Search PubMed⌕ Search

Biomedical subjects

T K Li

Publications and source records attributed to T K Li.

At least 145 records · Page 8Linked to original sources
PubMed1996

Cytochrome P4502E1 genotypes, alcoholism, and alcoholic cirrhosis in Han Chinese and Atayal Natives of Taiwan.

Genetic factors may play a role in the development of alcoholic liver disease (ALD). Cytochrome P4502E1 (CYP2E1) catalyzes the oxidation of ethanol, producing acetaldehyde and free radicals capable of reacting with and peroxidizing cell membranes. Polymorphisms have been identified in the 5-flanking region of the CYP2E1 gene that may alter the transcriptional activity. In our laboratory, no difference in c1 and c2 allele frequencies was observed between alcoholic patients with or without liver disease in Caucasian men, but there is reported data to the contrary for other populations. To determine if there is a differential susceptibility to ALD between ethnic groups that differ in the frequency of the c2 allele, we studied 30 Han Chinese with severe alcoholic liver disease. Allele frequencies of alcoholics with cirrhosis were compared with 46 alcoholic and 100 nonalcoholic Han individuals without liver disease. To identify the type A (homozygous for c1), type B (heterozygous for c1 and c2) and type C (homozygous for c2) genotypes, DNA encompassing the polymorphisms was amplified by polymerase chain reaction, slot-blotted, and probed with allele-specific oligonucleotides, No significant differences in c2 allele frequencies were found: 0.23 for alcoholics with severe liver disease, 0.20 for alcoholics without liver disease, and 0.26 for the normal population. There also was no difference in c2 allele frequencies between alcoholic and nonalcoholic Atayal natives from Taiwan. Therefore, our results suggest that the allelic variations at the CYP2E1 gene locus also do not significantly affect the development of alcoholism or ALD in Han Chinese and Atayal natives of Taiwan.

Adult↗
PubMed1996

Failure to find exon 7 polymorphism of the ADH7 gene in Chinese, Japanese, African-Americans, and Caucasians.

Class IV alcohol dehydrogenase (sigma-ADH) activity has been found in high levels in the stomach and esophagus, but not in liver. Gastric ADH activity has been reported to influence blood alcohol levels after oral ethanol ingestion, suggesting that sigma-ADH activity plays a role in first-pass metabolism. It has also been reported that women have lower sigma-ADH activity than men and that Asians have lower sigma-ADH activity than Caucasians and African-Americans. A genetic basis for these gender and ethnic differences in sigma-ADH activity has been postulated. A recent study in a Japanese subject found a point mutation in the codon for amino acid 287 of the ADH7 gene (which encodes sigma-ADH), changing the amino acid from glycine to valine. A polymerase chain reaction-sequencing assay was established to determine the frequency of this polymorphism in the Asian, Caucasian, and African-American populations. The polymorphism was not present in the 21 Asians, 15 Caucasians, and 3 African-Americans we genotyped, suggesting that if this polymorphism exists, its frequency is low in these ethnic groups. It is therefore unlikely to be responsible for the absence of sigma-ADH activity in gastric specimens from Asians.

Adult↗
PubMed1996

Isoflavonoid compounds extracted from Pueraria lobata suppress alcohol preference in a pharmacogenetic rat model of alcoholism.

The extract from an edible vine, Pueraria lobata, has long been used in China to lessen alcohol intoxication. We have previously shown that daidzin, one of the major components from this plant extract, is efficacious in lowering blood alcohol levels and shortens sleep time induced by alcohol ingestion. This study was conducted to test the antidipsotropic effect of daidzin and two other major isoflavonoids, daidzein and puerarin, from Pueraria lobata administered by the oral route. An alcohol-preferring rat model, the selectively-bred P line of rats, was used for the study. All three isoflavonoid compounds were effective in suppressing voluntary alcohol consumption by the P rats. When given orally to P rats at a dose of 100 mg/kg/day, daidzein, daidzin, and puerarin decreased ethanol intake by 75%, 50%, and 40%, respectively. The decrease in alcohol consumption was accompanied by an increase in water intake, so that the total fluid volume consumed daily remained unchanged. The effects of these isoflavonoid compounds on alcohol and water intake were reversible. Suppression of alcohol consumption was evident after 1 day of administration and became maximal after 2 days. Similarly, alcohol preference returned to baseline levels 2 days after discontinuation of the isoflavonoids. Rats receiving the herbal extracts ate the same amounts of food as control animals, and they gained weight normally during the experiments. When administered orally, none of these compounds affected the activities of liver alcohol dehydrogenase and aldehyde dehydrogenase. Therefore, the reversal of alcohol preference produced by these compounds may be mediated via the CNS. Data demonstrate that isoflavonoid compounds extracted from Pueraria lobata is effective in suppressing the appetite for alcohol when taken orally, raising the possibility that other constituents of edible plants may exert similar and more potent actions.

