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Biomedical subjects

G E Shambaugh

Publications and source records attributed to G E Shambaugh.

At least 55 records · Page 3Linked to original sources
PubMed1987

Enzyme markers of maternal malnutrition in fetal rat brain.

The impact of maternal starvation in late gestation on development of some enzymatic mechanisms concerned with neurotransmission and polyamine synthesis was studied in fetal rat brain. Between 17 and 20 d, acetylcholinesterase and choline acetyltransferase activity increased in fetal brains of fed dams, whereas maternal starvation from day 17 to day 20 resulted in heightened acetylcholinesterase but not choline acetyltransferase activity. Ornithine decarboxylase activity on a per-gram wet-weight basis fell between 17 and 20 d in fetal brain from fed dams. Increasing the duration of maternal starvation resulted in a progressive increase in fetal brain ornithine decarboxylase. Arginine and putrescine levels in the brain were lower in fetuses of starved mothers while spermidine and spermine concentrations were unchanged. Since the Km of ornithine decarboxylase for ornithine was found to vary directly with levels of putrescine in fetal brain, lower concentrations of putrescine and greater ornithine decarboxylase activity in fetal brains from starved mothers suggested that levels of this enzyme may be controlled in part by putrescine. Changes in the maternal nutritional state had no effect on the activity of glutamate decarboxylase in fetal brain, and tissue levels of the product, gamma-aminobutyric acid, were unchanged. Thus changes in ornithine decarboxylase and acetylcholinesterase activity in fetal brain may uniquely reflect biochemical alterations consequent to maternal starvation.

Animals↗
PubMed1986

The 1986 McCollum award lecture. Fuel-mediated teratogenesis during early organogenesis: the effects of increased concentrations of glucose, ketones, or somatomedin inhibitor during rat embryo culture.

Whole rat embryos were explanted at head-fold, late pre-somite stage (day 9.5 of gestation) and cultured in rat sera varyingly supplemented with glucose (3, 6, 9, or 12 mg/mL), D,L sodium beta-hydroxybutyrate (2, 4, 8, or 16 mM), or both (6 mg/mL D-glucose plus 8 mM beta-hydroxybutyrate). During 48 h culture, increasing glucose alone or beta-hydroxybutyrate alone effected growth retardation and faulty neural and extraneural organogenesis in dose-dependent fashion. Synergistic dysmorphogenic effects occurred when minimally teratogenic concentrations of glucose and beta-hydroxybutyrate were combined. Sera from diabetic animals containing somatomedin inhibitor bioactivity were also able to produce growth retardation and major developmental lesions in presence of amounts of glucose and ketones which of themselves were not teratogenic. Thus, aberrant fuels and fuel-related products can impair growth and organogenesis in early post-implantation embryo. Such fuel-mediated teratogenesis may be multifactorial and include possibilities for synergistic and additive interactions.

3-Hydroxybutyric Acid↗
PubMed1985

Ketone body metabolism in the mother and fetus.

Pregnancy is characterized by a rapid accumulation of lipid stores during the first half of gestation and a utilization of these stores during the latter half of gestation. Lipogenesis results from dietary intake, an exaggerated insulin response, and an intensified inhibition of glucagon release. Increasing levels of placental lactogen and a heightened response of adipose tissue to additional lipolytic hormones balance lipogenesis in the fed state. Maternal starvation in late gestation lowers insulin, and lipolysis supervenes. The continued glucose drain by the conceptus aids in converting the maternal liver to a ketogenic organ, and ketone bodies produced from incoming fatty acids are not only utilized by the mother but cross the placenta where they are utilized in several ways by the fetus: as a fuel in lieu of glucose; as an inhibitor of glucose and lactate oxidation with sparing of glucose for biosynthetic disposition; and for inhibition of branched-chain ketoacid oxidation, thereby maximizing formation of their parent amino acids. Ketone bodies are widely incorporated into several classes of lipids including structural lipids as well as lipids for energy stores in fetal tissues, and may inhibit protein catabolism. Finally, it has recently been shown that ketone bodies inhibit the de novo biosynthesis of pyrimidines in fetal rat brain slices. Thus during maternal starvation ketone bodies may maximize chances for survival both in utero and during neonatal life by restraining cell replication and sustaining protein and lipid stores in fetal tissues.

