official journal of Congeital Anomalies Research Association of Japan
Online ISSN : 2433-1503
Print ISSN : 0037-2285
Volume 30 , Issue 1
Congenital Anomalies
Showing 1-10 articles out of 10 articles from the selected issue
  • 1990 Volume 30 Issue 1 Pages 3
    Published: 1990
    Released: July 27, 2021
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  • 1990 Volume 30 Issue 1 Pages 5-16
    Published: 1990
    Released: July 27, 2021
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    ABSTRACT Exencephaly has been induced in mouse embryos by chlorambucil (CA), a cytotoxic agent. To understand the course of development of this mal- formation, open neural tube defects in CA-treated mice were examined using light and scanning electron microscopes (SEM). CA was given to the pregnant mice on day 7.4 of gestation. Embryos were removed and futed on gestational days 9.3- 9.4, 9.7-9.8 and 10.4, and compared to control embryos from untreated mice. By gestational day 9.4, all control embryos had closed neural tubes, except for the posterior neuropores, and well developed brain vesicles. By contrast, in the ex- perimental embryos the frequencies of open neural tube were 26/33 (78.8%), 32/ 40 (80.0%) and 23/66 (34.8%) on each day examined, respectively. Open neural tube defects were classified into six patterns according to the location and magnitude of the open area. The patterns of open neural tube on day 9.7-9.8 were diverse; however, in almost all cases on day 10.4 the open neural tube appeared in a region from the caudal forebrain to the rostral hindbrain. It was evident that an unusual pattern of closure of the neural tube was involved in forming the cranial neural tube. The present study shows that failure of closure of the cranial neural tube in the CA-treated mouse embryos can be defined as a primary neural tube defect (NTD), which can be, in part, repaired by unusual closure of the neural tube. At high magnifications of SEM, the neuroectodermal surfaces of the 9.0-day affected embryos often had a number of slender processes projecting from the neuroepithelial cells. “Ruffles” and “blebs” at the lateral edges of the neural folds were observed in both control and affected embryos.
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  • 1990 Volume 30 Issue 1 Pages 17-27
    Published: 1990
    Released: July 27, 2021
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    ABSTRACT DNA synthesis and cell condensation in the developing hand plate of the rat were examined by a BrdU/anti-BrdU immunohistochemical study. DNA-synthesizing cells were distributed uniformly in the mesenchyme of the hands until day 12.5 in rat embryos. From day 13.0, these cells were distributed in the interdigital mesenchymal areas, leaving rare labeled cells in sites of cell condensation (i.e., in the digital rays). After day 14.5, DNA-synthesizing cells were confined to the interdigital areas near the digital rays. On day 15.0, DNA- synthesizing cells appeared in the areas of joint formation. In the epidermis. DNA-synthesizing cells were uniformly found in the period of digital-ray for- mation. When the mesenchymal cells labeled on day 12.0 were followed from day 12.5 until day 14.0 of embryogenesis, they were found to become concen- trated in the digital rays. From these findings, we conclude that the cells which are synthesizing DNA and actively dividing in the mesenchyme at day 12.0 mig- rate to the digital rays, where they undergo cell condensation. The experimental models and techniques employed in this study will be useful for investigations of normal development as well as teratogenesis of the extremities.
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  • 1990 Volume 30 Issue 1 Pages 29-37
    Published: 1990
    Released: July 27, 2021
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    ABSTRACT Twelve patients with inherited shortening of the middle phalanx of both index fingers were found in 122 patients with congenital clinodactyly without any major hand anomalies. The morbidity rate in females was 53.6% and in male it was 50.0%. Webbing between the second and third toes was found in three, and clinodactyly of the second toe in four. Characteristic features of this anomaly are a short and delta-shaped or rhombus-shaped middle phalanx of the index finger. Hand pattern profiles revealed that the middle phalanges of the long and ring fingers are shortened to a variable degree.
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  • 1990 Volume 30 Issue 1 Pages 39-48
    Published: 1990
    Released: July 27, 2021
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    ABSTRACT Our previous study demonstrated thalidomide-induced anencephaly and holoprocencephaly at a high frequency in JW-NIBS rabbits. In order to know the early morphogenetic process of these two malformations, thalidomide was orally given to pregnant JW-NIBS rabbits on day 7 or on days 6-9 of gestation, and the embryos were examined on days 9-13 in histological sections and scanning electronmicroscopic specimens. The preponderant site of thalidomide-induced dysraphic change was the mid- frontal portion of the prosencephalic vesicle. A widely opened cephalic neural tube at this portion and consequent eversion of the telencephalic wall observed in day-9-embryos (23 1 hours postcoitus) was the first change of most anencephaly in this experiment. Incomplete closure of the cephalic neural tube under the closed surface ectoderm observed at the midfrontal portion of day-9-embryos was divided into two types: One type showed a contact of the neural folds but no histological continuation, and the other type evidenced a degeneration of the neuroepithelial tissue at the closing site and hypoplasia of the surrounding mesenchymal tissue. The mesenchymal tissue over the neuroepithelial layer showed curled cellular processes and a loose interconnection in scanning electronmicroscopic specimens. The midfrontal encephalocele observed in day-13-embryos could be regarded as the consequence of the former type of incomplete closure. Defective formation of the longitudinal fissure of the telencephalon due to the midfrontal encephalocele was the cause of holoprosencephaly later. Not only unclosure of the neural tube but also the latter type of incomplete closure was considered to manifest anencephaly.
