bluuebunny/crossref_metadata_2025 huggingface dataset:
The α2β1 integrin inhibitor rhodocetin binds to the A-domain of the integrin α2 subunit proximal to the collagen-binding site
Authors: EBLE Johannes A. , TUCKWELL Danny S.
Published: November 2003

Rhodocetin is a snake venom protein that binds to α2β1 integrin, inhibiting its interaction with its endogenous ligand collagen. We have determined the mechanism by which rhodocetin inhibits the function of α2β1. The interaction of α2β1 with collagen and rhodocetin differed: Ca2+ ions and slightly acidic pH values increased the binding of α2β1 integrin to rhodocetin in contrast with their attenuating effect on collagen binding, suggesting that rhodocetin preferentially binds to a less active conformation of α2β1 integrin. The α2A-domain [von Willebrand factor domain A homology domain (A-domain) of the integrin α2 subunit] is the major site for collagen binding to α2β1. Recombinant α2A-domain bound rhodocetin, demonstrating that the A-domain is also the rhodocetin-binding domain. Although the interaction of α2β1 with rhodocetin is affected by altering divalent cations, the interaction of the A-domain was divalent-cation-independent. The rhodocetin-binding site on the α2A-domain was mapped first by identifying an anti-α2 antibody that blocked rhodocetin binding and then mapping the epitope of the antibody using human–mouse α2A-domain chimaeras; and secondly, by binding studies with α2A-domain, which bear point mutations in the vicinity of the mapped epitope. In this way, the rhodocetin-binding site was identified as the α3–α4 loop plus adjacent α-helices. This region is known to form part of the collagen-binding site, thus attaining a mainly competitive mode of inhibition by rhodocetin.
Characterization of the anti-apoptotic mechanism of Bcl-B
Authors: ZHAI Dayong , KE Ning , ZHANG Haichao , LADROR Uri , JOSEPH Mary , EICHINGER Andreas , GODZIK Adam , NG Shi-Chung , REED John C.
Published: November 2003

Bcl-B protein is an anti-apoptotic member of the Bcl-2 family protein that contains all the four BH (Bcl-2 homology) domains (BH1, BH2, BH3 and BH4) and a predicted C-terminal transmembrane domain. Our previous results showed that Bcl-B binds Bax and suppresses apoptosis induced by over-expression of Bax; however, Bcl-B does not bind or suppress Bak. To explore the molecular basis for the differential binding and suppression of Bax and Bak, we studied the BH3 dimerization domains of Bax and Bak. Chimeric mutants of Bax and Bak were generated that swapped the BH3 domains of these pro-apoptotic proteins. Bcl-B associated with and blocked apoptosis induced by mutant Bak containing the BH3 domain of Bax, but not mutant Bax containing the BH3 domain of Bak. In contrast, Bcl-XL protein bound and suppressed apoptosis induction by Bax, Bak and both BH3-domain chimeras. A strong correlation between binding and apoptosis suppression was also obtained using a series of alanine substitutions spanning the length of the Bax BH3 domain to identify critical residues for Bcl-B binding. Conversely, using structure-based modelling to design mutations in the BH3-binding pocket of Bcl-B, we produced two Bcl-B mutants (Leu86→Ala and Arg96→Gln) that failed to bind Bax and that also were unable to suppress apoptosis induced by Bax over-expression. In contrast, other Bcl-B mutants that still bound Bax retained protective activity against Bax-induced cell death, thus serving as a control. We conclude that, in contrast with some other anti-apoptotic Bcl-2-family proteins, a strong correlation exists for Bcl-B between binding to pro-apoptotic multidomain Bcl-2 family proteins and functional apoptosis suppression.
SH2-containing inositol 5-phosphatases 1 and 2 in blood platelets: their interactions and roles in the control of phosphatidylinositol 3,4,5-trisphosphate levels
Authors: GIURIATO Sylvie , PESESSE Xavier , BODIN Stéphane , SASAKI Takehiko , VIALA Cécile , MARION Evelyne , PENNINGER Joseph , SCHURMANS Stéphane , ERNEUX Christophe , PAYRASTRE Bernard
Published: November 2003

Src homology domain 2-containing inositol 5-phosphatases 1 and 2 (SHIP1 and SHIP2) are capable of dephosphorylating the second messenger PtdIns(3,4,5)P3 (phosphatidylinositol 3,4,5-trisphosphate) and interacting with several signalling proteins. SHIP1 is essentially expressed in haematopoietic cells, whereas SHIP2, a closely related enzyme, is ubiquitous. In the present study, we show that SHIP1 and SHIP2 are expressed as functional PtdIns(3,4,5)P3 5-phosphatases in human blood platelets and are capable of interacting when these two lipid phosphatases are co-expressed, either naturally (platelets and A20 B lymphoma cells) or artificially (COS-7 cells). Using COS-7 cells transfected with deletion mutants of SHIP2, we demonstrate that the Src homology domain 2 of SHIP2 is the minimal and sufficient protein motif responsible for the interaction between the two phosphatases. These results prompted us to investigate the relative importance of SHIP1 and SHIP2 in the control of PtdIns(3,4,5)P3 levels in platelets using homozygous or heterozygous SHIP1- or SHIP2-deficient mice. Our results strongly suggest that SHIP1, rather than SHIP2, plays a major role in controlling PtdIns(3,4,5)P3 levels in response to thrombin or collagen activation of mouse blood platelets.
Lgl1, a mesenchymal modulator of early lung branching morphogenesis, is a secreted glycoprotein imported by late gestation lung epithelial cells
Authors: OYEWUMI Lami , KAPLAN Feige , SWEEZEY Neil B.
Published: November 2003

