Toshiro Ikeda

Apoptosis in placentas from human T-lymphotropic virus type I–seropositive pregnant women: a possible defense mechanism against transmission from mother to fetus

OBJECTIVE The mechanism by which the placenta serves as the barrier against mother-to-fetus transmission of microorganisms remains to be elucidated. Programmed cell death, apoptosis, is considered a cellular defense mechanism against infection. The hypothesis of this study is that apoptosis of human T-lymphotropic virus type I (HTLV-I)-infected placental villous cells is involved in the defense mechanism against mother-to-fetus transmission of HTLV-I. METHODS Apoptosis was compared in term placentas from eight HTLV-I-seropositive pregnant women and eight HTLV-I-seronegative pregnant women by the terminal deoxynucleotidyl transferase-mediated deoxyuridine nick end-labeling method. In addition, an in vitro cocultivation with an HTLV-I-infected lymphocyte cell line (MT-2 cells) was performed to examine whether placental villous cells were infected with HTLV-I and apoptosis was induced. RESULTS The incidence of apoptosis-positive cells (nuclei) in placentas from the HTLV-I-seropositive pregnant women was higher than in the HTLV-I-seronegative pregnant women (P < .02). Cocultivation with MT-2 cells showed that trophoblast cells were able to be infected with HTLV-I and that apoptosis was induced in the placental villous cells. CONCLUSION HTLV-I infection induces apoptosis in the placenta. We speculate that apoptosis may be involved in the defense mechanism of the placenta against mother-to-fetus transmission of HTLV-I.

Genomic Characterization of Chromosomal Insertions: Insights into the Mechanisms Underlying Chromothripsis

Chromosomal insertions are rare structural rearrangements, and the molecular mechanisms underlying their origin are unknown. In this study, we used whole genome sequencing to analyze breakpoints and junction sequences in 4 patients with chromosomal insertions. Our analysis revealed that none of the 4 cases involved a simple insertion mediated by a 3-chromosomal breakage and rejoining events. The inserted fragments consisted of multiple pieces derived from a localized genomic region, which were shuffled and rejoined in a disorderly fashion with variable copy number alterations. The junctions were blunt ended or with short microhomologies or short microinsertions, suggesting the involvement of nonhomologous end-joining. In one case, analysis of the parental origin of the chromosomes using nucleotide variations within the insertion revealed that maternal chromosomal segments were inserted into the paternal chromosome. This patient also carried both maternal alleles, suggesting the presence of zygotic trisomy. These data indicate that chromosomal shattering may occur in association with trisomy rescue in the early postzygotic stage.

Signature of backward replication slippage at the copy number variation junction

Copy number abnormalities such as deletions and duplications give rise to a variety of medical problems and also manifest innocuous genomic variations. Aberrant DNA replication is suggested as the mechanism underlying de novo copy number abnormalities, but the precise details have remained unknown. In our present study, we analyzed the del(2)(q13q14.2) chromosomal junction site observed in a woman with a recurrent pregnancy loss. Microarray analyses allowed us to precisely demarcate a 2.8 Mb deletion in this case, which does not appear in the database of human genomic variations. This deletion includes only one brain-specific gene that could not be related to the reproduction failure of the patient. At the junction of the deletion, we found that 11–13-nucleotide sequence, originally located at the proximal breakpoint region, was repeated four times with a single-nucleotide microhomology at the joint between each repeat. The proximal region and the distal region was finally joined with six-nucleotide microhomology. The structure of the junction is consistent with backward replication slippage proposed previously. Our data lend support to the notion that a common DNA replication-mediated pathway generates copy number variation in the human genome.

Ultrashort‐Time FISH for Identification of the Sex of Peripheral‐Blood Lymphocytes and Preimplantation Embryos

Objective: The aim of this study was to shorten the time required for sex determination using peripheral‐blood lymphocytes and blastomeres of human preimplantation embryos by fluorescence in situ hybridization (FISH).

Lethal persistent pulmonary hypertension of the newborn in Bohring-Opitz syndrome

Bohring–Opitz syndrome (BOS) is a rare disease with a number of characteristic features, including hypertelorism, prominent metopic suture, exophthalmos, cleft palate, abnormal posture, and developmental retardation. Here, we report a BOS patient presenting with lethal persistent pulmonary hypertension of the newborn (PPHN) and inspiratory respiratory failure. The female infant was treated with nitric oxide and vasodilator, which did not improve her condition. The inspiratory respiratory failure required management with deep sedation. She died on postnatal day 60 due to progressed heart failure. Whole exome sequencing revealed de novo mutation in the ASXL1 gene, c.1934dupG, p.Gly646TrpfsTer12.

Immunotherapy with Husband's Leukocytes to Primary Habitual Aborters and Autoantibodies in Their Sera

Objective: This study was performed to determine whether primary habitual aborters have an autoimmunological tendency and whether immunotherapy with leukocytes induces autoantibodies in their sera.