bluuebunny/crossref_metadata_2025_split huggingface dataset:
Transcriptional Activity of the Tandem Repeat Polymorphism in the 5′‐Flanking Region of the Human CYP2E1 Gene
Authors: Nomura Fumio , Itoga Sakae , Uchimoto Takayuki , Tomonaga Takeshi , Nezu Masahiko , Shimada Hideaki , Ochiai Takenori 
Published: November 2003

Background: There are remarkable interindividual differences in the expression of cytochrome P‐4502E1(CYP2E1), which in turn may alter susceptibility to alcohol‐related diseases and various cancers. We recently characterized the tandem repeat polymorphism in the 5′‐flanking region of the human CYP2E1 gene and found that subjects with the homozygous mutant‐type (A4/A4) may be at higher risk of developing esophageal cancer. In this study, we determined how this tandem repeat polymorphism alters transcriptional activities of the human CYP2E1 gene by transfection studies.Methods: The 5′‐flanking region (−2562 base pair to +9 base pair) of the CYP2E1 gene from three individuals of different genotypes (A2/A2, A2/A4, A4/A4) was amplified by polymerase chain reaction. The polymerase chain reaction products placed in front of a luciferase reporter gene were transfected into human hepatoblastoma cells, human esophageal cancer cells, and human uterus cancer cells. Transcriptional activities were determined by the dual‐luciferase assay. When indicated, ethanol (50 mM) was included in the culture medium. CYP2E1 messenger RNA levels in peripheral lymphocytes were measured by the real‐time reverse transcription‐polymerase chain reaction using the LightCycler system.Results: The construct including the tandem repeat region exhibited luciferase activities in both A2 and A4 type. It was of note that the activity produced by the A4 allele was significantly greater than that by A2 allele in HeLa cells (p < 0.001). CYP2E1 messenger RNA levels in peripheral blood lymphocytes were comparable between the two genotypes.Conclusion: Transcriptional activity of the mutant allele of the tandem repeat polymorphism in the 5′‐flanking region of the CYP2E1 gene is greater than that of the wild type.
Augmentation of Ethanol‐Induced Cell Damage and Activation of Nuclear Factor‐κB by Annexin IV in Cultured Cells
Authors: Sohma Hitoshi , Ohkawa Hiroko , Sakai Rie , Hashimoto Eri , Ukai Wataru , Saito Toshikazu 
Published: November 2003

Background: We previously reported that the amount of annexin IV expression was increased in culture cells by exposure to ethanol. Here, to investigate the physiologic role of annexin IV, we analyzed ethanol‐induced cytotoxicity and nuclear factor (NF)‐κB activity by using annexin IV‐overexpressed cells.Methods: Annexin IV overexpression was performed by transfection of expression vector, in which annexin IV complementary DNA was ligated, to culture cells (rat glioma C6 cells and human neuroblastoma SH‐SY5Y cells). Ethanol‐induced cytotoxicity was assayed by measuring the mitochondrial enzyme (dehydrogenase) activity or trypan blue exclusion. NF‐κB activity was measured by electrophoretic mobility shift assay with a κB‐oligonucleotide probe.Results: Ethanol‐induced cytotoxicity was increased by overexpression of annexin IV in both C6 cells and SH‐SY5Y cells. Annexin IV overexpression augmented ethanol‐induced NF‐κB activation.Conclusions: Ethanol‐induced increase in annexin IV expression might amplify ethanol‐induced cytotoxicity via NF‐κB activation.
Interaction Between S‐Propranolol and Ethanol in Mice Selectively Bred for Ethanol Sensitivity: The Inbred Short‐ and Long‐Sleep Mice
Authors: Deitrich Richard A. , Bludeau Pequita 
Published: November 2003