3-Hydroxybutyric Acid↗
PubMed1985

Distribution and density of subepithelial collagen in the endolymphatic sac in patients with Meniere's disease.

Our understanding of the histology and histopathology of the endolymphatic sac (ELS) is based on both temporal bone preparations and biopsy material. The current study will provide the basis for an ultrastructural analysis of the spectrum of pathologic changes observed in biopsy specimens from patients with endolymphatic hydrops in Meniere's disease. Emphasis is placed on the distribution and density of subepithelial collagen in the ELS of normal and hydropic patients. This study will be the light microscopic basis for an ultrastructural clinicopathologic correlation of inner ear tissue from the ELS with the clinical stage of the disease.

Aged↗
PubMed1984

Fetal fuels. VII. Ketone bodies inhibit synthesis of purines in fetal rat brain.

Maternal starvation in late gestation results in ketonemia and a lowered DNA content in fetal rat brain. Because purines are needed for formation of new RNA and DNA, we examined the de novo pathway for purine biosynthesis in fetal rat brain slices by measuring the incorporation of [14C]formate into [14C]adenine. Maternal starvation days 18-20 resulted in a slight but nonsignificant fall in purine biosynthesis from 0.230 +/- 0.006 to 0.216 +/- 0.006 mumol X g-1 X 2 h-1. Graded concentrations of DL-3-hydroxybutyrate (3OHB) produced a progressive inhibition of formate incorporation in fetal brain slices, and rates of purine biosynthesis in the presence of 5.4 mM 3OHB were significantly lower (P less than 0.01) in fetal brain slices from both fed and starved mothers, i.e., 0.199 +/- 0.006 and 0.189 +/- 0.006 mumol X g-1 X 2 h-1, respectively. Acetoacetate caused an inhibition similar in magnitude to 3OHB. That 3OHB did not act via a protein biosynthetic step was evidenced by unimpaired biosynthesis of purines and sustained 3OHB inhibition in the presence of 1 mM cycloheximide. Unlike the de novo pathway, the salvage pathway measured by incorporation of [8-14C]adenine into labeled nucleotides was not significantly inhibited even by supraphysiological levels of 3OHB (21.6 mM). Serial measurements of the de novo and salvage pathways in neonatal brain slices showed a maintenance of salvage activity during the first 2 wk but a progressive fall in activity of the de novo pathway. Thus ketone bodies could act to restrain the synthesis of purine nucleotide building blocks for new cell formation in fetal but not in neonatal rat brain.

3-Hydroxybutyric Acid↗
PubMed1983

Tumor involvement of the facial nerve.

Tumors involving the facial nerve are rare and challenging in both diagnosis and treatment. In this paper we report 18 cases of benign and malignant neoplasms involving the temporal portion of the facial nerve. The selection of those patients with facial paralysis who require detailed evaluation is discussed. Often, despite thorough evaluation of these patients, a preoperative diagnosis is unavailable or erroneous. An occasional patient may require surgical exposure of the nerve from the middle cranial fossa to the parotid gland.

Adult↗
PubMed1983

Fetal fuels VI. Metabolism of alpha-ketoisocaproic acid in fetal rat brain.

The metabolic regulation of alpha-ketoisocaproic acid was studied in fetal brain from rats. Starvation of the mother for days 18-20 did not alter CO2 evolution from alpha-ketoisocaproic acid in fetal brain slices but significantly diminished the incorporation of the branched-chain keto acids into leucine. When fetal brain slices from starved mothers were exposed to graded concentrations of labeled alpha-ketoisocaproic acid (0.05-2.5 mM), over 70% of the labeled products were consistently represented by leucine and less than 30% by CO2. Both beta-hydroxybutyrate and pyruvate, alone and in combination, diminished the amount of 14CO2 that evolved from alpha-ketoisocaproic acid-1-14C, but had no effect on the conversion of the keto acid to labeled leucine. It is concluded that exogenous alpha-ketoisocaproic acid is preferentially converted to leucine by fetal brain slices independent of the nutritional state of the mother. During maternal starvation, beta-hydroxybutyrate, by restraining irreversible decarboxylation of alpha-ketoisocaproic acid, could act to salvage the keto acid for conversion to leucine. Thus alpha-ketoisocaproic acid metabolism in the fetal brain may be regulated in part by altered metabolic functions in this structure and in part by changing components in circulating fuel mixtures reaching the fetus from the starved mother.

Animals↗