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Biomedical subjects

Y M Yu

Publications and source records attributed to Y M Yu.

At least 37 records · Page 2Linked to original sources
PubMed1997

TCA cycle flux estimates from NMR- and GC-MS-determined [13C]glutamate isotopomers in liver.

Infusion of 13C-labeled lactate into rabbits and the subsequent measurement of glutamate isotopomers by 13C nuclear magnetic resonance (NMR) spectroscopy enables one to calculate relative flow rates associated with the tricarboxylic acid (TCA) cycle, albeit with a lower precision than one would obtain using a perfused organ. Two factors contribute to the lower precision in the determination of relative flow rates for the in vivo system: 1) a poorly defined pyruvate input and 2) low levels of 13C-enriched oxaloacetate and acetyl-CoA isotopomers, which give rise to weaker glutamate isotopomer NMR signals. To help overcome these limitations, we introduce a procedure to 1) include experimental data from gas chromatography-mass spectrometry (GC-MS) and 2) account for the uncertainty in the labeling of the input to pyruvate by creating the labeling as a measurement that is subject to measurement error. The effects of the uncertainties in the input labeling, NMR data, and MS data are evaluated via a Monte Carlo method. The change in the precision of the relative fluxes for the cases of high/low NMR and high/low MS precision is given. An uncertainty in the lactate measurements of up to 10% does not add significantly to the imprecision of the relative flow rates.

Acetyl Coenzyme A↗
PubMed1996

Modulation of learned helplessness by 5-hydroxytryptamine2A receptor antisense oligodeoxynucleotides.

Serotonergic systems have been implicated in the pathogenesis of major depression in humans as well as in learned helplessness (LH), an animal model of depression. To understand the significance of neuronal responses in depression and LH that are mediated by serotonin (5-hydroxytryptamine, 5HT) receptors, we used intracerebroventricular injections to introduce a unique antisense oligonucleotide (ASO) to the 5HT2A receptor and determined its effect on LH behavior in Sprague-Dawley rats as determined by an escape-avoidance strategy. Of the rats injected with the 5HT2A receptor ASO, 8/16 rats met criteria for LH. By contrast, only 1/15 of the control group injected with 5HT2A sense oligonucleotide (SO) met criteria for LH. Quantitative receptor autoradiography revealed significant differences in 5HT2A receptor density between ASO and control sense oligonucleotides (SO), in close proximity to the injection site. Significant decreases in 5HT2A receptor density caused by oligonucleotide blockade were found in the CA3 hippocampal region. These data support the view that central 5HT, mediated by the 5HT2A receptor, participates in regulating behaviors that are affected by inescapable stress, and that the induction of behavioral depression may be specifically regulated via serotonergic pathways that terminate in this hippocampal subfield.

Animals↗
PubMed1996

Measurement of muscle protein synthesis by positron emission tomography with L-[methyl-11C]methionine.

Positron emission tomography (PET) with L-[methyl-11C]methionine was explored as an in vivo, noninvasive, quantitative method for measuring the protein synthesis rate (PSR) in paraspinal and hind limb muscles of anesthetized dogs. Approximately 25 mCi (1 Ci = 37 GBq) of L-[methyl-11C]methionine was injected intravenously, and serial images and arterial blood samples were acquired over 90 min. Data analysis was performed by fitting tissue- and metabolite-corrected arterial blood time-activity curves to a three-compartment model and assuming insignificant transamination and transmethylation in this tissue. PSR was calculated from fitted parameter values and plasma methionine concentrations. PSRs measured by PET were compared with arterio-venous (A-V) difference measurements across the hind limb during primed constant infusion (5-6 h) of L-[1-13C, methyl-2H3]methionine. Results of PET measurements demonstrated similar PSRs for paraspinal and hind limb muscles: 0.172 +/- 0.062 vs. 0.208 +/- 0.048 nmol-1.min-1.(g of muscle)-1 (P = not significant). PSR determined by the stable isotope technique was 0.27 +/- 0.050 nmol-1.min-1.(g of leg tissue)-1 (P < 0.07 from PET) and indicated that the contribution of transmethylation to total hind limb methionine utilization was approximately 10%. High levels of L-[methyl-11C]methionine utilization by bone marrow were observed. We conclude that muscle PSR can be measured in vivo by PET and that this approach offers promise for application in human metabolic studies.