Secreted glycoproteins serve a variety of functions related to cell–cell communication in developmental systems. We cloned LGL1, a novel glucocorticoid-inducible gene in foetal lung, and described its temporal and spatial localization in the rat. Disruption of foetal mesenchyme-specific LGL1 expression using antisense oligodeoxynucleotides, which was associated with a 50% decrease in lgl1 protein levels, inhibited airway epithelial branching in foetal rat gestational day 13 lung buds in explant culture. These findings suggested that lgl1 functions as a secreted signalling molecule. We now provide evidence supporting a role for lgl1 in mesenchymal–epithelial interactions that govern lung organogenesis. Lgl1 is a secreted glycoprotein with a conserved N-terminal secretory signal peptide. Using dual immunofluorescence, intracellular lgl1 was found to co-localize with markers of the Golgi apparatus and endoplasmic reticulum, consistent with its association with secretory vesicles. Using pulse–chase studies, we show that lgl1 is a stable protein with a half-life of 11.5 h. Furthermore, at gestational days 20 and 21 (term=22), foetal distal lung epithelial cells import lgl1 protein. Taken together, our findings support distinct roles for lgl1 as a mediator of glucocorticoid-induced mesenchymal–epithelial interactions in early and late foetal lung organogenesis.
Structural and functional roles of Cys-238 and Cys-295 in Escherichia coli phosphofructokinase-2
Authors: BAEZ Mauricio , RODRÍGUEZ Patricio H. , BABUL Jorge , GUIXÉ Victoria
Published: November 2003

Modification of Escherichia coli phosphofructokinase-2 (Pfk-2) with pyrene maleimide (PM) results in a rapid inactivation of the enzyme. The loss of enzyme activity correlates with the incorporation of 2 mol of PM/mol of subunit and the concomitant dissociation of the dimeric enzyme. The two modified residues were identified as Cys-238 and Cys-295. In the presence of the negative allosteric effector, MgATP, Cys-238 was the only modified cysteine residue. Kinetic characterization of the Cys-238-labelled Pfk-2 indicates that the enzyme is fully active, with the kinetic constants (Km, kcat) being almost identical to the ones obtained for the native enzyme. The modified enzyme is a monomer in the absence of ligands and, like the native enzyme, behaves as a tetramer in the presence of the nucleotide. However, in the presence of fructose-6-phosphate (fru-6-P) and ATP−4, the enzyme behaves as a dimer, suggesting that the monomers undergo re-association in the presence of the substrates and that the active species is a dimer. Modification of Pfk-2 with eosin-5-maleimide (EM) results in the labelling of Cys-295. This modified enzyme is inactive and is not able to bind to the allosteric effector, remaining as a dimer in its presence. Nonetheless, Cys-295-labelled Pfk-2 is able to bind to the substrate fru-6-P in an hyperbolic fashion with a Kd value that is 6-fold higher than the one determined for the native enzyme. These are the first residues to be implicated in the activity and/or structure of the Pfk-2.
A Comparative Analysis of the Air Quality Management Challenges and Capabilities in Urban and Rural English Local Authorities
Authors: Beattie C.I. , Longhurst J.W.S. , Woodfield N.K.
Published: November 2003

Local authorities in Great Britain have (in the main) completed their air quality review and assessments, the aim of the process being the identification of local hotspots where national air quality objectives are not likely to be met. Across Great Britain approximately 120 Air Quality Management Areas are in the process of being declared. Local authorities, in partnership with others, are required to write and implement an action plan outlining remedial measures to improve the air quality situation in these areas. This paper compares and contrasts the challenges facing urban and rural authorities in carrying out these responsibilities. The capabilities of urban, rural and those authorities defined as 'mixed' in implementing the review and assessment process also are discussed. The data presented indicate that, although urban authorities appear to be facing greater and more complex air quality challenges, rural areas are not without their own air quality challenges. The issues facing urban authorities are different from those facing their more rural counterparts. It is hypothesised that urban authorities have more effective frameworks in place for tackling the challenges of air quality action planning. This hypothesis is tested by questionnaire surveys and in the context of an urban and a rural case-study authority.
US Regionalism and Rationality
Authors: Basolo Victoria
Published: November 2003

