ABSTRACT Histopathological examination of the muscle and the iliac crest cartilage were performed in a one year 6-month-old girl with chondrodysplacia punctata. The patient's mother was also affected. Light micrographs of the cartilage revealed long, tongue-like processes extending into the osseous tissue in the osteochondral junction. Electron micrographs of the cartilage showed an increased number of lipid droplets in chondrocytes and more numerous hydroxyapatite clusters and matrix vesicles in the inter- territorial matrix. Pathological findings of the biopsied muscle included derangement and/or missing cross-striations, together with many vacuoles in the muscle fibers. These degenerative changes in both the muscle and the cartilage as well as many associated complications may suggest that chondrodysplasia punctata is a generalized metabolic disorder.
ABSTRACT Congenital malformations such as exencephaly occur at a high incidence in non-obese diabetic (NOD) mouse embryos (Otani et al., 1987a). Using in vitro culture and embryo transfer, genetic predispositions as well as environ- mental factors were suggested to be the causes (Tatewaki et al., 1987). Chromosomes of preimplantation embryos, cultured to transfer mutually be- tween non-obese diabetic (NOD) and ICR mice, were analyzed as a clue to elucidate the cause of developmental anomalies. Among these preimplantation embryos, aneuploidy, mixoploidy and structural anomalies were found, but in incidence of chromosomal anomalies there was no significant difference, statistically, between preimplantation embryos from diabetic mothers and those from non- diabetic mothers. These findings are considered to show that no increase in developmental abnormality in chromosomes occurs during the preimplantation stage.
ABSTRACT Sprague-Dawley rats were ' given L-phenylalanine intraperitoneally from the 8th to 11 th day of pregnancy. The hearts of the fetuses were examined on the 21st day of pregnancy. We found that the group given the higher doses of L-phenylalanine had significantly more heart defects than the group given the lower dose and the controls. Ventricular septa1 defect was found in 80 % of the fetuses with congenital deformities of the heart. [<C] Leucine uptake by the embryos was significantly lower in the group loaded with L-phenylalanine than in the controls. The activity of thymidine kinase, one of the rate-limiting enzymes in DNA synthesis, was significantly lower in the brain and heart tissues of the young rats loaded with L-phenylalanine than in the controls. Thus, when blood levels of phenylalanine are high in early pregnancy, an amino acid imbalance in the embryo occurs during fetal organogenesis. Also, thymidine kinase decreases, which may hinder DNA synthesis. Both of these mechanisms seem to be involved in the higher incidence of fetal heart malformations in maternal phenylketonuria.
ABSTRACT Pathological studies on autopsied brains of mentally and physically handicapped children disclose not infrequently various abnormalities at the histological and cytological levels, such as the abnormal cytoarchitecture, hetero- topic neuronal nests, abnormal orientation of neurons and tortuous dendrites. These abnormalities have generally been considered to result from the disorders of neuron production and/or mechanical obstruction of neuronal migration including abnormal radial fibers. Our experimental studies on the microcephalic mouse, which was induced either by prenatal or by postnatal administration of cytosine arabinoside, indicated that the following factors play important roles for above mentioned histological and cytological changes: (1) Disturbance of the neuron production following the destruction of the matrix layer. (2) Regional and incomplete regeneration of the matrix layer and delayed neuron production in the regenerated matrix layer. (3) Unbalanced and plastic synaptogenesis between the remaining neurons which have been produced prior to the destruction of the matrix layer, migrating young neurons produced in the regenerated matrix layer and the afferent fiber terminals which originate from subcortical neurons.