288 results on '"Matthews DE"'
Search Results
202. Stable isotope methods for nutritional investigation.
- Author
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Matthews DE and Bier DM
- Subjects
- Amino Acids metabolism, Body Water analysis, Carbohydrate Metabolism, Digestive System Physiological Phenomena, Energy Metabolism, Fatty Acids metabolism, Gas Chromatography-Mass Spectrometry, Humans, Isotopes, Kinetics, Mass Spectrometry, Nitrogen analysis, Proteins metabolism, Trace Elements analysis, Isotope Labeling instrumentation, Isotope Labeling methods, Nutritional Physiological Phenomena
- Published
- 1983
- Full Text
- View/download PDF
203. Glucose and amino acid metabolism in aging man: differential effects of insulin.
- Author
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Fukagawa NK, Minaker KL, Rowe JW, Matthews DE, Bier DM, and Young VR
- Subjects
- Adult, Aged, Aged, 80 and over, Humans, Insulin blood, Insulin Resistance, Middle Aged, Aging metabolism, Amino Acids metabolism, Glucose metabolism, Insulin pharmacology
- Abstract
Insulin is a major regulator of glucose and body protein homeostasis, both of which demonstrate age-related changes. To clarify insulin's role in these age-related changes and to compare age-related glucose and protein homeostatic responses, insulin-mediated aspects of glucose and amino acid metabolism were simultaneously examined in healthy postabsorptive young (n = 5, mean age, 25 years) and elderly (n = 5, mean age, 76 years) men. Primed constant infusions of L-[1-13C]leucine and L-[15N]alanine were administered during a basal period (0 to 180 minutes) and during four separate single rate euglycemic insulin infusions (180 to 360 minutes). Steady state insulin concentrations were 16 +/- 1, 29 +/- 3, 75 +/- 5, and 2407 +/- 56 microU/mL in the young and 23 +/- 4, 37 +/- 8, 96 +/- 11 and 3,357 +/- 249 microU/mL in the elderly at the different insulin infusion rates of 6, 10, 30, and 400 mU mU.m-2.min-1, respectively. For the 6 and 10 mU insulin infusion rates, a primed, constant infusion of [6,6 - 2H2]glucose permitted quantitation of hepatic glucose production. Glucose disposal rates adjusted for lean body mass (LBM) were lower in the elderly than in the young at the 6, 10, and 30 mU insulin infusion rates and similar in the two age groups in the 400 mU studies. Insulin dose-dependent reductions occurred in eight of ten plasma amino acids and were not influenced by age. There was an insulin dose-dependent reduction in plasma leucine flux which was similar in both age groups.(ABSTRACT TRUNCATED AT 250 WORDS)
- Published
- 1988
- Full Text
- View/download PDF
204. Purification and Characterization of S-Adenosyl-l-methionine:6a-Hydroxymaackiain 3-O-Methyltransferase from Pisum sativum.
- Author
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Preisig CL, Matthews DE, and Vanetten HD
- Abstract
The isoflavonoid phytoalexin pisatin is synthesized by Pisum sativum in response to microbial infection and certain other forms of stress. An enzyme which synthesizes pisatin by methylating the 3-hydroxyl of (+)6a-hydroxymaackiain (HMK) was extracted from CuCl(2)-stressed pea seedlings. The enzyme was enriched 370-fold by (NH(4))(2)SO(4) precipitation, DEAE chromatography, chromatofocusing, and hydrophobic interaction chromatography (HIC), to a specific activity of 8.2 microkatals per gram protein. Enzyme activity profiles from chromatofocusing and HIC columns suggested the presence of two isozymes, of pl 5.2 and 4.9. Nondenaturing gel filtration of the HIC-purified enzyme gave a single peak of activity at the same elution volume as BSA (66 kilodaltons); the active fractions showed two proteins upon SDS-PAGE, of M(r) 66,000 and 43,000. The smaller protein was most abundant in chromatographic fractions containing peak enzyme activity throughout purification. In a partially purified preparation, this 43 kilodalton protein was the only one photoaffinity labelled by [(3)H]S-adenosyl-l-methionine. The purified enzyme preferred the (+) over the (-) stereoisomer of HMK and other pterocarpans; overall, (+)HMK was the best substrate. K(m) values were 2.3 micromolar for (+)HMK and 35 micromolar for S-adenosyl-l-methionine. The methyltransferase had a pH optimum of 7.9 and no apparent divalent cation requirement.
- Published
- 1989
- Full Text
- View/download PDF
205. Determination of stable isotopic enrichment in individual plasma amino acids by chemical ionization mass spectrometry.
- Author
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Matthews DE, Ben-Galim E, and Bier DM
- Subjects
- Chromatography, Gas, Drug Stability, Isotope Labeling, Mass Spectrometry methods, Microchemistry, Amino Acids blood
- Published
- 1979
- Full Text
- View/download PDF
206. Glutamine and glutamate kinetics in humans.
- Author
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Darmaun D, Matthews DE, and Bier DM
- Subjects
- Adult, Biological Transport, Diet, Energy Intake, Extracellular Space metabolism, Glutamic Acid, Humans, Intracellular Fluid metabolism, Kinetics, Male, Nitrogen metabolism, Nitrogen Isotopes, Glutamates metabolism, Glutamine metabolism
- Abstract
To study glutamate and glutamine kinetics, 4-h unprimed intravenous infusions of L-[15N]glutamate, L-[2-15N]glutamine, and L-[5-15N]-glutamine were administered to healthy young adult male subjects in the postabsorptive state. Arterialized-venous blood samples were drawn and analyzed for glutamate and glutamine 15N enrichments. The fractional turnover rates of the tracer-miscible glutamate and glutamine pools were fast, 8.0 and 2.8% min-1, respectively. The glutamate tracer-miscible pool accounted for less than one-tenth the estimated free glutamate pool in the body. The plasma glutamate amino N, glutamine amino N and glutamine amide N rates of appearance were 83 +/- 22 (means +/- SD), 348 +/- 33, and 283 +/- 31 mumol X kg-1 X h-1, respectively. The glutamine amide N appearance rate was 20% slower than the amino N appearance rate, indicating that glutamine transaminase is an active pathway in human glutamine metabolism. From measurement of transfer of tracer 15N, we found that only 5% of the glutamine synthesized in cells and released into plasma was derived from intracellular glutamate that had mixed with plasma. These data demonstrate that intravenously administered tracers of glutamate or glutamine do not mix thoroughly with the intracellular pools, and their measured kinetics reflect transport rates through plasma rather than whole-body fluxes.
- Published
- 1986
- Full Text
- View/download PDF
207. On testing for a constant hazard against a change-point alternative.
- Author
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Matthews DE and Farewell VT
- Subjects
- Clinical Trials as Topic, Follow-Up Studies, Humans, Mathematics, Probability, Leukemia therapy
- Abstract
A frequently recurring question posed by leukemia researchers concerns a test of a constant failure rate against the alternative of a failure rate involving a single change-point. In answer to this question, a likelihood ratio test appropriate for the stated alternative is derived and simulated. Consideration is given also to tests based on alternatives in the log gamma family, which perform quite well when the change-point model is correct. A practical application is given.
- Published
- 1982
208. Muscle protein synthesis measured by stable isotope techniques in man: the effects of feeding and fasting.
- Author
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Rennie MJ, Edwards RH, Halliday D, Matthews DE, Wolman SL, and Millward DJ
- Subjects
- Adult, Carbon Dioxide blood, Carbon Isotopes, Humans, Keto Acids blood, Leucine metabolism, Male, Middle Aged, RNA metabolism, Eating, Fasting, Muscle Proteins biosynthesis
- Abstract
1. Measurements have been made of whole-body and skeletal muscle protein synthesis in fed and fasted adults with L-[1-13C]leucine. 2. The marked increase in whole-body synthesis on feeding largely reflects the changes in protein synthesis in muscle, which doubles on feeding, compared with a 40% increase in that of the rest of the body. 3. Skeletal muscle in fed man contributes more than half to total protein synthesis occurring in the whole body.
- Published
- 1982
- Full Text
- View/download PDF
209. Alanine kinetics in humans: influence of different isotopic tracers.
- Author
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Yang RD, Matthews DE, Bier DM, Lo C, and Young VR
- Subjects
- Adult, Body Height, Body Weight, Carbon Isotopes, Deuterium, Diet, Humans, Kinetics, Male, Nitrogen Isotopes, Alanine metabolism
- Abstract
Whole-body alanine kinetics were studied using continuous infusions of [15N]-, [3,3,3-2H3]-, [1-13C]-, and [3-13C]alanine tracers in healthy male subjects in the postabsorptive state. Alanine kinetics were highly dependent on the choice of isotopically labeled alanine. Highest rates of alanine flux (mean +/- SE) were obtained with the [3,3,3-2H3]alanine (474 +/- 41 mumol X kg-1 X h-1). [1-13C]- and [3-13C]alanine tracers gave intermediate values (297 +/- 12 and 317 +/- 22 mumol X kg-1 X h-1, respectively). The slowest rates of alanine turnover were measured with [15N]alanine (226 +/- 7 mumol X kg-1 X h-1). These results emphasize the heterogeneous metabolism of different portions of the alanine molecule and the importance of choosing an appropriate alanine tracer for studying different aspects of alanine metabolism.
