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Biomedical subjects

L Lumeng

Publications and source records attributed to L Lumeng.

At least 181 records · Page 10Linked to original sources
PubMed1984

Comparison of the use of L-tyrosine apodecarboxylase and D-serine apodehydratase for plasma pyridoxal phosphate assay.

The enzymatic methods for plasma pyridoxal 5'-phosphate (PLP) assay using L-tyrosine apodecarboxylase (apo-LTD) and D-serine apodehydratase (apo-DSD) were compared with respect to their operating characteristics, accuracy and precision. With the apo-LTD assay, the recovery of authentic PLP added to irradiated plasma was 96-100% and the precision for within-run and run-to-run replicates was 4-5% (coefficient of variation). The recovery of authentic PLP with the apo-DSD assay tended to be lower (viz., 95%) and the within-run and run-to-run coefficients of variation tended to be higher (viz., 5-6%), but these differences were not statistically significant. When these two assay methods were directly compared in determining the plasma PLP levels of 67 hospitalized patients, the regression lines exhibited correlation coefficients of 0.89 and 0.92 and slopes of 0.77 and 0.78, respectively. When the plasma PLP values were less than 7.5 ng/ml, the values determined by the apo-DSD assay tended to be higher than those measured by the apo-LTD method and vice versa. The lack of better agreement between the two assay methods may be explained by the fact that an inhibitor exists in plasma extracts that impairs the binding of PLP to apo-DSD and that the correction for this interference may not be uniform from one plasma sample to another. However, if one is willing to tolerate the small discrepancies between the values obtained by the apo-DSD and apo-LTD assays, these assay methods can be used interchangeably. The apo-DSD assay has the advantage of being easily adapted to a modern automated spectrophotometric centrifugal analyzer.

Apoenzymes↗
PubMed1984

Clearance and metabolism of plasma pyridoxal 5'-phosphate in the dog.

This study was undertaken to characterize the metabolic fate of plasma pyridoxal 5'-phosphate (pyridoxal-P), the role of various organs in mediating its degradation, and the contribution of urinary excretion. Anesthetized dogs underwent sham operation, hepatectomy, nephrectomy, or combined surgical removal of the stomach, small intestine, and the spleen; however, the kinetics of plasma pyridoxal-P clearance after the intravenous administration of 2.5 mg of this B6 vitamin were not altered. In anesthetized sham-operated dogs and in unanesthetized dogs, pyridoxal (product of pyridoxal-P hydrolysis) but not 4-pyridoxic acid (oxidation product of pyridoxal) accumulated in plasma and urine after pyridoxal-P administration. Urinary excretion of pyridoxal-P was negligible and it could not account for the rapid clearance of pyridoxal-P from the plasma. The rate of pyridoxal-P hydrolysis mediated by plasma alkaline phosphatase and the cellular elements in whole blood in vitro was also too slow to account for the rapid disappearance of plasma pyridoxal-P in vivo. These results indicate that (1) normally, the overall capacity of the body to hydrolyze circulating pyridoxal-P in plasma is so large that removal of the liver, kidneys, or the intestinal tract and spleen has little or no effect on the rate of plasma pyridoxal-P decay; and (2) plasma pyridoxal-P decay normally proceeds by way of hydrolysis to form pyridoxal. Because pyridoxal is not further oxidized by the liver and the amount of pyridoxal excreted in the urine accounts for less than 25% of the pyridoxal that can be derived from the injected pyridoxal-P load, the preponderant metabolic fate of plasma pyridoxal-P most likely involves its hydrolysis to pyridoxal and then the uptake of pyridoxal by extrahepatic tissues.

Alkaline Phosphatase↗
PubMed1983

Monoamine and metabolite levels in CNS regions of the P line of alcohol-preferring rats after acute and chronic ethanol treatment.

