bluuebunny/crossref_metadata_2025 huggingface dataset:
Loss of SOCS3 in T helper cells resulted in reduced immune responses and hyperproduction of interleukin 10 and transforming growth factor–β1
Authors: Kinjyo Ichiko , Inoue Hiromasa , Hamano Shinjiro , Fukuyama Satoru , Yoshimura Takeru , Koga Keiko , Takaki Hiromi , Himeno Kunisuke , Takaesu Giichi , Kobayashi Takashi , Yoshimura Akihiko
Published: April 2006

Suppressor of cytokine signaling (SOCS)3 is a major negative feedback regulator of signal transducer and activator of transcription (STAT)3-activating cytokines. Transgenic mouse studies indicate that high levels of SOCS3 in T cells result in type 2 T helper cell (Th2) skewing and lead to hypersensitivity to allergic diseases. To define the physiological roles of SOCS3 in T cells, we generated T cell–specific SOCS3 conditional knockout mice. We found that the mice lacking SOCS3 in T cells showed reduced immune responses not only to ovalbumin-induced airway hyperresponsiveness but also to Leishmania major infection. In vitro, SOCS3-deficient CD4+ T cells produced more transforming growth factor (TGF)-β1 and interleukin (IL)-10, but less IL-4 than control T cells, suggesting preferential Th3-like differentiation. We found that STAT3 positively regulates TGF-β1 promoter activity depending on the potential STAT3 binding sites. Furthermore, chromatin immunoprecipitation assay revealed that more STAT3 was recruited to the TGF-β1 promoter in SOCS3-deficient T cells than in control T cells. The activated STAT3 enhanced TGF-β1 and IL-10 expression in T cells, whereas the dominant-negative form of STAT3 suppressed these. From these findings, we propose that SOCS3 regulates the production of the immunoregulatory cytokines TGF-β1 and IL-10 through modulating STAT3 activation.
Helper T cell differentiation enters a new era: Le Roi est mort; vive le Roi!
Authors: Tato Cristina M. , Laurence Arian , O'Shea John J.
Published: April 2006

In the dark ages of T cell biology, we considered two fates for differentiated CD4+ T cells: T helper (Th)1 and Th2 cells. Now we know that the reality is much more complex and interesting. The newest Th cell subset produces the cytokine IL-17. New evidence shows that the IL-17–related cytokine IL-25 is essential for Th2 responses in two infectious disease models.
Improved scoring of functional groups from gene expression data by decorrelating GO graph structure
Authors: Alexa Adrian , Rahnenführer Jörg , Lengauer Thomas
Published: April 2006

Motivation: The result of a typical microarray experiment is a long list of genes with corresponding expression measurements. This list is only the starting point for a meaningful biological interpretation. Modern methods identify relevant biological processes or functions from gene expression data by scoring the statistical significance of predefined functional gene groups, e.g. based on Gene Ontology (GO). We develop methods that increase the explanatory power of this approach by integrating knowledge about relationships between the GO terms into the calculation of the statistical significance.

Results: We present two novel algorithms that improve GO group scoring using the underlying GO graph topology. The algorithms are evaluated on real and simulated gene expression data. We show that both methods eliminate local dependencies between GO terms and point to relevant areas in the GO graph that remain undetected with state-of-the-art algorithms for scoring functional terms. A simulation study demonstrates that the new methods exhibit a higher level of detecting relevant biological terms than competing methods.

Availability: topgo.bioinf.mpi-inf.mpg.de

Contact:  alexa@mpi-sb.mpg.de

Supplementary Information: Supplementary data are available at Bioinformatics online.
Large-scale identification of protein–protein interaction of Escherichia coli K-12
Authors: Arifuzzaman Mohammad , Maeda Maki , Itoh Aya , Nishikata Kensaku , Takita Chiharu , Saito Rintaro , Ara Takeshi , Nakahigashi Kenji , Huang Hsuan-Cheng , Hirai Aki , Tsuzuki Kohei , Nakamura Seira , Altaf-Ul-Amin Mohammad , Oshima Taku , Baba Tomoya , Yamamoto Natsuko , Kawamura Tomoyo , Ioka-Nakamichi Tomoko , Kitagawa Masanari , Tomita Masaru , Kanaya Shigehiko , Wada Chieko , Mori Hirotada
Published: April 2006

Protein–protein interactions play key roles in protein function and the structural organization of a cell. A thorough description of these interactions should facilitate elucidation of cellular activities, targeted-drug design, and whole cell engineering. A large-scale comprehensive pull-down assay was performed using a His-tagged Escherichia coli ORF clone library. Of 4339 bait proteins tested, partners were found for 2667, including 779 of unknown function. Proteins copurifying with hexahistidine-tagged baits on a Ni2+-NTA column were identified by MALDI-TOF MS (matrix-assisted laser desorption ionization time of flight mass spectrometry). An extended analysis of these interacting networks by bioinformatics and experimentation should provide new insights and novel strategies for E. coli systems biology.
From osseoperception to implant‐mediated sensory‐motor interactions and related clinical implications*
Authors: JACOBS R. , VAN STEENBERGHE D.
Published: April 2006

