Biomedical subjects
Publications and source records attributed to J Metcoff.
Fetal malnutrition is a common and potentially serious problem perinatally and for later growth and development. Unless sought in the neonate, fetal malnutrition is frequently missed but can be detected readily by a simple clinical examination.
Intracellular glycolytic regulating enzyme activities, pyruvate kinase (PK) and phosphofructokinase (PFK), adenylate kinase (AK), energy charge (Ech), free amino acids (ICAA), and protein synthesis (PS) were measured in polymorphonuclear leukocytes--used as a cell model--in 62 adults and 12 children with chronic renal failure, and 66 normal adults and 21 children as comparison controls. In normal subjects, children had significantly lower enzyme activities and cell amino acid levels but similar Ech and higher PS than adults. ICAA concentrations were significantly higher than plasma amino acid concentrations (PAA) in both groups, and the PAA were not correlated with, nor indicative of, the ICAA concentrations. The variance (R2) in PS could be largely accounted for by a combination ("set") of six ICAA, as determined by multivariate analysis. The sets differed in children vs adults, suggesting that different proteins were being synthesized. In the uremic patients, reduced PF, PFK, Ech, most ICAAs and PS were indicative of cellular malnutrition. For the uremic adults, the abnormalities in cell metabolism were modified by therapy--nondialyzed uremics being worst, CAPD patients best and approximately normal, and hemodialyzed intermediate. The uremic CAPD children had reduced, PK, PFK, AK, most ICAA, and PS. Ech was increased. Cellular malnutrition in children with chronic renal failure may contribute to their poor growth.
Not all mothers who smoke during pregnancy deliver small infants. Nutritional supplementation during pregnancy apparently protects the fetuses of some mothers. Our previous studies showed that plasma levels of carotene and cholesterol were correlated with birth weight. The present study examined the association between mid-pregnancy plasma levels of carotene and cholesterol and subsequent birth weight. In a prospective study of 388 women (47.8% smokers), levels of plasma nutrients and demographic and anthropometric measurements were obtained at 19 and 36 weeks' gestation and related to indices of infant size at birth. In non-smokers, the level of plasma cholesterol at mid-pregnancy correlated positively with birth weight. In contrast, in mothers who smoked more than ten cigarettes daily, the relationship of cholesterol to birth weight was dependent on the simultaneously observed level of plasma carotene. When plasma cholesterol and carotene concentrations were both low at mid-pregnancy, birth weight was low. On the other hand, when the carotene level was high and the cholesterol level low, birth weight was at least equivalent to that of non-smokers. The interactive effect of smoking, cholesterol, and carotene on birth weight was significant (P = .017) after adjusting for gestational age, sex, prenatal care, race, previous low birth weight infants, parity, weight at mid-pregnancy, and total weight gain during pregnancy. Among smokers, the smallest infants were born to mothers having the greatest decrease in plasma carotene between 19-36 weeks' gestation. Smokers whose plasma carotene remained constant or increased had larger infants; a similar association was not observed for cholesterol.(ABSTRACT TRUNCATED AT 250 WORDS)
Cellular energy-related bioactivities [energy charge = ATP + 0.5 ADP/(ATP + ADP + AMP)], enzyme activities adenylate kinase, pyruvate kinase, phosphofructokinase, glucose-6-phosphate dehydrogenase, free amino acids in plasma and cells, and protein synthesis (3H-leucine incorporation) were measured in granulocytes isolated from peripheral blood of 13 CAPD-treated adult patients. The values were compared with 37 normal adult controls, 29 of whom had complete data for all biochemical parameters. Eleven of the CAPD patients were studied a second time, 3 to 8 months after the first study. Initially, after 20 +/- 8 months of CAPD compared (P less than 0.05, only) to controls, the patients had normal or increased activities of the enzymes pyruvate kinase, phosphofructokinase, glucose-6-phosphate dehydrogenase, in contrast to previous results from hemodialyzed patients; but adenylate kinase, ATP, and protein synthesis were reduced. Concentrations of many amino acids in plasma were abnormal, including reduced valine, leucine, threonine, tryptophan, and tyrosine, as noted by others. Histidine, glutamic acid, and citrulline especially were increased. The intracellular concentrations of the essential amino acids were within normal limits, but citrulline, glycine, and taurine levels were markedly increased while glutamic acid and SAGN (serine + asparagine + glutamine) were decreased. With the second study, intracellular energy-related bioactivities and the abnormal concentrations of the amino acids in plasma were essentially unchanged. However, virtually all the intracellular amino acid concentrations were higher. These results also were in striking contrast to previously reported hemodialysis patients in whom the intracellular concentrations of the branched-chain amino acids and methionine as well as protein synthesis were strikingly decreased.(ABSTRACT TRUNCATED AT 250 WORDS)
Protein synthesis depends on a complete complement of precursor amino acids, specific acetylating enzymes, tRNA, and so forth. It has been related to metabolism of individual amino acids, eg, valine and leucine; however, the relation of protein synthesis to the ambient concentrations of amino acids in the intracellular and extracellular pools has not been defined. Using the viable, isolated granulocyte (leukocyte) as an in vitro cell model, protein synthesis (incorporation of 4,5-3H-leucine) has been related to simultaneous amino acid concentrations in the cell and plasma by multiple regression analysis. Fifty-five normal neonates and 30 normal adults were studied. Protein synthesis was higher in the infants than in the adults (3,527 vs 2,685 pmole/hr/mg DNA). The intracellular concentrations of most amino acids were higher than their concentrations in plasma, except for valine and citrulline, which were lower. The "aminograms" in the two pools also were very different. Forty-four percent of the variance (R2) in protein synthesis was accounted for by the intracellular concentrations of leucine, glycine, alanine, and taurine in neonates and 45% by a combination of threonine, valine, methionine, and histidine in adults. The intracellular concentrations of each of these predictor amino acids in adults were, in turn, related to different combinations of the plasma concentrations of threonine, phenylalanine, tryptophan, isoleucine, histidine, citrulline, ornithine, arginine, and glycine. Thus, it is possible to identify sets of intracellular amino acids that predict the level of protein synthesis and to delineate combinations of plasma amino acids whose levels account for a significant portion of the variance in the intracellular predictor amino acids in normal human infants and adults.