Alcohol Dehydrogenase↗
PubMed1996

Effects of taste aversion training on the acquisition of alcohol drinking in adolescent P and HAD rat lines.

Early alcohol drinking has been hypothesized to cause alcohol-related problems in adulthood. In addition, a potential role for genetic factors exist in the etiology of some types of alcoholism. The objective of the present study was to determine if taste aversion training to ethanol during adolescence in previously ethanol-naive, alcohol-preferring P and high-alcohol drinking HAD-1 lines of rats would retard or prevent the onset of high alcohol drinking. Taste aversion training began at 30 days of age. Male and female rat pups were fluid deprived for 24 hr before 30 min access to a 10% [v/v] ethanol solution, followed by an intraperitoneal injection of either saline or 0.15 M LiCl (10 ml/kg). A total of five training sessions were administered every other day with unrestricted access to water on intervening training days. Twenty-four hours after the last training trial, rats were given continuous free-choice between water and 10% ethanol for 4 weeks with food available and libitum. There were no obvious gender or line differences to the effects of taste aversion training. All LiCl-treated subjects avoided the usually preferred ethanol solution for the entire 4-week test period, whereas saline-treated rats steadily increased their alcohol intake to over 6.0 g/kg/day by week 4. Rats in the saline and LiCl-treated groups gained weight at comparable rates, and the groups did not differ in total fluid intake. The findings demonstrate that early environmental intervention can prevent the onset of high alcohol drinking in the selectively bred alcohol-preferring P and high-alcohol drinking HAD-1 lines of rats.

Age Factors↗
PubMed1996

Alcohol effects on the heritability of EEG spectral power.

To estimate the effects of a moderate dose of alcohol on heritability of the EEG power spectrum, 53 monozygotic and 38 like-sexed dizygotic Caucasian twin pairs (aged 30.0 +/- 7.0 years) were studied. Subjects were asked not to drink alcohol for 2 days and to fast after midnight before a protocol of: (1) a low fat meal at 8:00 AM; (2) a baseline EEG recording; (3) ingestion of alcohol over 10 min, which raised the breath alcohol concentration to 0.057 +/- 0.017% (SD); followed by (4) a postalcohol EEG recording 35.1 +/- 5.7 (SD) min after the start of drinking. One previous study (Propping, P., Hum. Genet. 35: 309-334, 1977) found that heritability (H2), the fraction of total variance in the EEG power that is attributable to genetic influences, increased after alcohol administration. In the current study, H2 of log-transformed, body-weight-adjusted spectral band power increased after alcohol for the theta-, alpha-slow, alpha-fast, beta-slow, and beta-fast bands (from an average of 0.47 to an average of 0.80). The increase in heritability was accompanied by a significant decrease in the within-pair differences of monozygotic cotwins for all of the same frequency bands except beta-fast. Because within-pair differences are expected to contain only environmental factors for the genetically identical individuals, it was concluded that alcohol decreases environmental variation of EEG power spectral density, causing the increase in H2.

Adult↗
PubMed1996

Effects of cholinergic agents on locomotor activity of P and NP rats.