- Published
- 1984
- Full Text
- View/download PDF
210. Energy intake and whole body protein dynamics in man.
- Author
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Bier DM, Motil KJ, Matthews DE, Burke JF, and Young VR
- Subjects
- Dietary Proteins metabolism, Energy Intake, Glucose biosynthesis, Humans, Kinetics, Leucine metabolism, Lysine metabolism, Male, Nitrogen metabolism, Oxidation-Reduction, Palmitic Acid, Palmitic Acids metabolism, Protein Biosynthesis, Energy Metabolism, Proteins metabolism
- Published
- 1981
211. Chenodeoxycholic acid pool size determination from children using isotope dilution mass spectrometry.
- Author
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Norman EJ, Heubi JE, Gelfand MJ, Dan P, and Matthews DE
- Subjects
- Humans, Mass Spectrometry methods, Radioisotope Dilution Technique, Chenodeoxycholic Acid analysis
- Abstract
An isotope dilution mass spectrometry method is described for determining chenodeoxycholic acid pool size in children. The stable isotopically labeled tracer, (11,12-2H2) chenodeoxycholic acid, was administered orally to children, and the enrichment of bile was measured by selected ion monitoring gas chromatography mass spectrometry. The level of (11,12-2H2)chenodeoxycholic acid enrichment found in the patient samples was in the range of 0.5 to 5%. Data are presented illustrating the duplication of this method in two independent laboratories using standard quadrupole mass spectrometers. This procedure provides the clinician with a non-radioactive method for determining chenodeoxycholic acid pool size which is especially beneficial in studies involving children and pregnant women.
- Published
- 1984
- Full Text
- View/download PDF
212. Glycine nitrogen metabolism in man.
- Author
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Matthews DE, Conway JM, Young VR, and Bier DM
- Subjects
- Adult, Amino Acids metabolism, Humans, Kinetics, Male, Nitrogen metabolism, Nitrogen Isotopes, Proteins metabolism, Serine metabolism, Urea urine, Glycine metabolism
- Published
- 1981
- Full Text
- View/download PDF
213. The effect of increased intracranial pressure (ICP) on gastric motility.
- Author
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Matthews DE, Heimansohn DA, Papaila JG, Lopez R, Vane DW, and Grosfeld JL
- Subjects
- Animals, Electrophoresis, Esophagus physiology, Stomach physiology, Gastrointestinal Motility, Intracranial Pressure
- Abstract
This study evaluates the effect of increased intracranial pressure (ICP) on gastric motility. Nine male cats (weight, 4.84 +/- 1.16 kg) were anesthetized with ketamine and underwent laparotomy for placement of bipolar (silver-silver chloride) electrodes on the serosal surface of the gastroesophageal junction (GEJ), antrum, and prepyloric areas of the stomach. At 1 week frontoparietal burr holes were performed with placement of an epidural Fogarty catheter. Migrating myoelectric complexes (MMCs) were evaluated at the GEJ, antrum, and prepyloric areas at varying levels of ICP (baseline and 20, 40, and 60 mm Hg) using balloon inflation. MMCs at the GEJ were triphasic with a period of 4 sec (+/- 1 sec) at baseline levels. At ICP levels above baseline, periodicity and waveforms at the GEJ became irregular. Waveforms became multiphasic with 1- to 2-sec periods and variable amplitudes. In the antral and prepyloric areas, duration and amplitude of the triphasic MMCs was unchanged from baseline. At 60 mm Hg ICP periodicity was significantly altered at both 1 and 2 weeks. MMCs returned to baseline levels with balloon deflation. The data indicate that elevated ICP (to 60 mm Hg) results in consistent and reproducible alterations of MMC periodicity, suggesting that such alterations may influence gastric motility.
- Published
- 1988
- Full Text
- View/download PDF
214. Whole-body leucine and lysine metabolism: response to dietary protein intake in young men.
- Author
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Motil KJ, Matthews DE, Bier DM, Burke JF, Munro HN, and Young VR
- Subjects
- Adolescent, Adult, Carbon Isotopes, Energy Metabolism, Humans, Kinetics, Nitrogen Isotopes, Oxidation-Reduction, Dietary Proteins, Leucine metabolism, Lysine metabolism
- Abstract
Whole-body leucine and lysine metabolism was explored in young adult men by a primed constant intravenous infusion of a mixture of L-[1-13C]leucine and L-[alpha-15N]lysine over a 4-h period. Subjects were studied after an overnight fast (postabsorptive state) or while consuming hourly meals (fed state) after adaptation to diets providing either a surfeit level of protein (1.5 g.kg body-1.day-1), a level approximating maintenance requirements (marginal intake) (0.6 g.kg body wt-1.day-1), or a grossly inadequate level (0.1 g.kg-1.day-1). The change in protein intake from a marginal to a surfeit level was associated with an increased leucine flux and incorporation of leucine into body protein. In the fed state, oxidation of leucine increased sharply and release of leucine from tissue protein diminished. When dietary protein intake was reduced from the requirement to inadequate level, leucine flux and body protein synthesis and protein breakdown were reduced, together with a smaller reduction in leucine oxidation. The response of the metabolism of [15N]lysine was responsible for maintenance of leucine and other essential amino acid economy, and they appear to be related to the nitrogen and amino acid requirements of the subject. These findings also demonstrate an effect of meals, modulated by their protein content, on the dynamics of whole-body amino acid metabolism.
- Published
- 1981
- Full Text
- View/download PDF
215. Stable isotope tracer methods for in vivo investigations.
- Author
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Bier DM and Matthews DE
- Subjects
- Activation Analysis methods, Adult, Amino Acids metabolism, Glycine metabolism, Humans, Isotopes analysis, Leucine metabolism, Male, Mass Spectrometry methods, Nitrogen Isotopes metabolism, Oxygen Isotopes metabolism, Proteins metabolism, Spectrum Analysis methods, Isotope Labeling methods, Nutritional Physiological Phenomena
- Abstract
During the last two decades, in parallel with the growth of modern electronics, several new techniques have been developed for measuring stable isotopic enrichments in biochemistry and medicine. The development and potential of these techniques are discussed. Of these methods, mass spectrometry has been developed and refined the fullest to quantitate stable isotope tracers in very minute samples and for very large dilutions of tracer. No single mass spectrometric technique can measure this entire range, and different techniques are used for different applications. Examples of the different methods are presented for determining whole-body amino acid and protein dynamics in humans with stable isotopically labeled amino acid tracers.
- Published
- 1982
216. Synthesis of the phytoalexin pisatin by a methyltransferase from pea.
- Author
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Sweigard JA, Matthews DE, and Vanetten HD
- Abstract
Previous labeling studies in vivo suggest that the terminal step of (+)pisatin biosynthesis in Pisum sativum L. is methylation of the phenol (+)6a-hydroxymaackiain (HMK). We have found that extracts from pea seedlings perform this reaction, using S-adenosylmethionine as the methyl donor. The enzyme activity was induced by microbial infection or treatment with CuCl(2), which elicit pisatin synthesis, though some activity was also present in healthy tissues. It has been reported that CuCl(2)-treated pea tissue provided with (-)HMK or (-)maackiain can synthesize (-)pisatin. Our extract showed no methyltransferase activity dependent on either of these substrates. Methylation of (+)maackiain was detectable, but much slower than that of (+)HMK.
- Published
- 1986
- Full Text
- View/download PDF
217. Hyperglucagonemia during insulin deficiency accelerates protein catabolism.
- Author
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Nair KS, Halliday D, Matthews DE, and Welle SL
- Subjects
- Adult, Amino Acids metabolism, Female, Hormones blood, Humans, Kinetics, Leucine metabolism, Male, Osmolar Concentration, Glucagon blood, Insulin deficiency, Proteins metabolism
- Abstract
Hyperglucagonemia coexists with insulin deficiency or insulin resistance in many conditions where urinary nitrogen excretion is increased, but the precise role of glucagon in these conditions is controversial. The purpose of this study was to evaluate the effect of hyperglucagonemia on protein metabolism in insulin-deficient subjects. We used the stable isotope of an essential amino acid (L-[1-13C]leucine) as a tracer of in vivo protein metabolism. A combined deficiency of insulin and glucagon was induced by intravenous infusion of somatostatin. Hyperglucagonemia and hypoinsulinemia were induced by infusions of somatostatin and glucagon. When somatostatin alone was infused leucine flux increased, indicating a 6-17% increase in proteolysis. When somatostatin and glucagon were infused, leucine flux increased, indicating a 12-32% increase in proteolysis. The increase in leucine flux during the infusion of somatostatin and glucagon was higher than the increase during infusion of somatostatin alone. Somatostatin alone did not change leucine oxidation, whereas the somatostatin plus glucagon increased leucine oxidation 100%. We conclude that hyperglucagonemia accelerates proteolysis and leucine oxidation in insulin-deficient humans.
- Published
- 1987
- Full Text
- View/download PDF
218. Protein and substrate metabolism during starvation and parenteral refeeding.
- Author
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Tracey KJ, Legaspi A, Albert JD, Jeevanandam M, Matthews DE, Brennan MF, and Lowry SF
- Subjects
- Adult, Body Weight, Calorimetry, Indirect, Glucagon blood, Glucose metabolism, Glycine metabolism, Humans, Insulin blood, Leucine metabolism, Male, Methylhistidines blood, Methylhistidines urine, Nitrogen urine, Starvation blood, Starvation urine, Parenteral Nutrition, Proteins metabolism, Starvation metabolism
- Abstract
1. Healthy male volunteers underwent 10 days of hospitalized protein-calorie starvation and a subsequent 10 day repletion phase with complete intravenous nutritional support (IVF). Non-protein calories were provided as either all D-glucose or as 50% D-glucose/50% lipid. 2. In comparison with starvation, whole-body protein breakdown, as assessed by [15N]glycine, [13C]leucine and urinary excretion of 3-methylhistidine (3-MH), was diminished during IVF. The administration of parenteral nutrition did not specifically suppress peripheral tissue protein breakdown, as measured by extremity 3-MH efflux. 3. Despite the differential insulin response to D-glucose/amino acid (50 +/- 6 m-units/ml) as compared with the D-glucose/lipid/amino acid regimen (25 +/- 4 m-units/ml), there was no difference in nitrogen retention between the regimens. Indirect calorimetric determinations revealed that oxidation of substrate during IVF was related to the proportion of D-glucose and lipid infusion.