Previously reported studies showed that protein-calorie malnutrition (PCM) in children is associated with significant alterations in muscle cell composition, characterized by increased cell water and Na, with decreased concentrations of K, Mg, and some glycolytic and citric acid cycle metabolites. In PCM, the i.c. H2O and levels of Na and K were significantly related, by multiple regression analysis, to the combined set of simultaneously measured levels of cell metabolites, phosphoenolpyruvate, pyruvate, alpha-ketoglutarate, and oxaloacetate. Cell bioactivities also were affected by PCM. Activities of the enzymes pyruvate kinase and malic and isocitric dehydrogenases were significantly reduced in muscle homogenates of PCM children. Kinetic analysis of pyruvate kinase indicated an 8-10-fold reduction in maximal velocity of the enzyme, consistent with a reduction in enzyme protein. Additionally, reduced levels of ATP and the equilibrium constant of the adenylate kinase system were observed in leukocytes of PCM children. Alterations in the activity of the energy-dependent Na pump have been noted by others in association with the accumulation of i.c. Na in severe malnutrition. Neither protein synthesis nor amino acid pools was measured in these previously reported studies. Recent data from several laboratories show that the "profiles" of i.c. and plasma amino acids are very different, both in uremics and in control subjects. In control subjects, with leukocytes as the cell model, the level of protein synthesis can be predicted by multiple regression analyses from simultaneously measured levels of plasma or i.c. amino acids. Intracellular amino acids are better predictors. Of 19 intracellular amino acids, a combination of five accounted for 54% of the variance in protein synthesis in normal, healthy adults. Levels of these predictor cell amino acids can, in turn, be predicted by different combinations of apparently unrelated plasma amino acids. In adult uremic patients stabilized by hemodialysis, with leukocytes as the cell model, levels of ATP, energy charge, adenylate kinase and pyruvic kinase activities were reduced. Others have reported increased i.c. water and Na contents, and impaired Na pump activity. Cell levels of methionine and the branched-chain amino acids, valine, leucine, and isoleucine, and protein synthesis also were significantly reduced. By multiple regression analysis, the observed levels of protein synthesis and energy charge in the hemodialyzed uremic patients were largely accounted for by different combinations of intracellular amino acid than in healthy subjects.(ABSTRACT TRUNCATED AT 400 WORDS)
We hypothesized that more rapidly growing preterm infants would have higher rates of protein synthesis than term infants, and that protein synthesis would be more closely related to intracellular than plasma levels of amino acids. Neutrophils, used as a cell model, were isolated from 1-3 ml blood of 63 infants 27-44 wk postconceptual age. Protein synthesis (3H-leucine incorporation, pmol/h/mg DNA), and 19 amino acids in the leukocytes (nmol/mg DNA) and plasma (nmol/ml) were quantified. Protein synthesis was related inversely to birth weight and gestational age, i.e. the smaller and more preterm the infant the higher the rate of protein synthesis. Multiple regression analysis limited to six steps indicated that some plasma amino acids (Val, Ile, Phe, Asp, Ala, Tau) accounted for a significant (p = 0.03), but relatively small, proportion, 23%, of the variance in protein synthesis. A greater proportion of the variance in protein synthesis was explained by a set of six intracellular amino acids (Leu, Met, Tyr, Gly, Ala, Tau), with R2 = 36%, p = 0.001. Further, multiple regression identified specific combinations of six plasma amino acids which best explained ("predicted") the levels of each intracellular amino acid predictor of protein synthesis (R2 = 0.4-0.5, p less than 0.001-0.0001). Activities of some rate-limiting glycolytic enzymes, pyruvate kinase and phosphofructokinase, were correlated with protein synthesis in the leukocytes (p = 0.036, and 0.002, respectively). Phosphofructokinase, the major regulating enzyme in glycolysis, also was negatively correlated with birth weight and gestational age.(ABSTRACT TRUNCATED AT 250 WORDS)
Of 824 women screened, 410 were enrolled at midpregnancy in a prospective, randomized, controlled nutrition intervention study. Of these, 226 were predicted as likely to have small or large babies, 184 to have average-sized babies. Two hundred thirty eight mothers received USDA Women, Infants and Children (WIC) Food Supplementation vouchers from midpregnancy, 172 did not. Leukocyte protein synthesis (as a cell model) was significantly higher (p = 0.009) by 36 weeks gestation in supplemented mothers. Mean birth weight of their babies was greater, 3254 vs 3163 g, (+91 g) p = 0.039, adjusted for sex, gestational age, prenatal visits, pregnancy interval, smoking, and previous low birth weight infants. Controlling for entry weight obviated the significance of the difference, except for WIC supplemented smokers (greater than 10 cigarettes/day) whose babies were significantly heavier by +168 g (p = 0.017) than those of unsupplemented smokers. WIC partially protects fetal growth in smokers.