Background: We have studied the effect of a β‐adrenergic blocking agent, S‐propranolol, on the response of mice to anesthetic doses of ethanol. We used the selectively bred short and long sleep (ISS and ILS) mice. These mice were selected for their differential sensitivity to anesthetic doses of ethanol and then inbred. The study was prompted by the finding that the effect of ethanol on the firing rate of cerebellar Purkinje cells is modulated by β‐adrenergic input. In addition, this firing rate depression by ethanol is highly correlated with the anesthetic potency of ethanol. We were attempting to find a behavioral correlate of this effect of β‐adrenergic agents in the ISS and ILS mice.Methods: We studied the effect of S‐propranolol plus ethanol on the sleep time and blood ethanol at awakening in the inbred ILS and ISS mice. We administered anesthetic doses of ethanol with and without S‐propranolol. We conducted studies of the rate of disappearance of ethanol in the presence of S‐propranolol and carried out sleep time and metabolic studies with mice in an incubator held at 32 to 33°C.Results: We found that S‐propranolol caused a prolonged anesthetic time brought about by ethanol but only in ISS mice. There was no significant difference in the blood ethanol levels at awakening with or without S‐propranolol, indicating that S‐propranolol had no effect on the brain sensitivity. Subsequently, we showed that this was due to a profound hypothermia caused by a combination of S‐propranolol and ethanol. This was greater in the ISS mice because a larger dose of ethanol was required for the anesthetic effect of ethanol. The effect on ethanol disappearance rate, temperature drop, and anesthesia time all were largely reversed by placing the animals in an incubator at 32 to 33°C.Conclusions: Profound hypothermia lowers the ethanol disappearance rate when both S‐propranolol and ethanol are given. The effect of S‐propranolol is likely due to the blockade of β‐adrenergic receptors that prevents thermogenic responses to the hypothermia brought about by ethanol. The results indicated that there might be a genetic effect controlling the hypothermic response to the combination of S‐propranolol and ethanol. Further experiments to investigate this are reported in a subsequent article. We could find no evidence of a central nervous system effect of S‐propranolol on the hypnotic actions of ethanol in these strains of mice.
Ethnic Differences in Driving After Drinking and Riding With Drinking Drivers Among Adolescents
Authors: Walker Samantha , Treno Andrew J. , Grube Joel W. , Light John M. 
Published: November 2003

Background: This study examined the relationship between ethnicity and driving after drinking (DD) and riding with drinking drivers (RWDD) while controlling for drinking patterns, driving practices, and background demographic characteristics including age and gender.Methods: Using random‐digit dialing procedures, 1534 young adults ranging from 15‐ to 20‐years of age(mean = 17.6) living in California were recruited to participate in a telephone survey. Latinos, African Americans, and Asian Americans were oversampled to allow cross‐group comparisons.Results: Rates of DD were lower for females than for males and were also lower for African Americans and Asian Americans than for whites. However, after we controlled for drinking patterns and driving practices, the results showed Latinos at greater risk for DD than white adolescents. Compared with whites and males, Asian American and female adolescents were less likely to report RWDD. When drinking patterns and driving practices were taken into account, Latino adolescents were nearly twice as more likely to ride with drinking drivers than whites.Conclusions: These findings indicate a greater need for directing prevention efforts to target Latino youth and youth at risk. Moreover, research aimed at elucidating the social and environmental factors involved in the low prevalence rates of DD and RWDD among Asian American youth may indicate possible protective factors to DD and RWDD operating within the Asian American community.
Short‐Term Selection for the Interaction Between S‐Propranolol and Ethanol in Mice
Authors: Deitrich Richard A. , Bludeau Pequita 
Published: November 2003