Experiments were undertaken to compare the selectively bred, alcohol-preferring (P) and alcohol-nonpreferring (NP) rat lines for differences in the locomotor activity (LMA) response to intracerebroventricular infusions of muscarinic- and nicotinic-cholinergic agents. Scopolamine, a nonselective muscarinic antagonist (40 to 120 micrograms/0.5 microliters), dose-dependently increased LMA in both P and NP rats (up to 90 to 100% above baseline; p < 0.05). On the other hand, pirenzepine, a selective M1 muscarinic antagonist (10 to 80 micrograms/0.5 microliters), decreased LMA in P and NP rats (as much as 35 to 40% below control values; p < 0.05). Mecamylamine, a nicotinic antagonist (20 to 80 micrograms/0.5 microliters), also decreased LMA in P and NP rats (as much as 30 to 40% below baseline; p < 0.05). The agonist nicotine (20 to 80 micrograms/0.5 microliters) dose-dependently decreased LMA in both P and NP rats (to a maximum of approximately 60 to 65% below control values; p < 0.05). Based on standardized z-scores, NP rats were more sensitive (p < 0.05) to the locomotor depressant effects of nicotine than P rats, whereas no differences were observed for standardized z-scores between the P and NP lines on the effects of scopolamine, pirenzepine, or mecamylamine on LMA. The results suggest that subtypes of muscarinic and nicotinic receptors are involved in regulating LMA in a complex manner, with the M1 subtype possibly mediating behavioral activation, and that P and NP rats may possess innate differences in CNS nicotinic receptors regulating LMA.

Alcohol Drinking↗
PubMed1996

Serotonin2C receptors and serotonin2C receptor-mediated phosphoinositide hydrolysis in the brain of alcohol-preferring and alcohol-nonpreferring rats.

To examine the role of serotonin2C (5HT2C) receptors in alcohol drinking behavior, the binding indices of 5HT2C receptors were determined in various brain regions of alcohol-preferring (P) and alcohol-nonpreferring (NP) rats. 5HT2C receptor-mediated phosphoinositide hydrolysis in the choroid plexus of P and NP rats was also determined. It was observed that the densities of 5HT2C receptors are significantly higher in the hippocampus, the amygdala, and the choroid plexus, but not in the cortex of P rats compared with NP rats. The Kd values of [3H]mesulergine binding to 5HT2C receptors were not different in these brain regions of P rats compared with NP rats. It was also observed that 5HT-stimulated [3H]inositol 1-phosphate formation was significantly higher in the choroid plexus of P rats compared with NP rats. The results of this study indicate that the numbers of 5HT2C receptors are higher in the hippocampus, the amygdala, and the choroid plexus, and that 5HT2C receptor-mediated phosphoinositide hydrolysis is more elevated in the choroid plexus of P rats compared with NP rats. Thus, it seems from these results that increased 5HT2C receptors may be involved in the genetic vulnerability to alcohol drinking behavior.

Alcohol Drinking↗
PubMed1996

Simultaneous measurement of ethanol and ethyl-d5 alcohol by stable isotope gas chromatography-mass spectrometry.

Efforts to define gender- and ethnic-dependent differences in ethanol first-pass metabolism by gastric mucosa and liver have been limited by a lack of analytical tools that distinguish ethanol concurrently administered by oral and intravenous routes. A stable isotope gas chromatography-mass spectrometry method for simultaneous measurement of ethanol and ethyl-d5 alcohol in serum was developed to meet this need. The assay was linear from 1 to 30 mmol/L. The limit of quantification was 1 mmol/L. Analytical imprecision (CV) was <10%. Analytical recovery was >90%. Specificity was based on retention time and reproducibility of ion ratios. The assay was free from interference by other volatile alcohols. Simultaneous oral administration of ethanol and ethyl-d5 alcohol produced nearly identical pharmacokinetic profiles. Simultaneous oral ingestion of ethanol and intravenous infusion of ethyl-d5 alcohol, adjusted for gastric emptying time, revealed decreased bioavailability of ethanol by the oral route. The method described is sufficient to study the first-pass metabolism of ethanol.

Administration, Oral↗
PubMed1995

Identification and characterization of an immunophilin expressed during the clonal expansion phase of adipocyte differentiation.

Mouse 3T3-L1 cells differentiate into fat-laden adipocytes in response to a cocktail of adipogenic hormones. This conversion process occurs in two discrete steps. During an early clonal expansion phase, confluent 3T3-L1 cells proliferate and express the products of the beta and delta members of the CCAAT/enhancer binding protein (C/EBP) family of transcription factors. The cells subsequently arrest mitotic growth, induce the expression of the alpha form of C/EBP, and acquire the morphology of fully differentiated adipocytes. Many of the genes induced during the terminal phase of adipocyte conversion are directly activated by C/EBP alpha, and gratuitous expression of this transcription factor is capable of catalyzing adipose conversion in a number of different cultured cell lines. The genetic program undertaken during the clonal expansion phase of 3T3-L1 differentiation, controlled in part by C/EBP beta and C/EBP delta, is less clearly understood. To study the molecular events occurring during clonal expansion, we have identified mRNAs that selectively accumulate during this phase of adipocyte conversion. One such mRNA encodes an immunophilin hereby designated FKBP51. In this report we provide the initial molecular characterization of FKBP51.