Eighteen uremic patients received i.v. infusions of a mixture of amino acids three times per week for 3 months in an effort to improve cellular amino acid imbalance and related cell bioactivities. They were a subset of 42 uremic patients stabilized by maintenance hemodialysis and were characterized by reduced cellular levels of threonine, isoleucine, methionine, and ornithine, with increased levels of aspartate, glycine, arginine, tyrosine, and phenylalanine. Protein synthesis (3H-leucine incorporation), energy level [energy charge = (ATP + 1/2 ADP)-(ATP + ADP + AMP)], and activity of the rate-limiting glycolytic enzyme pyruvate kinase were reduced in these patients compared with 32 control normal subjects. The circulating leukocyte (88 +/- 5% granulocytes) was used as a cell model. Previously, multiple regression best-subset analysis showed that a combination of the cell levels of aspartate, valine, isoleucine, ornithine, lysine, and tryptophan could "explain" 40% of the variance in protein synthesis in these patients. Similarly, a combination of the levels of aspartate, glutamic acid, glycine, ornithine, and arginine were "predictive" of the level of energy charge. We hypothesized that protein synthesis and energy level would be improved if the amino acid infusions normalized the intracellular levels of those amino acids that were predictive of the bioactivities. After 3 months of amino acid infusions, levels of the predictive intracellular amino acids were not improved, but deviated further from baseline values. Failure to detect significant improvement in the cell bioactivities is attributed to inability to correct the imbalance in the intracellular amino acid pool.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Whether fetal growth retardation could be induced by diets apparently adequate in protein and energy sources, but imbalanced relative to a single amino acid, was investigated. Pregnant rats were fed one of three diets: either a basal (B) 6% casein diet supplemented by L-methionine (L-Met) and a 5% mixture of essential plus 4.5% small neutral non-essential amino acids, which provided 4 kcal and 0.16 g protein-equivalent/g diet and was complete in other essential nutrients; an experimental (E) diet [same, except 0.4% L-threonine (L-Thr) supplement omitted]; or a control (C) diet, life B, but containing 20% casein. A total of 343 fetuses and their placentas were delivered by Caesarean section usually on day 21 of pregnancy but occasionally on day 20 or 22. Food consumption was similar in all groups (kcal/100 g rat/day); however, protein intake of the B and E rats was bout half that of the C group. Net maternal weight gain (excluding uterus + contents) was +8% in C. )% in B and -12% in E group dams. Body weight, length, volume, brain weight and placental weight, adjusted by multiple regression analysis to standardize for maternal prepregnant weight, length, litter size, net weight gain and duration of gestation, were significantly reduced in 155E greater than 156 B greater than 32C fetuses. Protein restriction accounted for 30-59% of the total observed variance in birth measures of the B versus C group fetuses; and the Thr-limiting amino acid imbalance for 36% of the total variance between the E and B groups. Imbalanced diets containing excess dispensable amino acids with adequate net protein and caloric intakes during pregnancy induce fetal growth retardation (F GR), which is increased by limiting threonine. Net maternal weight loss does not prevent F GR in rats under these conditions.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
In a study of the relationship of maternal nutrition to fetal development, the free amino acid concentration was determined in the plasma of 43 subjects sampled between the 20th to 30th (25 +/- 3.7) week of pregnancy. Significant positive correlations were found between mothers' 25-week plasma levels of aspartic acid, serine, alanine, tyrosine, ornithine, and arginine, and babies' size at birth. The concentration of total free amino acids in plasma from mothers of fetally malnourished infants, was significantly lower than that from mothers having normal babies. The branched chain amino acids isoleucine and valine were at normal levels, suggesting a sparing effect for these amino acids.
One hundred thirty-seven courses of furosemide therapy were given to 106 hospitalized pediatric patients with salt and water retention associated with cardiac or renal disease. The diuretic was effective and safe in the pediatric age group when administered acutely as a parenteral medication and over a long-term course by the oral route in the doses and at the time intervals used in this study. On the basis of each kilogram of body weight, the infants with edema as a result of cardiac failure and the children with edema secondary to renal disease responded equally well to furosemide therapy.