- Published
- 1988
- Full Text
- View/download PDF
219. Leucine metabolism in type II diabetes mellitus.
- Author
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Staten MA, Matthews DE, and Bier DM
- Subjects
- Adult, Blood Glucose analysis, Diabetes Mellitus metabolism, Female, Humans, Insulin blood, Middle Aged, Obesity, Diabetes Mellitus, Type 2 metabolism, Leucine metabolism
- Abstract
Severe muscle wasting is a well-recognized characteristic of untreated insulin-deficient diabetes mellitus, a condition in which leucine turnover and oxidation are accelerated. To ascertain whether a similar circumstance exists in type II diabetes when insulin is present but with reduced efficacy, we investigated leucine turnover and oxidation in five obese type II diabetic women by tracer infusion of L-[1-13C,15N]leucine in the postabsorptive state both before and after intensive insulin therapy. With conventional treatment, the type II diabetic women received 61 +/- 33 (SD) U/day of insulin, and their fasting plasma glucose averaged 194 +/- 41 (SD) mg/dl. Leucine carbon flux (QC), nitrogen flux (QN), and oxidation (C) averaged 6.4 +/- 1.2, 15.6 +/- 4.6, and 1.4 +/- 0.3 mmol/h, respectively. These values were not different from the respective values of 6.6 +/- 1.3, 17.0 +/- 8.3, and 1.0 +/- 0.2 mmol/h in matched obese nondiabetic controls, suggesting that leucine metabolism is not altered in insulin-treated type II diabetics. After a week of intensive insulin therapy in which the same diabetic subjects received 94 +/- 36 U/day of insulin, postabsorptive plasma glucose declined to 117 +/- 26 mg/dl. Leucine QC (6.2 +/- 1.0), QN (14.8 +/- 3.7), and C (1.5 +/- 0.5 mmol/h) were unaltered by the increased insulin therapy. Thus, obese type II diabetics had normal leucine kinetics but were hyperglycemic while receiving conventional insulin therapy. Additional intensive insulin therapy in these diabetic subjects improved plasma glucose but did not alter leucine kinetics.(ABSTRACT TRUNCATED AT 250 WORDS)
- Published
- 1986
- Full Text
- View/download PDF
220. The stimulus-secretion coupling of amino acid-induced insulin release. Metabolic response of pancreatic islets of L-glutamine and L-leucine.
- Author
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Malaisse WJ, Sener A, Malaisse-Lagae F, Welsh M, Matthews DE, Bier DM, and Hellerström C
- Subjects
- Animals, Glutamine metabolism, Insulin Secretion, Islets of Langerhans drug effects, Leucine metabolism, Models, Biological, NAD metabolism, NADP metabolism, Rats, Glutamine pharmacology, Insulin metabolism, Islets of Langerhans metabolism, Leucine pharmacology
- Abstract
L-Glutamine markedly enhances insulin release evoked by L-leucine in rat pancreatic islets. The metabolic situation found in the islets exposed to both L-glutamine and L-leucine was investigated. L-Leucine slightly decreased the rate of L-glutamine deamidation, inhibited the conversion of glutamate to 2-ketoglutarate by transamination, increased the oxidative deamination of L-glutamate, stimulated the recirculation of 2-ketoglutarate to glutamate and inhibited the further oxidative metabolism of 2-ketoglutarate. L-Glutamine slightly decreased the rate of L-leucine conversion to 2-ketoisocaproate, but inhibited more severely the conversion of 2-ketoisocaproate to acetoacetate and CO2. Several of these findings appeared attributable to activation of glutamate dehydrogenase by L-leucine. When allowance was made for the influence of exogenous amino acids on the oxidation of endogenous fatty acids, a close parallelism was found between the rate of generation of reducing equivalents or O2 uptake and the insulin secretory response to L-leucine and/or L-glutamine. These findings reinforce the view that the process of nutrient-stimulated insulin release coincides with and may be attributable to an increase in catabolic fluxes in the islet cells.
- Published
- 1982
221. Bioavailability of dietary urea nitrogen in the breast-fed infant.
- Author
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Fomon SJ, Bier DM, Matthews DE, Rogers RR, Edwards BB, Ziegler EE, and Nelson SE
- Subjects
- Administration, Oral, Humans, Infant, Nitrogen urine, Nitrogen Isotopes, Nutritive Value, Breast Feeding, Nitrogen pharmacokinetics, Urea metabolism
- Published
- 1988
- Full Text
- View/download PDF
222. In vivo measurement of leucine metabolism with stable isotopes in normal subjects and in those with cirrhosis fed conventional and branched-chain amino acid-enriched diets.
- Author
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Millikan WJ Jr, Henderson JM, Galloway JR, Warren WD, Matthews DE, McGhee A, and Kutner MH
- Subjects
- Adult, Aged, Amino Acids, Branched-Chain blood, Amino Acids, Branched-Chain metabolism, Energy Metabolism, Female, Humans, Kinetics, Leucine blood, Liver metabolism, Male, Metabolic Clearance Rate, Middle Aged, Amino Acids, Branched-Chain administration & dosage, Dietary Proteins administration & dosage, Leucine metabolism, Liver Cirrhosis metabolism
- Abstract
Low plasma levels of branched-chain amino acids, leucine, isoleucine, and valine are postulated to play an etiologic role in hepatic encephalopathy. Supplementation is advocated to reverse encephalopathy and improve nutritional status and survival. We measured in vivo leucine metabolism in normal individuals (n = 5) and in two groups of patients with cirrhosis (n = 8) with a primed continuous infusion of L-[15N, 1-13C] leucine to quantitate the following parameters of leucine metabolism: nitrogen and carbon fluxes, oxidation, contribution to protein synthesis, breakdown of endogenous protein to leucine, deamination and reamination to/from ketoisocaproate. Studies were performed in the fasting and fed states with a conventional enteral diet (Propac) and a branched chain-enriched diet (one third Propac plus two thirds Hepatic-Aid). In vivo leucine metabolism was similar in the fasting and fed states in normal individuals in patients with cirrhosis and with both diets when studied at a protein intake of 0.6 gm/kg ideal body weight/day. When fed these diets, oxidation increased (p less than 0.05) and breakdown decreased (p less than 0.05). The Hepatic-Aid diet increased (p less than 0.05) nitrogen and carbon fluxes significantly more than did the standard diet. Four additional patients with cirrhosis on a diet with more protein were studied (0.75 gm/kg ideal body weight/day). Carbon and nitrogen fluxes, oxidation, synthesis, and deamination were increased (p less than 0.05) when patients with cirrhosis were fed the Propac diet compared with those who fasted. The Hepatic-Aid diet further increased (p less than 0.05) all parameters except synthesis and did not decrease protein breakdown. These data show that patients with cirrhosis metabolize leucine in vivo in a manner identical to that of normal subjects and that leucine-enriched formulas increase oxidation to CO2 without improving protein synthesis.
- Published
- 1985
223. Glutamine and glutamate nitrogen exchangeable pools in cultured fibroblasts: a stable isotope study.
- Author
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Darmaun D, Matthews DE, Desjeux JF, and Bier DM
- Subjects
- Cells, Cultured, Fibroblasts metabolism, Glutamic Acid, Humans, Ion Exchange, Skin cytology, Body Fluids metabolism, Glutamates metabolism, Glutamine metabolism, Intracellular Fluid metabolism, Nitrogen metabolism, Skin metabolism
- Abstract
Glutamine's role as an energetic fuel has been extensively studied in the past using 14C- and 3H-labeled tracers in cultured human cells. Yet another prominent role of glutamine, that of a nitrogen shuttle, cannot be approached without an N-tracer. We therefore used 15N-labeled glutamine and glutamate to address the following questions: 1) is it possible to study the exchangeable pools of intracellular free glutamine and glutamate nitrogen with stable isotope methods? and 2) to what extent is intracellular glutamine pool regulated by extracellular glutamine? We observed that: 1) intracellular [15N]-glutamine enrichment reached a plateau at 80% within 20 min of incubation in a buffer containing 0.7 mM pure 15N-glutamine and no glutamate; in contrast, intracellular 15N-glutamate enrichment rose only to 40% after 4 hours of incubation in a buffer containing 0.5 mM pure 15N-glutamate and no glutamine; 2) the cell-free glutamine content was tightly dependent on extracellular glutamine level, while the cell-free glutamate remained steady irrespective of the extracellular glutamate level; 3) the cells took up glutamine and glutamate against a concentration gradient; the rate of glutamine uptake accounted for 90% of the cell glutamine turnover rate; and 4) when cells were confronted with a glutamine-free medium, only one fourth of intracellular glutamine was derived from the exchangeable glutamate. We conclude that: 1) The size and turnover rate of the intracellular pool of free glutamine nitrogen are measureable using stable isotope methodology; 2) glutamine uptake from the extracellular medium accounts for most of glutamine turnover rate in cultured fibroblasts; and 3) intracellular free glutamate is divided up between several pools in cultured human fibroblasts.
- Published
- 1988
- Full Text
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224. Helminthosporium maydis Race T Toxin Induces Leakage of NAD from T Cytoplasm Corn Mitochondria.
- Author
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Matthews DE, Gregory P, and Gracen VE
- Abstract
The mechanism by which Helminthosporium maydis race T toxin inhibits respiration dependent on NAD(+)-linked substrates in T cytoplasm corn mitochondria was investigated. The toxin did not cause leakage of the soluble matrix enzyme malate dehydrogenase from the mitochondria or inhibit malate dehydrogenase or isocitrate dehydrogenase directly. The toxin did increase the permeability of the inner membranes of T cytoplasm, but not N cytoplasm, mitochondria to NAD(+). Added NAD(+) partially or fully restored toxin-inhibited electron transport in T cytoplasm mitochondria. Thiamin pyrophosphate had a similar effect when malate was the substrate. It was concluded that the inhibition of respiration of NAD(+)-linked substrates by the toxin is due to depletion of the intramitochondrial pool of NAD(+) and other coenzymes.