Animals↗
PubMed1996

Kinetics of plasma arginine and leucine in pediatric burn patients.

The dynamic status of whole-body arginine and leucine was investigated in eight severely burned (mean 55% of body surface area) pediatric patients (mean age 5.3 y) at a mean of 16 d after their initial injury. Plasma amino acid kinetics were estimated by using primed constant intravenous infusions of L-[13C-guanidino]arginine and L-[I-13C]leucine given for 4 h. Each patient was studied twice within 2 d. The patients were studied either in a "basal" state, which involved removal of amino acids from the total parenteral nutrition (TPN) solution for 8 h before the tracer study, or while receiving complete TPN. Nitrogen intake was 0.58 +/- 0.08 g.kg-1.d-1 with nonprotein energy intake equivalent to 197 +/- 29 kJ.kg-1.d-1. Plasma leucine and arginine fluxes (mumol.kg-1.h-1) were 208 +/- 35 and 108 +/- 18 for basal and 290 +/- 38 and 195 +/- 22 for TPN periods, respectively. Leucine oxidation was 42 +/- 7 and 59 +/- 9 mumol.kg-1.h-1 for basal and TPN periods, respectively, indicating a higher rate of leucine loss in the absence of a leucine intake than that expected for healthy individuals. The arginine kinetic data implied little net de novo arginine synthesis and further suggested increased rates of arginine degradation from burn injury. The expected rate of urea excretion, based on the basal rate of leucine oxidation, agreed closely with the measured output of urinary urea. These findings suggest that arginine is a conditionally indispensable amino acid for maintaining body protein homeostasis and nutrition in severely burned pediatric patients. The metabolic response of these children appears to be quantitatively similar to that for severely burned adult patients.

Amino Acids↗
PubMed1996

Human catechol-O-methyltransferase pharmacogenetics: description of a functional polymorphism and its potential application to neuropsychiatric disorders.

Catechol-O-methyltransferase (COMT) inactivates catecholamines and catechol drugs such as L-DOPA. A common genetic polymorphism in humans is associated with a three-to-four-fold variation in COMT enzyme activity and is also associated with individual variation in COMT thermal instability. We now show that this is due to G-->A transition at codon 158 of the COMT gene that results in a valine to methionine substitution. The two alleles can be identified with a PCR-based restriction fragment length polymorphism analysis using the restriction enzyme Nla III. The identification of a gentic marker associated with significant alterations in enzyme activity will facilitate the analysis of a possible role for the COMT gene in neuropsychiatric conditions in which abnormalities in catecholamine neurotransmission are believed to occur, including mood disorders, schizophrenia, obsessive compulsive disorder, alcohol and substance abuse, and attention deficit hyperactivity disorder. In addition, this polymorphism may have pharmacogenetic significance in that it will help make it possible to identify patients who display altered metabolism of catechol drugs.

Catechol O-Methyltransferase↗
PubMed1996

Characterization of novel non-toxic Bacillus thuringiensis isolates from Korea.

Four Bacillus Thuringiensis isolates from soil samples produced parasporal inclusions which were non-toxic to insects. The isolates were named B. thuringiensis NTB-1, NTB-2, NTB-3 and NTB-4. The parasporal inclusions were shown to be ovoid by phase contrast and scanning electron microscopy. The serotypes of the four isolates were determined by agglutination using 33 antisera; NTB-1 and NTB-4 seemed to be subsp. israelensis, and NTB-2 seemed to be subsp. pondicheriensis. NTB-3 did not react with the 33 antisera. However, comparison of parasporal protein and plasmid DNA patterns of the four isolates with those of 15 known non-toxic B. thuringiensis strains demonstrated that the four isolates are novel.