Background: We have previously demonstrated that there is an interaction between S‐propranolol, a β‐adrenergic blocking agent, and ethanol on the hypnotic sensitivity of inbred short‐ and long‐sleep mice (ISS and ILS). We found that the interaction was due to an additive hypothermic effect of ethanol and S‐propranolol that markedly decreased the disappearance rate of ethanol. There was no discernible effect of S‐propranolol on the hypnotic actions of ethanol as evidenced by the waking blood ethanol levels. Because ISS mice were more sensitive to this effect than were ILS mice, it seemed that there was a genetic effect to the response. Therefore, we carried out a short‐term breeding project to determine whether the response could be selectively bred.Methods: We used the heterogeneous stock of mice from the Institute for Behavioral Genetics to carry out the selection study. The index for selection was the difference in sleep time between the same animal treated with propranolol and ethanol versus treatment with saline and ethanol at least 1 week apart.Results: In four generations, we were able to achieve separation between mice with a large difference in sleep time (high line) from those with a smaller difference in sleep (low line) time. There was no difference between the average blood ethanol at awakening in the high line versus the low line. The effect was not due to a difference in rate of propranolol metabolism between the two lines. Sleep time with ethanol alone was not different between the high and low lines.Conclusions: The magnitude of the interaction between ethanol and S‐propranolol is controlled by alleles with polymorphisms present in the HS stock of mice. The response is most likely due to a difference in the mechanisms of thermogenesis controlled by the β‐adrenergic receptors in muscle and fat. Because there were no sleep time differences between the high and low lines given ethanol alone, central nervous system sensitivity to ethanol is not a correlated response to the selection.
The Cyclic AMP/Protein Kinase A Signal Transduction Pathway Modulates Tolerance to Sedative and Hypothermic Effects of Ethanol
Authors: Yang Xioaju , Oswald Lynn , Wand Gary 
Published: November 2003

Background: An expanding body of literature indicates the important role of the cAMP/PKA signaling pathway in establishing initial sensitivity to alcohol as well as being involved in certain forms of tolerance to ethanol. The use of mice with heterozygous inactivation of the Gnas gene encoding Gsα allowed us to explore the relationship between tolerance to ethanol and cAMP/PKA signaling.Methods: Mice with the targeted disruption of one Gsα allele were compared with wild‐type littermates in their initial sensitivity to ethanol‐induced sedation and hypothermia and then monitored for the development of tolerance during two subsequent bouts of intoxication. Components of the cAMP/PKA signaling pathway were analyzed in ethanol‐naïve mice and again following the development of tolerance to ethanol to better understand the contribution of this signaling pathway to the acquisition of tolerance.Results: During the initial exposure to ethanol, mice with the targeted disruption of one Gsα allele (Gnas) were more sensitive to the sedative effects of ethanol compared with wild‐type littermates. Wild‐type mice developed within‐session tolerance to ethanol‐induced hypothermia whereas Gnas mice did not. Following the subsequent ethanol treatments, wild‐type mice developed between‐session tolerance to the sedative effects of ethanol to a greater degree than mice with heterozygous inactivation of the Gnas gene. The development of tolerance to the sedative effects of ethanol was accompanied by increased expression of phospho‐CREB in the cerebellum, hippocampus, and frontal cortex. No changes in phospho‐CREB expression were detected in these brain regions in mice with heterozygous inactivation of the Gnas gene.Conclusion: The results show that cAMP/PKA signal transduction modulates sensitivity to sedative and hypothermic effects of ethanol. This signal transduction system also influences the acquisition of within‐session and between‐session tolerance. The mechanism through which cAMP/PKA signaling modulates the development of tolerance remains to be elucidated but may involve changes in phospho‐CREB expression.
Tobacco Use is Associated With Reduced Central Serotonergic Neurotransmission in Type 1 Alcohol‐Dependent Individuals
Authors: Berggren Ulf , Fahlke Claudia , Eriksson Matts , Balldin Jan 
Published: November 2003