- Published
- 1979
- Full Text
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225. Solubilization and Reconstitution of Pisatin Demethylase, a Cytochrome P-450 from the Pathogenic Fungus Nectria haematococca.
- Author
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Desjardins AE, Matthews DE, and Vanetten HD
- Abstract
Some isolates of the fungus Nectria haematococca Berk. and Br. can demethylate pisatin, a phytoalexin from pea (Pisum sativum L.). Pisatin demethylation appears to be necessary for tolerance to pisatin and virulence on pea, and is catalyzed by a microsomal cytochrome P-450. We now report solubilization of this enzyme from N. haematococca microsomes. Pisatin demethylase activity was obtained in the high speed supernatant of detergent treated microsomes, if detergent was removed before assay. The CO-binding spectrum of the soluble enzyme preparation indicated the presence of cytochrome P-450. Cholic acids were the most effective of the detergents tested for solubilizing enzyme activity. Loss of enzyme activity during solubilization was reduced by certain protease inhibitors, but not by substrate, reducing agents, antioxidants, or phospholipids. The most effective solubilization medium tested was 1% sodium cholate, 100 millimolar potassium phosphate, 500 millimolar sucrose, 1 millimolar phenylmethylsulfonyl fluoride, pH 7.5, which yielded approximately 30% of the pisatin demethylase and over 95% of the NADPH-cytochrome c reductase in the soluble fraction. Demethylase activity was lost when the reductase was removed by adsorption on 2',5'-ADP-agarose. The demethylase activity of reductase-free fractions could be restored by adding a reductase preparation purified approximately 100-fold from microsomes of N. haematococca isolate 74-8-1, which does not demethylate pisatin. We conclude that pisatin demethylase requires NADPH-cytochrome c reductase for activity. The inability of some isolates to demethylate pisatin appears to be due to the absence of a suitable cytochrome P-450, rather than to a lack of functional reductase.
- Published
- 1984
- Full Text
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226. [Regulation of protein metabolism by cortisol and insulin. In vivo study in man using amino acids labeled with stable isotopes].
- Author
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Darmaun D, Robert JJ, Matthews DE, Young VR, and Bier DM
- Subjects
- Humans, Insulin deficiency, Kinetics, Adrenocortical Hyperfunction metabolism, Amino Acids metabolism, Hydrocortisone physiology, Insulin physiology
- Published
- 1986
227. Epinephrine's effect on metabolic rate is independent of changes in plasma insulin or glucagon.
- Author
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Staten MA, Matthews DE, Cryer PE, and Bier DM
- Subjects
- Adult, Blood Glucose metabolism, C-Peptide blood, Epinephrine blood, Fatty Acids, Nonesterified blood, Glycerol blood, Growth Hormone blood, Humans, Hydrocortisone blood, Hydroxybutyrates blood, Insulin metabolism, Insulin Secretion, Islets of Langerhans metabolism, Lactates blood, Male, Norepinephrine blood, Basal Metabolism drug effects, Epinephrine pharmacology, Glucagon blood, Insulin blood, Somatostatin pharmacology
- Abstract
Epinephrine's effect to increase metabolic rate is accompanied by changes in the plasma concentrations of insulin, glucagon, and metabolic substrates. Because both glucagon and insulin have been reported to affect thermogenesis, these hormones might contribute to or modify the thermogenic response to epinephrine. To determine if the epinephrine-induced increase in metabolic rate is secondary to changes in glucagon or insulin or to changes in the fuels modulated by these hormones, metabolic rate was measured by indirect calorimetry in five normal weight post-absorptive young men on three occasions: study A, an intravenous epinephrine infusion alone; study B, a 4-h "islet clamp" consisting of somatostatin infusion with basal insulin and glucagon replacement; and study C, an intravenous epinephrine infusion combined with the islet clamp. A 1-h base-line period preceded 2 h of epinephrine infusion. During the 4-h islet clamp (study B), metabolic rate and plasma concentrations of epinephrine, insulin, glucagon, and glucose remained unchanged. During the infusion of epinephrine alone (study A), metabolic rate and concentrations of glucagon, free fatty acids, and C-peptide increased as expected. Also as expected, the glycemic response to epinephrine infusion was much larger when insulin and glucagon levels were fixed with the islet clamp (study C). In contrast, the metabolic rate and the free fatty acid concentration responded similarly to epinephrine infusion when insulin and glucagon were fixed (study C) and when they were changing (study A). We conclude that epinephrine increases metabolic rate independently of physiological changes in plasma glucagon or insulin or the circulating fuels they modulate.
- Published
- 1989
- Full Text
- View/download PDF
228. Leucine kinetics during three weeks at submaintenance-to-maintenance intakes of leucine in men: adaptation and accommodation.
- Author
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Young VR, Gucalp C, Rand WM, Matthews DE, and Bier DM
- Subjects
- Adaptation, Biological, Adult, Amino Acids blood, Amino Acids, Branched-Chain blood, Diet, Dose-Response Relationship, Drug, Humans, Kinetics, Leucine administration & dosage, Leucine deficiency, Male, Nitrogen metabolism, Oxidation-Reduction, Leucine metabolism, Nutritional Requirements
- Abstract
Previous results of short-term diet studies of leucine kinetics have suggested that the currently accepted requirement value for the amino acid in adults is too low. In the present study the effects of a more prolonged diet period at low leucine intakes on leucine kinetics and nitrogen balance (NB) were explored in healthy young men. They (4 or 5 subjects per group) received an adequate leucine intake (80 mg/kg/d) for 1 or 2 weeks (Period 1) followed by either 7, 14 or 30 mg/kg/d for 3 weeks (Period 2) with a return to 80 mg/kg/d for 1 week (Period 3). Estimates of leucine fluxes (LF), oxidation (LO) and balance (LB) were based on a constant intravenous infusion of L-[1-13C]leucine, at end of Period 1, at 1 and 3 weeks of Period 2 and on days 1 and 3 of Period 3. At all three intakes LF and LO, during the fed state, fell between 1 and 3 weeks of Period 2. LB was negative at 1 week of Period 2 for all groups but had approached equilibrium by 3 weeks. N balance at 3 weeks was similar for all groups but during Period 3 was significantly higher (P less than 0.05) and markedly positive (+18 mgN/kg/d) for the 7 and 14 mg groups, compared with the 30 mg group (+4 mgN/kg/d), indicating that 'depletion' had occurred at the lower leucine intakes during Period 2. Our interpretation is that LB was approached by an adaptation in the 30 mg group whereas it was achieved in the 7 and 14 mg groups by an accommodation, associated with a reduced and low rate of leucine uptake into protein (LF minus LO). Thus, the leucine requirement was judged to be greater than 14 mg/kg/d, a level currently accepted as the upper range of the requirement for healthy adults. The significance of these findings for assessment of nutrient requirements is discussed, with emphasis on the limitation of NB measurements for evaluation of human amino acid requirements.
- Published
- 1987
229. The clinical course of 53 patients with venocclusive disease of the liver after marrow transplantation.
- Author
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McDonald GB, Sharma P, Matthews DE, Shulman HM, and Thomas ED
- Subjects
- Aspartate Aminotransferases blood, Bilirubin blood, Humans, Jaundice etiology, Prognosis, Risk, Water-Electrolyte Balance, Bone Marrow Transplantation, Hepatic Veins pathology, Liver Diseases etiology
- Abstract
Two hundred fifty-five patients received chemoradiotherapy and a marrow graft for treatment of malignancy. Fifty-three developed venocclusive disease (VOD) of the liver. The clinical presentation was characterized by jaundice, fluid retention, ascites, upper abdominal pain, and encephalopathy. Insidious weight gain was the first sign of VOD, occurring a mean of 6.2 +/- 5.2 days after transplantation, followed shortly by jaundice. Twenty-four patients (45%) had a serious, progressive liver disease, but the others recovered a mean of 21.6 days after the onset of jaundice. Analysis of pretransplant factors did not disclose a significant association with serious VOD. Patients with serious VOD had significantly higher maximal values for bilirubin and SGOT, gained more weight, and were more likely to have encephalopathy. Supportive treatment did not appear to influence the outcome.
- Published
- 1985
- Full Text
- View/download PDF
230. Metabolic effects of very low calorie weight reduction diets.
- Author
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Hoffer LJ, Bistrian BR, Young VR, Blackburn GL, and Matthews DE
- Subjects
- Alanine blood, Amino Acids metabolism, Energy Intake, Female, Humans, Leucine blood, Nitrogen metabolism, Obesity diet therapy, Diet, Reducing adverse effects, Obesity metabolism
- Abstract
A randomized comparison trial of two very low calorie weight reduction diets was carried out for 5 or 8 wk in 17 healthy obese women. One diet provided 1.5 g protein/kg ideal body weight; the other provided 0.8 g protein/kg ideal body weight plus 0.7 g carbohydrate/kg ideal body weight. The diets were isocaloric (500 kcal). Amino acid metabolism was studied by means of tracer infusions of L-[1-13C]leucine and L-[15N]alanine. After 3 wk of adaptation to the diets, nitrogen balance was zero for the 1.5 g protein diet but -2 g N/d for the 0.8 g protein diet. Postabsorptive plasma leucine and alanine flux decreased from base line by an equal extent with both diets by approximately 20 and 40%, respectively. It was concluded that protein intakes at the level of the recommended dietary allowance (0.8 g/kg) are not compatible with nitrogen equilibrium when the energy intake is severely restricted, and that nitrogen balance is improved by increasing the protein intake above that level. Basal rates of whole body nitrogen turnover are relatively well maintained, compared with total fasting, at both protein intakes. However, turnover in the peripheral compartment, as evidenced by alanine flux, may be markedly diminished with either diet.
