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Biomedical subjects

A M Nemeth

Publications and source records attributed to A M Nemeth.

14 recordsLinked to original sources
PubMed1984

Biological systems: recognition of covariance.

'Hold all variables constant except one', is not a feasible approach to the study of the many biological systems in which variables are not independent, but covariant. Covariance means that the efficacy of a variable depends on the values of other variables. The presence of covariance in biological systems must be recognized in the design of experiments and the analysis of results.

Analysis of Variance↗
PubMed1983

Regulation of monooxygenation during development of chick embryo liver: role of cytochrome P-450 isozymes and NADPH.

The endoplasmic reticulum of the liver cell, supplied with molecular oxygen and NADPH, can monooxygenate a variety of lipid soluble compounds including steroids and many drugs. The essential enzymatic steps are carried out by cytochrome P-450 and NADPH cytochrome P-450 reductase. There are several molecular forms (isozymes) of cytochrome P-450 in liver, and it has been shown that their relative concentrations change during development and in response to phenobarbital. Because substrate specificities of the isozymes differ to some extent, changes in the isozyme pattern should alter the pattern of substrate utilization if the isozymes are controlling the rates of monooxygenation. We found that the rates of testosterone hydroxylation and the oxidative N-demethylations of benzphetamine, codeine, and ethylmorphine were equal in endoplasmic reticulum isolated from chick embryo liver on day 11 of egg incubation, and this equality was unaffected by age or phenobarbital. Thus, monooxygenation rates do not appear to be controlled by the isozymes of cytochrome P-450. A factor that might affect the pattern of steroid and drug utilization by endoplasmic reticulum may be the availability of reducing equivalents. Lowering the concentration of NADPH to one half-optimum values in our reaction mixtures (0.5 to 0.25 mM) diminished the monooxygenation rate of benzphetamine by 8%, of testosterone by 40%, and of codeine and ethylmorphine by 60%. These differential effects were independent of age and phenobarbital. Thus, the pattern of substrate utilization by the monooxygenase system in vivo is probably altered by changes in the tissue concentration of NADPH.

Animals↗
PubMed1976

Proliferation of endoplasmic reticulum with its enzyme, UDP-glucuronyltransferase, in chick embryo liver during culture. Effects of phenobarbital.

UDP-Glucuronyltransferase (GT) activity increases in chick embryo liver during culture from zero to a steady-state level at or above adult values. The GT activity (o-aminophenol as acceptor) is located entirely in the membranes of the endoplasmic reticulum (ER) and the question arises whether ER increases along with GT. Earlier work showed that the synthesis and degradation rates of GT can be varied in culture over wide ranges by choosing embryo livers of different ages and both phenobarbital. In the present study we measured the GT activities and the concentrations of ER (using stereologic methods) in 5- and 11-day embryo liver during culture with and without phenobarbital. We found that GT and ER always increased in a constant ratio of 2.2 X 10(-9) U of GR activity per square micrometer of membrane, suggesting that the synthesis and degradation of GT are coupled to the synthesis and degradation of ER. A general structure for ER is proposed to explain this finding.

Animals↗
PubMed1972

Development of phenobarbital-sensitive control mechanisms for uridine diphosphate glucuronyltransferase activity in chick embryo liver.

Uridine diphosphate (UDP) glucuronyltransferase activity in chick liver rises at hatching from near zero to adult levels. This rise will occur prematurely in embryo liver during organ culture. Increase in enzyme activity during organ culture differs with embryo age: in liver from 11-day old embryos it ceases at adult values; in liver from 5-day old embryos it continues to much higher-than-adult levels. Phenobarbital added to culture medium accelerates these rises in enzyme activity and elevates the plateau reached in 11-day embryo liver to that observed in 5-day embryo liver. Kinetic analysis of the changes in enzyme activity induced by phenobarbital during culture suggests that the regulatory mechanisms for enzyme activity are different in 5- and 11-day embryo liver and that these differences reflect developmental changes occurring in ovo.

Age Factors↗
PubMed1971

Factors controlling development of chick embryo liver cells during organ culture.

The 5 day chick embryo liver cell still lacks many of the ultrastructural features of the adult liver cell. During organ culture on rafts over Eagle's medium, it develops electron-opaque mitochondria with granules, biliary microvilli, and compact Golgi complexes containing what appears to be secretory material. Rough ER proliferates and free ribosomes become bound to membrane. Thus, the 5 day cell, exposed only to simple nutrients (glucose, amino acids, vitamins) develops the general appearance of the adult liver cell except for the continued absence of smooth ER and glycogen. The significance of this incomplete differentiation and the factors controlling development are discussed in the light of accompanying metabolic changes.

