bluuebunny/crossref_metadata_2025_split huggingface dataset:
Deletion of the Fyn‐Kinase Gene Alters Behavioral Sensitivity to Ethanol
Authors: Boehm Stephen L. , Peden Laura , Chang Rose , Harris R. Adron , Blednov Yuri A. 
Published: August 2004

Background: An earlier study showed that deletion of the fyn‐kinase gene enhanced sensitivity to ethanol's sedative hypnotic effects and suggested that this was associated with diminished fyn‐kinase phosphorylation of NMDA receptors. The authors of that study speculated that this resulted in an inability of the null mutants to develop acute tolerance to ethanol, leading to the longer ethanol‐induced sleep times. However, in vivo acute tolerance to ethanol was not examined directly.Methods: To address the role of fyn‐kinase in mediating acute tolerance, as well as sensitivity to several other behavioral effects of ethanol, we studied an independently generated population of fyn null mutant and wild‐type mice.Results: Homozygous mutants exhibited longer ethanol sleep times that could not be attributed to differences in initial sensitivity, and impaired acute tolerance to the motor incoordinating effects of ethanol as measured by using the stationary dowel, but not the rotarod. Fyn‐kinase null mutants were more sensitive to the anxiolytic effects of ethanol when tested using the elevated plus maze, and males displayed a lower preference for ethanol in a two‐bottle choice paradigm. Finally, mutant and wild‐type mice did not differ in sensitivity to the hypothermic effects of ethanol. The genotypes also did not differ in blood‐ethanol clearance, eliminating a metabolic explanation for these behavioral differences.Conclusions: These results show that fyn‐kinase modulates acute tolerance to ethanol and suggest a role for fyn in mediating ethanol's anxiolytic and reinforcing properties.
Ethanol Increases Extracellular Dopamine Concentration in the Ventral Striatum in C57BL/6 Mice
Authors: Tang Amanda , George Magnia A. , Randall Judith A. , Gonzales Rueben A. 
Published: August 2004

Background: Mesolimbic dopamine is thought to play a role in the reinforcing properties of ethanol, but ethanol‐induced changes in extracellular dopamine in the ventral striatum have not been well characterized in mouse models.Methods: Two experiments were used to characterize the pharmacodynamic response of ethanol in the ventral striatum in C57BL/6 mice. The first experiment determined the effect of ethanol on ventral striatal dopamine in male and female mice after intraperitoneal injection of either 2.0 g/kg ethanol or saline. The second experiment was a replication in males, except that the mice were habituated to intraperitoneal injections before the dialysis experiment.Results: Distinct patterns of dopamine activity in response to ethanol were demonstrated in male and female C57BL/6 mice. A significant increase in dialysate dopamine relative to saline injection was observed in females but not in males. With habituation to intraperitoneal injection before the dialysis experiment, ethanol administration caused a significant dopamine response in males as well. A linear decline was observed in dialysate ethanol concentrations after the peak concentration was reached. Concurrent analysis of the time course of dopamine and ethanol content showed that the dopamine response declined significantly faster than the ethanol concentrations.Conclusions: The C57BL/6 mouse strain is a justifiable model system for studying the mechanisms involved in ethanol regulation of mesolimbic dopamine activity. Habituation to intraperitoneal injection should be used in male C57BL/6 mice for experiments in which the dopamine response is measured after intraperitoneal injection of a drug. The dissociation between dopamine and ethanol may indicate an acute neural adaptation to ethanol‐induced dopamine response in the ventral striatum after a single ethanol injection.
Hepatic Apoptosis and Proliferation in Male and Female Rats Fed Alcohol: Role of Cytokines
Authors: Colantoni Alessandra , Idilman Ramazan , De Maria Nicola , La Paglia Nancy , Belmonte Joseph , Wezeman Frederick , Emanuele Nicholas , Van Thiel David H. , Kovacs Elizabeth J. , Emanuele Mary Ann 
Published: August 2004