- Published
- 1984
- Full Text
- View/download PDF
231. Comprehensive mental health care in a pediatric dialysis-transplantation program.
- Author
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VanLeeuwen JJ and Matthews DE
- Subjects
- Adolescent, Child, Child Psychiatry, Counseling, Family Therapy, Female, Hospital Departments, Humans, Kidney Failure, Chronic therapy, Male, Parent-Child Relations, Social Work, Stress, Psychological, Tissue Donors, Transplantation, Homologous, Comprehensive Health Care, Kidney Transplantation, Mental Health Services, Pediatrics, Peritoneal Dialysis, Renal Dialysis
- Abstract
The dialysis-transplantation (D-T) program at The Hospital for Sick Children, Toronto has a mental health component directed by a psychiatrist and a social worker. As of Jan. 1, 1975, 53 kidney transplants had been carried out on 44 children. Patients and their families are counselled continuously by the psychiatrist and the social worker before, during and after transplantation. Members of the multidisciplinary team meet regularly to plan treatment for the children. Mental health issues are an integral part of team discussions and help determine D-T program policy. Psychological preparation, mental health consultation, therapeutic intervention and continuous counselling prevent many of the mental health problems that plague a D-T program.
- Published
- 1975
232. Leucine metabolism in aging humans: effect of insulin and substrate availability.
- Author
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Fukagawa NK, Minaker KL, Young VR, Matthews DE, Bier DM, and Rowe JW
- Subjects
- Adult, Aged, Aged, 80 and over, Amino Acids blood, Amino Acids pharmacology, Carbon Isotopes, Humans, Isotope Labeling methods, Male, Reference Values, Aging metabolism, Insulin pharmacology, Leucine metabolism
- Abstract
To elucidate the relative roles of insulin (I) and amino acid (AA) availability on body protein economy and AA kinetics, we compared whole body leucine kinetic responses, using a 360-min constant infusion of L-[1-13C]leucine, during administration of an L-AA solution to six healthy young (21-25 yr) and six healthy old (72-87 yr) men (study 1) to those when the AA solution was given in conjunction with a euglycemic I clamp (study 2). In study 1, serum I increased significantly (P less than 0.02) by 4 +/- 1 and 4 +/- 2 microU/ml in young (Y) and old (O) men, respectively. In study 2, I was raised to 91 +/- 7 (Y) and 88 +/- 7 (O) microU/ml; the glucose infusion to maintain euglycemia in the Y was significantly greater than in the O (8.0 +/- 0.1 vs. 6.8 +/- 1.9 mg.kg-1.min-1). Leucine flux and oxidation increased significantly in both age groups during the administration of AA. Estimates of leucine released from protein breakdown declined (P less than 0.01) by 18 and 20% in study 1 and 2, respectively, in the young and by 12 and 44%, respectively, in the elderly. Rates of leucine incorporation into protein increased (P less than 0.01) similarly in both age groups and in both studies. These findings emphasize the importance of AA availability in the stimulation of protein synthesis and suggest that insulin's major role in vivo is to repress whole body proteolysis. Furthermore, despite evidence of an age-related decline in glucose disposal, the elderly had similar leucine kinetic responses to hyperaminoacidemia.
- Published
- 1989
- Full Text
- View/download PDF
233. Branched-chain amino acid nitrogen transfer to alamine in vivo in dogs. Direct isotopic determination with [15N]leucine.
- Author
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Galim EB, Hruska K, Bier DM, Matthews DE, and Haymond MW
- Subjects
- Amino Acids blood, Animals, Carbon metabolism, Dogs, Hindlimb metabolism, Isoleucine metabolism, Leucine metabolism, Nitrogen metabolism, Alanine metabolism, Amino Acids, Branched-Chain metabolism
- Abstract
To investigate the contribution of branched-chain amino acids as a nitrogen source for alanine in vivo, dogs were infused with l-[(15)N]leucine, l-[U-(14)C]leucine, l-[2,3,3,3-(2)H(4)]alanine, and d-[6,6-(2)H(2)]-glucose. (14)C and (15)N isotopic equilibrium in plasma leucine, and deuterium enrichment in arterial and femoral plasma glucose and alanine were achieved within 3 h of initiation of the respective isotope infusion in all animals. The average flux of leucine determined by [(15)N]leucine was 5.4 mumol.kg(-1).min(-1), whereas using [(14)C]leucine it was 3.7 mumol.kg(-1).min(-1). Turnover rates for alanine and glucose were 11.0 and 17.2 mumol.kg(-1).min(-1), respectively.[(15)N]alanine was detected as early as 30 min, but nitrogen isotopic equilibrium in alanine was not achieved until 6 h. The absolute rate of leucine nitrogen transfer to alanine was 1.92 mumol.kg(-1).min(-1), which represented 41-73% (mean 53%) of leucine's nitrogen and 15-20% (mean 18%) of alanine's nitrogen. Fractional extraction of alanine and leucine by the dog hindlimb was 35 and 24%, respectively. Average net alanine balance was -6.7 mumol.leg(-1).min(-1), reflecting a release rate (17.4 mumol.kg(-1).min(-1)) that exceeded the rate of uptake (10.8 mumol.leg(-1).min(-1)). Of the leucine taken up by the hindlimb, 34% transferred its nitrogen to alanine and 8% was oxidized to CO(2). Since the latter value reflects transamination as well as irreversible catabolism, the nitrogen derived from the oxidation of leucine by the hindlimb could account for only 25% of the observed (15)N incorporation into alanine. The significantly faster flux of leucine nitrogen when compared with leucine carbon suggests significant recycling of the leucine alpha-ketoacid. These studies demonstrate that leucine is a major donor of nitrogen to circulating alanine in vivo.
- Published
- 1980
- Full Text
- View/download PDF
234. Quantitative aspects of glucose production and metabolism in healthy elderly subjects.
- Author
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Robert JJ, Cummins JC, Wolfe RR, Durkot M, Matthews DE, Zhao XH, Bier DM, and Young VR
- Subjects
- Adult, Aged, Blood Glucose metabolism, Breath Tests, Female, Glucose biosynthesis, Glucose Tolerance Test, Humans, Insulin blood, Insulin metabolism, Insulin Secretion, Kinetics, Liver metabolism, Male, Aging, Glucose metabolism
- Abstract
The metabolic basis for the reduced glucose tolerance that occurs during aging in humans has been explored with the aid of a primed constant intravenous infusion method of labeled glucose (6-3H; 6,6,2H- and U-13C-glucose). Healthy young adult men and women (24 +/- 3 yr) and elderly men and women (75 +/- 4 yr) participated in a series of studies designed to quantify rates of plasma glucose appearance, oxidation, and recycling while subjects were in the postabsorptive (basal) state and to determine rates of hepatic glucose production and glucose disappearance in response to intravenous glucose at approximately 1 and 2 mg x kg-1min-1 and also 4 mg x kg-1min-1 without or with a simultaneous infusion of insulin to maintain normoglycemia. Basal rates of glucose production were 2.41 +/- 0.06 and 2.18 /+/- 0.05 mg x kg-1min-1 in the young adults and elderly, respectively (P less than 0.05). Recycling of glucose carbon and glucose oxidation rates did not differ significantly between the two age groups. Infusion of unlabeled glucose reduced hepatic glucose production to the same extent in the two groups, indicating that the mechanisms responsible for altered hepatic glucose production with intravenous glucose administration remain intact during human aging. Plasma insulin changes were similar in young adult and elderly subjects receiving 4 mg x kg-1min-1 unlabeled glucose except that the higher plasma glucose levels in the elderly were associated with higher insulin levels. For elderly subjects, the amount of exogenous insulin required to maintain normoglycemia at the 4 mg x kg-1min-1 glucose infusion rate was about twice that necessary in young adults.
- Published
- 1982
- Full Text
- View/download PDF
235. Recombinant growth hormone enhances muscle myosin heavy-chain mRNA accumulation and amino acid accrual in humans.
- Author
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Fong Y, Rosenbaum M, Tracey KJ, Raman G, Hesse DG, Matthews DE, Leibel RL, Gertner JM, Fischman DA, and Lowry SF
- Subjects
- Adult, Growth Hormone blood, Growth Hormone therapeutic use, Human Growth Hormone, Humans, Insulin blood, Leucine metabolism, Male, Oxidation-Reduction, Parenteral Nutrition, Starvation metabolism, Amino Acids metabolism, Growth Hormone analogs & derivatives, Muscles metabolism, Myosins genetics, RNA, Messenger metabolism, Recombinant Proteins therapeutic use, Starvation therapy
- Abstract
A potentially lethal complication of trauma, malignancy, and infection is a progressive erosion of muscle protein mass that is not readily reversed by nutritional support. Growth hormone is capable of improving total body nitrogen balance, but its role in myofibrillar protein synthesis in humans is unknown. The acute, in situ muscle protein response to an infusion of methionyl human growth hormone was investigated in the limbs of nutritionally depleted subjects during a period of intravenous refeeding. A 6-hr methionyl growth hormone infusion achieved steady-state serum levels comparable to normal physiologic peaks and was associated with a significant increase in limb amino acid uptake, without a change in body amino acid oxidation. Myosin heavy-chain mRNA levels, measured by quantitative dot blot hybridization, were also significantly elevated after growth hormone administration. The data indicate that methionyl growth hormone can induce intracellular amino acid accrual and increased levels of myofibrillar protein mRNA during hospitalized nutritional support and suggest growth hormone to be a potential therapy of lean body wasting.