Levels of norepinephrine (NE), dopamine (DA), 3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA), serotonin (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) were determined in 8 brain regions of the P line of alcohol-preferring rats following: (a) an IP injection of 2.5 g ethanol/kg body wt; (b) 8 and 15 weeks of chronic free-choice drinking of 10% ethanol; (c) 15 weeks of chronic free-choice drinking of 10% ethanol and 24 hours of withdrawal; and (d) 7 weeks of forced administration of 5% ethanol in liquid diet. One hour after IP injection of 2.5 g ethanol/kg body wt, the levels of DOPAC and HVA increased 209-45% in the cerebral cortex (CTX) and striatum (STR). A 209% lower content of NE in the CTX of the ethanol group was the only other statistically significant difference observed. Chronic free-choice drinking of 10% ethanol for 8 weeks (6.5 +/- 0.4 g ethanol/kg/day) or 15 weeks (7.8 +/- 0.2 g ethanol/kg/day) and the chronic forced administration of ethanol in liquid diets (up to 13.2 +/- 0.2 g ethanol/kg/day) did not produce any consistent pattern of alterations in the levels of the monoamines or their metabolites in the 8 CNS regions. After 15 weeks of chronic free-choice drinking of 10% ethanol, withdrawal from alcohol also did not produce alterations in the content of the monoamines or their metabolites. These data indicate that acute administration of hypnotic doses of ethanol increases the metabolism of specific dopaminergic neurons in the CNS of the P rat, but monoamine levels and metabolism are not altered after chronic (7-15 weeks) alcohol consumption.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1983

Initial sensitivity and acute tolerance to ethanol in the P and NP lines of rats.

We recently reported that selectively bred, alcohol-preferring (P) and alcohol-nonpreferring (NP) rats differ in sensitivity to a single sedative-hypnotic dose of ethanol, as measured by performance in the jump test. The present study examines the contributions of initial sensitivity and acute tolerance development to this difference. Initial sensitivity, assessed by brain alcohol content upon loss of the aerial righting reflex, was not significantly different between P and NP groups given 3 g ethanol/kg body weight intraperitoneally. Acute tolerance was indexed from blood alcohol concentrations (BAC) upon recovery of jumping performance following two successive ethanol doses. Practiced P and NP rats were required to jump 35 cm to a descending platform following the IP injection of 2.0 g ethanol/kg. The NP group took significantly longer (74 min) than the P (33 min) group whereupon BAC1 of NP rats (234 mg%) was significantly lower than that of P rats (250 mg%). A second injection (1.0 g/kg) was given immediately after the animals reached the 35 cm criterion. Again, NP rats took significantly longer (124 min) than P rats (52 min) to jump 35 cm and BAC2 of NP animals was lower (295 mg%) than that of P rats (343 mg%). The difference between BAC2 and BAC1, the measure of tolerance development, was significantly larger for P rats (90 mg%) than for NP rats (61 mg%). No significant differences in blood ethanol elimination were observed between the groups. The data indicate no difference in initial sensitivity between P and NP animals but that P rats develop acute tolerance more rapidly and/or to a greater degree than do NP rats. The results are consistent with a relationship in these selectively bred lines of rats between alcohol preference and the development of acute tolerance.

Animals↗
PubMed1983

Biliary excretion of 14C-labeled vitamin B-6 in rats.

The biliary excretion of vitamin B-6 was studied in the intact rat and isolated perfused rat liver. In the whole animal, 21% of the radioactivity administered intravenously as [14C]pyridoxine was excreted in the urine over 4 hours, whereas only 2.1% was recovered in the bile. In the perfused liver, 3% of the radioactivity added to the medium was detected in the bile after 4 hours of perfusion. These data suggest that biliary excretion and enterohepatic circulation of vitamin B-6 probably play only a minor role in the overall economy of this vitamin. The concentration of the radiolabeled B-6 compounds in the bile of perfused liver was much higher than that in the perfusate and the pattern of the distribution of radioactivity among difference B-6 compounds was also different. These results suggest that [14C]pyridoxine and its metabolites are released separately by the hepatocytes into the bile and the perfusate and that paracellular transport of vitamin B-6 is not the predominant pathway for the biliary excretion of this vitamin.

Animals↗
PubMed1983

A blinded prospective study comparing four current noninvasive approaches in the differential diagnosis of medical versus surgical jaundice.

