Kazushige Ikeda

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

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

The intrauterine expression of surfactant protein D in the terminal airways of human fetuses compared with surfactant protein A

Abstract. We investigated the expression of surfactant protein (SP)-D in pulmonary epithelial cells, compared with the expression of SP-A. A total of 15 fetuses aborted at 8, 15, 19, 20, 21 and 23 weeks gestation and four premature babies who were stillborn or died after birth between May 1997 and October 2001 were included in this study. Fetuses showing any findings associated with preterm premature rupture of membranes or infection were excluded. We performed immunohistochemical examinations for SP-D and SP-A. SP-D was not detected by immunostaining at 8, 15 and 19 weeks gestation. At 21 weeks gestation, SP-D was weakly localized, in some cases (5/9), in the epithelial lining of both bronchioles and terminal airways. In contrast at 21 weeks gestation, SP-A was more markedly detected in the epithelial lining of both bronchioles and terminal airways in all cases but not detected in bronchioles and terminal airways at 8, 15 and 19 weeks gestation. Conclusion: the findings in this investigation suggests that the production of SP-D in fetal human lungs begins in the bronchiolar and terminal epithelium from about 21 weeks of gestation.

Digynic triploid infant surviving for 46 days

We report on a triploid infant who survived for 46 days. She had severe intrauterine growth retardation, relative macrocephaly, and a small, noncystic placenta, which are manifestations compatible with type II phenotype. Cultured amniotic fluid cells, skin fibroblasts, cord blood, and peripheral blood lymphocytes all showed a nonmosaic 69,XXX karyotype. Analysis of chromosomal heteromorphisms and microsatellite DNA polymorphisms in the infant and her parents indicated that the extra haploid set in the infant resulted from nondisjunction at maternal second meiosis. Postzygotic, mitotic nondisjunction was ruled out because of the presence of both homozygous and heterozygous markers of maternal origin. A search of the literature demonstrated five triploid infants, including the girl we described, who survived 4 weeks or more, and the parental origin of whose triploidy was studied: four were digynic and one was diandric. These findings support the notion that type II triploids are digynic in parental origin and that they survive longer than type I, diandric triploids.

Clinical manifestations of Bacillus cereus meningitis in newborn infants.

Abstract: Bacillus cereus (B. cereus) meningitis sometimes occurs in patients with risk factors, which are associated with central nervous system (CNS) anomalies, surgical or anaesthetic access to CNS. We observed two cases of B. cereus meningitis in neonates without such risk factors. The clinical courses of both neonates were fulminant, and routine antibiotic therapy failed. Intracranial haemorrhage was evident at autopsy. According to the previous neonatal case reports and our experience, we found that six of seven neonates were premature babies admitted to the neonatal intensive care unit, five died within a week of onset of the disease, and six had intracranial haemorrhage. We speculate that B. cereus meningitis may occur in neonates, even without any of the risk factors previously described in adult case reports, and that the clinical manifestations of the meningitis might be chjpccterized by the high incidence of intracranial haemorrhage and poor mortality.

Intrauterine MRI with single-shot fast-spin echo imaging showed different signal intensities in hypoplastic lungs.

Abstract Ultrasonography is used for the prenatal diagnosis of hypoplastic lungs. However, ultrasound poses problems because of difficulties in getting the entire lung in perspective and the results depend on the skill of the examiner. When the alveolar formation of the fetal lung is retarded, the fetus is predicted to show an altered density on MRI using an SSFSE sequence due to a varied amount of alveolar lung fluid. We present a case of twins who showed a marked difference in signal intensity of the lung on MRI, which was useful for predicting the fetal pathophysiology. Intrauterine MRI provides the possibility of diagnosing hypoplastic lungs prenatally.

Iridic and retinal coloboma associated with prenatal methimazole exposure

Michihiko Aramaki, IsamuHokuto, TadashiMatsumoto, Hitoshi Ishimoto,Makoto Inoue, Tokuhiro Kimura, Yo-ichi Oikawa, Kazushige Ikeda, Yasunori Yoshimura, Takao Takahashi, and Kenjiro Kosaki* Department of Pediatrics, Keio University School of Medicine, Tokyo, Japan Department of Obstetrics, Keio University School of Medicine, Tokyo, Japan Department of Ophthalmology, Keio University School of Medicine, Tokyo, Japan Department of Pathology, Keio University School of Medicine, Tokyo, Japan Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan

Two-Step Biochemical Differential Diagnosis of Classic 21-Hydroxylase Deficiency and Cytochrome P450 Oxidoreductase Deficiency in Japanese Infants by GC-MS Measurement of Urinary Pregnanetriolone/ Tetrahydroxycortisone Ratio and 11β-Hydroxyandrosterone