summary  Osseointegration of implants in the jaw bone has been studied thoroughly, dealing with various aspects such as bone apposition, bone quality, microbiology, biomechanics, aesthetics, etc. A key issue that has received much less attention is the physiologic integration of the implant(s) and the associated prosthesis in the body. The latter aspect is however very important to obtain new insights in oral functioning with implant‐supported prostheses. Amputated patients rehabilitated with a lower limb prosthesis anchored to the bone by means of an osseointegrated implant, have reported that they could recognize the type of soil they were walking on. Clinical observations on patients with oral implants, have confirmed a special sensory perception skill. The underlying mechanism of this so‐called ‘osseoperception’ phenomenon remains a matter of debate, because extraction of teeth involves elimination of the extremely sensitive periodontal ligaments while functional reinnervation around implants is still uncertain. Histological, neurophysiological and psychophysical evidence of osseoperception have been collected, making the assumption more likely that a proper peripheral feedback pathway can be restored when using osseointegrated implants. This implant‐mediated sensory‐motor control may have important clinical implications, because a more natural functioning with implant‐supported prostheses can be attempted. It may open doors for global integration in the human body.
Mechanisms of oral somatosensory and motor functions and their clinical correlates*
Authors: SESSLE B. J.
Published: April 2006

summary  This article provides a review of somatosensory and motor pathways and processes involved in oral sensorimotor function and dysfunction. It reviews somatosensory processes in peripheral tissues, brainstem and higher brain centres such as thalamus and cerebral cortex, with a particular emphasis on nociceptive mechanisms. It also outlines some of the circuits and processes involved in reflexes and motor control. In addition, it emphasizes the concept of neuroplasticity and its applicability to oro‐facial pain, to motor control and motor learning, and to adaptation to changes in the oral sensory environment such as may occur with the placement of dental implants.
Implant‐retained overdenture following hemiglossectomy: a 10‐year clinical case report
Authors: TAIRA Y. , SEKINE J. , SAWASE T. , ATSUTA M.
Published: April 2006

summary  A clinical evaluation of an implant‐supported overdenture placed in the edentulous mandible after hemiglossectomy is described. The deltopectoral flap covering the mandibular ridge was replaced with a free mucosal graft. Four Brånemark system implants were inserted into the anterior part of the mandible, but one of the four fixtures did not show osseointegration. The superstructure was designed as a spaced round bar‐attachment supported by three implants so as to retain the complete overdenture. In addition to the metal clip, a silicone‐based soft denture liner material was applied in the female portion of the attachment so as to prevent the attachment from making a clattering noise upon mastication. Although the overdenture required adjustment at regular intervals, the treatment was successful both aesthetically and functionally for up to at least 10 years.
Scleral rupture in dogs, cats, and horses
Authors: Rampazzo Antonella , Eule Corinna , Speier Sandra , Grest Paula , Spiess Bernhard
Published: April 2006

Objectives  The aim of this retrospective study was to summarize the most frequent clinical signs, ultrasonographic, and histological findings accompanying scleral rupture as a result of blunt trauma in dogs, cats, and horses.

Animals studied and procedures  Thirty small animals and three horses diagnosed with scleral rupture resulting from blunt trauma. B‐mode ultrasonography was performed on 20 animals. Histopathology was carried out on 18 enucleated globes.

Results  In small animals, 80% presented hyphema, 60% subconjunctival hemorrhage, and 53% eyelid and conjunctival swelling. In horses, 100% presented eyelid and conjunctival swelling, 67% hyphema, subconjunctival hemorrhage, and collapsed anterior chamber. Ultrasonographic findings were an area with ill‐defined scleral margins (90%), echoic/hyperechoic contents in the anterior and posterior chamber (55%) and in the vitreous (80%). In small animals, scleral rupture location noted on gross examination was: at the posterior pole (4), close to the optic nerve (3), near the limbus (2), and in the dorsal aspect of the globe (1). In horses, the lesion was located at the limbus (3). In small animals, histopathology showed presence of hemorrhage in the anterior, posterior chamber, and vitreous (94%), retinal detachment (94%), choroidal edema and hemorrhages (88%), and choroidal detachment as a result of suprachoroidal hemorrhage (88%). The same lesions were found in the globes of two horses. In small animals, rupture location noted on histopathology was: at the posterior pole (8), close to the optic nerve (4), near the limbus (1), near the ciliary body (1).

Conclusions  The most frequent clinical signs observed were hyphema, subconjunctival hemorrhage, and eyelid and conjunctival swelling. Ultrasonographic findings suggestive for scleral rupture were ill‐defined scleral borders and/or echoic/hyperechoic material in the cavities of the globe. On histopathology, lesions severely altering the anatomy of the eye structures were: hemorrhage into the chambers of the globe, subretinal and suprachoroidal hemorrhage leading to retinal and choroidal detachment, respectively. In small animals, the most frequent locations for scleral rupture were the posterior pole and close to the optic nerve, whereas in horses it was the limbus.
Ontology mappings to improve learning resource search
Authors: Gašević Dragan , Hatala Marek
Published: April 2006

This paper proposes an ontology mapping‐based framewrowrk that allows searching for learning resources using multiple ontologies. The present applications of ontologies in e‐learning use various ontologies (eg, domain, curriculum, context), but they do not give a solution on how to interoperate e‐learning systems based on different ontologies. The proposed solution uses a mapping ontology that is a part of a recent Semantic Web initiative, the Simple Knowledge Organisation System. On top of that, we develop and implement two search algorithms. Finally, we evaluated the solution by developing a system that helps students search for relevant learning resource using a local context (ie, course curriculum) ontology.
Cross-Border Co-Operation between Northern Ireland and the Republic of Ireland: Neo-Functionalism Revisited
Authors: Tannam Etain
Published: April 2006