Regionalism continues to be proffered as a policy prescription for US metropolitan ills. While many urban scholars discuss the benefits of regional approaches to problem-solving, others question, and sometimes dismiss, the possibility of widespread, comprehensive regionalism. This latter group generally takes one of two perspectives. First, they argue that local autonomy and fragmentation prohibit regional collaboration. Secondly, rational choice theorists claim jurisdiction-centred economic interest spurs intraregional competition and impedes cooperation. Although both perspectives can be criticised as overdeterministic, they appear to be supported by the limited number of examples of comprehensive metropolitan co-operation in the US. This article identifies a theoretical connection and empirical similarity between these views of impediments to regionalism. The author argues that strategies suggested by rational-based collective action theory apply to either the autonomy or competition argument; however, she notes that empirical results raise questions about adopting a strict rational-based model. The author warns against a premature dismissal of regionalism as a viable policy prescription without further research and recommends a promising path for future research on comprehensive regional co-operation.
Changing Gender Roles, Shifting Power Balance and Long-distance Migration of Couples
Authors: Smits Jeroen , Mulder Clara H. , Hooimeijer Pieter
Published: November 2003

Long-distance migration of couples requires joint decision-making within the household. The uneven power balance between men and women and traditional gender roles have given rise to the concepts of 'tied stayer' (usually the male partner) and 'tied mover' (usually the female). Since these concepts were introduced, women have gained economic power and gender roles have changed. The paper analyses the effects of these changes on the determinants of the long-distance migration of couples, using data for the Netherlands. For 1977, the results reflect the 'classic' pattern of family migration: the male's human capital counted more than the female's and a male age advantage led to more migration. Women seemed to use their power mostly to prevent migration. By 1996, the dominance of the male's human capital had largely disappeared and the effect of an age advantage had become more symmetrical. The results point to the emergence of a new pattern, with a more equal power balance within couples.
'Making Friends or Making Things?': Interfirm Transactions in the Sheffield Metal-working Cluster
Authors: Watts H.D. , Wood A.M. , Wardle P.
Published: November 2003

The paper comprises an examination of the material inputs of a sample of 70 small firms in the Sheffield metal-working cluster and an assessment of the extent to which purchases are accompanied by face-to-face (embodied) transactions. It is shown that there are no significant differences between the level of embodied transactions accompanying local (intra-cluster) material links and those associated with non-local flows. It seems that, on this measure at least and within this cluster, the Sheffield metal-working cluster lacks the dense network of embodied transactions with local suppliers suggested in the wider literature. The lower-than-expected measures of embodied transactions suggest that one of the mechanisms for the transfer of knowledge between buyers and suppliers within an industrial cluster is poorly developed in this particular case.
Shifts in Tokyo's World City Status and the Urban Planning Response
Authors: Saito Asato , Thornley Andy
Published: November 2003

The position of a city in any hierarchy of world importance is not a static phenomenon. This paper takes the example of Tokyo and explores its interaction with the dramatic economic and political events in Japan over the past 20 years. Although Tokyo is widely regarded as one of the top three 'world cities', the argument is supported that it retained many national characteristics, partly based on its location in a 'developmental state'. As national fortunes have changed, so has Tokyo's relationship with its global environment. The paper focuses on strategic urban policy and the way that this reflects Tokyo's world role, as perceived by national and city governments. Three phases in approach are identified since the 1980s. Twenty years ago Japan was experiencing economic boom and this was reflected in dramatic development projects in Tokyo. The concept of 'world city' was used at this time to legitimise such development. The 1990s were viewed in Japan as 'the lost decade' with great uncertainty over policy direction as the boom collapsed and urban policy in Tokyo entered a phase of inertia. It is argued that the city is now entering a third phase in which a new competitive attitude is emerging regarding the role of Tokyo and this is leading to changes in strategic urban policy. However, this new approach is still embedded in old structures and conceptions and hence there are tensions in developing future policy.
Trying to Understand Low-income Housing Subsidies: Lessons from the United States
Authors: Grigsby William G. , Bourassa Steven C.
Published: November 2003

This article asks why nations subsidise their low-income housing sectors and offers five reasons: to improve public health; to reduce societal injustice; to preserve the social order; to increase equality of opportunity; and, to accommodate population growth. After discussing those reasons in some detail, they are used as a framework for exploring some salient questions about low-income housing policy in the US. It is suggested that the framework would also be useful for analysis of low-income housing policies in other countries. It is concluded that the largest low-income housing subsidy programme in the US—the Section 8 voucher programme-is inapt.
Round and Round the Roundabout: Czech Roma and the Vicious Circle of Asylum-seeking
Authors: Castle-Kanĕrová Mit'a
Published: November 2003

