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Biomedical subjects

J A Geelen

Publications and source records attributed to J A Geelen.

30 records · Page 2Linked to original sources
PubMed1980

The influence of excess vitamin A on neural tube closure in the mouse embryo.

The effect of excess vitamin A on the closure of the neural tube in mouse embryos was examined with light microscopy, transmission and scanning electronmicroscopy. The embryos were treated with the vitamin just before closure of the brain vesicles and examined during the following 24 h, a period during which under normal conditions the brain completely closes. At 18--24 h after treatment the external features of the treated specimens began to differ from those of the controls. In the treated embryos the neural walls folded laterally and became widely separated, whereas those of the controls folded dorsomedially and fused in the midline. Histologically, the first difference between treated and control embryos was noted at two hours after treatment, when large intercellular spaces appeared between the neuroepithelial cells of the treated embryos. These spaces were mainly present between the apical ends of the wedge-shaped neuroepithelial cells. This accumulation of intercellular spaces interfered with the normal morphogenetic movement of the neural walls which remained convex instead of becoming concave. This convex bending resulted in non-closure of the neural tube. In addition to the appearance of large intercellular spaces some neuroepithelial cells as well as some mesenchymal, endothelial, and surface ectoderm cells showed swelling and degeneration as a result of the vitamin A treatment. This cell degeneration probably contributes to failure of the neural tube to close due to loss of cohesion at the luminal surface and the lack of mesenchymal support needed for the elevation of the neural walls. However, the increase of intercellular spaces at the apical side of the neuroepithelium is in all probability the major cause for the failure of the neural tube to close.

Animals↗
PubMed1979

Light microscopic and ultrastructural observations in advanced stages of induced exencephaly and spinal bifida.

This investigation was performed to demonstrate the morphologic basis of the elevation of fetal proteins in the amniotic fluid of fetuses with neural tube defects. Pregnant rats were treated with hypervitaminosis. A to induce exencephaly or with trypan blue to produce spina bifida aperta. The malformations were studied on days 15-20. On day 15 of gestation, edema developed in the primitive nervous tissue. This was followed by the appearance of quickly expanding hemorrhages throughout the ventricular and intermediate zones. Some capillaries did not rupture but collapsed and showed degenerative changes of the endothelium, probably due to lack of blood perfusion. The ventricular layer in exencephaly and spina bifida aperta was exposed to the amniotic cavity due to non closure of the neural tube. On day 17, this superficial lining of the primitive nervous tissue was disrupted by the expanding hemorrhages and subsequent necrosis. As a result vast amounts of fetal blood and cell debris were extruded into the amniotic fluid. During days 18 to 20, the degeneration of the nervous tissue proceeded rapidly. This process showed the same features in the ventricular cells, the primitive neurons and the neurons. Initially it was characterized by condensation of the nuclear chromatin and the cytoplasm, irregular outlines and breakdown of the plasma membrane. Only part of the cell debris was phagocytozed by macrophages. It is concluded that the leakage of fetal serum and cell debris causes the elevation of fetal protein levels in the amniotic fluid of fetuses with open neural tube defects.

Abnormalities, Drug-Induced↗
PubMed1979

Hypervitaminosis A induced teratogenesis.

In the past decade, the toxicology of reproduction has become increasingly important. This branch of toxicology focuses on mutagenic and embryotoxic effects. The study of embryotoxicity requires an extensive knowledge of the interaction of drugs and embryonic tissues, normal and abnormal developmental processes, and the susceptible stages during prenatal development. Hypervitaminosis A is one of the most extensively studied teratogens. It produces defects in almost all organ systems. Therefore, this article will first of all review the vitamin A-induced malformations in several organ systems. Moreover, it will discuss their morphogenesis and the susceptible developmental stages. Thus, the first ten chapters will cover the following subjects: malformations of the nervous system, ocular malformations, malformations of the ear, craniofacial malformations, cleft palate, defects of the circulatory system, defects of the respiratory systems, defects of the digestive tract, urogenital defects, skeletal malformations, and abnormal postnatal development. Since in general little is known about the mechanisms involved in the induction of congenital defects, we think it is of great value to review the knowledge and experience that have been gathered by the experimental work with hypervitaminosis A. Therefore, the next chapters will discuss the following subjects: teratogenic effects in different species, minimum effective dose, interaction with other agents, influence of chemical form, solvent, and route of administration, pathophysiology of vitamin A embryotoxicity, and hypervitaminosis A and human pregnancy.

Abnormalities, Drug-Induced↗