Adipocytes↗
PubMed1995

Calcitonin gene-related peptide (CGRP) content and CGRP receptor binding sites in discrete forebrain regions of alcohol-preferring vs. -nonpreferring rats, and high alcohol-drinking vs. low alcohol-drinking rats.

This study showed that alcohol-preferring (P) rats and high alcohol-drinking (HAD) rats possess fewer calcitonin gene-related peptide (CGRP) receptor binding sites than their respective controls in the central amygdaloid nucleus (CeA) which is known to be related to anxiety. Since P and HAD rats are selectively bred for high alcohol preference, and alcohol can produce anxiolytic effect, one can postulate that P and HAD rats preferentially drink alcohol in order to obtain its anxiolytic effect. This study supports a hypothesis that deficit of CGRP receptors in the CeA of P and HAD rats may contribute to alcohol preference.

Amygdala↗
PubMed1995

Cimetidine inhibition of human gastric and liver alcohol dehydrogenase isoenzymes: identification of inhibitor complexes by kinetics and molecular modeling.

Cimetidine, an H2-receptor antagonist, is one of the most commonly prescribed drugs in the world. It has been reported to increase blood alcohol concentrations in drinking individuals. To determine if this increase could be due to inhibition of alcohol dehydrogenase activity, the effect of the drug on ethanol oxidation by gastric sigma sigma alcohol dehydrogenase and liver beta 2 beta 2, pi pi, and chi chi alcohol dehydrogenase isoenzymes was observed. Cimetidine inhibited all isoenzymes studied except chi chi; the chi chi isoenzyme showed no inhibition up to 5 mM cimetidine. Inhibition of the alcohol dehydrogenase isoenzymes by the H2-receptor antagonists nizatidine, ranitidine, and famotidine was negligible. Docking simulations with the beta 2.NAD+.4-iodopyrazole X-ray structure indicated that cimetidine fit well into the substrate binding site. The substitution on the thiazole ring of nizatidine, however, prevented docking into the binding site. Cimetidine inhibition of ethanol oxidation by sigma sigma and beta 2 beta 2 was competitive with varied ethanol, exhibiting Ki values of 2.8 +/- 0.4 mM and 0.77 +/- 0.07 mM, respectively. Cimetidine inhibition of ethanol oxidation by pi pi was noncompetitive with varied ethanol (Ki = 0.50 +/- 0.03 mM). Inhibition of ethanol oxidation by sigma sigma and beta 2 beta 2 with varied NAD+ was competitive. These results, together with the cimetidine inhibition kinetics of acetaldehyde reduction by sigma sigma and beta 2 beta 2, with either varied NADH or varied acetaldehyde, are consistent with cimetidine binding to two enzyme species. These species are free enzyme and the productive enzyme.NAD+ complex.

Alcohol Dehydrogenase↗
PubMed1995

Expression and kinetic characterization of recombinant human stomach alcohol dehydrogenase. Active-site amino acid sequence explains substrate specificity compared with liver isozymes.

A full-length 1966-base pair clone of the human class IV alcohol dehydrogenase (sigma-ADH) was isolated from a human stomach cDNA library. The 373-amino acid sigma-ADH encoded by this cDNA was expressed in Escherichia coli. The specific activity of the recombinant enzyme for ethanol oxidation at pH 7.5 and 25 degrees C, calculated from active-site titration of NADH binding, was 92 +/- 9 units/mg. Kinetic analysis of the catalytic efficiency (kcat/KM) of recombinant sigma-ADH for oxidation of primary alcohols indicated broad substrate specificity. Recombinant human sigma-ADH exhibited high catalytic efficiency for oxidation of all-trans-retinol to all-trans-retinal. This pathway is important in the synthesis of the transcriptional regulator all-trans-retinoic acid. Secondary alcohols and 3 beta-hydroxysteroids were inactive with sigma-ADH or were oxidized with very low efficiency. The KM of sigma-ADH for ethanol was 25 mM, and the KM for primary straight chain alcohols decreased substantially as chain length increased. There are important amino acid differences in the alcohol-binding site between the human class IV (sigma) and human class I (beta) alcohol dehydrogenases that appear to explain the high catalytic efficiency for all-trans-retinol, the high kcat for ethanol, and the low catalytic efficiency for secondary alcohols of sigma-ADH relative to beta 1-ADH. For example, modeling the binding of all-trans-retinol in the human beta 1-ADH structure suggested that coordination of retinol to the active-site zinc is hindered by a loop from residues 114 to 120 that is at the entrance to the alcohol-binding site. The deletion of Gly-117 in human sigma-ADH and a substitution of Leu for the bulky Tyr-110 appear to facilitate retinol access to the active-site zinc.