This article follows earlier discussions about the current status of Romani refugees and migrants within Europe and the role of human rights in the process of accession of Central European states to the European Union (EU), in the Cambridge Review of International Affairs, Volume 13, Number 2. Romani migration opens up central issues of democratisation in Eastern Europe and of the role played by the EU in shaping that process. Human rights appear to have been accorded secondary importance and were replaced by the political doctrines of accession as efforts to manage and control migration, particularly of so-called undesirable migrants, such as the Roma, have reached a hiatus. The argument offered here is that discrimination of the Roma has been defined as no more than a social problem so that governments, both East and West, can proceed with the political agenda of enlargement. To demonstrate this point, the article reviews some Czech governmental documentation related to the treatment of Roma and places it within the context of the debate around accession within the broader framework of EU harmonisation of immigration policies.
Satan, Father of Revolution or Prince of Exile: The Reflection of Identity Transformation inĀyinah-hā-yi Dardār
Authors: Khorrami Mohammad Mehdi
Published: November 2003

Hushang Golshiri'sĀyinah-hĀ-yi DardĀris not an easy read. Its possibilities do not present themselves without effort, and, on first reading the novel does not generate a very positive reaction. In fact, for reasons that will be discussed later, the first reading brings up seemingly negative points about this work. It is essential to underline these seemingly negative points because when one takes into account the technical structure of the novel, those same negative points change into the elements which giveĀyinah-hĀ-yi DardĀrits strength. To provide a context for the description of these elements, we should begin with a short summary of the story.

Āyinah-hā-yi Dardāris a quasi-travelogue. Ebrahim, the narrator, is a writer who rehearses the elements of his travelogue chiefly through writing about the process of writing the travelogue. He talks about his trip to a few European countries and retells parts of stories he has read to different Iranian communities residing abroad.
The Sick Men of Persia: The Importance of Illness as a Factor in the Interpretation of Modern Iranian Diplomatic History
Authors: Afkhami Amir Arsalan
Published: November 2003

Studies of Iranian Political History often Assume that the Repercussions of physical or mental illness on leadership are inconsequential in determining the course of history. Globally, very few scholars have attempted to systematically examine the effects of illness on leaders and Iranian historians seem to evade this topic entirely. One reason may be a reluctance to grapple with medical issues that they might feel exceed their expertise. Another explanation, one frequently offered by medical historians, is the lack of reported clinical information on patients due to rules of medical confidentiality to which their physicians were bound. While aversion to grappling with medical terminology is understandable, the unwillingness of historians of Iran to explore the illnesses of their subjects might also stem from cultural sensibilities with respect to medical privacy and traditional notions of a leader's stoicism in the face of disease.
Top Manager and Institutional Effects on the Adoption of Innovations: The Case of Teleworking 1
Authors: Perez Manuela
                      Perez , Sanchez Angel
                      Martinez , De Luis Carnicer Maria
                      Pilar
Published: November 2003

In spite of the advances in information and communication technologies, the implementation of teleworking is still behind early expectations. The slow adoption of teleworking may be explained by different organizational drivers that influence its implementation. This article reports the empirical findings of a survey conducted among a sample of Spanish companies to identify potential drivers and constraints based on top manager and institutional perspectives. The results indicate that the potential of teleworking is influenced by the manager's perception of teleworking benefits and barriers, the manager's tenure, the company's use of information and communication technologies, the company's degree of innovation, the proportion of salespeople, women and middle-age employees in the workforce, and the company size. Top manager factors seem to have more influence in the decision to adopt teleworking, while institutional factors are more significant in the potential diffusion in the company.
The Formalist Revolution of the 1950s
Authors: Blaug Mark
Published: November 2003

Something happened to economics in the decade of the 1950s that is little appreciated by most economists and even by professional historians of economic thought. The subject went through an intellectual revolution as profound in its impact as the so-called Keynesian Revolution of pre-war years. I call it the Formalist Revolution after Ward (1972, pp. 40–41), who was the first to recognize the profound intellectual transformation of economics in the years after World War II.
Remembering Economics
Authors: Hammond J. Daniel
Published: November 2003

I showed a draft of my presidential address to a friend the other day. He read for a few minutes, then looked up at me and said, “Your address will be remembered long afterThe Wealth of Nations, Ricardo'sPrinciples, andThe General Theoryare all forgotten, but not until then!”

Remembering is what we who read, write, and teach history of economics are about. Historians preserve memory; we collect historical facts, organize them, and store them in conceptual filing systems. Remembering accurately and fully is hard work. Memory is tricky. It is always incomplete. It is well known that different witnesses to an event such as a traffic accident can remember the event quite differently, so that their accounts of what happened seem incompatible with each other. They may even appear not to be reports of the same event.
Denying Human Homogeneity: Eugenics & The Making of Post-Classical Economics
Authors: Peart Sandra J. , Levy David M.
Published: November 2003

The question we propose to address is how did economics move from the classical period characterized by the hardest possible doctrine of initial human homogeneityall the observed differences among people arise from incentives, luck, and historyto become comfortable with accounts of human behavior which alleged foundational differences among and within races of people? (Darity 1995) In this paper, we shall argue that early British eugenics thinkers racialized economics in the post-classical period.
McCulloch, Scrope, and Hodgskin: Nineteenth-Century Versions of Julian Simon
Authors: Kern William S.
Published: November 2003

