early stress protein to protect against neuronal death in the HIE brain.

Prostaglandin D2 protects neonatal mouse brain from hypoxic ischemic injury.

Prostaglandin D2 (PGD) is synthesized by hematopoietic PGD synthase (HPGDS) or lipocalin-type PGDS (L-PGDS), depending on the organ in which it is produced, and binds specifically to either DP1 or DP2 receptors. We investigated the role of PGD2 in the pathogenesis of hypoxic-ischemic encephalopathy (HIE) in neonatal mice at postnatal day 7. In wild-type mice, hypoxia-ischemia increased PGD2 production in the brain up to 90-fold compared with the level in sham-operated brains at 10 min after cessation of hypoxia. Whereas the size of the infarct was not changed in L-PGDS or DP2 knock-out mouse brains compared with that in the wild-type HIE brains, it was significantly increased in HPGDS-L-PGDS double knock-out or DP1 knock-out mice. The PGD2 level in L-PGDS, HPGDS, and HPGDS-L-PGDS knock-out mice at 10 min of reoxygenation was 46, 7, and 1%, respectively, of that in the wild-type ones, indicating the infarct size to be in inverse relation to the amount of PGD2 production. DP1 receptors were exclusively expressed in endothelial cells after 1 h of reoxygenation, and cerebral blood flow decreased more rapidly after the onset of hypoxia and did not return to the baseline level after reoxygenation in HPGDS-L-PGDS knock-out mice. Endothelial cells were severely damaged in HPGDS-L-PGDS and DP1 knock-out mice after 1 h of reoxygenation. In the human neonatal HIE brain, HPGDS-positive microglia were increased in number. In conclusion, it is probable that PGD2 protected the neonatal brain from hypoxic-ischemic injury mainly via DP1 receptors by preventing endothelial cell degeneration.

CMV DNA detection in dried blood spots for diagnosing congenital CMV infection in Japan.

Human cytomegalovirus (CMV) is a leading congenital infectious agent in developed countries. In the past, the incidence of congenital infection has been rather low in Japan because a high seroprevalence of CMV present in young women. However, this seroprevalence has been decreasing in recent years, so that the incidence of congenital CMV infection in Japanese neonates may increase and approach the level seen in other developed countries. The method was used for detecting CMV DNA reported by Barbi et al. [Barbi et al. (1996): Clin Diagn Virol 6:27-32] using a dried blood spot on filter paper, to diagnose congenital CMV infection in Japanese neonates. This method is effective and less laborious than virus isolation both for epidemiological studies and for identifying asymptomatic infected babies. Japanese neonates (1,176) were examined; two of who were asymptomatic were found to be infected.