Animals↗
PubMed1996

Quantitative aspects of interorgan relationships among arginine and citrulline metabolism.

The quantitative roles of the splanchnic region and the kidneys in whole body (WB) arginine and citrulline metabolism were assessed in postabsorptive mongrel dogs with primed constant intravenous infusions of [15N2-guanidino, 5,5-2H2]arginine and [13C-ureido]citrulline or [13C-guanidino]arginine and [15N]urea tracers. Isotope and metabolite concentration balances of arginine and citrulline were measured across the gut, liver, splanchnic region, and kidneys, together with WB arginine and citrulline fluxes and urea production rate. The WB citrulline flux and rate of citrulline to arginine (C-A) conversion were 16 and 9.4 mumol.kg-1.h-1, respectively. Concentration balance of citrulline across kidneys was +8.2 mumol.kg-1.h-1, and metabolism of citrulline by kidneys was 8.7 mumol.kg-1.h-1, which was derived about equally from intestine and liver. The appearance rate of citrulline-derived arginine in renal vein was 6.8 mumol.kg-1.h-1. These three separate estimates of C-A conversion within the kidneys were in good agreement, indicating 40% of blood C-A conversion occurring outside kidneys. These findings of interorgan metabolism are discussed in reference to the current knowledge derived largely from studies in laboratory rodents.

Animals↗
PubMed1996

Developmental changes and differential regulation by testosterone and estradiol of growth hormone receptor expression in the rabbit.

To investigate the effects of testosterone and estradiol (E2) on growth hormone receptor (GH-R) gene expression, we measured GH-R mRNA levels in relation to the changes of sex steroid concentrations in the normal male rabbits aged 1-12 months and after administration of testosterone or E2 to castrated male rabbits. In the normal animals, E2 levels were below the detection limit in all age groups, and testosterone levels were below the detection limit at 1 month, increased at 2 months and reached the plateau of the adult levels after 4 months. Liver GH-R mRNA levels were low at 1 month, reached a peak at 2 months and then decreased slightly thereafter. In the castrated animals, liver and growth plate GH-R mRNA levels were increased in the testosterone-treated group (162.0 +/- 12.0%, p < 0.025; 128.4 +/- 7.6%; p < 0.025) and reduced in the E2-treated group (29.6 +/- 6.2%, p < 0.005; 53.6 +/- 11.3%, p < 0.025). Sex steroid administration did not result in any significant change in GH-R mRNA levels in striated muscle, kidney and heart. Serum GH concentrations were increased in E2 (15.3 +/- 7.7 microg/l vs 4.8 +/- 2.2 microg/l, p < 0.025) but the increase was not significant in testosterone-treated animals (8.4 +/- 7.7 microg/l vs 4.8 +/- 2.2 microg/l). Both testosterone and E2 treatment resulted in a reduction of mean serum growth hormone-binding protein (GHBP) levels compared to control animals (1077 +/- 422 pmol/l, p < 0.01; 1137 +/- 443 pmol/l, p < 0.01; 2308 +/- 565 pmol/l). We conclude that in addition to their stimulatory effect on GH secretion, testosterone and E2 have opposite effects on GH-R gene expression in liver and growth plate in the rabbit. The modulation of GH-R expression by sex steroids may be important for growth during sexual maturation in mammals.

Aging↗
PubMed1996

Arginine: new and exciting developments for an "old" amino acid.