Age Factors↗
PubMed1969

Factors influencing premature induction of UDP-glucuronyltransferase activity in cultured chick embryo liver cells.

Very young (5-day-old) chick embryo livers during organ culture on rafts over a chemically defined nutrient medium precociously develop, from zero, adult levels of UDP-glucuronyltransferase activity. Induction of enzyme does not require DNA synthesis or mitosis, or exposure to hormones, serum, or tissue extracts. Thus, this functional differentiation of embryo liver is apparently not dependent on cell proliferation or on extrinsic substances other than simple nutrients.UDP-glucuronyltransferase activity develops rapidly also in embryo liver cells cultured as monolayers or aggregates; specific activity of enzyme on a protein basis increases at the same rate in cells undergoing widely different rates of cell division, and net protein synthesis. These findings suggest that precocious development of UDP-glucuronyltransferase activity in chick embryo liver is due, not to incidents of culture, but to removal from the embryonic environment. Supporting this, chick embryo liver grafted to the chorioallantoic membrane does not develop UDP-glucuronyltransferase activity until subsequently transferred to an in vitro cell culture system.

Animals↗
PubMed1968

Placental transport of free palmitic and linoleic acids in the guinea pig.

Radioisotopic tracers were used to measure the unidirectional transfer rates of free fatty acids across the placenta of fed and fasted pregnant guinea pigs. Free (14)C-labeled palmitic and linoleic acids (in serum) were injected simultaneously into a jugular vein of an anesthetized pregnant guinea pig. Serial samples of maternal blood were collected from a carotid artery; fetal blood was collected from the umbilical vein of an exposed fetus. Analysis of maternal and fetal plasma revealed that: (a) the half-lives of free palmitic and linoleic acid in maternal plasma are approximately 1.3 min and 0.7 min, both in fed animals with low plasma concentrations of these acids and in fasted animals with high concentrations; (b) free linoleic and palmitic acids cross the placenta from maternal to fetal plasma in a ratio of approximately 2.0, a value which appears not to change as the transfer rates of these acids from maternal to fetal plasma are increased by fasting the mother. It is suggested that the ratio in which free linoleic and palmitic acids cross the placenta from maternal to fetal plasma is determined by the ratio of the unbound free linoleic and palmitic acid concentrations in maternal plasma. A comparison of several species indicates that a much greater proportion of fetal fatty acids comes from the mother in the guinea pig and rabbit than in the rat, the sheep, or man.

Adipose Tissue↗
PubMed1967

Development of uridine diphosphate-glucuronyltransferase activity in cultures of chick-embryo liver.

1. The liver of the domestric fowl (Gallus gallus) remains capable of conjugating o-aminophenol with glucuronic acid after 8 days' culture. The pathway of o-aminophenyl glucuronide formation in cultured liver, as in fresh tissue, includes the enzyme UDP-glucuronyltransferase. 2. UDP-glucuronyltransferase activity in chick-embryo liver increases on culture from very low to adult values within 6-8 days. 3. The development of UDP-glucuronyltransferase activity in cultured chick-embryo liver requires certain serum factors in the medium. The requirements change with embryo age. Liver from embryos younger than 15 days develops enzyme activity equally well in media containing either foetal or adult serum; liver from embryos older than 16 days develops activity only with adult serum. The development of enzyme activity in liver from the older embryos appears to be stimulated by diffusible factors in adult serum and inhibited by diffusible factors in foetal serum. It is suggested that the stimulation and inhibition of enzyme formation by small, diffusible molecules may be part of the mechanism regulating UDP-glucuronyltransferase activity in vivo. 4. Liver from 19-day-old chick embryos cultured with foetal serum begins to develop UDP-glucuronyltransferase activity if transferred to an adult-serum medium. Its capacity to develop UDP-glucuronyltransferase activity in adult serum survives in a foetal-serum medium for at least 5 days, the longest period tested. 5. The activity of UDP-glucuronyltransferase reached in 19-day chick-embryo liver after 1 or 2 days with adult serum is maintained without further increase after transfer to a foetal-serum medium. After 3 days with adult serum UDP-glucuronyltransferase activity continues to increase when the tissue is transferred to a foetal-serum medium. Thus liver from 19-day-old embryos requires 3 days with adult serum before development of enzyme activity becomes independent of a continuous adult-serum environment.

Aging↗