>This article revisits the question of whether the European Union and/or Anglo-Irish policy initiatives have increased cross-border co-operation between the Republic of Ireland and Northern Ireland. The applicability of neo-functionalism to the Irish/Northern Irish case is re-examined in the light of the Good Friday Agreement (GFA) and EU Peace programmes.
Mr Crosland's Nightmare? New Labour and Equality in Historical Perspective
Authors: Meredith Stephen
Published: April 2006

This article has, as its broad context, the question of the ideological location of New Labour. Particularly, it aims for a broad reassessment of the relationship between Croslandite and New Labour conceptions of equality. Critics of the present Labour government suggest that it has clearly abandoned any commitment to Labour's historic ‘central organising principle’. This article argues, somewhat against the grain, that New Labour's approach to equality rests firmly within the tradition of revisionist social democracy established by Anthony Crosland. It argues that such critics simultaneously underplay the revisionist element of Crosland's thinking, the sometimes circumspect nature of Crosland's egalitarianism and the degree to which the (New) Labour government has applied underlying principles of equality to a wider programme of social justice and economic efficiency in dramatically changed circumstances.
On the International Linkages between Trade and Merger Policies*
Authors: Saggi Kamal , Yildiz Halis Murat
Published: April 2006

In a three‐country model, this paper investigates linkages between merger incentives of exporting firms and the trade policy of an importing country. When exporting firms come from only one country, the tariff response of the importing country reverses the welfare effects of a merger in the exporting country. If there exist two exporting countries, a merger creates two types of conflicting international externalities. First, a merger in one exporting country increases profits of all firms. Secondly, non‐merged firms lose if the importing country is free to raise its tariff in response to a merger of foreign exporters.
The Intervention Principle
Authors: Grinols Earl L.
Published: April 2006

This paper investigates efficient policy interventions in market economies, establishing a general policy intervention result and explaining why more general results are not possible. The paper shows the applicability of the methodology to a number of new results in the theory of international trade, including policy intervention in the presence of increasing returns to scale. The analytical tools are not based on calculus, but set theory, agent optimization, and market clearing. They apply to discrete comparisons as well as for small changes.
Transboundary Pollution and International Migration
Authors: Kondoh Kenji
Published: April 2006

We analyze the welfare effects of international migration in the presence of transboundary pollution. We use a simplified Copeland and Taylor (1999) model, where the (developed) home country's pollution abatement technology is superior to that of the (less developed) foreign country. If there is no trade, workers will migrate from the foreign country to the home country. The foreign country gains from migration, but whether the home country gains or not depends on the abatement‐technology gap and the magnitude of the coefficient of transboundary pollution. World welfare will increase under migration. If there is free trade in goods, international migration occurs when the home country specializes in the production of the environmentally sensitive good. In this case, migration will result in increased production of the manufactured good and increase the level of world pollution.
Multinational Firms and Strategic FDI Subsidies
Authors: Ishii Yasunori
Published: April 2006

A simple three‐stage game model of an international Cournot duopoly, consisting of domestic and foreign multinational firms, is exploited to examine strategic FDI subsidies. While in the first stage the governments decide the optimal FDI subsidies, the firms endogenously choose their FDI levels (or subsidiary plant sizes) in the second stage and their output–export levels in the third stage. Thus, this paper finds that while the outflow and inflow FDI subsidies have different effects on firms’ FDI choices, the FDI subsidies are used as tools for the implementation of strategic policies and that the optimal FDI subsidies vary, depending on whether the governments assess labor employment.
Reconsidering Real Interest Parity for Traded and Nontraded Goods
Authors: Kim Jaebeom
Published: April 2006

The goal of this paper is to examine the hypothesis of real interest rate parity by contrasting real interest rates across traded and nontraded goods under flexible exchange rates. We employ panel unit root tests to investigate the stationarity of real interest rate differentials. In particular, empirical results support the mean‐reverting property of real interest rate differentials for interest rates measured in terms of traded goods.
THE 2005 LAWRENCE R. KLEIN LECTURE: EMERGENT CLASS STRUCTURE*
Authors: Matsuyama Kiminori
Published: April 2006

This article presents a model of the emergent class structure, in which a society inhabited by inherently identical households may be endogenously split into the rich bourgeoisie and the poor proletariat. For some parameter values, the model has no steady state where all households remain equally wealthy. In this case, the model predicts emergent class structure or the rise of class societies. Even if every household starts with the same amount of wealth, the society will experience “symmetry‐breaking” and will be polarized into two classes in steady state, where the rich maintain a high level of wealth partly due to the presence of the poor, who have no choice but to work for the rich at a wage rate strictly lower than the “fair” value of labor. The nonexistence of the equal steady state means that a one‐shot redistribution of wealth would not be effective, as wealth inequality and the class structure would always reemerge. Thus, the class structure is an inevitable feature of capitalism. For other parameter values, on the other hand, the model has the unique steady state, which is characterized by perfect equality. In this case, the model predicts dissipating class structure or the fall of class societies. Even if the society starts with significant wealth inequality, labor demand by the rich employers pushes up the wage rate so much that workers will escape from the poverty and eventually catch up with the rich, eliminating wealth inequality and the class structure in the long run. In an extension, we introduce self‐employment, which not only provides the poor with an alternative to working for the rich, but also provides the rich with an alternative to investment that creates jobs. Due to this dual nature of self‐employment, the effects of self‐employment turn out to be quite subtle. Yet, within the present framework, it is possible to offer a complete characterization of the steady states even in the presence of self‐employment.
GREENHOUSE‐GAS EMISSION CONTROLS IN AN OPEN ECONOMY*
Authors: Ishikawa Jota , Kiyono Kazuharu
Published: April 2006