- Published
- 1989
- Full Text
- View/download PDF
236. Leukocyte endogenous mediator alters protein dynamics in rats.
- Author
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Yang RD, Moldawer LL, Sakamoto A, Keenan RA, Matthews DE, Young VR, Wannemacher RW Jr, Blackburn GL, and Bistrian BR
- Subjects
- Animals, Hydroxyproline urine, Kinetics, Male, Methylhistidines urine, Rabbits, Rats, Rats, Inbred Strains, Tyrosine metabolism, Interleukin-1, Proteins metabolism, Proteins pharmacology
- Abstract
Leukocyte endogenous mediator (LEM), a low-molecular-weight peptide synthesized by monocytic cells during phagocytosis, has been implicated as the host's initiator of the protein metabolic response to infection and inflammation. To determine whether administration of LEM would alter protein kinetics, appearance and oxidation of plasma tyrosine as well as the rates of protein synthesis in liver and skeletal muscle were determined in fasted rats that received a 30-hour continuous infusion of either physiologic saline, LEM, or heat-inactivated LEM. The LEM was obtained from rabbit peritoneal exudate and the treatment solutions supplied 2.8 X 10(8) cell equivalents/100 g of body weight (BW) per day. Endogenous tyrosine oxidation increased from 4.0 +/- 0.4 mumol/100 g BW/h to 5.4 +/- 0.7 mumol/100 g BW/h in animals infused with heat-inactivated LEM and to 7.5 +/- 1.5 mumol/100 g BW/h in rats receiving LEM (P less than 0.01). Nonsecretory protein synthesis in the liver was greatest in rats administered LEM (2239 +/- 325 mg/d) when compared with control groups receiving physiologic saline (1122 +/- 195 mg/d) or heat-inactivated LEM (1374 +/- 62 mg/d; P less than 0.01), whereas skeletal protein synthetic rates were unchanged. Rates of muscle and collagen protein breakdown were estimated from the urinary excretion rate of Nt-methylhistidine and hydroxyproline, respectively, and their excretion rose by 30% (P less than 0.05) and 42% (P less than 0.05) with LEM administration. These results suggest that administration of LEM stimulates a mobilization of amino acids from peripheral tissues to support increased visceral protein anabolism while whole body amino acid oxidation is also enhanced. Since similar effects follow fever and infection, these results suggest that LEM may play an underlying role in the protein metabolic response to infection and inflammation.
- Published
- 1983
- Full Text
- View/download PDF
237. Role of counterregulatory hormones in the catabolic response to stress.
- Author
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Gelfand RA, Matthews DE, Bier DM, and Sherwin RS
- Subjects
- Adult, Amino Acids blood, Ammonia urine, Blood Glucose metabolism, Blood Urea Nitrogen, Energy Metabolism, Epinephrine blood, Female, Glucagon blood, Humans, Hydrocortisone blood, Male, Methylhistidines urine, Norepinephrine blood, Obesity metabolism, Time Factors, Triiodothyronine blood, Hormones physiology, Stress, Physiological metabolism
- Abstract
Patients with major injury or illness develop protein wasting, hypermetabolism, and hyperglycemia with increased glucose flux. To assess the role of elevated counterregulatory hormones in this response, we simultaneously infused cortisol (6 mg/m2 per h), glucagon (4 ng/kg per min), epinephrine (0.6 microgram/m2 per min), and norepinephrine (0.8 micrograms/m2 per min) for 72 h into five obese subjects receiving only intravenous glucose (150 g/d). Four obese subjects received cortisol alone under identical conditions. Combined infusion maintained plasma hormone elevations typical of severe stress for 3 d. This caused a sustained increase in plasma glucose (60-80%), glucose production (100%), and total glucose flux (40%), despite persistent hyperinsulinemia. In contrast, resting metabolic rate changed little (9% rise, P = NS). Urinary nitrogen excretion promptly doubled and remained increased by approximately 4 g/d, reflecting increased excretion of urea and ammonia. Virtually all plasma amino acids declined. The increment in nitrogen excretion was similar in three additional combined infusion studies performed in 3-d fasted subjects not receiving glucose. Cortisol alone produced a smaller glycemic response (20-25%), an initially smaller insulin response, and a delayed rise in nitrogen excretion. By day 3, however, daily nitrogen excretion was equal to the combined group as was the elevation in plasma insulin. Most plasma amino acids rose rather than fell. In both infusion protocols nitrogen wasting was accompanied by only modest increments in 3-methylhistidine excretion (approximately 20-30%) and no significant change in leucine flux. We conclude: (a) Prolonged elevations of multiple stress hormones cause persistent hyperglycemia, increased glucose turnover, and increased nitrogen loss; (b) The sustained nitrogen loss is no greater than that produced by cortisol alone; (c) Glucagon, epinephrine, and norepinephrine transiently augment cortisol-induced nitrogen loss and persistently accentuate hyperglycemia; (d) Counterregulatory hormones contribute to, but are probably not the sole mediators of the massive nitrogen loss, muscle proteolysis, and hypermetabolism seen in some clinical settings of severe stress.
- Published
- 1984
- Full Text
- View/download PDF
238. Glucose and insulin effects on the novo amino acid synthesis in young men: studies with stable isotope labeled alanine, glycine, leucine, and lysine.
- Author
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Robert JJ, Bier DM, Zhao XH, Matthews DE, and Young VR
- Subjects
- Adult, Alanine biosynthesis, Amino Acids metabolism, Blood Glucose analysis, Glycine biosynthesis, Humans, Hyperglycemia metabolism, Infusions, Parenteral, Leucine metabolism, Lysine metabolism, Male, Nitrogen metabolism, Amino Acids biosynthesis, Glucose pharmacology, Insulin pharmacology
- Abstract
We have explored interrelationships between te dynamic aspects of whole body glucose and alanine and glycine metabolism in adult humans. Using a primed, continuous intravenous infusion of [1-13C] leucine or lysine given simultaneously with [2H3] or [15N]alanine or [15N]glycine, respectively, whole body alanine and glycine fluxes and their rates of de novo synthesis were determined in three experiments with healthy young men. Subjects were studied in the post-absorptive state and during a 150 min period of an intravenous infusion with unlabeled glucose, at a rate of 4 mg.kg-1 min-1. In one experiment, insulin was given together with the glucose infusion to maintain normoglycemia. In the other two studies, subjects received glucose alone. For the post-absorptive state, alanine flux (mean +/- SEM) was 381 +/- 26 and 317 +/- 18 mumole.kg-1 hr-1 in two separate experiments and glycine flux was 240 +/- 22 mumole.kg-1 hr-1. De novo synthesis of alanine and glycine accounted for 75%-81% and 81% of flux, respectively. Infusion with glucose alone raised plasma glucose to a mean level of 152 mg/dl and increased alanine flux, due to a rise in alanine synthesis of 98 mumole.kg-1 hr-1 (p less than 0.01). Glycine flux and synthesis rate were unaffected by the glucose infusion. When insulin was given with glucose to maintain normoglycemia, the rate of alanine synthesis was unchanged. Because glucose uptake rate, measured with [6,6-2H2] glucose was the same whether glucose was infused along or with exogenous insulin, these results support the view that the circulating plasma glucose level itself may affect alanine synthesis and that the hyperglycemic state is an important factor in regulating interorgan nitrogen transfer, via alanine, in various pathophysiologic states.
- Published
- 1982
- Full Text
- View/download PDF
239. The effect of enteral nutritional support on skeletal muscle protein synthesis and whole-body protein turnover in fasted surgical patients.
- Author
-
Ward MW, Halliday D, Matthews DE, Matthews SM, Peters JL, Harrison RA, Clark CG, and Rennie MJ
- Subjects
- Aged, Diet, Fasting, Food, Formulated, Gastrointestinal Neoplasms therapy, Humans, Intubation, Gastrointestinal, Middle Aged, Preoperative Care, Protein Biosynthesis, Enteral Nutrition, Gastrointestinal Neoplasms surgery, Muscles metabolism, Proteins metabolism
- Abstract
Whole-body and muscle protein turnover have been studied in surgical patients, before abdominal surgery after an 18-h fast, using infusion of 1-[13C]leucine. Four patients received an unmodified hospital diet and four received extra nutritional support (1800 kcal, 70 g protein) by naso-jejunal tube for 7-10 d previously. In patients who received nutritional support there were significantly greater values of whole-body protein synthesis (+42 per cent, P less than 0.05) and breakdown (+45 per cent, P less than 0.01) and muscle protein synthesis (+36 per cent, P less than 0.05) than in those who received the unmodified hospital diet.
- Published
- 1983
240. Protein dynamics in skeletal muscle after trauma: local and systemic effects.
- Author
-
Downey RS, Monafo WW, Karl IE, Matthews DE, and Bier DM
- Subjects
- Actins metabolism, Animals, Burns metabolism, Forelimb, Hindlimb, Male, Muscles metabolism, Myosins metabolism, Nitrogen urine, Oxygen Consumption, Rats, Rats, Inbred Strains, Skin injuries, Tyrosine metabolism, Muscle Proteins metabolism, Muscles injuries
- Abstract
Injury is attended by accelerated skeletal muscle proteolysis. Accurate definition of this hypercatabolic response and its mediation is requisite for specific therapy. We measured protein dynamics in the incubated and intact epitrochlearis and soleus muscles excised from both forelimbs and both hindlimbs of rats 4 days after injury by either a single hind limb scald (90 degrees C water for 3 seconds; metabolic rate (MR) + 15%, urinary urea nitrogen (UUN) + 10%) or a 5% excision (dorsal skin removed to fascia; MR + 40%, UUN + 90%). Protein synthesis (3H phenylalanine incorporation) increased only in the injured soleus from the scalded hind limb (+100%). Actin and myosin breakdown (3-methylhistidine release) increased in all muscles tested and was consistently larger in epitrochlearis than in soleus muscles. Breakdown of the mixed protein pool (tyrosine release) increased but less so than 3-methylhistidine and did not reach significance in the uninjured soleus muscle of scalded rats. With respect to fiber type, white fiber epitrochlearis muscle demonstrated a more pronounced elevation of both measures of breakdown but at a lower metabolic rate than did red fiber soleus muscle. Increasing MR was associated with a linear increase in soleus proteolysis but no further change in epitrochlearis breakdown. We conclude that protein breakdown is increased in skeletal muscle distant from injury; however, even when metabolic stress is severe, synthesis is unchanged. Muscles of different fiber composition are not equally labile. Furthermore, myofibrillar protein is more labile than the mixed protein pool.