Arginine (2-amino-5-guanidino pentanoic acid) was shown in 1895 by Hedin to be present in the proteins of horn. Metabolic nitrogen balance studies, conducted in 1957 by Rose in human adults and in 1959 by Snyderman and coworkers in young infants revealed that a dietary source of this amino acid was not an obligatory requirement for growth and maintenance of nitrogen homeostasis in healthy individuals. Hence, it was initially classified as a non-essential (dispensable) amino acid and, perhaps, for reasons of this classification arginine did not receive the earlier attention it now deserves, in relation to an understanding of the nutritional biochemistry and physiology of its metabolism in humans subjects. However, there is currently a considerable interest in the cellular and tissue functions, as well as clinical, therapeutic significance, of arginine. In this paper we review the multiple functions of arginine, including its role in the L-arginine-nitric oxide pathway, cellular regeneration, immune function, protein synthesis and protein breakdown. We then consider some in vivo aspects of the physiology of arginine metabolism, which varies greatly among eukaryotes, with particular reference to humans. Against this background, studies of arginine in the nutrition of humans under various pathophysiological conditions are reviewed briefly. Finally, a new, updated concept for the metabolic basis for the "conditional essentiality" of arginine is proposed.

Arginine↗
PubMed1996

[Comparison between two diagnostic methods of computer's mathematic model and clinical diagnosis on TCM syndromes of rheumatoid arthritis].

Based on the test result of 14 trace elements in hair of 163 cases of rheumatoid arthritis, we used one of the methods of the computer's mathematic model, DYNAMIC to assign the patients to five groups among multidimensional space. Then, another method, M-DEC was used to diagnose it back on one plane. The result was compared with that by the usual clinical diagnosis, also five groups were obtained, the group of Deficiency of both Liver and Kidney, syndrome of intermingled Cold with Heat, Deficiency of Qi and Yin, syndrome of Dampness-Heat stagnating in collaterals and syndrome of Phlegm-Dampness stagnating in collaterals. And Kappa was 0.77, greater than 0.6. It displayed the consistency in observation of these two methods, which was shown reliable. After that, we have detected the sensitivity of the syndrome diagnosis by computer's mathematic model method, the result was 96.67% and the specificity of that was 95.15%. So we consider this method could give us an objective judgment on TCM syndromes of rheumatoid arthritis.

Adult↗
PubMed1995

Expression and synergistic effect of three types of crystal protein genes in Bacillus thuringiensis.

Bacillus thuringiensis NT0423 newly isolated from sericultural farms in Korea produces quite atypical bipyramidal crystals of a common major band of ca. 130 kDa, and has dual specificity against Lepidoptera and Diptera. To enforce the Diptera toxicity of B. thuringiensis NT0423, cryIVD and cytA genes were transformed into B. thuringiensis NT0423. The transformant B. thuringiensis PT0529 was obtained from introduction of pCG5 into B. thuringiensis NT0423 by electroporation. The expression of crystal proteins in B. thuringiensis PT0529 was characterized by SDS-PAGE and electron microscopy. The results showed that crystalline inclusions of host, CryIVD and CytA were clearly observed in B. thuringiensis PT0529. Furthermore, the toxicity of B. thuringiensis PT0529 against Diptera was highly enforced by synergistic effect.

Animals↗
PubMed1995

Plasma arginine and leucine kinetics and urea production rates in burn patients.

We measured plasma arginine and leucine kinetics and rates of urea production (appearance) in 12 severely burned patients (mean body surface burn area, 48%) during a basal state (low-dose intravenous glucose) and while receiving routine, total parenteral nutrition ([TPN] fed state) including an L-amino acid mixture, supplying a generous level of nitrogen (mean, 0.36 g N.kg-1.d-1). The two nutritional states were studied in random order using a primed 4-hour constant intravenous tracer infusion protocol. Stable-nuclide-labeled tracers were L-[guanidino-13C]arginine, L-[1-13C]leucine, [18O]urea, and NaH13CO3 (prime only), with blood and expired air samples drawn at intervals to determine isotopic abundance of arginine, citrulline, ornithine, alpha-ketoisocaproate ([KIC] for leucine), and urea in plasma and 13CO2 in breath. Results are compared with data obtained in these laboratories in healthy adults. Leucine kinetics (flux and disappearance into protein synthesis) indicated the expected higher turnover in burn patients than in healthy controls. Mean leucine oxidation rates are also higher and compared well with values predicted from urea production rates, provided that urea nitrogen recycling via intestinal hydrolysis is taken into account. The plasma urea flux was also higher than for normal subjects. Arginine fluxes as measured in the systemic whole body, via the plasma pool, were correspondingly higher in burned patients than in healthy controls and were in good agreement with values predicted from leucine-KIC kinetics. However, systemic whole-body arginine flux measured via the plasma pool was only 20% of the arginine flux estimated from the urea flux plus the rate of protein synthesis.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

