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C I LEVENE

Publications and source records attributed to C I LEVENE.

At least 19 recordsLinked to original sources
PubMed1962

Studies on the mode of action of lathyrogenic compounds.

The lathyrogenic effect of INAH in the chick embryo may be measured by the increase in the extractibility of collagen from the bones with 1 M NaCl. Incubation of these bones in vitro with carbonyl compounds diminishes the amount of extractible collagen; with D-L-glyceraldehyde the reversal of the INAH effect is complete. This reversal effect is dependent on the time and temperature of incubation and on the quantity of D-L-glyceraldehyde, but is independent of the pH of the incubating medium, the optical form of the glyceraldehyde, or the metabolism of the cells; this suggests that it depends on a simple chemical combination. D-L-glyceraldehyde also reverses completely the extractibility of collagen from the bones of embryos rendered lathyrogenic with BAPN, semicarbazide, and hydrazine hydrate. The hypothesis has been advanced "that lathyrogenic agents act by blocking carbonyl groups on the collagen molecule, thus preventing cross-linking essential to normal maturation; normal maturation may be restored by the addition of carbonyl groups which act by competing either for the lathyrogen or for functional sites on the collagen molecule." In support of this hypothesis, it has been shown that purified lathyritic guinea pig collagen takes up lesser amounts of 2,4-dinitrophenylhydrazine-a compound which combines with carbonyl groups-than does normal collagen; it has been shown that lathyritic collagen still possesses the ability to form segment-long-spacing (SLS) collagen, but that these fibres are much thinner than normal; this is due perhaps to blockade of groups essential for lateral cross-linking of the tropocollagen unit. It has also been shown that normal, purified guinea pig collagen which has been pretreated with INAH, takes up lesser amounts of 2,4-dinitrophenylhydrazine and forms much thinner SLS fibres than the untreated controls.

Animals↗
PubMed1961

Structural requirements for lathyrogenic agents.

Using the chick embryo assay system, a series of organic compounds was tested for lathyrogenic activity; lathyrogenic compounds were shown to fall into 4 groups-nitriles, ureides, and 2 new groups-hydrazides and hydrazines, forming a spectrum of diminishing potency in their ability to produce solubility of collagen and skeletal deformities. Pyridoxal was seen to reverse to a great degree the effects on collagen solubility and skeletal deformity produced by the ureides and hydrazides, though not by the nitriles; its effect was considered to be due to the formation of a Schiff's complex between the aldehyde and the terminal amine of the lathyrogen. Evidence is presented to show that lathyrogens do not act as inhibitors of monoamine oxidases or as chelate-forming agents, nor, in the case of isoniazid, as an anti-nicotinamide agent.

Animals↗
PubMed1961

The lathyrogenic effect of isonicotinic acid hydrazide (INAH) on the chick embryo and its reversal by pyridoxal.

When applied to the chorio-allantoic membrane of the chick embryo, isoniazid was shown to produce an increase in the fragility of the embryo and in the amount of collagen which was extractable from the bones with cold 1 M sodium chloride. The administration of pyridoxal reversed these phenomena almost completely. The effect of isoniazid differed from that of beta-aminopropionitrile in that the latter was of greater magnitude, and was not affected by pyridoxal; whereas beta-aminopropionitrile caused skeletal deformities, isoniazid even at 12 times the concentration produced no deformities. The aldehyde group of pyridoxal was shown to be necessary for its interaction with isoniazid.

Aminopropionitrile↗
PubMed1959

Morphologic evidence for collagen changes in chick embryos treated with beta-aminopropionitrile.

Electron microscope analysis of thin sections of intact skin from 17 day chick embryos injected with beta-aminopropionitrile 3 days earlier, revealed markedly increased dispersion in fibril diameter both above and below the narrow distribution of normal fibril size. Extraction with cold 1 M neutral saline caused a dissolution of the fibrils to fine filaments of varying diameters. Histologic examination of the connective tissue of lathyritic skin prior to extraction revealed little difference from the normal. After extraction the collagen either disappeared almost entirely or was observed as a homogeneous smear. These results of morphologic analysis are consistent with previous chemical studies, supporting the thesis that lathyrogenic agents induce disruption of intermolecular cross-linking within normally insoluble collagen fibrils, allowing them to dissolve in cold neutral salt solutions.

Aminopropionitrile↗
PubMed1959

Alterations in state of molecular aggregation of collagen induced in chick embryos by beta-aminopropionitrile (lathyrus factor).

The lathyrogenic agents, beta-aminopropionitrile and semicarbizide, when applied to the chorio-allantoic membrane of the chick embryo produced a dramatic increase in fragility of the embryo. This alteration was not associated with a change in the concentration of collagen, except in aorta, but was accompanied by a sharp increase in the amount of collagen extractible in cold 1 M NaCl from skin, bone, and aorta. Increase in fragility and extractible collagen began within 3 hours after introduction of the agent and rose steadily for at least 72 hours. Essentially no collagen could be extracted from tissues of normal chick embryos. Both fragility and amount of extractible collagen were dosage- and time-dependent. It is concluded that the extractible collagen in lathyrism consists of a large proportion of dissolved fibers previously insoluble and formed prior to administration of the agent. The data also suggest that the "lathyritic" collagen in vivo is not in molecular dispersion but in an aggregate or fibrillar form. It is dispersed by cooling. The extracted collagen could be reconstituted to typical striated fibrils in vitro and the molecule appeared to be normal in the gross, with regard to asymmetry ratio and intramolecular helical structure. The evidence at hand suggests that at least one of the defects induced by lathyrogenic agents is an interference with the normal intermolecular cross-linking within the collagen fibril.

Aminopropionitrile↗