A prospective study was undertaken to compare the diagnostic accuracy of clinical evaluation, ultrasound, computed tomography, and technetium 99m-HIDA or -PIPIDA biliary scans in distinguishing between intrahepatic and extrahepatic jaundice. A final diagnosis was established in each of the 50 patients who completed the study, among whom 29 had intrahepatic cholestasis and 21 had extrahepatic obstruction. In the diagnosis of extrahepatic obstruction, the sensitivities of clinical evaluation, ultrasound, computed tomography, and nuclear medicine biliary scan were 95%, 55%, 63%, and 41%, respectively; the specificities were 76%, 93%, 93%, and 88%; and the overall accuracies were 84%, 78%, 81%, and 68%. These data support the conclusion that when the clinical evaluation is carefully performed, it is the single most effective noninvasive means of detecting extrahepatic biliary obstruction in a jaundiced patient. Although ultrasound, computed tomography, and radionuclide biliary scan are less sensitive, they are highly reliable if they indicate that extrahepatic obstruction is present. A flow chart of invasive and noninvasive approaches for evaluation of the jaundiced patient is presented.

Adult↗
PubMed1983

Intrahepatic cholestasis and sicca complex after thiabendazole. Report of a case and review of the literature.

Thiabendazole is a relatively safe and effective agent with a wide range of activity against nematodes infesting the gastrointestinal tract. A 55-yr-old man developed prolonged jaundice and sicca complex after a course of thiabendazole therapy. Endoscopic retrograde cholangiopancreatography demonstrated normal biliary tree and pancreatic ducts. Liver biopsy was consistent with a drug-induced intrahepatic cholestatic reaction. The patient recovered completely from his liver injury, but the sicca complex persisted 1 yr after the drug was given. The literature on thiabendazole-induced cholestasis and its association with sicca complex is reviewed.

Biopsy↗
PubMed1982

Transport of pyridoxine and pyridoxal 5'-phosphate in isolated rat liver mitochondria.

The transport of [14C]pyridoxal-P and [14C]pyridoxine into isolated rat mitochondria was studied by centrifugal filtration. The incubation medium contained 20 mM 2-oxoglutarate and 10 mM inorganic phosphate to inhibit metabolism of pyridoxal-P by the mitochondria. The ratio of [14C]pyridoxine space to [3H]H2O space rapidly attained unity independent of the [14C]pyridoxine concentration in the medium and remained unchanged for up to 90 min of incubation. These data suggest simple passive diffusion for the transport of pyridoxine into the mitochondria. By contrast, the ratio of [14C]pyridoxal-P space to [3H]H2O space rose rapidly to exceed 1 in the first 15 min and continued to rise at a slower rate for as long as it was measured. The accumulation of [14C]pyridoxal-P was not decreased by inhibitors and uncouplers of oxidative phosphorylation. Fractionation of the mitochondria with digitonin revealed that 19 and 340 pmol of [14C]pyridoxal-P/mg of protein were taken up by the mitochondria at 15 and 60 min of incubation, respectively. Most of the uptake in the first 15 min occurred in the intermembrane space, whereas the largest increase of [14C]pyridoxal-P between 15 and 60 min of incubation appeared in the matrix fraction. Significant binding of the [14C]pyridoxal-P to proteins in the two compartments was demonstrated by gel filtration. These data indicate that pyridoxal-P can rapidly enter the intermembrane space of isolated mitochondria, but its penetration into the matrix occurs at a slower and more sustained rate (i.e. 9-16 pmol/h/mg of protein). It is concluded that the transport of pyridoxal-P into isolated rat liver mitochondria is energy-independent and is most consistent with passive diffusion facilitated by protein binding once this coenzyme enters the different compartments of the mitochondria.

Animals↗
PubMed1982

Different sensitivities to ethanol in alcohol-preferring and -nonpreferring rats.