Relations among arginine, citrulline, ornithine, and leucine kinetics in adult burn patients.

Plasma fluxes of arginine, citrulline, and leucine, and the rate of conversion of labeled citrulline to arginine (Qcit-->arg) were determined in nine severely burned patients (mean: 56% body surface burn area, mean 10 d postinjury) while they received total parenteral nutrition (TPN) including an L-amino acid mixture that supplied a generous amount of nitrogen (mean: 0.39 +/- 0.02 g.kg-1.d-1). Plasma fluxes were also studied in these patients during a basal state (low-dose intravenous glucose) by using a primed, 4-h constant intravenous tracer-infusion protocol. Stable-nuclide labeled tracers were L-[15N-15N-guanidino,5,5,2H2]arginine; L-[13C-ureido]citrulline; L-[1-13C]leucine; and NaH13CO3 (prime only), with blood and expired air samples drawn at intervals to determine isotopic abundance of arginine, citrulline, ornithine, and alpha-ketoisocaproate (KIC; for leucine) in plasma and 13CO2 in breath. Leucine kinetics (flux and disappearance into protein synthesis) confirmed the anticipated higher protein turnover in these burn patients compared with healthy control subjects. The plasma arginine fluxes were correspondingly higher in burn patients than in healthy control subjects. However, the citrulline flux and rate of conversion of citrulline to arginine were not higher than values obtained in our laboratories in healthy adult subjects. We hypothesize that the higher rates of arginine loss from the body after burn injury would need to be balanced by an appropriate exogenous intake of preformed arginine to maintain protein homeostasis and promote recovery from this catabolic condition.

Adult↗
PubMed1995

Whole body arginine metabolism and nitric oxide synthesis in newborns with persistent pulmonary hypertension.

Despite the potential relevance of the L-arginine-nitric oxide (NO) pathway in the pathophysiology of pulmonary hypertension, no in vivo studies of the kinetics of arginine and NO have been conducted previously in this population. The terminal guanidino N-atom of L-arginine is the precursor for NO, which is oxidized to the stable inorganic nitrogen oxides, nitrite (NO2-) and nitrate (NO3-). Thus, synthesized NO is detected in serum or urine as NO2- and NO3-. The purpose of this investigation was to compare studies of whole body arginine metabolism twice in nine patients with persistent pulmonary hypertension of the newborn (PPHN), using a primed constant i.v. infusion of L-[guanidino-15N2,5,5(2)H2]arginine and L-[5,5,5(2)H3]leucine, first during acute pulmonary vasoconstriction and again during convalescence, and thereby to characterize quantitative aspects of whole body arginine kinetics and NO production, as estimated from the rate of transfer of the 15N-guanidino-label of arginine to urinary nitrate (15NO3-). Arginine flux rates were 84.1 +/- 8.6 mumol.kg-1 h-1 (mean +/- SEM) during acute pulmonary hypertension and increased to 125 +/- 13.2 (p < 0.05) during convalescence, whereas leucine fluxes were unchanged (168.5 +/- 15 versus 178.8 +/- 10.2 mumol.kg-1 h-1), and comparable to those reported in healthy newborns. During convalescence total urinary nitrate excreted increased by 66% (p < 0.05), urinary 15NO3- increased from 0.29 +/- 0.07 to 0.74 +/- 0.15 mumol.d-1 (p < 0.05), and the rate of plasma arginine conversion to NO increased from 10.3 +/- 2.2 to 45.6 +/- 13 mumol.d-1 (p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Arginine↗
PubMed1995

A natural vaccine candidate strain against cholera.