To examine how greenhouse‐gas emission controls affect a country's industrial and trade structures, this article presents an open economy model that has both Ricardian and Heckscher–Ohlin features. We specifically compare emission quotas, emission taxes, and emission standards. The patterns of production and trade critically hinge on those policy tools. It is shown that a domestic emission control may lead to carbon leakage and may not reduce the world emissions, and that emission standards may work as a “hidden” production subsidy toward an emission‐intensive industry.
IDENTIFICATION AND ESTIMATION OF EXCHANGE RATE MODELS WITH UNOBSERVABLE FUNDAMENTALS*
Authors: Chambers Marcus J. , McCrorie J. Roderick
Published: April 2006

This article is concerned with issues of model specification, identification, and estimation in exchange rate models with unobservable fundamentals. We show that the continuous‐time model proposed by Gardeazabal, Regúlez, and Vázquez (International Economic Review 38 (1997), 389–404) is not identified and that this property is characteristic of the discrete‐time representation of the model that they used as the basis for estimation by simulated method of moments. We briefly discuss the implications of this result in the context of the asset‐market model of exchange rates with unobservable fundamentals.
ECONOMIC DEVELOPMENT UNDER ALTERNATIVE TRADE REGIMES*
Authors: Castro Rui
Published: April 2006

How does openness affect economic development? This question is answered in the context of a dynamic general equilibrium model of the world economy, where countries have technological differences that are both sector neutral and specific to the investment goods sector. Relative to a benchmark case of trade in credit markets only, consider (i) a complete restriction of trade and (ii) a full liberalization of trade. The first change decreases the cross‐sectional dispersion of incomes only slightly, and produces a relatively small welfare loss. The second change, instead, decreases dispersion by a significant amount, and produces a very large welfare gain.
Assessment of Childhood Depression
Authors: Chrisman Allan , Egger Helen , Compton Scott N. , Curry John , Goldston David B.
Published: April 2006

Background:  Depression as a disorder in childhood began to be increasingly recognised in the 1970s. Epidemiologic community and clinic‐based studies have characterised the prevalence, clinical course, and complications of this illness throughout childhood and adolescence into adulthood. This paper reviews two instruments for assessing depression in prepubertal children – the Dominic Interactive and The Preschool Age Psychiatric Assessment. Both instruments are useful in screening for psychiatric disorders and reliably identifying the presence of depressive symptoms in young children.
Children's Explanations of Aggressive Incidents at School Within an Attribution Framework
Authors: Joscelyne Trish , Holttum Sue
Published: April 2006

Background:  Previous research suggests children use different types of attribution to explain bullying. The research, however, has not explored links between children's attributions.

Method:  This study explores the types of, and links between, attributions made by children about bullying situations. Seventeen 9‐ and 10‐year‐olds were interviewed at school. Types of attributions and links between attributions were categorised using content analysis.

Results:  The results suggest that children make a range of linked attributions that can be coded into characterological and behavioural and a new category named ‘feelings’.

Conclusions:  The findings are linked to previous research, and implications for clinical and school interventions are discussed.
Plasticizers as Contaminants in Commercial Ethanol
Authors: Goldstein Dora B. , Feistner Gottfried J. , Faull Kym F. , Tomer Kenneth B.
Published: April 2006

A batch of 95% ethanol caused unusually strong disordering of biomembranes, which could be detected either by fluorescence anisotropy in synaptosomal membranes or by electron paramagnetic resonance spectroscopy in erythrocyte membranes. The contaminated batches of ethanol were visibly fluorescent when evaporated on filter paper. The adulterants were separated by capillary gas chromatography and the ubiquitous pollutant dioctylphthalate was identified by its low resolution electron impact mass spectrum. The remaining peaks, which were not recognized by any of the available mass spectral libraries, were identified by high resolution electron impact and chemical ionization mass spectrometry and low resolution tandem mass spectrometry using fast atom bombardment ionization; they were triethylene glycol esters and aryl phosphates. All the contaminants are industrial plasticizers. Distillation resulted in loss of the strong disordering properties of the alcohol.
DSM‐III Criteria for Alcohol Abuse: Associations with Alcohol Consumption Behavior
Authors: Tarter Ralph E. , Arria Amelia M. , Moss Howard , Edwards Norann J. , Van Thiel David H.
Published: April 2006

DSM‐III criteria for diagnosing alcohol abuse in a sample of hospitalized alcoholics highly correlated with each other and were poorly correlated with self‐reported drinking pattern, quantity, and consequences of alcohol consumption. These findings question the specificity and the construct validity of the DSM‐III criteria for diagnosing alcohol abuse.
Quantification of Individual Sensitivities to Ethanol in Selective Breeding Experiments: Difference Scores Versus Regression Residuals
Authors: Crabbe John C. , Weigel Ronald M.
Published: April 2006