The sensitivity of the P and NP rats to ethanol was determined by the jumping test [23]. Proper interpretation of this test requires knowledge of the regional differences in the distribution of ethanol as a function of time after ethanol injection. Ethanol concentration in brain was higher than those in tail blood and skeletal muscle within the initial 30 min following the intraperitoneal injection of ethanol and was also higher than that in cerebral blood in the first 15 min. However, after 60 min, ethanol concentrations in brain and tail blood were identical. After ethanol injection (2 g/kg), the P rats jumped 88, 78, 85, 54 and 19% higher than the NP rats at 30, 60, 120, 180 and 240 min, respectively. The tail blood ethanol concentrations did not differ between the P and NP rats after 60 min. The P rats also jumped higher than the NP rats after injection of 1.5 and 2.5 g/kg ethanol. These results indicate that the P rats are innately less sensitive to the effects of ethanol than the NP rats.

Alcoholism↗
PubMed1982

Regional brain levels of monoamines in alcohol-preferring and -nonpreferring lines of rats.

Regional brain levels of serotonin (5-HT), 5-hydroxyindoleacetic acid (5-HIAA), dopamine (DA) and norepinephrine (NE) were determined in alcohol-naive rats from lines selectively bred for alcohol preference (P) and alcohol aversion (nonpreference, NP). Based on comparison by a standard t-test, the P rats had 12% lower NE in the pons-medulla, 20% higher NE and 16% lower DA content in the cerebral cortex (CX) than did the NP rats. However, the predominant finding was that the levels of 5-HT and 5-HIAA were 12-26% lower for the P than for the NP rats in the CX, hippocampus (HIP), corpus striatum (STR), thalamus (TH) and hypothalamus (HY). Regional CNS monoamines from a group of independently bred, stock Wistar rats were also compared with the NP and P groups to determine if the selectively bred rats differed widely from an unselected population. In most instances, the NP and P rats fell within the range of the stock group. When the stock group was included in an analysis of variance of the data, post-hoc differences between the NP and P groups that remained significant were the lower levels of 5-HT (and in some cases 5-HIAA) in the CX, HIP, STR, TH and HY of the P group. In the HY and HIP, the 5-HT levels of the P and NP animals diverged significantly in opposite directions from those of the stock group, possibly suggesting an involvement of these regional serotonergic systems in alcohol preference.

Alcoholism↗
PubMed1982

Effects of intravenous ethanol and of 4-methylpyrazole on alcohol drinking in alcohol-preferring rats.

Studies were undertaken to determine if elevated blood alcohol concentrations (BAC), produced by intravenous (IV) infusion of ethanol or by intraperitoneal (IP) administration of 4-methylpyrazole (4-MP), could reduce the free-choice oral alcohol consumption of adult male alcohol-preferring rats (P-rats). The IV infusion of ethanol either on a 24 or 12 (dark) hourly dose schedule reduced the amount of ethanol voluntarily ingested. There was a significant (p less than 0.05) inverse correlation between the amount of ethanol consumed orally and the amount of ethanol infused. Daily fluid and caloric intakes were not compromised. When the amount of ethanol infused was 85% or more of the control oral intake, there was a significant correlation between ethanol intake and tail-blood alcohol levels, taken at 5 min (r = 0.98; p less than 0.05) and 55 min (r = 0.93, p less than 0.05) after the last dark cycle infusion. Below the preinfusion level of 85%, the BAC were variable and did not correlate well with total ethanol intake. After a single IP injection of 4-MP, 90 mg/kg body wt, BAC increased from 10 mg% to 50-65 mg% for 2-3 days. Concomitant with the rise in BAC, these animals decreased their drinking of 10% ethanol and proportionately increased their water intake. The present studies suggest that pharmacological factors, distinct from orosensory cues, are important in regulating voluntary ethanol drinking behavior in the P-rats.

Alcohol Drinking↗
PubMed1982

Induction of dependence on ethanol by free-choice drinking in alcohol-preferring rats.