Alcohol Dehydrogenase↗
PubMed1995

The delta opioid receptor antagonist naltrindole attenuates both alcohol and saccharin intake in rats selectively bred for alcohol preference.

This study demonstrates that the selective delta receptor antagonists ICI 174864 and naltrindole (NTI) attenuate alcohol intake in a dose-dependent manner, without altering water intake, in rats selectively bred for alcohol preference. ICI 174864 had a very limited duration of action, as evidenced by the fact that suppression of alcohol intake lasted for only an hour following ICI 174864 administration. NTI, when administered in a dose of 10 mg/kg, suppressed alcohol intake by 28%. Increasing the dose of NTI to 15 mg/kg produced a 44% suppression of alcohol intake, but a further increase to 20 mg/kg did not produce greater suppression than was seen with a dose of 15 mg/kg (46% versus 44%, respectively). This suggests that NTI is maximally effective in suppressing alcohol intake at a dose of 15.0 mg/kg. NTI displayed a long duration of action, as evidenced by attenuation of alcohol drinking that lasted for at least 8 h following drug treatment. Administering the maximally effective dose of NTI (15 mg/kg) in two parts, separated by 4 h, served to prolong the duration of action of NTI and produced an attenuation of alcohol intake, but not water intake, that lasted for at least 28 h. The effect of NTI on alcohol intake was not specific for alcohol, as evidenced by the fact that NTI reduced the intake of saccharin solutions with and without alcohol.

Alcohol Drinking↗
PubMed1995

The delta 2-opioid receptor antagonist naltriben selectively attenuates alcohol intake in rats bred for alcohol preference.

The relative importance of different opioid receptor types in mediating alcohol drinking behavior compared with the intake of other ingesta can be determined by characterizing the effects of selective opioid antagonists on the intake of various ingesta. Nonselective opioid receptor antagonists suppress the intake of many ingesta including alcohol, food, water, and sweets. Two distinct subtypes of delta-opioid receptors, delta 1 and delta 2, have recently been identified in rodent brain. We have previously reported that naltrindole (NTI), which blocks both delta 1 and delta 2 receptors, suppresses both alcohol and saccharin intake in rats selectively bred for high alcohol preference (P line). We now report that naltriben (NTB), an opioid antagonist that is selective for delta 2-opioid receptors, suppresses alcohol intake in rats of the P line and the effect appears to be both specific for alcohol and independent of alcohol palatability. NTB may reduce alcohol intake by attenuating the reinforcing pharmacological properties of alcohol.

Alcohol Deterrents↗
PubMed1995

Quantitative immunocytochemical evaluation of serotonergic innervation in alcoholic rat brain.

Neurotoxicity can be divided into three levels: depletion, degeneration and denervation. The first level is determined by the transmitter content, and the second and third levels, which require anatomical evaluation, can be analyzed by quantitative immunocytochemistry on a specific neurotransmitter system. An antibody specific to serotonin (5-HT) can reveal detailed normal as well as degenerative morphology of 5-HT neurons. Quantitative alterations of 5-HT fibers in a particular brain region indicate degenerative or plastic changes. This study demonstrates quantitative immunocytochemistry by using image analysis of immunostained 5-HT fibers in selectively-bred, alcohol-preferring and nonpreferring rats, which are known to have divergent drinking behaviors, and 5-HT contents in specific brain regions. The method of the image analysis is described in detail and the advantages and disadvantages of using this method to detect the degeneration of a particular fiber system are discussed. The 'area density' traditionally measured in image analysis was converted (with Zhou-Tam formula) into 'volume density' to correct the mismeasurement of fibers through the optical depth. Quantitative immunostaining shows that the difference in 5-HT fiber density in particular brain regions between the two rat lines is consistent with changes in content of the 5-HT/5-HIAA and hypersensitivity of 5-HT1 a receptor. This result indicates either (a) the 5-HT content is too low to be detected in the nerve terminals; (b) degeneration of 5-HT fibers occurs in P rats sometime during development; or (c) a smaller number of 5-HT fibers was preprogrammed in the brain regions of P than NP rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Alcohol Drinking↗
PubMed1995

