Lipid peroxidation and the degradation of cytochrome P-450 heme.
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Biomedical subjects
Publications and source records attributed to M Jacobson.
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The central connections of retinal ganglion cells are retinotopically organized, producing a "map" of the retina on the surface of the optic tectum. Exactly how and when individual ganglion cells develop the position-dependent properties (termed locus specificities) subserving formation of the map is unknown, but the positional information that each ganglion cell will use in this process is specified in the early Xenopus embryo during a critical period at stages 28-32. We report two methods for isolating eye primordia from the axial cues of the animals during this critical period and for then allowing the eyes to form retinotectal connections in a carrier embryo. The results show that, as early as optic vesicle stages 22-23, the eyes already contain orthogonal reference axes, that positional information can be specified with respect to these axes in vitro, and that the specification process itself may only entail a transition from a reversible to an irreversible state.
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Administration of certain commonly used barbiturates containing allyl groups, such as secobarbital, allobarbital, or aprobarbital to rats treated chronically with a microsomal enzyme inducer causes a rapid destruction of the liver microsomal hemoprotein that serves as the terminal oxidase for drug metabolism. In contrast, barbiturates without an allyl group do not have this effect. The decrease in this hemoprotein, cytochrome P(450), by the barbiturates containing an allyl group could also be demonstrated in an in vitro liver microsomal system requiring reduced nicotinamide adenine dinucleotide phosphate. These results suggest that the barbiturates containing an allyl group are converted to a metabolite that leads to the destruction of cytochrome P(450).
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In the normal development of retinotectal connections, the site in the tectum at which an optic fiber synapses is related to the position of its ganglion-cell body in the retina. How and when the ganglion cells acquire information about their positions is unknown, but the positional information that each ganglion cell will ultimately act upon is determined or specified at embryonic stages 28-32 in the clawed frog, Xenopus laevis. Here we report that once positional information has been so specified, it remains stable when the eye is "back-grafted" into the orbit of a stage-28 host, or cultured in vitro for up to 10 days before grafting into the orbit of a stage-38 host. Thus, the ganglion cells of these eyes form tectal connections appropriate to their original positions in the donor orbits and independent of their final positions in the host orbits. We conclude that specification of positional information involves stable changes in the phenotypic properties of the differentiating retinal cells that (i) render the cells refractory to information about changes in their positions after stage 32 and (ii) commit each ganglion cell to the development of a unique property (locus specificity) that predisposes its axon to synapse at a particular locus in the retinotectal map.
Neuronal specificity in retinal ganglion cells of Xenopus subserves the orderly connections of the optic nerve fibers in the tectum. This specificity derives from positional information acquired by the developing retina at embryonic stages 28-31. Here we report that ganglion cells of embryonic stage 28 eyes can acquire positional information with reference to the major axes of the body not only in the ocular orbit but also at other positions on the side of the body. When returned to the orbit this eye will form appropriate retinotectal connections. Conversely, retinal ganglion cells of stage 31 eyes, which have acquired positional information in the orbit, will retain their original neuronal positional specificities if the formation of retinotectal connections is delayed by grafting the eye to the flank for 30 days before returning it to the orbit. We conclude that neuronal specificity of retinal ganglion cells (a) does not derive from "inducers" unique to the periocular tissues; and (b) persists for some time independently of the establishment of retinotectal connections.
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