Background: The female liver is more sensitive to the toxic effect of chronic alcohol intake than the male liver. The aim of the study was to compare the influence of gender and sex hormonal status on apoptosis and cell proliferation following chronic ethanol intake.Methods: Male and female rats were pair fed for 8 weeks a liquid diet containing 36% of their total daily calories as ethanol (ETOH group) or sucrose (control group). Liver samples were analyzed for apoptosis and hepatocyte proliferation by immunohistochemistry. The hepatic production of factors able to influence cell death and proliferation, such as tumor necrosis factor alpha (TNFα) and interleukin 6 (IL‐6) were determined.Results: In both male and female rats, ethanol intake promoted apoptosis in the liver. This effect of ethanol was more evident in female than male rat livers. Hepatic TNFα levels, which promote apoptosis, are significantly more elevated in female than in male livers. Hepatic IL‐6 production, which promotes hepatocyte proliferation, was induced by ethanol only in males, but not female animals.Conclusion: This observed difference in cytokine responses may contribute to the enhanced sensitivity of female liver to EtOH‐induced injury.
Testing Combined Pharmacotherapies and Behavioral Interventions for Alcohol Dependence (The COMBINE Study): A Pilot Feasibility Study
Authors:   The COMBINE Study Research Group
Published: August 2004

Background: Medications (such as naltrexone and acamprosate) as well as behavioral therapies have been previously reported to be effective in the reduction of alcohol intake and to prevent relapse drinking. However, the efficacy of using several medications alone or together in combination with behavioral therapies has not been widely investigated. The purpose of this study was to evaluate the feasibility of this combined therapy approach to apply it to a larger scale multisite clinical trial. Outcome focused on recruitment, retention, adherence to study parameters and medication, physical complaints, and physiologic toxicity.Methods: At 11 sites, 108 individuals with alcohol dependence were randomized in a double blind fashion to receive placebo, naltrexone, or acamprosate alone or in combination. In addition, some individuals were randomized to receive Medical Management (MM) provided by a health care practitioner alone or in combination with an enhanced behavioral intervention, Combined Behavioral Intervention (CBI), delivered by a trained therapist. A final group received CBI alone without pills. All participants were treated and assessed for a maximum of 16 weeks.Results: The attendance at therapy and research visits, and medication adherence and tolerability were good with no statistical differences between the medication or behavioral intervention groups. Over 75% of participants completed the week‐16, end of study, assessment and the average medication adherence (percent of total pills taken) was about 65%. The level and types of physical complaints were not unexpected and similar among the medication and placebo groups. There were no group differences in liver or kidney toxicity. Importantly, the combination of naltrexone and acamprosate did not present significantly more physical complaints than either alone.Conclusions: Sufficient numbers of alcohol dependent participants can be recruited and retained in a relatively sophisticated outpatient trial combining medications and behavioral interventions. Participant adherence to the trial protocol including medication regimens was at acceptable levels. Physical complaints and organ toxicity were within expected and acceptable levels. Based on these results a larger scale study utilizing these methodologies appears feasible.
The evolution of ICT‐based learning environments: which perspectives for the school of the future?
Authors: Bottino Rosa Maria 
Published: August 2004

AbstractThis paper briefly outlines the evolution of ICT‐based learning environments discussing some of the main aspects that have characterised such evolution (eg, technological evolution, changed cognitive and pedagogical frameworks, changed role assigned to ICT‐based systems in education). The objective is to point out how the implementation of innovative learning environments, based on advanced technology, is the result of the strict interrelation between educational and cognitive theories, technological opportunities and teaching and learning needs. In this paper some indications for current and future evolution are evidenced. Reference is made to an ICT‐based multi‐environment system that supports teaching and learning activities in the domain of arithmetic problem solving at compulsory school level.
Providing access to electronic information resources in further education
Authors: Banwell Linda , Ray Kathryn , Coulson Graham , Urquhart Christine , Lonsdale Ray , Armstrong Chris , Thomas Rhian , Spink Siân , Yeoman Alison , Fenton Roger , Rowley Jennifer 
Published: August 2004