Background: Reduced central serotonergic neurotransmission in alcohol dependence may be attributed to the effects of cigarette smoking (and possibly more specifically to nicotine) rather than to alcoholism or its subtypes. The aim of the present study was therefore to compare central serotonergic neurotransmission in tobacco‐using (cigarette smokers and users of smokeless tobacco, i.e., snuffers) alcohol‐dependent individuals to that of tobacco‐nonusing alcohol‐dependent individuals.Methods: The central serotonergic neurotransmission was assessed by the prolactin (PRL) response to the serotonin‐releasing agent D‐fenfluramine (30 mg orally). Male subjects (n= 37) aged 20–65 years were recruited for this purpose. They were all type 1 alcohol‐dependent individuals and had ended their alcohol intake the day before the D‐fenfluramine challenge test.Results: There was no difference in baseline PRL concentrations between tobacco‐using (n= 18) and tobacco‐nonusing (n= 19) alcohol‐dependent individuals. On the other hand, the maximum PRL response after D‐fenfluramine was significantly lower in the tobacco‐using group as compared to the tobacco‐nonusing individuals.Conclusion: Whether the reduction in central serotonergic neurotransmission in tobacco‐using alcohol‐dependent individuals is pre‐existing or a result of tobacco use remains to be elucidated.
Expression of hNP22 Is Altered in the Frontal Cortex and Hippocampus of the Alcoholic Human Brain
Authors: Depaz Iris , Ito Masayuki , Matsumoto Izuru , Niwa Shin‐ichi , Kroon Paul , Wilce Peter A. 
Published: November 2003

Background: Human neuronal protein (hNP22) is a gene with elevated messenger RNA expression in the prefrontal cortex of the human alcoholic brain. hNP22 has high homology with a rat protein (rNP22). These proteins also share homology with a number of cytoskeleton‐interacting proteins.Methods: A rabbit polyclonal antibody to an 18‐amino acid epitope was produced for use in Western and immunohistochemical analysis. Samples from the human frontal and motor cortices were used for Western blots (n= 10), whereas a different group of frontal cortex and hippocampal samples were obtained for immunohistochemistry (n= 12).Results: The hNP22 antibody detected a single protein in both rat and human brain. Western blots revealed a significant increase in hNP22 protein levels in the frontal cortex but not the motor cortex of alcoholic cases. Immunohistochemical studies confirmed the increased hNP22 protein expression in all cortical layers. This is consistent with results previously obtained using Northern analysis. Immunohistochemical analysis also revealed a significant increase of hNP22 immunoreactivity in the CA3 and CA4 but not other regions of the hippocampus.Conclusions: It is possible that this protein may play a role in the morphological or plastic changes observed after chronic alcohol exposure and withdrawal, either as a cytoskeleton‐interacting protein or as a signaling molecule.
Longitudinal Model Predicting Partner Violence Among White, Black, and Hispanic Couples in the United States
Authors: Field Craig A. , Caetano Raul 
Published: November 2003

Background: A limited amount of information pertaining to ethnic‐specific risk factors associated with intimate partner violence across time currently exists. The current study examines ethnic‐specific longitudinal predictors of male‐to‐female and female‐to‐male partner violence (MFPV and FMPV) in white, black, and Hispanic couples in the U.S. general population.Methods: In 1995, a total of 1635 married or cohabitating couples 18 years of age or older living in households in the 48 contiguous states participated in a national survey that used a multistage probability sampling procedure with 100 primary sampling units and included oversamples of blacks and Hispanics. In 2000, the follow‐up survey had an overall response rate of 72% and included 406 white, 232 black, and 387 Hispanic intact couples.Ethnic‐specific regression models predicting MFPV and FMPV at follow‐up were developed. The risk factors of interest included male and female reports of history of childhood abuse, exposure to parental violence, impulsivity, alcohol problems, frequency of drinking five or more drinks per occasion, volume of alcohol consumed per week in average standard drinks, approval of marital aggression and male‐to‐female and female‐to‐male partner violence at baseline. MFPV and FMPV in 1995 and 2000 were based on the Conflict Tactics Scale Form R.Results: Black and Hispanic couples were at approximately three times greater risk of MFPV and two times greater risk of FMPV at follow‐up in comparison to white couples even after controlling for sociodemographic characteristics, alcohol consumption, and psychosocial variables. Extreme specific models indicated that among blacks, MFPV was a significant predictor of MFPV and FMPV at follow‐up. In contrast, among Hispanics, FMPV was a significant predictor of FMPV and MFPV at follow‐up.Conclusions: Ethnic‐specific multivariate logistic regression models indicated that the predictors of MFPV and FMPV including psychosocial variables, alcohol use, and alcohol‐related problems varied by ethnicity. These findings contribute to our continually growing knowledge base regarding ethnic differences associated with the development of intimate partner violence and have important implications for prevention and intervention.
Dopamine Activity in the Nucleus Accumbens During Consummatory Phases of Oral Ethanol Self‐Administration
Authors: Doyon William M. , York Jennifer L. , Diaz Laurea M. , Samson Herman H. , Czachowski Cristine L. , Gonzales Rueben A. 
Published: November 2003