Studies were performed to examine whether chronic voluntary consumption of ethanol by the selectively-bred, alcohol-preferring P-rats produces physical dependence. Body weight reduction, food restriction and flavoring the 10% ethanol solution increased ethanol consumption from 7 to 14 g ethanol/kg body weight/day when water was freely available. Under similar conditions, consumption by selectively-bred, alcohol-nonpreferring NP-rats increased from 1 to 12 g/kg/day. Removal of ethanol after eight weeks induced physical signs of withdrawal in both lines of animals. In two subsequent studies, P-rats were given food, water and unflavored 10% ethanol ad lib for 15 and 20 weeks; ethanol consumption was 7.2 and 5.6 g/kg/day, respectively. Upon removal of ethanol, manifestations of withdrawal, scored blind in one experiment, developed in 85% of the animals and persisted for 72 hours. Importantly, none in the control groups of P and NP rats given water only exhibited these signs. The ethanol withdrawn groups were hyperactive in both the open-field and the head-poke apparatus. These results indicate that sufficient ethanol was voluntarily consumed by the selectively-bred alcohol-preferring P-rats under free-feeding conditions to produce physical dependence.

Alcohol Drinking↗
PubMed1981

Metabolism of vitamin B6 in rat liver mitochondria.

The capacity of rat liver mitochondria to transport and metabolize B6 compounds has been studied. In B6-sufficient rats, 20% of the B6 content in liver is located in mitochondria. The ratio of pyridoxal-P to pyridoxamine-P in isolated mitochondria is increased with 2-oxoglutarate as substrate and decreased with glutamate. Isolated mitochondria contain pyridoxal-P(pyridoxamine-P) hydrolase activity in the intermembranous space. They exhibit no pyridoxal kinase activity and less than 5% of the pyridoxamine-P(pyridoxine-P) oxidase activity in cytosol and cannot synthesize pyridoxal-P or pyridoxamine-P from pyridoxine, pyridoxal, or pyridoxine-P. When isolated hepatocytes are incubated with [14C]pyridoxine, [14C]pyridoxal-P synthesized in the cytosol is taken up by mitochondria at a rate approximating linearity. Additionally, as reflected by the lower specific radioactivity of [14C]pyridoxal-P in mitochondria than that in cytosol, the extent of mixing of newly synthesized and endogenous pools of pyridoxal-P in these subcellular compartments is heterogeneous. When cytosol from hepatocytes incubated with [14C]pyridoxine is dialyzed to equilibrium, a dialyzable pool of [14C]pyridoxal-P with specific radioactivity similar to that of the added [14C]pyridoxine is identified. It appears that pyridoxal-P from this newly synthesized pool is preferentially transported into mitochondria or secreted and degraded by hepatocytes.

Animals↗
PubMed1980

Reye's syndrome in three siblings. Association with type A influenza infection.

Reye's syndrome occurred simultaneously in three siblings. All had characteristic changes in liver histology ascertained by light and electron microscopy. The two patients with the most severe disease also had serum that caused marked stimulation of mitochondrial state 4 respiration in vitro. Histocompatibility locus antigen typing showed that no unique haplotypes were shared by all three children. There was no evidence of exposure to aflatoxins, pesticides, or other substances that have been previously postulated to be associated with Reye's syndrome. Influenza A/Brazil/11/78-like virus was isolated from one patient, and all three patients had a fourfold or greater rise in hemagglutination-inhibiting antibody to H1N1 influenza virus.

Antigens, Viral↗
PubMed1980

Rate-determining factors for ethanol metabolism in vivo during fasting.

Fasting produces a decrease in ethanol elimination rate of as much as 40% in rats and hamsters. In order to identify the biochemical process responsible for this change, the maximal activity of ADH, the cytosolic free NAD+/NADH ratio and the concentration of ethanol and acetaldehyde in liver were measured in both fed and 48 h fasted rats and hamsters after ethanol administration. While the maximal ADH activity of liver decreased 40% or more with fasting, only a small difference in NAD+/NADH ratio was observed between fed and fasted animals both 1 and 2 h following the administration of ethanol. Calculations of the steady-state rates of oxidation of ethanol by rat ADH revealed that the enzyme is rate-limited primarily by the concentration of free NAD+ in cytosol but that the steady-state rates of ethanol oxidation by ADH are 80-90% of the in vivo ethanol elimination rates. With fasting, the percentage decrease in steady-state rates was identical to that for ADH activity and for the in vivo elimination rate. These results indicate that changes in rates of oxidation of NADH and acetaldehyde contribute little toward the decrease in ethanol elimination rate associated with fasting but that the change in liver ADH activity or content is primarily responsible.

Acetaldehyde↗