AbstractThis article aims to provide a baseline for future studies on the provision  and support for the use of digital or electronic information services (EIS) in further education. The analysis presented is based on a multi‐level model of access, which encompasses access to and availability of information and communication technology (ICT) resources, access to and availability of EIS resources, and the third leg of staff skills and their development. The research was conducted within the third cycle of the JISC (Joint Information Services Committee) User Behaviour Monitoring and Evaluation Framework, in 2001/2002. Evidence was gathered from library and information service web sites and various stakeholders, including library and information service staff, academic staff and students to generate insights into the provision of access to EIS in further education. Sector‐wide funding initiatives have had a significant impact on ICT infrastructures, and these attract a positive response from students. EIS are represented on some library web sites but both web site development and EIS availability is very much less advanced than in higher education. Staff, however, lack sufficient dedicated access to ICT to be able to develop their own skills and use. There remains a low level of access to electronic information resources, with only limited access to these resources through library web sites. LIS managers face a number of challenges in enhancing this provision, including licensing arrangements, tight budgets that need to be spread across many discipline areas, and the absence of EIS designed specifically for the further education student. The other key challenge lies in the provision of time and opportunity for academic and LIS staff to develop their ICT and EIS skills, and, more generally in the further development of the role of Information and Learning Technology (ILT) Champions.
Challenges and issues in designing inquiry on the Web
Authors: Lim Byung‐Ro 
Published: August 2004

AbstractThe purpose of this study is to discuss major issues in designing inquiries on the web. Instructional designers face a lot of difficulties and challenges to deal with in the course of designing inquiry experiences for learners in the online environment, a complex and ill‐structured learning environment. Facilitating inquiry or using an inquiry‐based learning approach on the web has both advantages and disadvantages. Instructional designers need to acknowledge the design issues arising in each and every phase of the design process. Utilising appropriate design strategies, instructional designers can provide positive learning experiences for their online learners. For this purpose, three representative cases in the context of teacher professional development were examined and six major issues were identified as follows: (1) seeking a balance between a system‐generated guide and human facilitator, (2) visual representation of the inquiry process, (3) motivating learners with the right question, (4) engaging learners in various learning activities, (5) guiding the inquiry process with various scaffolds, and (6) maximising learning by coordinating resources, tools and the community of inquiry. This study explains each issue in great detail and provides possible guides for instructional designers to handle the issue.
Personality, Threat, and Cognitive and Emotional Reactions to Stressful Intercultural Situations
Authors: Van Der Zee Karen , Van Oudenhoven Jan Pieter , De Grijs Ellen 
Published: August 2004

AbstractThe present study examined individual differences in appraisal of and affective reactions to intercultural situations. A sample of 160 students filled out the Multicultural Personality Questionnaire (MPQ) and participated in an experiment in which they received a description of an intercultural situation that was either high or low in potential stressfulness. Individuals with high scores on the intercultural dimensions appraised the potentially stressful situation more positively and showed more positive and less negative reactions to the situation than did individuals with low scores on the MPQ. Interestingly, following a Terror Management Intervention (TMI), individual differences in emotional reactions to intercultural situations disappeared. The results could only partially be replicated using a general personality questionnaire, suggesting that these findings have at least some specificity to intercultural personality dimensions.
Fracture risk of women with primary biliary cirrhosis: no increase compared with general population controls
Authors: Boulton‐Jones J. R. , Fenn R. M. F. , West J. , Logan R. F. A. , Ryder S. D. 
Published: August 2004

SummaryAim : Patients with primary biliary cirrhosis may be at increased risk of osteoporosis but to what extent this is reflected in an increased fracture risk is unknown. We have enquired about the fracture experience of female primary biliary cirrhosis patients compared with sex‐ and age‐matched controls.Methods : Patients aged 30–75 with primary biliary cirrhosis and age‐matched controls were sent a postal questionnaire asking about their fracture history and details of risk factors for osteoporosis.Results : 85 eligible patients with primary biliary cirrhosis and 116 controls responded. Forty‐one per cent of patients with primary biliary cirrhosis and 30% of controls reported ever having had a fracture odds ratio 1.5 (95% confidence interval: 0.80–2.89). Twenty‐eight per cent of primary biliary cirrhosis patients and 23.3% of controls reported a fracture after the age of 30, odds ratio 1.2 (95% confidence interval: 0.57–2.56), and 14.1% of primary biliary cirrhosis patients and 12.1% of controls reported a low impact fracture of the long bones or of the vertebrae odds ratio 1.0 (95% confidence interval: 0.31–2.68).Conclusions : No overall increased fracture risk in patients with primary biliary cirrhosis was observed. As a group, unselected patients with primary biliary cirrhosis do not represent a population at particularly high risk of osteoporotic fracture and thus targeting them for osteoporosis screening and treatment is not justified. Further work investigating subgroups of patients with primary biliary cirrhosis at potentially high risk of osteoporosis, such as those with advanced disease or severe cholestasis is required.
Effect of acid on duodenal blood flow and mucus secretion measured by reflectance spectrophotometry: a prospective, randomized‐controlled study
Authors: Ramirez F. C. , Holland J. F. , Harker J. , Leung F. W. 
Published: August 2004