InThe Ultimate Resource(1981, 1996), and in many other publications over the last several decades, Julian Simon put forth controversial views regarding the connection between natural resource scarcity, population growth, and economic progress. Simon argued, in contrast to those espousing the limits to growth, that natural resources were not getting scarcer, but more abundant, and that a large and growing population was an asset rather than a liability in the pursuit of economic growth.
Kjeld Philip and His Views on Fiscal Policy
Authors: Topp Niels-Henrik
Published: November 2003

The developments in macroeconomic theory in the 1930s had far-reaching theoretical implications for the attitude towards fiscal policy. In the following decades numerous articles and books analyzed the effects of fiscal policy on the economic activity. The analyses were often closely related to the Keynesian macroeconomic framework and the multiplier. The object of this paper is to draw attention to a book which analyzed fiscal policy from a different perspective.
Imperial reproductions: the circulation of colonial images across popular genres and media in the 1920s and 1930s
Authors: Polezzi Loredana
Published: November 2003

The Fascist phase of the Italian colonial experience was characterized by the diffusion of colonial discourses and imagery across Italian culture. Significantly, it was frequent for the same people to produce texts belonging to diverse genres, often cutting across different media and irrespective of distinctions between elite and popular audiences. Concentrating on representations of the East African territories which were eventually to constitute the Africa Orientale Italiana (AOI), the article analyses the way in which a selected number of images of the colonies spread across different genres and media, arguing in favour of an interdisciplinary approach to colonial processes of representation. Textual and visual mappings of Africa inscribed its territories with European symbols, value systems and signifiers. Geographers and travel writers, in particular, had a fundamental role in creating not only the physical but also the mental space for colonization. They enacted the transformation of East Africa from the dangerous and unmapped setting of the heroic acts of individual explorers to the stage for a collective colonial effort. In their footsteps there followed the discourse of tourism and the tourist industry, which was meant to integrate the image of the colonies with that of the peninsula.
The cultural construction of Italy in Albania and vice versa: migration dynamics, strategies of resistance and politics of mutual self-definition across colonialism and post-colonialism
Authors: Mai Nicola
Published: November 2003

This article analyses the shifting ways in which Italy has been strategically represented in Albania during the different key passages of the latter's relatively recent history as a sovereign independent state. As a parallel narrative, the article also examines the way Albania has been equally strategically represented in Italy before and during the two periods in which Italy has been militarily involved in Albania, and the way this has been consistent with an attempt to elaborate and sustain a politically strategic definition of Italian identity and culture. The history of the asymmetrical relationship between Albania and Italy is deeply embedded in the social, cultural and political environments that are on the two shores of the Adriatic Sea. The cultural construction of Albania in Italy and vice versa of Italy in Albania should be linked to seemingly independent instances of domestic reforms. The dynamics of projective identification or dis-identification stemming from these instances should be seen as intertwined within two parallel processes of mutual definition encompassing both the colonial and the postcolonial relations between and within the two countries.
The dopamine release inhibitor CGS 10746B blocks conditioned physical signs of morphine withdrawal
Authors: RODRÍGUEZ‐ARIAS M , AGUILAR MA , MIÑARRO J
Published: November 2003

Environment previously paired with morphine withdrawal leads to conditioned physical signs of withdrawal, this effect being modulated by additional exposition to morphine administration. In this study, the putative role of dopamine in conditioned withdrawal signs is evaluated by administering the dopamine release inhibitor CGS 10746B prior to suffering two naloxone‐induced withdrawals in a distinctive environment associated or not with morphine administration. The results show that dopamine seems to be necessary for the development of conditioned somatic signs of morphine withdrawal, as animals which received CGS 10746B do not present paw tremor or body shakes when they are placed in the environment paired with two previously induced withdrawals. On the other hand, the conditioned decrease in aggression is not affected by the dopamine release inhibitor. Taken together, our results confirm a critical role for dopamine in the processes of conditioning to the aversive physical signs of withdrawal.
Detecting crack and other cocaine use with fastpatches
Authors: LIBERTY HILARY JAMES , JOHNSON BRUCE , FORTNER NEIL , RANDOLPH DORIS
Published: November 2003

A continuing social problem is presented by the large number of individuals who use crack cocaine. Recent research has identified unique pyrolysis products of crack or burned cocaine as anhydroecgonine methylester (AEME) and ecgonidine (ECD) through gas chromatography/mass spectrometry (GC/MS) that allow for the detection of crack use distinct from other cocaine use. However, there have been no large‐scale studies to document the presence and prevalence of these substances in sweat. A new sweat‐testing appliance called a fastpatch was developed for this study. Through mild heating and a slightly larger collection pad than a standard Pharmchek ™ sweat patch, this product shows the promise of shorter required wear periods than standard sweat patches, and possibly longer time‐periods of detected use. One hundred and eighty subjects wore 360 fastpatch prototypes (one per hand). However, subsequent analysis determined that only one patch per subject was needed to obtain sufficient sweat eluate for GC/MS. Cocaine use was detected in sweat of 92% of subjects through GC/MS, comparing favorably with 91% with EMIT urinalysis. Crack metabolites were detected in 54% of subjects. The predominant analyte detected was AEME. There were no significant differences in detection rates between 15‐, 20‐ and 30‐minute wear periods. All wear periods detected both cocaine use in general and crack use successfully. These results suggest that crack use as distinct from other cocaine use can be detected in sweat and that fastpatches are a promising new way to detect drugs of abuse.
Alcohol addiction: evaluation of alcohol abstinence after a year of psycho‐medical‐social treatment
Authors: GIUFFREDI C , DI GENNARO C , MONTANARI A , BARILLI A , VESCOVI PP
Published: November 2003