Nagoshi et al. (Alcohol Clin Exp Res 10:343–349, 1986) have argued recently that the use of postdrug minus predrug difference scores to assess individual variability in sensitivity or tolerance to ethanol is not to be recommended. Unreliability of variables can result in biased estimates of response to treatment. Instead of difference scores, they recommend using residual scores from the regression of posttreatment on pretreatment measures. We were interested in the consequences of employing difference scores versus regression residuals for a related, but different purpose: the choice of individual animals to be mated for a selective breeding study. The availability of data from such a selective breeding experiment ongoing in the laboratory of one of us (JCC) allowed us to compare directly the effects of use of change and residual scores as criteria for selection. The selection is for maximal hypothermic sensitivity of mice to an acute dose of ethanol. In our sample, difference scores were highly correlated with regression residuals. In practical terms, almost 75% of the individuals chosen for mating by the change score method would also have been chosen by the residual score method. We conclude that for selective breeding experiments, the use of difference scores does not necessarily introduce sampling bias, is unlikely to affect the ultimate outcome of selection, and may be a more meaningful variable for the physiological process studied.
Effects of Aging and Testosterone Administration on Liver Alcohol Dehydrogenase Activity in Male Fischer 344 Rats
Authors: Rikans Lora E. , Kling O. Ray
Published: April 2006

The activity of alcohol dehydrogenase was measured in liver cyto‐solic fractions of male Fischer 344 rats at ages representing young adulthood, middle age, and old age. The activities were 1.7 ± 0.1, 2.3 ± 0.1, and 2.6 ± 0.2 μmol/min/g liver in rats aged 4–5, 14–15, and 24–25 months, respectively. Hepatic alcohol dehydrogenase activity in female rats (3.4 ± 0.2 μmol/min/g liver) was the same in young as in old rats. Castration increased alcohol dehydrogenase activity in young males to levels found in females, and testosterone administration reversed the effect. However, neither physiological nor pharmacological doses of the hormone restored the elevated enzyme activities of old male rats to levels found in young male rats.
Alcohol, Pregnancy, and Prostaglandins
Authors: Randall Carrie L , Anton Raymond F , Becker Howard C
Published: April 2006

Basic scientists and clinicians alike are in agreement that children of alcoholic mothers are at risk for a variety of birth defects. These defects have been labeled fetal alcohol syndrome or, in a milder form, fetal alcohol effects. Prevention or therapeutic intervention of this disorder requires an understanding of the mechanism of action of alcohol on the developing fetus. This paper addresses the possible role of prostaglandins as biochemical mediators of the teratogenic actions of alcohol.
Purification of Human Liver Aldehyde Dehydrogenase by High‐Performance Liquid Chromatography and Identification of Isoenzymes by Immunoblotting
Authors: Johnson Charles T , Bosron William F , Harden Colleen A , Li Ting‐Kai
Published: April 2006

Human liver aldehyde dehydrogenase (ALDH) exists in multiple molecular forms. Two different isoenzymes of ALDH have been purified which will oxidize acetaldehyde to acetate. ALDH1 is localized principally in hepatocyte cytosol and exhibits a Km for acetaldehyde of about 0.1 mM at pH 9.5. ALDH2 is mitochondrial in origin and exhibits low Km for acetaldehyde, about 1 μM. We have developed rapid purification procedures for ALDH1 and ALDH2 by use of agarose‐AMP affinity chromatography and high‐performance anion‐exchange liquid chromatography (HPLC). The method takes less time and affords higher yields of the labile ALDH isoenzymes than conventional column chromatography methods. A previously uncharacterized ALDH form has been identified by anion‐exchange HPLC which exhibits high Km for acetaldehyde, about 1 mM, and is very labile. Polyclonal antibodies to the purified ALDH1 and ALDH2 isoenzymes have been prepared. As evidenced by immunoblotting of starch gels containing the purified isoenzymes, anti‐ALDH1 does not crossreact with ALDH2 and anti‐ALDH2 does not crossreact with ALDH1. The anti‐ALDH2 antibody identifies the “inactive” variant of ALDH2 in Japanese livers exhibiting the “deficient” ALDH2 phenotype. The sensitivity of detection of ALDH isoenzymes in liver homogenate‐supernatants by immunoblotting of starch gels is about 10‐fold greater than that by activity staining.
Acute Alcohol Intoxication in Women: Relationship to Dose and Menstrual Cycle Phase
Authors: Sutker Patricia B. , Goist Kenneth C. , King Alan R
Published: April 2006

This study investigated relationships between metabolic responses to acute alcohol intoxication and phases of the female menstrual cycle among women demonstrated to have ovulated during two consecutive cycles. Subjects were administered moderate (0.66 ml/kg) and high (1.0 ml/kg) alcohol doses during the early follicular, ovulatory, and midluteal phases of the menstrual cycles. Radioimmunoassays (RIAs) of serum estradiol, progesterone, luteinizing hormone (LH), and follicle‐stimulating hormone (FSH) levels were performed from blood collected before each alcohol administration. Results showed decreased elimination times, reduced areas under the BAC‐time curve (AUCs), and faster disappearance rates associated with the midluteal menstrual phase compared to the early follicular and ovulatory phases which were consistent for both moderate and high alcohol doses. Decreased elmination times, smaller AUCs, and faster disappearance rates were associated with increased levels of progesterone, elevated progesterone to estradiol ratios, and decreased FSH levels. No differences were found in absorption time or peak BAC across phases of the menstrual cycle.
The Role of Endothelium in Tolerance to Ethanol‐Induced Contraction of the Rat Aorta
Authors: Knych Edward T
Published: April 2006