SummaryBackground : In animals, hydrochloric acid increases blood flow and mucus secretion in the duodenal mucosa. A significant correlation between index of haemoglobin oxygen saturation and mucosal blood flow, and between change in index of haemoglobin concentration and mucus thickness, respectively, has been demonstrated by reflectance spectrophotometry.Aim : To examine the effect of topical hydrochloric acid upon mucosal blood flow and mucus secretion in the human duodenum.Methods : This prospective study of 120 patients undergoing routine upper endoscopy, examined the effect of topical 0.1 n hydrochloric acid or 0.9% saline on the duodenal bulb in a randomized, double‐blind fashion. Duodenal mucosal index of haemoglobin oxygen saturation and index of haemoglobin concentration were measured by endoscopic reflectance spectrophotometry before and after hydrochloric acid or saline.Results : Baseline index of haemoglobin oxygen saturation, calculated blood flow and index of haemoglobin concentration measurements were comparable between hydrochloric acid (n = 60) and saline (n =60) treated groups. A history of current use of non‐steroidal anti‐inflammatory drug was associated with a significantly lower baseline index of haemoglobin oxygen saturation and calculated blood flow. Hydrochloric acid resulted in a significant increase in index of haemoglobin oxygen saturation and calculated blood flow, but a decrease in index of haemoglobin concentration, reflecting an increase in mucus thickness compared with saline.Conclusions : Our observations in humans confirm data in animal studies that topical exposure to hydrochloric acid induces an increase in duodenal mucosal blood flow and mucus secretion. Post hoc analysis of the data also revealed that attenuation of basal duodenal mucosal blood flow is associated with a history of current non‐steroidal anti‐inflammatory drug use. Endoscopic reflectance spectrophotometry appears to be adequate to assess factors that influence duodenal defence mechanisms of blood flow and mucus secretion in humans.
Helicobacter pyloriinfection prevents the occurrence of the tolerance phenomenon of histamine H2 receptor antagonists
Authors: Fujisawa T. , Adachi K. , Komazawa Y. , Mihara T. , Azumi T. , Katsube T. , Furuta K. , Kazumori H. , Kinoshita Y. 
Published: August 2004

SummaryBackground: The attenuated anti‐secretory activity of H2 receptor antagonists (H2RA) during continuous administration is referred to as the tolerance phenomenon. However, it is not clarified whetherHelicobacter pyloriinfection affects the occurrence of tolerance to H2RA. It is also not clarified whether the tolerance phenomenon occurs to a new H2RA, lafutidine.Aim: To investigate the occurrence of the tolerance phenomenon in subjects with and withoutH. pyloriinfection during the continuous administration of lafutidine and famotidine.Subjects and Methods: Subjects were 20 healthy male volunteers (sevenH. pyloripositive and 13H. pylorinegative cases). All subjects were examined by ambulatory intragastric pH monitoring five times without medication, on the first and 15th day of the administration of 20 mg b.d. famotidine and 10 mg b.d. lafutidine in a cross‐over fashion.Results: The tolerance phenomenon was not observed inH. pylori‐positive subjects during the 15‐day‐long administration of both H2RAs. In contrast, the tolerance phenomenon was observed inH. pylorinegative subjects, which has been previously reported.Conclusions: This study demonstrated thatH. pyloriinfection affects the tolerance phenomenon during continuous administration of H2RAs.
Relationship between body mass index, diet, exercise and gastro‐oesophageal reflux symptoms in a community
Authors: Nandurkar S. , Locke G. R. , Fett S. , Zinsmeister A. R. , Cameron A. J. , Talley N. J. 
Published: August 2004