E1 Tor Vibrio cholerae (EVC) strains may be classified into two kinds-epidemigenic (EEVC) strains and non-epidemigenic (NEEVC) strains-based on a phage-biotyping system. A large number of EEVC strains have been screened for toxigenic and putative colonization attributes. One such naturally occurring strains (designated IEM101) has been found which is devoid of genes encoding cholera toxin (CT), accessory cholera enterotoxin (ACE), zonula occludens toxin (ZOT), but possesses RS1 sequences and toxin-coregulated pilus A gene (icpA) although icpA is poorly expressed. It expresses type B pili but does not possess type C pili. It is an E1 Tor Ogawa strain and does not cause fluid accumulation in rabbit ilcal loop tests. Active immunization of rabbits with strain IEM101 elicited good protection against challenge with virulent strains of V. cholerae O1. Oral administration caused no side effects in 15 human volunteers, colonized the gut for four to ten days and elicited good immune responses.

Animals↗
PubMed1994

Nitric oxide production is intensely and persistently increased in tissue by thermal injury.

NO is a major messenger molecule which regulates immunity and vascular tone, serves as a neurotransmitter and participates in wound healing. It has also been known to be increased in vivo by thermal injury. Urinary nitrate excretion and tissue levels of NO synthase activity were measured after a non-lethal thermal injury. Urinary nitrate excretion decreased by 90% 24-48 h after injury, but dramatically increased by 10-fold thereafter for 30-40 days after injury and remained elevated until the wound healed. This response was inhibited by a competitive inhibitor of NO synthase. These rates of urinary nitrate excretion suggest that NO production is dramatically affected by injury in a pattern that is distinct from that observed after lipopolysaccharide administration. On the basis of these findings, we suggest that the hyperdynamic cardiovascular and hypermetabolic responses seen to continue weeks after thermal injury could be a result of the autocrine and paracrine effects of NO generated locally within the tissues in addition to that generated by inflammatory cells.

Amino Acid Oxidoreductases↗
PubMed1994

Plasma arginine kinetics in adult man: response to an arginine-free diet.

To explore the response of whole-body arginine metabolism to a change in arginine intake, plasma arginine kinetics were investigated in eight healthy adult men who received an L-amino acid diet supplying an Arg-rich or Arg-free intake for 6 days before undergoing a tracer study on day 7. The tracer protocol lasted for 8 hours. For the first 3 hours subjects remained in the postabsorptive (fasted) state, and during the following 5 hours they consumed small meals at 30-minute intervals. Primed continuous intravenous infusions of L-[guanidino-13C]arginine, L-[5,5,5-2H3]leucine, and [15N2]urea were administered to estimate plasma amino acid fluxes and the rate of urea production. For the fasted and fed states, plasma arginine fluxes (mumol.kg-1.h-1, mean +/- SD) were 69 +/- 8 and 87 +/- 12 (P < .01), respectively, for the Arg-rich diet and 63 +/- 14 and 51 +/- 7 (P < .01, from Arg-rich) for the Arg-free diet. Compared with the Arg-rich results, fed-state plasma arginine and ornithine concentrations were decreased (P < .01) and citrulline concentration was increased (P < .01) during the Arg-free diet period. Leucine fluxes and rates of urea production did not differ between the diet groups. The lower fed-state arginine flux in subjects receiving the Arg-free compared with the Arg-rich diet appears to be entirely due to the decreased rate of entry of arginine from the intestine in the former group.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