After 2 days of intoxication an endothelium‐dependent tolerance to ethanol‐induced contraction of the rat aorta develops. This study investigates the possibility that the observed tolerance may be due to the recently described endothelium‐dependent vasodilator system which mediates the action of several potent vasodilators. The maximum response induced by ethanol in control and intoxicated aortic rings with endothelium was significantly increased by treatment with eicosatetraynoic acid and methylene blue. In addition, these agents significantly decreased the EC50 of ethanol in intoxicated but not control rings with endothelium. The response of control and intoxicated aortic rings without endothelium was unaltered by eicosatetraynoic acid or methylene blue. Indomethacin, nordihydroguaiaretic acid, and FPL 55712 did not alter either the maximum response or the EC50 of ethanol in control or intoxicated rings with endothelium. These observations support the hypothesis that the endothelium‐dependent tolerance observed in the aorta may be due to the release of an endothelium‐derived relaxing factor.
The Effect of Ethanol on the Brain Catecholamine Systems in Female Mice, Rats, and Guinea Pigs
Authors: Alari L. , Lewander T , Sjöquist B.
Published: April 2006

The effect of acute ethanol administration on the concentrations of dopamine (DA), norepinephrine (NE) and their metabolites (3,4‐dihydroxyphenylacetic acid [DOPAC], homovanillic acid [HVA], 3,4‐dihydroxyphenylglycol [DHPG] and 4‐hydroxy‐3‐methoxyphenylglycol [HMPG]) in brains of female mice, rats, and guinea pigs were investigated. A subhypnotic dose (2 g/kg) or a hypnotic dose (4 g/kg) of ethanol was administered intraperitoneally and the animals were killed 45 min later. In the rat the DA levels were unchanged, while the NE concentrations were decreased after both doses of ethanol. The DA levels did not change in the mouse and guinea pig, while the concentrations of NE showed a minor decrease in the mouse but were unaffected in the guinea pig. After 4 g/kg of ethanol the DOPAC and HVA concentrations were elevated significantly in all three species, and after 2 g/kg the DOPAC levels were increased in the rat and guinea pig brains and the HVA levels in the mouse and guinea pig brains. In the mouse and rat brain the DOPAC + HVA concentrations indicated a dose response relationship: 4 g/kg was significantly more effective than 2 g/kg. The DHPG concentration increased in the rat brain after both 2 and 4 g/kg, while the HMPG concentrations increased significantly only after 2 g/kg. In the mouse and guinea pig the brain DHPG concentrations remained unchanged, while the HMPG concentrations increased after both 2 and 4 g/kg ethanol.
Diethyl Ether Inhibits Ethanol Metabolism in Vivo by Interaction with Alcohol Dehydrogenase
Authors: Normann Per Trygve , Ripel Åse , Mørland Jørg
Published: April 2006

The ethanol disappearance rate was determined in fed rats given 20‐40 mM ethanol and anesthetized with pentobarbital (control group) and diethyl ether. The control ethanol disappearance rate was 0.27 ± 0.02 mM/min (±SD, n= 4). Rats anesthetized with diethyl ether (blood levels of 9–13 mM) revealed an ethanol disappearance rate of 0.13 ± 0.05 mM/min (±SD, n= 7), i.e., 52% inhibition of the control rate.

Kinetic studies on crystalline and lyophilized alcohol dehydrogenase from equine liver demonstrated that 20 mM diethyl ether inhibited the initial rate of ethanol oxidation by 55%. By using ethanol as the variable substrate the inhibition of alcohol dehydrogenase was described by a mixed noncompetitive/uncompetitive mechanism.
The Antisocial and the Nonantisocial Alcoholic: Clinical Distinctions in Men with Major Unipolar Depression
Authors: Lewis Collins E , Rice John , Andreasen Nancy , Endicott Jean , Rochberg Nanette
Published: April 2006

Depressed, alcoholic men were divided into those with and those without antisocial personality (ASP). The ASP alcoholics had a more severe, crosssectional clinical picture; they had a higher rate of drug use disorder and more alcohol‐related symptomatolgy. The medical complications of alcoholism were related to the duration of heavy drinking whereas the nonmedical complications (the psychosocial and pathologic‐intake problems) were related to ASP, duration of heavy drinking, and their interaction.
Effects of Alpha‐Methylparatyrosine on Voluntary Consumption of Ethanol, Water, and Solid Food in UChA and UChB Rats
Authors: Contreras Selfa , Alvarado Rosa
Published: April 2006

The effect of daily doses of 80 mg/kg (intraperitoneal) of alphamethylparatyrosine, AMPT (inhibitor of tyrosine hydroxylase) on the voluntary consumption of ethanol, water, and solid food was studied in rats of both sexes belonging to the UChA (lower ethanol consumer) and UChB (high ethanol consumer) strains. The consumptions during the treatment period were compared to those of the preceeding one (basic).

Decrease of ethanol and solid food intake and increase of that of water in UChB rats and only a decrease of solid food intake in UChA rats were observed.