The aim of this study was to evaluate alcohol abstinence in alcoholics and their family relationships after a year of treatment. The 100 alcoholics recruited were divided into two groups: ALC, where treatment consisted of clinical control and meetings of with the family consulting together with their relatives at the Centre for Study and Treatment of Alcoholism and CAT, where treatment consisted of clinical control and weekly attendance together with their relatives at Alcoholics‐in‐Treatment‐Clubs (CAT). The clinical condition of the sample was assessed by laboratory data. The subjects were given an MQ‐Quant questionnaire, based on an artificial neural network (ANN) model, which analyses the communicative fatigue of their interactions. The same examination was applied after 1 year excluding patients relapsed and their relatives. Psycho‐medical‐social treatment by the attendance of alcoholics and their families into a Multifamily Community induces alcohol abstinence of about 79%. This percentage is greater than psycho‐medical treatment carried out in the Centre of Alcoholism for ALC group (50%). We observed a significant difference between the communicative fatigue of the ALC group compared to the CAT group.
Alcohol inflammation and coronary heart disease
Authors: IMHOF ARMIN , KOENIG WOLFGANG
Published: November 2003

This overview summarizes the experimental and epidemiological evidence linking alcohol consumption and the immune system. It focuses on findings supporting the notion that moderate alcohol consumption exerts anti‐inflammatory effects which may explain, at least in part, the reduced risk of coronary heart disease morbidity and mortality in these subjects. Alcohol consumption has been shown consistently to be associated with all‐cause mortality in a J‐ or U‐shaped manner. This is due primarily to reduced risk of coronary heart disease (CHD) mortality among moderate consumers of alcohol compared to abstainers and heavy drinkers. Several mechanisms have been suggested by which moderate alcohol consumption could lower risk of CHD. However, changes in lipids, such as increased HDL cholesterol and apolipoprotein A1 or a favourable haemostatic profile, can only partly explain the beneficial effects. Recently, anti‐inflammatory effects of moderate intake of alcohol have been considered as an additional possible explanation, as inflammation has a fundamental role in the initiation, progression and the thrombotic complications of atherosclerosis.
Involvement of brain ethanol metabolism on acute tolerance development and on ethanol consumption in alcohol‐drinker (UChB) and non‐drinker (UChA) rats
Authors: TAMPIER LUTSKE , QUINTANILLA MARÍA ELENA
Published: November 2003

Acute tolerance that develops in minutes of an ethanol exposure appears to influence voluntary ethanol consumption in our two selected bred lines, UChA (low ethanol drinker) and UChB (high ethanol drinker) rats. We have reported previously that an acute intraperitoneal (i.p.) dose of ethanol (2.3 g/kg) induces both an increase in acute tolerance and a long‐lasting increase in voluntary ethanol consumption in UChB rats. In the present paper we investigated the involvement of acetaldehyde produced centrally during ethanol oxidation by brain catalase and its oxidation by mitochondrial aldehyde dehydrogenase, on acute tolerance development and on voluntary ethanol consumption by rats. Acute tolerance developed to motor impairment induced by a dose of ethanol of 2.3 g/kg administered i.p. was evaluated by the tilting plane test. Voluntary ethanol consumption by the rat with free access to a 10% v/v ethanol was measured daily. Both parameters were evaluated in controls, saline‐pretreated and ethanol‐injected rats. One group of rats that received the ethanol injection was pretreated with 3‐amino‐1,2,4‐triazole (AT), a catalase inhibitor, and another group was pretreated with disulfiram, an aldehyde dehydrogenase inhibitor. Brain catalase and aldehyde dehydrogenase activities were measured in both groups of rats. Results show that acute tolerance to motor impairment, as well as ethanol consumption induced by ethanol, appears to be the consequence of acetaldehyde formed centrally during ethanol oxidation via the catalase system, because pretreatment of rats with the catalase inhibitor attenuated the increase in acute tolerance development and the increase in voluntary ethanol consumption in UChB rats that received the acute i.p. dose of ethanol. Moreover, the acetaldehyde metabolizing enzyme also appears to be an important factor in the modulation of acute tolerance development and voluntary ethanol consumption in UChA and UChB rats. The results lead us to propose that the possible mechanism by which the i.p. injection of ethanol to UChB rats induces an increase in ethanol consumption is the development of acute tolerance, where acetaldehyde formed during brain ethanol metabolism via catalase and its subsequent oxidation via aldehyde dehydrogenase have an important role.
Release of neurotransmitters from rat brain nerve terminals after chronic ethanol ingestion: differential effects in cortex and hippocampus
Authors: SABRIÀ JOSEFA , TORRES DÁMASO , PASTÓ MANEL , PERALBA JOSEP , ALLALI‐HASSANI ABDELLAH , PARÉS XAVIER
Published: November 2003