Association between low contents of dopamine and serotonin in the nucleus accumbens and high alcohol preference.

The contents of dopamine (DA), 3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA), serotonin (5-HT), and 5-hydroxyindoleacetic acid (5-HIAA) were determined in the nucleus accumbens (ACB), frontal cortex (FR), anterior striatum (AST), and hippocampus (HIP) of adult male rats from the F2 generation of P x NP intercrosses. Rats were tested for their alcohol preference and were divided into two groups, depending on their alcohol intake. Rats in the high drinking group (n = 11) had ethanol intakes > 5g/kg/day, whereas the low drinking group (n = 15) had values < 1 g/kg/day. The content of DA in the ACB was lower (p < 0.001) in the high alcohol drinking group (46 +/- 2 pmol/mg tissue) than in the low intake rats (61 +/- 3 pmol/mg tissue). However, the contents of DOPAC and HVA in the ACB were similar for both groups. There were no differences between the two groups in the contents of DA in the FR or AST. The content of 5-HT in the ACB was lower (p < 0.05) in high alcohol drinking rats (6.3 +/- 0.3 pmol/mg tissue) than in the low intake group (7.0 +/- 0.2 pmol/mg tissue). The content of 5-HIAA in the ACB of the high intake rats was also lower than the level for the low drinking rats. There were no differences in the contents of 5-HT or 5-HIAA in the FR, HIP, and AST between the two groups. The results confirm a phenotypic association between abnormal DA and 5-HT systems projecting to the ACB and high alcohol drinking behavior in the P line of rats.

Alcohol Drinking↗
PubMed1995

ADH2 gene polymorphisms are determinants of alcohol pharmacokinetics.

The class I hepatic alcohol dehydrogenases (ADHs) are primarily responsible for ethanol metabolism in humans. Genetic polymorphism at the ADH2 locus results in the inheritance of isozymes of strikingly different catalytic properties. The most common ADH2 allele, ADH2*1, encodes the low K(m) isozyme subunit beta 1. The ADH2*3 allele encodes a high-activity isozyme subunit of alcohol dehydrogenase, beta 3, identified in approximately 25% of African-Americans. The Vmax of beta 3 beta 3-ADH is 30 times greater than that of the beta 1 beta 1-ADH. Therefore, we hypothesized that the rate of ethanol metabolism, an important factor in the toxicity of ethanol, in persons with beta 3-containing ADH, either beta 3 beta 3- or beta 1 beta 3-ADH, would be faster than that of persons with only beta 1 beta 1-ADH. We tested this hypothesis with ethanol administered orally to healthy, young African-Americans. Three hundred and twenty-six African-American men and women were genotyped using polymerase chain reaction amplification of their leukocyte DNA followed by hybridization with allele-specific probes. One hundred twelve volunteers, selected by genotype, received an oral dose of ethanol designed to produce a blood ethanol concentration of 80 mg/dl (0.080 g/dl), when the blood alcohol concentration-time curve was extrapolated back to time 0. Ethanol metabolic rates (beta 60s) were determined in the 112 subjects from the slope of the pseudolinear portion of the blood ethanol concentration-time curves. The mean beta 60 of African-Americans having beta 3-containing ADH isozymes had significantly faster ethanol elimination rates than those with only beta 1 beta 1-ADH isozymes. There were no significant differences in body weight, ethanol intake in the week before testing, peak breath ethanol concentration, time to peak, or volume of distribution between the genotype groups. Within each of these groups, men had lower ethanol disappearance rates than women. These results demonstrate in vivo the kinetic differences of ADH2 isozymes that may influence individual risk for the effects of ethanol.

Adult↗