Search PubMed⌕ Search

Biomedical subjects

D A Beckman

Publications and source records attributed to D A Beckman.

44 records · Page 3Linked to original sources
PubMedDate not supplied

Sources of amino acids for protein synthesis during early organogenesis in the rat. I. Relative contributions of free amino acids and of proteins.

Rat conceptuses on the 10th day of gestation were cultured for 27 h in whole rat serum. An addition of either [3H]leucine or [3H]leucine-labelled rat serum proteins was made once during the culture period, and the acid-soluble and acid-insoluble radioactivities of embryo and visceral yolk sac measured at harvesting. The extent of radiolabel incorporation into embryonic and yolk-sac proteins increased linearly with the duration of exposure of the conceptus to the radiolabelled leucine or radiolabelled serum proteins, indicating roughly constant rates of incorporation, per unit mass of tissue, throughout the culture period. The incorporation rates, expressed as clearances, were 0.73 and 0.78 microliter/mg tissue protein/h for embryo and yolk sac, respectively, when the source was [3H]leucine; and 1.8 and 1.3 microliters/mg tissue protein/h, for embryo and yolk sac, respectively, when the source was [3H]leucine-labelled serum proteins. It is estimated, from the known leucine and protein concentrations in serum, that protein contributed over 99 per cent of the leucine supplied to the conceptus for its protein synthesis. In parallel experiments, measurements were made on cultures conducted in the presence of an antiserum against rat visceral yolk sac (100 micrograms/ml). Antiserum profoundly inhibited incorporation of radioactivity into embryo and yolk-sac proteins, when the source was 3H-labelled protein, a result consistent with the known ability of the antiserum to inhibit pinocytosis in the yolk sac. Antiserum also decreased incorporation from [3H]leucine in the yolk sac, suggesting that a proportion of the free leucine entering the yolk sac does so by pinocytosis. The failure of antiserum to affect incorporation of [3H]leucine into the embryo probably indicates that leucine can enter the embryo without the mediation of yolk-sac pinocytosis. The primacy of protein, as a source of amino acids for the organogenesis-stage embryo, is consistent with the serious effects, in terms of embryonic death and malformation, that result from the interruption of amino acid supply when either pinocytosis or lysosomal proteolysis in the yolk sac is inhibited.

Amino Acids↗
PubMedDate not supplied

Pinocytosis in the rat visceral yolk sac: potential role in amino acid nutrition during the fetal period.

At 9.5 to 10.5 days post-conception (p.c.) the rat embryo receives amino acids primarily by pinocytosis of maternal proteins by the visceral yolk sac (VYS) endodermal cells and their subsequent digestion in lysosomes. As this mechanism may also contribute to the nutritional support of the rapidly growing fetus later in gestation, this study determines the potential of the VYS to contribute to the amino acid needs of the rat fetus on 13.5, 15.5 and 17.5 days p.c. Wistar rats were killed on 11.5, 13.5, 15.5, 17.5 and 19.5 days p.c. and the protein content of fetuses, VYSs and serum was determined. Additional VYSs were isolated on the same days p.c. and the uptake of [14C]sucrose, a measure of fluid-phase pinocytosis, was determined. The rate of protein accretion by the fetus and the capacity of the VYS to pinocytose and digest proteins were calculated on 13.5, 15.5 and 17.5 days p.c. There was a decrease in pinocytic capacity, per mg protein, over the period of development studied but, owing to the growth of the tissue, the total capacity of the yolk sac to pinocytose and digest proteins increased from 13.5 to 17.5 days p.c. Comparison of the VYSs capacity to pinocytose and digest proteins and the rate of protein accretion by the fetus suggests that the VYS could support a significant proportion of the increase in protein content of the growing fetus. This conclusion is reinforced by the limited capacity of the maternal plasma to supply free amino acids to the fetus.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acids↗
PubMedDate not supplied

Mechanisms of amino acid supply to the rat conceptus in normal and abnormal development.

Using in vitro and in vivo models, we have shown that protein is an important source of amino acids from 8.5 to 17.5 d postconception, a significant portion of postimplantation development in the rat. This satisfactorily explains why inhibition of protein pinocytosis and digestion by the visceral yolk sac may lead to congenital malformations, growth retardation, and intrauterine death during organogenesis and growth retardation and death during fetal stages. In humans, this process may be just as important and possibly just as vulnerable to inhibition, but other placental or paraplacental tissues may be involved in addition to the secondary yolk sac.

Amino Acids↗
PubMedDate not supplied

Leucine sources for 10.5-day rat conceptus in vivo.

Protein has been shown to be the principal source of leucine for the Day 8.5 to 10.5 rat conceptus in culture. It could be argued that this finding applies only after adaptation to culture conditions and does not apply in vivo. This possibility was investigated using an isotope-dilution technique after i.v. injection of [3H]leucine into Day 10.5 pregnant rats. Specific radioactivity of free leucine in the conceptus was 8 to 10% of that in maternal plasma. Slow exchange of leucine with the maternal circulation and fetal tissue protein turnover were judged to be inadequate as explanations for the observed isotope dilution. Taken together, our results and those from in vitro studies are consistent with a major contribution of leucine coming from the degradation of protein in vivo, probably involving the visceral yolk sac. Our results suggest that mechanisms of amino acid supply to the conceptus identified using whole-embryo culture mirror those in vivo.

Animals↗
PubMedDate not supplied

Environmental teratogens.

By far the largest category of malformations, 65% falls into the group of those with an unknown cause(s). Purely genetic causes of malformations (autosomal and cytogenetic), estimated to produce 20 to 25% of all human malformations, comprise the largest group of congenital malformations with known etiology. Although environmental causes of human malformations account for 10% or fewer of malformations, most of these environmentally induced malformations are related to maternal disease states. Fewer than 1% of all human malformations are related to drug exposure, chemicals, or radiation, but studies of environmentally induced malformations are important because they may teach us how to predict and test for teratogenicity, understand the mechanisms of teratogenesis from all etiologies, and provide a means by which human malformations can be prevented.

Abnormalities, Drug-Induced↗