Biomedical subjects

N L Bucher

Publications and source records attributed to N L Bucher.

At least 37 records · Page 2Linked to original sources

PubMed1982

Stimulation of DNA synthesis in primary cultures of adult rat hepatocytes by rat platelet-associated substance(s).

Experiments in whole animals have shown that normally quiescent adult rat hepatocytes are induced to proliferate by blood borne substances, which we are now probing in primary monolayer cultures. Under our conditions, freshly isolated adult hepatocytes do not proliferate actively in a defined medium, but are stimulated to synthesize DNA--an essential first step--by either serum or an EGF-hormone combination. Stimulation of [3H]thymidine incorporation into hepatocyte DNA by addition of dialyzed mouse, human, horse, or bovine (fetal, newborn, or calf) serum, whose activities are all similar, is regularly surpassed by an EGF-insulin mixture without serum. This, in turn, is exceeded by dialyzed normal rat serum, which is several times more potent than the other sera tested. Removal of blood platelets reduces the activity of normal rat serum by over 50%. Heat inactivation (56 degrees C) causes a similar loss, but heat treatment of platelet-poor serum fails to cause further reduction. The activity of mouse and human serum is not reduced by platelet removal. Serum from partially hepatectomized rats is not significantly more stimulatory than normal rat serum, and its activity is depressed in the same way by platelet deprivation and heat inactivation. Lack of enhancement by partial hepatectomy is not consonant with whole animal studies and requires further investigation. The heat-labile portion of the DNA synthesis-stimulating activity of rat serum appears to derive from platelets. This activity differs from the well-characterized heat-stable human PDGF. Its relation to other reported platelet-associated growth factors is still undetermined.

Animals↗

PubMed1981

DNA synthesis in primary cultures of adult rat hepatocytes in a defined medium: effects of epidermal growth factor, insulin, glucagon, and cyclic-AMP.

Epidermal growth factor (EGF) especially in combination with insulin and glucagon, has been shown to stimulate DNA synthesis in liver cells, both in the whole animal and in cell cultures. As a further development we have found that in primary monolayer cultures of freshly isolated adult rat liver parenchymal cells, in which contamination with nonparenchymal cells was negligible, DNA synthesis was substantially stimulated by these substances. In control cultures, incorporation of [3H]thymidine into DNA and labeling of nuclei in autoradiographs was low. The stimulation by EGF was enhanced by insulin and glucagon, whereas these hormones by themselves exhibited only limited activity. These observations were made in cultures of hepatocytes that were never exposed to serum, even during cell isolation and plating. Hence for stimulation of DNA synthesis under these conditions neither serum factors nor interactions with other types of cells or their products were required. The effects of glucagon were reproduced by substances that elevate intracellular concentration of cyclic-AMP, including cholera toxin, isoproterenol, and methylisobutylxanthine. These various substances, especially EGF, glucagon, or cyclic-AMP, altered the morphological characteristics of the cultures during early stages, promoting cellular spreading and aggregation.

Animals↗

PubMed1980

Effect of acute and chronic ethanol intoxication on hepatic regeneration.

We studied the effects of acute and chronic ethanol feeding on hepatic regeneration in rats following partial hepatectomy and toxic liver injury produced by D-galactosamine. Ethanol, when administered as a single dose (6 gm/kg), inhibited 3H-thymidine incorporation into hepatic DNA; this effect depended in part on the time of ethanol feeding following partial hepatectomy. Multiple ethanol feedings produced an even greater inhibition, which persisted for at least 48 hr after partial hepatectomy. Rats chronically fed ethanol for 30 days also failed to achieve a hepatic proliferative response to either partial hepatectomy or D-galactosamine induced hepatitis comparable to isocaloric pair-fed controls. These investigations suggest that there may be a certain metabolic state in the hepatocyte cell cycle which is most susceptible to the action(s) of ethanol; inhibition of liver regeneration by acute or chronic ethanol consumption may result in delayed recovery from prior or coincident liver injury.

Alcoholic Intoxication↗

PubMed1979

Negligible role of adrenal hormones in regulation of DNA synthesis in livers of partially hepatectomized rats.

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Adrenal Cortex Hormones↗

PubMed1979

Inhibition of hepatic regeneration in rats by acute and chronic ethanol intoxication.

We studied the effects of acute and chronic ethanol feeding on hepatic regeneration in rats after partial hepatectomy and toxic liver injury produced by D-galactosamine. Ethanol, when administered as a single dose (6 g/kg), inhibited 3H-thymidine incorporation into hepatic DNA; this effect depended in part on the time of ethanol feeding after partial hepatectomy. Multiple ethanol feedings produced an even greater inhibition, which persisted for at least 48 hr after partial hepatectomy. Rats chronically fed ethanol for 30 days also failed to achieve a hepatic proliferative response to either partial hepatectomy or D-galactosamine-induced hepatitis, comparable with isocaloric pair-fed controls. These investigations suggest that there may be a certain metabolic state in the hepatocyte cell cycle that is most susceptible to the action(s) of ethanol; inhibition of liver regeneration by acute or chronic ethanol consumption may result in delayed recovery from prior or coincident liver injury.

Alcoholic Intoxication↗

PubMed1977

Hormonal factors concerned with liver regeneration.

Hepatic regeneration in partially hepatectomized, eviscerated rats, and survival in mice infected with lethal doses of murine hepatitis virus, are both strikingly promoted by combined administration of insulin and glucagon. These two hormones, although potent promotors, fail as initiators of hepatocyte proliferation in animals with intact liver, which suggests a requirement for additional factors, probably derived from non-portal-splanchnic organs. We now find that continous intraperitoneal infusion of epidermal growth factor (EGF) initiates DNA synthesis, as determined by incorporation of [3H] thymidine, in livers of adult rats in vivo. The rise in DNA labelling, which is small with EGF alone, is augmented by addition to the infusion of either glucagon or insulin. This is in agreement with reports on adult hepatocytes in culture. Whether EGF has a physiological role in regulating liver growth under normal conditions in vivo remains to be determined.

Age Factors↗

PubMed1976