Background: This present study was designed to clarify the role of dopamine in the nucleus accumbens during operant ethanol self‐administration by separating bar pressing (ethanol seeking) from ethanol consumption. Furthermore, we sought to define the relationship between ethanol in the brain and the accumbal dopamine response after oral self‐administration of ethanol.Methods: Two separate groups of male Long‐Evans rats were trained to bar press with 10% ethanol or water. Rats were trained to elicit an escalating number of bar presses across daily sessions before gaining access to the drinking solution for 20 min. Microdialysis was performed before (during a waiting period), during, and after bar pressing and drinking. A handling control group was included, but did not receive training.Results: A significant increase in dopamine occurred during placement of the rats into the operant chamber in trained rats and handling controls. The lever‐pressing period did not produce an increase in dialysate dopamine. Accumbal dopamine was increased in the first 5 min of ethanol, but not water, consumption. Ethanol appeared in the dialysate sample following ethanol availability, and peak concentrations were reached at 10 min. Most of the ethanol and water consumption occurred within 5 min of fluid access. The probes were distributed in the core (32%), shell (32%), and core plus shell (36%) regions of the nucleus accumbens.Conclusions: The enhancement of dopamine during transfer into the operant chamber does not depend on anticipation or operant training with ethanol or water reinforcement. Furthermore, the difference between the time course of accumbal dopamine and ethanol in dialysates suggests that the dopamine response is not solely due to pharmacological effects of ethanol. The dopamine response may be associated with the stimulus properties of ethanol presentation, which would be strongest during consumption.
Reinforcement From Pharmacological Effects of Ethanol in Newborn Rats
Authors: Petrov Evgeniy S. , Varlinskaya Elena I. , Spear Norman E. 
Published: November 2003

Background: The preweanling period in the rat is characterized by acceptance of substantial amounts of ethanol and susceptibility to its reinforcing effects. It has been unclear, however, whether the neurobiological basis of ethanol reinforcement properties at this age is in ethanol's olfactory, gustatory, or pharmacological effects.Methods: The effectiveness of intraperitoneal (ip) ethanol as a reinforcer for newborn (3‐hr‐old) rats was tested toward separation of the orosensory and pharmacological sources of ethanol reinforcement. Responsiveness to a test nipple by pups given such pairings was compared with that of pups given unpaired presentations of the nipple and ethanol.Results: Reinforcement was assessed in terms of response to a surrogate nipple 1 hr after a single pairing of a similar nipple providing water (conditioned stimulus) and ip injection of ethanol (0.125, 0.25, 0.50, or 0.75 g/kg; unconditioned stimulus). Significant effects of ethanol reinforcement occurred with the lower doses (0.125 and 0.25 g/kg); higher doses of ethanol (0.50 and 0.75 g/kg) had no significant reinforcement effect. A second experiment determined that for conditioning with ip ethanol as the unconditioned stimulus, a conditioned stimulus consisting of only ingesting water or only suckling on an empty nipple also yielded significant reinforcing effects of ethanol, although with less strength than their combination. Both reinforcing doses of ethanol, 0.125 and 0.25 g/kg, yielded detectable concentrations of ethanol in the blood 5 min after injection, which were sustained at a significantly lower level 60 min after administration.Conclusions: These data indicate that aside from possible, and likely weak, hematogenic sources of gustatory and olfactory attributes of ethanol, the basis of ethanol's reinforcement effect in neonatal rats is primarily pharmacological. For the pharmacological effects of ethanol to be reinforcing for the neonatal rat, concurrent appetitive activity on a nipple providing a fluid may be necessary for a substantial effect with this paradigm.