BACKGROUND The clinical differential diagnosis of classic 21-hydroxylase deficiency (C21OHD) and cytochrome P450 oxidoreductase deficiency (PORD) is sometimes difficult, because both deficiencies can have similar phenotypes and high blood concentrations of 17α-hydroxyprogesterone (17OHP). The objective of this study was to identify biochemical markers for the differential diagnosis of C21OHD, PORD, and transient hyper 17α-hydroxyprogesteronemia (TH17OHP) in Japanese newborns. We established a 2-step biochemical differential diagnosis of C21OHD and PORD. METHODS We recruited 29 infants with C21OHD, 9 with PORD, and 67 with TH17OHP, and 1341 control infants. All were Japanese and between 0 and 180 days old; none received glucocorticoid treatment before urine sampling. We measured urinary pregnanetriolone (Ptl), the cortisol metabolites 5α- and 5β-tetrahydrocortisone (sum of these metabolites termed THEs), and metabolites of 3 steroids, namely dehydroepiandrosterone, androstenedione (AD4), and 11β-hydroxyandrostenedione (11OHAD4) by GC-MS. RESULTS At a cutoff of 0.020, the ratio of Ptl to THEs differentiated C21OHD and PORD from TH17OHP and controls with no overlap. Among metabolites of DHEA, AD4, and 11OHAD4, only 11β-hydroxyandrosterone (11HA), a metabolite of 11OHAD4, showed no overlap between C21OHD and PORD at a cutoff of 0.35 mg/g creatinine. CONCLUSIONS A specific cutoff for the ratio of Ptl to THEs can differentiate C21OHD and PORD from TH17OHP and controls. Additionally, the use of a specific cutoff of 11HA can distinguish between C21OHD and PORD.

Expression and distribution of tight junction proteins in human amnion during late pregnancy.

Amnion is the innermost layer of the fetal membrane and has been suggested to regulate the volume of amniotic fluid via the amniotic epithelium. The transepithelial pathway is generally restricted by tight junctions (TJs). Thus far, human amniotic TJs have not been identified. In this study, we determined whether the human amniotic epithelium contains TJs. Reverse transcription polymerase chain reaction (RT-PCR) and western blotting analyses showed that the human amniotic epithelium has TJ components, such as occludin, ZO-1, and at least 2 types of claudins, i.e., claudin-4 and claudin-7. The TJ components were found to localize in the lateral membranes and cytoplasm at 35 weeks of gestation; these components disappeared from the lateral membrane at 37 weeks of gestation. Organ culturing of the amnion at 37 weeks gestation induced the relocalization of the TJ proteins from the cytoplasm to the lateral membranes. Furthermore, in cultured amniotic epithelial cells, dexamethasone induced the downregulation of the protein expression of TJs. These findings suggest that the human amniotic epithelium has TJs that disrupt during late pregnancy. The disruption may be induced by several factors such as glucocorticoids present in the amniotic fluid during late pregnancy.

Nine Japanese patients with immotile-dyskinetic cilia syndrome: An ultrastructural study using tannic acid-containing fixation

Respiratory cilia and sperm flagella of nine Japanese patients with immotile-dyskinetic cilia syndrome were studied ultrastructurally by using a tannic acid-containing fixative. Respiratory cilia from two female patients with Kartageners syndrome and one male patient with situs inversus and sinobronchitis were completely immotile and lacked both dynein arms. However, approximately 30% of the spermatozoa from the male patient were weakly motile. In four patients with immotile cilia syndrome without Kartageners triad, immotile respiratory cilia generally lacked the inner dynein arms. Two clinically unusual cases, an 11-year-old boy and a 29-year-old woman with prolonged saccharin test, recurrent bronchitis, and bronchiectasia, possessed motile respiratory cilia. Ultrastructurally, both dynein arms were normal, but numerous defective central pairs (more than 50% and 70%, respectively) were seen, and the defect in the second case was similar to the transposition of microtubules reported by Sturgess et al (N Engl J Med 303:318-322, 1980). However, defects in the first case were unique and may be congenital. We propose a new type of dyskinetic cilia syndrome with defective central pairs. Additionally, nasal cilia from a 35-year-old man with immotile cilia syndrome contained excess large singlets within ciliary axonemes consisting of 17 protofilaments.

A congenital anterior diaphragmatic hernia with massive pericardial effusion requiring neither emergency pericardiocentesis nor operation. A case report and review of the literature.

Abstract All previously reported cases of anterior diaphragmatic hernia with massive pericardial effusion were treated by pericardiocentesis and radical surgery during the early neonatal period. However, we initially followed the course of our patient in the neonatal period. Subsequently, elective surgery was performed at 70 days of age. Including our case, cardiac tamponade has not been observed in any previously reported cases of congenital anterior diaphragmatic hernia with massive pericardial effusion. Conclusion: Emergency pericardiocentesis and surgery are not always required immediately after birth, even when the presence of this condition is suspected by prenatal diagnosis. Our observation may be beneficial to preterm low birth weight infants with this condition.