These effects cannot be ascribed to blocking of dopaminergic or noradrenergic synapses, since this dose of AMPT inhibits the in vivo synthesis of both catecholamines.
Discriminant Analysis of the Self‐Administered Alcoholism Screening Test
Authors: Davis Leo J. , Hurt Richard D , Morse Robert M , O'Brien Peter C.
Published: April 2006

For a sample of 1156 patients (520 alcoholics and 636 nonalcoholics), discriminant function analyses were performed on the total score, a nine‐item version, and a two‐item version of the Self‐Administered Alcoholism Screening Test (SAAST). With sensitivities set at 90 and 95%, specificities for the total score and nine‐item versions ranged from 96.4 to 99.4%. Cross‐validation of the nine‐item version with the “jackknife” procedure resulted in only one additional misclassi‐fication of the 1156 subjects. Separate analyses of the male and female samples revealed that more items entered the discriminant function for women than for men and resulted in a higher, although clinically nonsignificant, percentage of correct classification for women. The results strongly support the use of either the total score or the nine‐item version of the SAAST in large‐scale screening for alcoholism in a medical patient population.
Neuroendocrine, Psychophysiological and Subjective Reactivity to an Alcohol Placebo in Male Alcoholic Patients
Authors: Dolinsky Zelig S , Morse David E , Kaplan Richard F , Meyer Roger E , Corry Douglas , Pomerleau Ovide F
Published: April 2006

Alteration in neuroendocrine activity associated with the regulation of energy metabolism and food intake may play a role in characterizing the alcohol dependent state. Alcoholics, when compared to controls, demonstrated significantly larger and more rapid glucose and insulin responses following the consumption of a placebo beer, which they believed contained alcohol. The existence of significant correlations between peak neuroendocrine responses and desire to drink, anxiety, as well as psychophysiological responses in alcoholics suggests the potential multivariate nature of the biological/behavioral state associated with alcohol dependence.
Chronic Alcohol Consumption Reduces the Cortical Layer Volumes and the Number of Neurons of the Rat Cerebellar Cortex
Authors: Tavares M. A. , Paula‐Barbosa M. M. , Cadete‐Leite A.
Published: April 2006

Past work showed that chronic alcohol consumption induces massive degeneration in the rat cerebellar cortex. In order to provide details of these effects, the cortical cell numbers and the cerebellar layer volumes were studied in adult rats fed alcohol for 1, 3, 6, 12, and 18 months and compared with respective age‐matched controls. Significant decreases of granular and molecular layer volumes were found after 3 and 6 months of alcohol feeding, respectively. No significant differences were found in the Purkinje cell layer volume. Neuron countings showed that granule cells and molecular layer interneurons were the earliest and most severely affected populations. A decrease in the number of Purkinje cells was observed only after 18 months of alcohol consumption and Golgi cells were not significantly reduced. Thus, we concluded that cerebellar neurons have a selective vulnerability to alcohol which might alter the balance between excitatory and inhibitory limbs of the cerebellar circuitry.
Biologically Active Phytoestrogens Are Present in Bourbon
Authors: Gavaler Judith S. , Rosenblum Elaine R , Van Thiel David H. , Eagon Patricia K , Pohl Clifford R , Campbell Ian M , Gavaler Joan
Published: April 2006

The nonethanol congeners of bourbon have been found to possess estrogenic activity when tested using an in vivo oophorectomized rat bioassay, as well as an in vitro estrogen receptor assay system. The phytoestrogen, biochanin A, as well as the plant sterol, β‐sitosterol, were identified in the bourbon preparation using gas chromatography/mass spectrometry. These findings, using three methodological approaches, demonstrate that bourbon contains at least one biologically active phytoestrogen and suggest that the effects of alcoholic beverage use or abuse, particularly as they relate to endocrine systems, should not be viewed as resulting solely from exposure to ethanol.
Effects of Serotonin Uptake Blockade on Food, Water, and Ethanol Consumption in Rats
Authors: Gill K. , Amit Z.
Published: April 2006

Previous research has demonstrated that the serotonin uptake blocker, zimeldine, reduced voluntary ethanol consumption in rats and humans. It has been suggested that zimeldine interfered with the processes that mediate the reinforcement derived from ethanol ingestion. However, there are considerable data which suggest that serotonergic pharmacological agents may produce a general inhibition of food and fluid consumption. The present investigation was therefore designed to directly examine the effects of zimeldine on food intake. The results indicated that zimeldine had a potent anorexic action. Furthermore, the drug appeared to primarily affect food intake, with secondary decreases in the fluid most closely associated with prandial drinking. The results were discussed in terms of the effects of serotonin uptake blockade on motivational processes in general.
Effects of Alcohol on Experimental Atrial Fibrillation
Authors: Nguyen Thach N. , Friedman Howard S. , Mokraoui Abdel Malec
Published: April 2006

The association of alcohol abuse, especially binge drinking, and atrial fibrillation, recently termed “holiday heart,” has been recognized for some time. The effects of alcohol on atrial fibrillation, however, have not been studied. Accordingly, measurements of hemodynamics and duration of electrically induced atrial fibrillation were made in α‐chloralose anesthetized dogs during the 30 min before and during a 30‐min intravenous infusion of 1.7 g/kg of ethanol (25%, v/v), which produced an average infusion concentration of 254 ± 21 mg/dl. Average cardiac output, left ventricular (LV) peak dp/dt, and pulmonary artery mean pressure did not change, whereas LV systolic (116 ± 8 to 107 ± 9 mm Hg, p < 0.05) and aortic mean (95 ± 7 to 87 ± 9 mmHg, p < 0.05) pressures decreased. Heart rate and atrioventricular conduction in sinus rhythm, and atrial and ventricular activity in atrial fibrillation also did not change. Despite a decrease in arterial pH, duration of atrial fibrillation decreased (356 ± 143 to 93 ± 38 sec, p < 0.05). Moreover, at 15 min, when average ethanol concentration was 208 ± 20 mg/dl, and aortic mean pressure (95 ± 7 to 85 ± 8 mm Hg, p < 0.05), pulmonary artery mean pressure (16 ± 2 to 14 ± 2 mm Hg, p < 0.05), and LV peak dp/dt (1563 ± 143 to 1285 ± 167 mm Hg‐sec−1, p < 0.05) were reduced, duration of atrial fibrillation was less than control (356 ± 143 to 114 ± 56 sec, p < 0.05). Thus, at blood levels of ethanol in which the vasodilatory and myocardial depressant effects of ethanol are evident, alcohol has an antiatrial fibrillatory effect.
The Hangover Hypothesis and the Influence of Moderate Social Drinking on Mental Ability
Authors: Bowden Stephen C. , Walton Nigel H. , Walsh Kevin W.
Published: April 2006