To gain a better insight into the alterations of brain function after chronic ethanol, we measured the release of various neurotransmitters from nerve terminals of cortex and hippocampus isolated from rats chronically fed with ethanol. The K + ‐evoked release of [3 H]acetylcholine (ACh), [3 H]dopamine (DA), [3 H]glutamate (Glu) and [3 H]noradrenaline (NA) was determined in superfused synaptosomes of brain cortex and hippocampus from rats exposed to the Lieber‐DeCarli alcohol liquid diet for 5 weeks. In cortical synaptosomes, chronic ethanol administration did not affect the release of ACh and of DA, while significantly decreasing the release of Glu and NA. The endogenous levels of NA, DA and their metabolites were unchanged. In hippocampal synaptosomes the only effect of chronic alcohol was an increased release of Glu. It can be concluded that at presynaptic level chronic ethanol alters brain neurotransmitter systems selectively. Glutamatergic and noradrenergic nerve terminals from cortex are more vulnerable than those from hippocampus.
Predicting language outcome in infants with autism and pervasive developmental disorder
Authors: Charman Tony , Baron‐Cohen Simon , Swettenham John , Baird Gillian , Drew Auriol , Cox Antony
Published: November 2003

Background: To examine longitudinal associations between diagnosis, joint attention, play and imitation abilities and language outcome in infants with autism and pervasive developmental disorder.

Methods and Procedures: Experimental measures of joint attention, play and imitation were conducted with a sample of infants with autism spectrum disorder at age 20 months. Language outcome was assessed at age 42 months. A within‐group longitudinal correlational design was adopted.

Outcomes and Results: Language at 42 months was higher for children with a diagnosis of pervasive developmental disorder than for children with a diagnosis of autism. Language at follow‐up was also positively associated with performance on experimental measures of joint attention and imitation, but not with performance on experimental measures of play and ‘goal detection’ at 20 months, nor with a non‐verbal intelligence quotient, although these associations were not examined independent of diagnosis. However, floor effects on the measure of play at 20 months and the small sample size limit the conclusions that can be drawn.

Conclusions: Individual differences in infant social‐communication abilities as well as diagnosis may predict language outcome in preschoolers with autism spectrum disorders. Attention should be directed at assessing these skills in 2‐ and 3‐year‐old children referred for a diagnosis of autism spectrum disorder. Imitation and joint attention abilities may be important targets for early intervention.
Narrative skills of children with communication impairments
Authors: Norbury Courtenay Frazier , Bishop Dorothy V. M.
Published: November 2003

Background: Narrative assessment is sensitive to the communication impairments of children with specific language impairment and those with autistic spectrum disorders. Although both groups of children tend to show deficits in narrative, it is unclear whether these deficits are qualitatively different and how language and pragmatic ability may impact on narrative competence. Comparing these two groups of children with children who exhibit pragmatic language impairment without autism may help to clarify these issues.

Aims: This study explored the relationship between structural language ability and pragmatic competence in narrative in children with communication impairments and typically developing children.

Methods and Procedures: Diagnostic status was determined using the Children's Communication Checklist. All children were asked to generate a narrative to the wordless picture book Frog, Where are You? (Mayer 1969). Narratives were analysed according to their global structure, local linguistic structure and the child's ability to provide evaluative comments, especially about mental or emotional states.

Outcomes and Results: No group differences were seen in global structure or evaluation. Children with specific language impairment and autistic disorder made more syntactic errors, and children with autism were significantly more likely to provide ambiguous references in the story. No significant relationships were evident between the Children's Communication Checklist and narrative measures. The complexity of language used was related to evaluation in the clinical groups.

Conclusions: Narrative is a good way of assessing linguistic ability in older children with communication impairments. Core language abilities rather than pragmatic skill or diagnostic status are likely to influence narrative development.
A Diet High in Saturated Fat and Sucrose Alters Glucoregulation and Induces Aortic Fatty Streaks in New Zealand White Rabbits
Authors: Yin Weidong , Yuan Zhonghua , Wang Zongbao , Yang Baotang , Yang Yongzong
Published: November 2003