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  • 1990 Volume 30 Issue 1 Pages 49-68
    Published: 1990
    Released: July 27, 2021
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    ABSTRACT Animal model for congenital anomalies induced by chromosome aberrations is explained in mice. Exencephaly is the most conspicuous external malformations among mice trisomies and partial trisomies. Characteristic cardio- vascular malformations are observed in Ts 16, 13 and 14. The association of persistent common atrioventricular (A-V) canal in Ts 16 pro- vides an excellent morphological homology to human trisomy 2 1. Observations on A-Vcanal endocardial cushions of Ts 16 fetuses showed i) hypoplastic endocardi- al cushions, ii) delayed appearance ofmesenchymal cells into cushions. and iii) failed fusion of endocardial cushions. The conotruncal malformations were observed in every fetus of Ts 16. Abnormal aortic arch was observed in about half of the cases. Further, the thymus was always hypoplastic. The combination of these anomalies suggests that Ts 16 had abnormal development similar to DiCeorge anomaly in these regions. In enlarged hearts of 7hp and t”L1rb2, which have deletions on chromosonie 17, the ventricular septum bulged so extremely into ventricle that the bilateial ventricular outflow tract was markedly obstructed. From 14 days of pregnancy on, generalized edema was often observed in some of trisomic and ThP fetuses. Histological examination of Ts 16 and Thp fetuses demonstrated that the essence of the fetal edema was cystic hygroma, which is sometimes encountered in human fetuses with chromosome aberrations. Investigations by an animal model with chromosome aberrations did offer new information which remains somewhat scanty in early embryonic stage.
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  • 1990 Volume 30 Issue 1 Pages 69-78
    Published: 1990
    Released: July 27, 2021
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    ABSTRACT In Japan, the overall incidence rates of birth defects among fetal deaths were 2.5% for singletons and 3.2% for twins during 1979-1985. The difference is significant at the 5% level. The incidence rate of anencephalus among fetal deaths during the period was higher in singletons than twins in each year, whereas the incidence rate of congenital hydrocephalus among twins was similar to that among singletons except in 1985. The concordance rates were 5.7% for anencephalus, 9% for spina bifida, and 15% for congenital hydrocephalus during the period. In two cases one twin had anencephalus and the other congenital hydrocephalus, and in one case one twin had anencephalus and the other spina bifida. Nationwide data on 112 sets of conjoined twins who died as fetuses or in the postnatal period during 1979-1985 were analysed. Female conjoined twins ac- counted for 60% of cases. The incidence rate of conjoined twins remained constant throughout the period except in 1985. The overall incidence rate was 10 per million births. A maternal age effect was found in mothers over the age of 40, where the highest incidence rate occurred. The incidence rate increased with birth order.
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  • 1990 Volume 30 Issue 1 Pages 79-92
    Published: 1990
    Released: July 27, 2021
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    ABSTRACT Insufficient as well as excessive amounts of essential micronutrients such as vitamins and minerals are known to be deleterious to developing embryos in mammals. However, no detailed analysis of the effects of biotin deficiency on mammalian embryos has been reported. We demonstrated that maternal biotin deficiency produced a high incidence of external and skeletal malformations in mice, although the dams showed no clinical signs of biotin deficiency during gestation. The prominent malformations were craniofacial and limb malformations such as cleft palate, micrognathia, and micromelia. A dose-response relationship was observed in the incidences of the respective malformations. The formation of secondary palatal processes and limb buds was delayed at midgestation in these biotin-deficient mouse embryos, probably leading later to cleft palate and limb malformations. When the teratogenicity of biotin deficiency was compared in three mammalian species, striking species and strain differences were detected. Excess retinoids are embryotoxic and teratogenic in mammals, causing especially high incidences of craniofacial and limb malformations. We examined the mechanism of action of retinoic acids (13-cis-, 4-oxo-13-cis-, and all-trans-) on the cranio- facial tissues of mouse embryos using whole embryo culture and primary cell culture. In cultured embryos, retinoic acids caused overall embryonic growth retardation, particularly in the facial processes (maxillary, mandibular, and nasal). Histological examination of mouse embryos at midgestation showed that cranial neural crest cells were not migratory and demonstrated pyknotic nuclei in the mesenchyme adjacent to the epithelium in nasal processes. Biochemical analysis revealed that retinoic acids also inhibit DNA synthesis and the proliferation of mesenchymal cells in facial processes, a finding that is relevant to the mechanisms of retinoic acid- induced craniofacial malformations. It is proposed that the role of micronutrients in embryonic growth and development should be evaluated at the cellular level using whole embryo culture and embryonic cell culture.
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  • 1990 Volume 30 Issue 1 Pages 93-95
    Published: 1990
    Released: July 27, 2021
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    ABSTRACT A rapid procedure was developed for staining fetal rat specimens. Full-term rat fetuses were fiied in 99% ethanol and only thoracoabdominal organs were removed. Without skinning and removing adipose tissue and eye balls, the specimens were placed in 85% ethanol containing 1.5% KOH and 0.0015% alizarin red S for 5 days. The specimens were macerated in 1% aqueous KOH and cleared in 50% glycerin solution. The skeleton was visible through surrounding tissue containing adipose tissue which became transparent.
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  • 1990 Volume 30 Issue 1 Pages 95-100
    Published: 1990
    Released: July 27, 2021
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