The “hangover” hypothesis proposes that there is some residual effect of low to moderate alcohol intake on the nervous system after the blood alcohol level has returned to zero. This notion has been invoked to explain the putative effects of moderate alcohol consumption on mental ability. We evaluated the hangover hypothesis by attempting to predict cognitive performance from self‐reports of alcohol consumed during the week prior to testing. We found no meaningful evidence to support the notion that moderate alcohol Ingestion produces a measurable toxic effect on brain function after the period of acute intoxication.
Ethanol Inhibits Some of the Early Effects of Epidermal Growth Factor in Vivo
Authors: Gerhart Mary J. , Reed B. Y. , Veech R. L.
Published: April 2006

Charles River male Wistar rats (200–300 g) were meal fed for 9–10 days, injected with either saline, epidermal growth factor (EGF), ethanol, or ethanol combined with EGF and their livers were freeze clamped 5 min after intraperitoneal injection of EGF. Metabolites were measured and the redox state and phosphorylation potential were calculated. Epidermal growth factor alone elevated hepatic content of glucose 1‐P, glucose 6‐P, fructose 6‐P, and 3‐phosphoglycerate 1.2–1.3‐fold when compared to saline treatment. Ethanol alone decreased hepatic content of 3‐phosphoglycerate and phosphoenolpyruvate 3.2–3.7‐fold below saline‐treated levels. Ethanol, in combination with EGF, decreased hepatic values for 3‐phosphoglycerate and phosphoenolpyruvate 2.0–2.3‐fold from saline treatment but elevated the content of phosphoenolpyruvate 1.6‐fold over ethanol treatment alone. Epidermal growth factor inhibited pyruvate kinase activity 1.3‐fold when compared to saline controls but ethanol in the presence of EGF facilitated the recovery of activity of this enzyme.
Alcohol Intolerance in the Hypereosinophilic Syndrome
Authors: Lederman Jolanta , Hasselbalch Hans , Hippe Erik
Published: April 2006

Alcohol intolerance presented as an initial symptom in two patients with hypereosinophillc syndrome. In patient 1 alcohol intolerance persisted during the whole course of disease, while in patient 2 all symptoms including alcohol intolerance disappeared after treatment with prednisolone and vincristine. Alcohol intolerance seems to be influenced by hypereosinophilla and may be of clinical value in the evaluation of the activity of the malignant disorder.
Increase in Tryptophan Oxygenase Activity in Alcoholic Patients
Authors: Buydens‐Branchey L. , Branchey M. , Worner T. M. , Zucker D. , Aramsombatdee E. , Lieber C. S.
Published: April 2006

This study was conducted in order to assess whether chronic excessive alcohol consumption affects the activity of the liver enzyme tryptophan oxygenase which is rate limiting along the most important pathway of catabolism.

Five alcoholics were studied twice, once shortly after admission to an Inpatient unit and the second time 1 month later. On each study day patients were given a trptophan load of 50 mg/kg. Kynurenine in the urines (which reflects tryptophan oxygenase activity) was measured for a period of 8 hr following the load and showed a significantly enhanced activity of the enzyme shortly after cessation of drinking. This increased activity enzyme could explain the lowered tryptophan levels we have previously reported in alcoholics. The increase in enzyme activity may have been mediated by a rise in glucocorticoid hormones. In all instances, plasma cortisol measured hourly for 6 hr after the start of the experiment, was higher shortly after cessation of drinking than 1 month later.
Comparative Metabolic Effects of Chronic Ethanol Intake and Undernutrition in Pregnant Rats and Their Fetuses
Authors: Testar Xavier , Llobera Miquel , Herrera Emilio
Published: April 2006

Female rats receiving ethanol in the drinking water before and during gestation (ET) were compared to pair‐fed animals (PF) and normal controls (C) fed ad libitum. On the 21st day of gestation the maternal body and liver weight, blood glucose, and plasma protein concentrations were lower in ET and PF animals as compared to C. In contrast to C or PF mothers, ET‐fed mothers had higher circulating β‐hydrox‐ybutyrate and triacylglyceride levels and β‐hydroxy‐butyrate/aceto‐acetate ratio. Liver triacylglycerides were increased whereas liver glycogen concentration was reduced in ET‐fed animals. Only fetal body and liver weights and blood glucose were lower in both ET and PF than in C. Blood β‐hydroxy‐butyrate was increased and liver glycogen was decreased only in ET fetuses. There were no differences among the groups in fetal circulating β‐hydroxy‐butyrate/acetoacetate ratio, plasma proteins, and triacylglycerides or liver triacylglyceride content. Results indicate that certain changes in ET mothers are specifically produced by the ethanol intake rather than undernutrition. Further, metabolic changes occurring in the fetus are influenced by the ethanol effects in the mother and these actions may be added to those directly produced by the ethanol crossing the placenta.