SummaryBackground : Body mass index (BMI) is a risk factor for gastro‐oesophageal reflux but may simply be explained by diet and lifestyle.Aim : We aimed to determine the contribution of BMI, diet and exercise to GER.Methods : Community subjects (n = 211, mean age =36 years, 43% males) completed validated questionnaires on gastro‐oesophageal reflux, energy expenditure (Harvard Alumni Activity Survey), dietary intake (Harvard Food Frequency Questionnaire) and measures of personality and life event stress. Diet, exercise, BMI and other potential risk factors for reflux were analysed using logistic regression analyses.Results : The overall mean (±s.d.) BMI was 26.6 (±5.7); 79 (37%) reported infrequent (<weekly) reflux and 16 (8%) reported frequent (≥weekly) reflux. The median caloric intake was 2097 cal/day and the median daily energy expenditure was 1753 cal/day. Among those with BMI > 25, 10% reported frequent reflux compared to 4% of those with BMI ≤ 25. In a model which included age, sex and Symptom Checklist‐90 somatisation T‐score, BMI was associated with reflux (OR per 5 units = 1.9, 95% CI: 1.2, 3.0). In models which included diet and exercise variables, BMI but not diet or exercise was associated with reflux.Conclusion : BMI may be associated with symptomatic gastro‐oesophageal reflux independent of diet and exercise.
Quinaldine 4‐Oxidase from Arthrobacter sp. Rü61a, a Versatile Procaryotic Molybdenum‐Containing Hydroxylase Active towards N‐Containing Heterocyclic Compounds and Aromatic Aldehydes
Authors: Stephan Ingrid , Tshisuaka Barbara , Fetzner Susanne , Lingens Franz 
Published: August 2004

Quinaldine 4‐oxidase from Arthrobacter sp. Rü61a, an inducible molybdenum‐containing hydroxylase, was purified to homogeneity by an optimized five‐step procedure. Molecular oxygen is proposed as physiological electron acceptor. Electrons are also transferred to artificial electron acceptors with E′o > −8 mV. The molybdo‐iron/sulfur flavoprotein regiospecifically attacks its N‐heterocyclic substrates: isoquinoline and phthalazine are hydroxylated adjacent to the N‐heteroatom at C1, whereas quinaldine, quinoline, cinnoline and quinazoline are hydroxylated at C4. Additionally, the aromatic aldehydes benzaldehyde, salicylaldehyde, vanillin and cinnamaldehyde are oxidized to the corresponding carboxylic acids, whereas short‐chain aliphatic aldehydes are not.Quinaldine 4‐oxidase is compared to the two molybdenum‐containing hydroxylases quinoline 2‐oxidoreductase from Pseudomonas putida 86 [Tshisuaka, B., Kappl, R., Hüttermann, J. & Lingens, F. (1993) Biochemistry 32, 12928–12934] and isoquinoline 1‐oxidoreductase from Pseudomonas diminuta 7 [Lehmann, M., Tshisuaka, B., Fetzner, S., Röger, P. & Lingens, F. (1994) J. Biol. Chem. 269, 11254–11260] with respect to the substrates converted and the electron‐acceptor specificities. These dehydrogenases hydroxylate their N‐heterocyclic substrates exclusively adjacent to the heteroatom. Whereas the aldehydes tested are scarcely oxidized by quinoline 2‐oxidoreductase, isoquinoline 1‐oxidoreductase catalyzes the oxidation of the aromatic aldehydes, although being progressively inhibited. Neither quinoline 2‐oxidoreductase nor isoquinoline 1‐oxidoreductase transfer electrons to oxygen. Otherwise, the spectrum of electron acceptors used by quinoline 2‐oxidoreductase and quinaldine 4‐oxidase is identical. However, isoquinoline 1‐oxidoreductase differs in its electron‐acceptor specificity.Quinaldine 4‐oxidase is unusual in its substrate and electron‐acceptor specificity. This enzyme is able to function as oxidase or dehydrogenase, it oxidizes aldehydes, and it catalyzes the nucleophilic attack of N‐containing heterocyclic compounds at two varying positions depending on the substrate.