ABSTRACT An autopsy case of Klippel-Feil syndrome with the classical triad of short neck, low posterior hairline and limitation of neck movement is reported. The patient died of cardiac failure resulting from complicated serious cardiovascular anomalies such as double outlet right ventricle, congenital mitral valve stenosis and coarctation of aorta. The condition was also complicated by radial ray deficiency of the left arm and asymmetry of the thyroid gland. Narrowing of the left subclavian and axillary arteries was detected by angiography while the patient was alive, a finding which may suggest the etiology of this congenital anomaly complex.
ABSTRACT This study was undertaken to elucidate the pathogenesis of the hydrocepha- lus and aqueductal stenosis induced by intracerebral mumps virus inoculation in suck- ling hamsters. Mild ventricular dilatation became apparent after 5 days of inoculation. Focal denuding of the ependymal layer and subsequent aqueductal stenosis were observed by 14 days after inoculation. The virus antigen was detected not only in the ependymal cells and choroid plexus, but also in some neurons in the cerebral cortex, hippocampus, midbrain and cerebellum. In the cerebral aqueduct, the orderly arrangement of the cilialy clusters was destroyed on the 5th day after inoculation. After 10 days, proliferation of GFAP positive cells was noticed around the cerebral aqueduct and subsequently caused aqueductal stenosis. In the advanced state of hydrocephalus, the cerebellum was displaced down- ward and showed an elongated, atrophic and sleevelike structure similar to the Arnold-Chiari malformation. It was suggested that the extensive damage of the ependymal cilia may account for early ventricular dilatation, and subsequent aqueductal stenosis with glial proliferation is the main cause of the advanced hydrocephalus. It has not yet been determined whether the mumps virus can pass through the human placenta or not. If it can, however, our results strongly suggest that mumps virus infection in the human fetus will cause congenital hydrocephalus.
ABSTRACT Intraperitoneal inoculation of suckling hamsters with parainfluenza virus type 3 (PIV-3) caused hydrocephalus in about 17% of animals thus treated. In the inoculated hamsters, the PIV-3 antigen was found to be located in the choroid plexus and ependymal cells of the ventricular system. This finding suggests that the PIV-3 inoculated intraperitoneally transferred to the choroid plexus from the blood stream and invades this tissue first, and then gradually affects the ependymal cells of the ventricular system. The pathologic findings obtained in this experiment showed a close similarity with those obtained in our previous experiment on mumps virus induced hydrocephalus. It was conjectured that PIV-3 induced hydrocephalus was caused by the same pathogenesis with the hydrocephalus by mumps virus infection. Our results strongly suggest that the PIV is a probable candidate for human congenital hydrocephalus of unknown origin, since PIV is the most common myxovirus.
ABSTRACT The teratogenic effect of chlorambucil (CA), given during proliferation of matrix cells of the brain following the closure of the neural tube, on the development of central nervous system in mouse embryos was investigated histologically. CA (4, 8 or 15 mg/kg) was given orally to pregnant mice on day 9, 10, 11 or 12 of gestation by single shot, and the fetuses were examined on day 18 of gestation. Significant decrease in the brain size and microcephaly occurred in fetuses treated with CA regardless of the gestational age studied. The microcephalic brains were characterized by the severe reduction of the cerebral hemispheres in a rostrocaudal direction rather than in the lateral directions. The fetal brains from mice given a low dosage of 4 mg/kg CA maintained normal cerebral cortex, but higher dosages (8 or 15 mg/kg) showed severe dysplasia of all the cerebral histological structures. In the groups treated with 8 or 15 mg/kg CA on day 10 or 11 of gestation, severe cranial malformations, identified as cranioschisis or encephalocele, were often observed. The malformed brains with cranioschisis showed an extensive necrosis of the brain tissue around the lesions. The present study shows that the microcephaly induced by cytotoxic teratogens such as CA, given.during the proliferative period of matrix cells after closure of the neural tube, is different from that induced during the migratory period of the neuroblasts, and suggests that the degeneration of the brain tissue by the cytotoxic agent may induce the partial anencephaly in mice.
ABSTRACT The rodent embryo culture has widely been spread as a technique in teratogenicity studies. However, the whole embryo culture of rabbits has not been developed. Pregnant rabbits are usually used in a teratogenicity test as a non-rodent animal to examine the species specificity. Rabbit embryos of the Japanese White strain on day 10 of gestation (the time of copulation = day 0) were cultured at 38°C for 48 hours in 100% rabbit serum. The 35 ml bottles with 5 ml serum were gassed with 95070 02 and 5% C02 continuously. The yolk sac and amniotic sac were opened 24 hours after the beginning of the culture. At the end of the culture, embryos were examined for somite number, as well as protein content and crown-rump length. Embryos cultured for 48 hours from day 10 seemed to be well developed as well as in vivo embryos. These results showed that rabbit embryo culture became a useful system for the study of reproductive and developmental toxicology, teratology and developmental biology.
ABSTRACT In order to contribute to international harmonization on reproductive and developmental toxicity studies of pharmaceutical drugs, European Community (EC) has introduced the drafts of guidelines for the tests in succession. The draft 11 was announced on June 21, 1991 and the Committee on the Guidelines of Reproductive and Develop- mental Toxicity Studies, Japanese Teratology Society reviewed it on July 12, 1991. Six general and 50 individual comments were drawn up. It is hoped that through hot inter- national discussion with supporting scientific data, the true international harmonization of the guidelines on reproductive and developmental toxicity studies will be achieved.