- Published
- 1986
241. Relationship of plasma leucine and alpha-ketoisocaproate during a L-[1-13C]leucine infusion in man: a method for measuring human intracellular leucine tracer enrichment.
- Author
-
Matthews DE, Schwarz HP, Yang RD, Motil KJ, Young VR, and Bier DM
- Subjects
- Adult, Carbon Isotopes, Dietary Proteins pharmacology, Humans, Infusions, Parenteral, Intracellular Fluid metabolism, Isotope Labeling, Male, Keto Acids blood, Leucine blood
- Abstract
The keto analog of leucine, alpha-ketoisocaproate (KIC), is formed intracellularly from leucine and is released, in part, into the systemic circulation. Therefore. KIC can be used to estimate intracellular leucine tracer enrichment in man during labeled-leucine tracer experiments without requiring tissue biopsy samples. This approach was studied in young, healthy, male adults maintained on different dietary protein intakes from generous (1.5 g kg-1d-1) to deficient (0.0 g kg-1d-1) for 5-7 day periods. At the end of each dietary period, the volunteers were given a primed, continuous infusion of L-[1-13C]leucine either after an overnight fast (postabsorptive state) or while being fed hourly aliquots of the same diet. The plasma concentrations of all 3 branched-chain amino and keto acid pairs were measured from early morning blood samples taken from 4 subjects at 4 different levels of protein intake. Leucine concentration showed a weak correlation, and valine concentration showed a strong correlation with protein intake; isoleucine and the 3 keto acids did not. However, each branched-chain amino acid concentration was strongly correlated with its corresponding keto acid concentration. In plasma samples obtained during the L-[1-13C]leucine infusions, the ratio of [1-13C]KIC to [1-13C]leucine enrichment ratio remained relatively constant (77 +/- 1% over the wide range of dietary protein intakes and for both the fed and postabsorptive states. For the tissues from which the plasma KIC originates, the rate of plasma leucine into cells will account for approximately 77% of the intracellular leucine flux with the remaining 23% coming primarily from leucine release via protein breakdown. The constant nature of the plasma KIC to leucine 13C enrichment ratio implies that relative changes in leucine kinetics will appear the same under many dietary circumstances regardless of whether plasma leucine or KIC enrichments are used for the calculations.
- Published
- 1982
- Full Text
- View/download PDF
242. Quantitative aspects of glycine and alanine nitrogen metabolism in postabsorptive young men: effects of level of nitrogen and dispensable amino acid intake.
- Author
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Yu YM, Yang RD, Matthews DE, Wen ZM, Burke JF, Bier DM, and Young VR
- Subjects
- Adult, Amino Acids blood, Amino Acids, Essential administration & dosage, Dietary Proteins administration & dosage, Humans, Male, Models, Biological, Nitrogen blood, Alanine biosynthesis, Amino Acids administration & dosage, Glycine biosynthesis, Nitrogen administration & dosage
- Abstract
The nutritionally indispensable amino acids (IAA) alone do not maintain body nitrogen (N) balance; a source of "nonspecific" nitrogen from dispensable amino acids (DAA), such as from glycine and alanine or other N compounds, is required. However, the in vivo regulation of the metabolism of these amino acids in humans with varying nutritional states has received little study. Hence, the effects of N intake and the IAA:DAA ratio on kinetic aspects of whole-body alanine and glycine metabolism were examined in eight healthy young adult male subjects. They received an L-amino acid diet supplying N equivalent to about 1.5 g and 0.6 g protein (N X 6.25) per kilogram body weight per day. All were studies at each N level with the IAA:DAA ratio (wt/wt) of 1:1 and 1:0, each for a 7-d diet period. Constant primed, intravenous infusions of L-[1-13C]leucine together with either L-[15N]alanine (four subjects) or [15N]glycine (four subjects) were given to each subject at the end of the diet period, after an overnight fast, to determine rates of de novo whole-body alanine and glycine N synthesis. The rate of alanine synthesis was similar (P greater than 0.05) for all four diets. Glycine de novo N synthesis declined (P less than 0.01) with removal of dietary DAA, especially at the lower intake, where the mean rates [micromoles/(kilogram X hour)] were 59 and 20 for 1:1 and 1:0 ratios, respectively. The possible significance of reduced rates of glycine N synthesis for maintenance of protein nutritional status in the healthy adult is discussed.
- Published
- 1985
- Full Text
- View/download PDF
243. Physiological hypercortisolemia increases proteolysis, glutamine, and alanine production.
- Author
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Darmaun D, Matthews DE, and Bier DM
- Subjects
- Adult, Glucagon blood, Humans, Hydrocortisone pharmacology, Infusions, Intravenous, Insulin blood, Kinetics, Male, Reference Values, Alanine blood, Glutamine blood, Hydrocortisone blood, Leucine blood, Phenylalanine blood, Proteins metabolism
- Abstract
Physiological elevations of plasma cortisol levels, as are encountered in stress and severe trauma, were produced in six normal subjects by infusing them with 140 micrograms.kg-1.h-1 of hydrocortisone for 64 h. Amino acid kinetics were measured in the postabsorptive state using three 4-h infusions of L-[1-13C]leucine, L-[phenyl-2H5]-phenylalanine, L-[2-15N]glutamine, and L-[1-13C]alanine tracers 1) before, 2) at 12 h, and 3) at 60 h of cortisol infusion. Before and throughout the study, the subjects ate a normal diet of adequate protein (0.8 g.kg-1.day-1) and energy intake. The cortisol infusion raised plasma cortisol levels significantly from 10 +/- 1 to 32 +/- 4 micrograms/dl, leucine flux from 83 +/- 3 to 97 +/- 3 mumol.kg-1.h-1, and phenylalanine flux from 34 +/- 1 to 39 +/- 1 (SE) mumol.kg-1.h-1 after 12 h of cortisol infusion. These increases were maintained until the cortisol infusion was terminated (64 h). These nearly identical 15% increases in two different essential amino acid appearance rates are reflective of increased whole body protein breakdown. Glutamine flux rose from 325 +/- 28 to 453 +/- 28 mumol.kg-1.h-1 by 12 h of cortisol infusion and remained elevated at the same level at 64 h. The increase in flux was primarily due to a 55% increase in glutamine de novo synthesis. Alanine flux increased from 207 +/- 13 to 285 +/- 23 mumol.kg-1.h-1 with acute hypercortisolemia and increased further to 475 +/- 59 mumol.kg-1.h-1 at 60 h of cortisol infusion, a result primarily of increased alanine de novo synthesis.(ABSTRACT TRUNCATED AT 250 WORDS)
- Published
- 1988
- Full Text
- View/download PDF
244. Protein composition of the bovine mitochondrial ribosome.
- Author
-
Matthews DE, Hessler RA, Denslow ND, Edwards JS, and O'Brien TW
- Subjects
- Animals, Cattle, Electrophoresis, Polyacrylamide Gel, Escherichia coli, Macromolecular Substances, Molecular Weight, Ribosomal Proteins isolation & purification, Mitochondria analysis, Ribosomal Proteins analysis, Ribosomes analysis
- Abstract
The protein complement of the bovine mitochondrial ribosome has been analyzed by two-dimensional electrophoresis in polyacrylamide gels to determine the number and molecular weights of the ribosomal proteins. Salt-washed ribosomal subunits are found to contain a total of 85 ribosomal proteins, 84 of which are electrophoretically distinct between the two subunits. These proteins are also electrophoretically distinguished from those of cytoplasmic ribosomes. This large number of proteins does not appear to be due to contamination by cytoplasmic ribosomal proteins or by adherent nonribosomal proteins. The molecular weights of these proteins are considerably larger than those of Escherichia coli ribosomal proteins, and are similar to those of bovine cytoplasmic ribosomal proteins. The sum of the molecular weights of the 85 proteins agrees well with that predicted by physical chemical measurements of the total mass of protein in the two subunits. Bovine mitochondrial ribosomes thus contain about twice as much protein as RNA, a highly unusual composition in comparison to the other kinds of ribosomes which have been characterized to date. In addition, it appears that the ribosomal proteins themselves are less basic than the proteins of most other ribosomes.
- Published
- 1982
245. Response of alanine metabolism in humans to manipulation of dietary protein and energy intakes.
- Author
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Yang RD, Matthews DE, Bier DM, Wen ZM, and Young VR
- Subjects
- Adult, Blood Urea Nitrogen, Dietary Carbohydrates administration & dosage, Humans, Kinetics, Leucine metabolism, Male, Mathematics, Nitrogen metabolism, Alanine metabolism, Dietary Proteins administration & dosage, Energy Intake
- Abstract
Healthy young adult men were studied with 3 different series of dietary regimens: different levels of protein intake ranging from 1.5 to 0.0 g . kg-1 . day-1; different levels of dietary energy intake; and an excessive intake of protein (3.9 g . kg-1 . day-1). Under each dietary condition, subjects were infused postabsorptively with L-[1-13C]leucine, L-[15N]alanine, and L-[3,3,3-2H3]alanine to measure leucine and alanine kinetics. Leucine flux was significantly reduced when protein intake was restricted (maximum reduction = 24%), but changed insignificantly with dietary energy change or excessive protein intake. Alanine flux and de novo synthesis increased significantly when protein intake was restricted (maximum increase = 50%), changed proportionally with changes in dietary energy, and was significantly reduced with high protein intake. Stepwise regression showed that dietary carbohydrate intake, not protein intake, was the primary factor affecting alanine de novo synthesis. In addition, the alanine 2H tracer produced a 2.5-fold greater measure of alanine de novo synthesis than did the alanine 15N tracer.
- Published
- 1986
- Full Text
- View/download PDF
246. Exercise-mediated peripheral tissue and whole-body amino acid metabolism during intravenous feeding in normal man.
- Author
-
Albert JD, Matthews DE, Legaspi A, Tracey KJ, Jeevanandam M, Brennan MF, and Lowry SF
- Subjects
- Adult, Forearm, Glycine metabolism, Humans, Leg, Leucine metabolism, Male, Amino Acids metabolism, Exercise, Parenteral Nutrition
- Abstract
1. The effect of a daily submaximal exercise regimen on whole-body and peripheral tissue amino acid metabolism during weight-stable intravenous feeding (IVF) was evaluated in 11 normal volunteers. Five of the subjects performed 1 h of daily bicycle exercise at 75 W during IVF, while the remaining six subjects received IVF without daily exercise. Body nitrogen balance, leg and forearm plasma amino acid flux and whole-body kinetics were measured before and on day 10 of IVF using a [1-13C]leucine and [15N]glycine tracer. 2. At the end of the IVF period, exercised subjects demonstrated leg uptake of total amino acids (237 +/- 103 nmol min-1 100 ml-1 of tissue, mean +/- SEM) which was significantly (P less than 0.05) different than in non-exercised subjects (-1101 +/- 253 nmol min-1 100 ml-1 of tissue). 3. In the non-exercised forearm, a significant (P less than 0.05) decrease in total amino acid flux was observed in exercised subjects (-162 +/- 88 nmol min-1 100 ml-1 of tissue) compared with non-exercised subjects (-460 +/- 105 nmol min-1 100 ml-1 of tissue) on day 10 of IVF. 4. Efflux of 3-methylhistidine significantly (P less than 0.05) decreased from the leg in those subjects who performed daily exercise (-0.29 +/- 0.12 nmol min-1 100 ml-1 of tissue) compared with those subjects receiving IVF without daily exercise (-1.46 +/- 0.35 nmol min-1 100 ml-1 of tissue).(ABSTRACT TRUNCATED AT 250 WORDS)
- Published
- 1989
- Full Text
- View/download PDF
247. The role of human growth hormone in the regulation of cholesterol and bile acid metabolism.
- Author
-
Heubi JE, Burstein S, Sperling MA, Gregg D, Subbiah MT, and Matthews DE
- Subjects
- Adolescent, Bile metabolism, Child, Child, Preschool, Cholesterol blood, Cholesterol, HDL, Cholesterol, LDL, Feces analysis, Female, Growth Hormone therapeutic use, Humans, Lipoproteins, HDL blood, Lipoproteins, LDL blood, Male, Sterols metabolism, Triglycerides blood, Bile Acids and Salts metabolism, Cholesterol metabolism, Growth Hormone deficiency
- Abstract
Cholesterol and bile acid metabolism was studied in 16 children with human GH (hGH) deficiency (11 with isolated hGH deficiency and 5 with multiple trophic hormone deficiency) before and after 6 months of hGH therapy. We measured plasma lipid concentrations, biliary lipid composition, and cholesterol saturation indices; calculated the bile acid pool size measured by the isotopic dilution technique using the stable isotope chenodeoxycholic-[11,12-d2] acid; and measured cholesterol and bile acid synthetic rates by sterol balance techniques. In all 16 patients, plasmas lipid concentrations were unchanged after hGH therapy; total plasma cholesterol was 182 +/- 10 (+/-SEM) mg/dl before and 179 +/- 9 mg/dl after treatment, high density lipoprotein-cholesterol was 47 +/- 2 mg/dl before and 49 +/- 3 mg/dl after treatment, low density lipoprotein-cholesterol was 112 +/- 10 mg/dl before and 111 +/- 8 mg/dl after therapy, and triglyceride was 113 +/- 13 mg/dl before and 107 +/- 10 mg/dl after hGH therapy. Biliary lipid composition and cholesterol saturation in 10 patients were similar to those in controls and unchanged with hGH therapy. Cholesterol synthesis (n = 14) was unchanged (7.6 +/- 1.4 vs. 9.6 +/- 1.2 mg/kg X day); however, bile acid synthesis (n = 15) increased from 3.1 +/- 0.4 to 4.3 +/- 0.6 mg/kg X day (P less than 0.025) after therapy. The chenodeoxycholate pool size (n = 8) was significantly reduced (P less than 0.025) before hGH treatment (416 +/- 64 mg/m2) compared to that in controls (617 +/- 45 mg/m2) and increased to 620 +/- 72 mg/m2 after hGH therapy (P less than 0.05). Chenodeoxycholate pool size expansion during hGH therapy was, at least in part, caused by an increase in hepatic bile acid synthesis. These findings suggest that hGH may indirectly modulate cholesterol metabolism through regulation of hepatic cholesterol 7 alpha-hydroxylase activity, the rate-limiting enzyme of bile acid synthesis.
- Published
- 1983
- Full Text
- View/download PDF
248. Whole body leucine metabolism in adolescents with Crohn's disease and growth failure during nutritional supplementation.
- Author
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Motil KJ, Grand RJ, Matthews DE, Bier DM, Maletskos CJ, and Young VR
- Subjects
- Adolescent, Body Height, Body Weight, Child, Crohn Disease complications, Crohn Disease diagnosis, Enteral Nutrition, Female, Food, Formulated, Humans, Male, Crohn Disease metabolism, Diet, Dietary Proteins administration & dosage, Energy Intake, Growth Disorders etiology, Leucine metabolism
- Abstract
The adaptive response of whole body leucine metabolism to nutritional supplementation was determined in 6 adolescents with Crohn's disease and growth failure. Five healthy adolescents served as controls for body composition studies. In the first study period, all subjects received a constant diet comparable to usual intakes. In the second period, the patients were given overnight intragastric supplemental feedings that increased dietary protein and energy intakes approximately 40% (to 3.2 g/kg . day and 96 kcal/kg . day, respectively). During each dietary period, O2 consumption, nitrogen balance, whole body potassium (40K), and urinary creatinine measurements were obtained on all adolescents, and the patients received a primed, constant, intravenous infusion of [13C]leucine for 4 h in the fed state. Plasma leucine and expired carbon dioxide 13C-enrichments were determined by mass spectrometric techniques. In the first study, O2 consumption and nitrogen balances were similar between groups; in patients, 40K and urinary creatinine were reduced by 30% and 36%, respectively. With nutritional supplementation, nitrogen balance increased fourfold; O2 consumption and 40K increased by 32% and 10%, respectively. Similarly, whole body leucine flux increased from 166.9 +/- 5.9 to 201.3 +/- 11.2 mumol/kg . h (p less than 0.05) due to a 66% increase in leucine incorporation into body protein (p less than 0.01) and a 41% decrease in leucine oxidation (p less than 0.05). Thus, these studies demonstrate that the mechanisms responsible for lean body mass accretion during nutritional supplementation in adolescents with Crohn's disease and growth failure are increased rates of amino acid incorporation into body protein (via protein synthesis) and decreased rates of amino acid oxidation.
- Published
- 1982
249. The use of deuterated phenylalanine for the in vivo assay of phenylalanine hydroxylase activity in children.
- Author
-
Matalon R, Matthews DE, Michals K, and Bier D
- Subjects
- Child, Child, Preschool, Gas Chromatography-Mass Spectrometry methods, Humans, Infant, Time Factors, Tyrosine blood, Deuterium, Phenylalanine, Phenylalanine Hydroxylase metabolism
- Abstract
Fifteen children, five with phenylketonuria (PKU), five with hyperphenylalaninaemia, and five phenotypically normal but at risk of being carriers for PKU, were given [ring 2H5]phenylalanine orally in amounts ranging from 75 mg/kg to 10 mg/kg. Plasma was assayed for [2H5]phenylalanine and [2H4]tyrosine at hourly intervals, the amino acids being measured as the N-acetyl, n-propyl esters by gas chromatography-mass spectroscopy. The results obtained were calculated as the log of the ratio [2H5]phenylalanine: [2H4]tyrosine in the plasma. The five patients with PKU had ratios of infinity because no [2H4]tyrosine was measured in their plasma during the experimental period. The patients with hyperphenylalaninaemia had log ratios over 2.00 throughout the assay period. Among the five normal children three are considered to be carriers for PKU as the logarithms of the [2H5]phenylalanine: [2H4]tyrosine ratios were 1.77, 1.73, and 1.33 and remained over 1.00 during the assay period. The other children had log ratios of 1.16 and 1.00 at the first hour which dropped below 1.00 subsequently, suggesting normal activity of phenylalanine hydroxylase.
- Published
- 1982
- Full Text
- View/download PDF
250. Effect of tracer infusion site on measurement of bicarbonate-carbon dioxide metabolism in dogs.
- Author
-
Downey RS, Mellone A, and Matthews DE
- Subjects
- Animals, Arteries, Bicarbonates administration & dosage, Bicarbonates blood, Carbon Dioxide blood, Dogs, Female, Infusions, Parenteral, Kinetics, Veins, Bicarbonates metabolism, Carbon Dioxide metabolism
- Abstract
Ten dogs were given a primed infusion of H13CO3- for 220 min while under general anesthesia. Isotopic steady state was reached within 60 min in exhaled CO2, femoral arterial blood HCO3-, and femoral venous blood HCO3-. Halfway through each infusion study, the site of tracer infusion was changed either from the central aorta to a peripheral vein, or vice versa. The mean HCO3(-)-CO2 flux measured from blood HCO3- enrichments was 15.7 +/- 2.1 (SD) mmol X kg-1 X h-1. The mean fraction of tracer recovered in exhaled CO2 was 79 +/- 7% (SD) of the infused dose. No significant difference in either HCO3- flux or recovery of tracer was found between the venous and arterial infusions of tracer. These results indicate that when venous administration of HCO3- tracer is compared with central arterial infusion, the initial loss of tracer into expired CO2 is an unimportant consideration in experiments measuring HCO3- kinetics.
- Published
- 1986
- Full Text
- View/download PDF
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