A new and convenient animal model for studying peripheral
vascular and coronary artery disease in diabetes was established
in this study. Male New Zealand White rabbits weighing approximately
2 kg were divided into 2 groups: a normal control group fed
standard laboratory chow and a diabetogenic diet–fed group received
a high‐fat/high‐sucrose diet. The high‐fat/high‐sucrose diet
(contained 10% lard and 37% sucrose) feeding was maintained for
6 months. Plasma total cholesterol, high‐density lipoprotein (HDL)
cholesterol, triglyceride, superoxide dismutase, nitric oxide, nitric
oxide synthase, insulin, and glucose were quantitated at monthly
or bimonthly intervals. The aortic fatty streak lesions were quantified
following lipid staining with Sudan IV. The aortic samples
were observed by electron microscopy. High plasma triglyceride
and glucose concentrations were induced. At the end of 6 months,
the aortic fatty streak lesions were present in the animals′ vascular
specimens. As far as we know, this is the first report that demonstrates
that New Zealand White rabbits can develop obvious aortic
fatty streaks by feeding a high‐fat/high‐sucrose diet. Our results
suggest that NewZealand White rabbits fed a high‐fat/high‐sucrose
diet would provide a convenient model for studying peripheral vascular
and coronary artery disease in diabetes.
Type 2 Diabetes—Effect of Compensatory Oversecretion as a Reason for β‐Cell Collapse
Authors: Grill Valdemar , Björklund Anneli
Published: November 2003

Insulin secretion declines progressively before and during the
course of type 2 diabetes. Evidence indicates that this process is,
in part, secondary to increased requirement for insulin secretion
that is brought about by insulin resistance and by hyperglycemia.
The effects of over‐secretion extend far beyond a mere reduction
of available insulin stores and may cause not only functional but
also structural damage. The time is ripe for clinical studies, which
explore the therapeutic potential of reducing over‐secretion.
Effects of Aminoguanidine on Lipid and Protein Oxidation in Diabetic Rat Kidneys
Authors: Yavuz Dilek Gogas , Küçükkaya Belgin , Ersöz H. önder , Yalçin A. Süha , Emerk Kaya , Akalin Sema
Published: November 2003

Nonenzymatic glycation of tissue and plasma
proteins may stimulate the production of oxidant
and carbonyl stress in diabetes. The aim
of this study was to evaluate the effects of
aminoguanidine (AG) on lipid peroxidation,
protein oxidation and nitric oxide (NO) release
in diabetic rat kidneys. After induction of diabetes
with streptozotocin, female Wistar rats
were divided into 2 groups. Group DAG (n=9)
rats were given AG hydrogen carbonate (1 g/L)
in drinking water and group D (n=8) was diabetic
control rats given only tap water. Group
H (n=8) was followed as healthy controls. At
the end of an 8 week period, NO release, lipid
and protein oxidation were determined in kidney
tissues. NO release was significantly lower
in diabetic rats compared with healthy controls
(p<0.05). Lipid peroxidation was significantly
high in group D (3.9 ± 0.3 nmol MDA/g tissue)
compared with the group DAG (2.6 ± 0.1 nmol
MDA/g tissue, p<0.01) and group H (2.4 ± 0.2
nmol MDA/g tissue). Protein oxidation was
significantly higher in diabetics than healthy
controls (563.8 ± 23.9, 655.8 ± 7.2 , 431.5 ±
8.8 mmol carbonyl / g tissue for group DAG, D
and H, respectively, p< 0.05). A positive correlation
between albuminuria and thiobarbituric
acid reactive substance (TBARS) levels (r= 0.54,p<0.005) and carbonyl content (r=0.70,
p<0.0005) in kidney homogenate were
observed.

Although AG treatment had no effect on NO
release, it significantly decreased lipid peroxidation
in diabetic rat cortices. Consequently
increased lipid peroxidation ‐as well as‐ protein
oxidation could be involved in the pathogenesis
of diabetic albuminuria.
Potentiation of Mitogenic Activity of Platelet‐Derived Growth Factor by Physiological Concentrations of Insulin via the MAP Kinase Cascade in Rat A10 Vascular Smooth Muscle Cells
Authors: Yamada Hitomi , Tsushima Toshio , Murakami Hitomi , Uchigata Yasuko , Iwamoto Yasuhiko
Published: November 2003

Hyperinsulinemia has been shown to be
associated with diabetic angiopathy. Migration
and proliferation of vascular smooth muscle
cells (VSMC) are the processes required for the
development of atherosclerosis. In this study,
we attempted to determine whether insulin
affects mitogenic signaling induced by plateletderived
growth factor (PDGF) in a rat VSMC
cell line (A10 cells). PDGF stimulated DNA
synthesis which was totally dependent on Ras,
because transfection of dominant negative Ras
resulted in complete loss of PDGF‐stimulated
DNA synthesis. Initiation of DNA synthesis
was preceded by activation of Raf‐1, MEK and
MAP kinases (Erk 1 and Erk2). Treatment of
the cells with PD98059, an inhibitor of MAPK
kinase (MEK) attenuated but did not abolish
PDGF‐stimulated DNA synthesis, suggesting
that MAPK is required but not essential for
DNA synthesis. PDGF also stimulated phosphorylation
of protein kinase B (Akt/PKB) and
p70 S6Kinase (p70S6K) in a wortmannin‐sensitive
manner. Rapamycin, an inhibitor of
p70S6K, markedly suppressed DNA synthesis.
Low concentrations of insulin (1‐10 nmol/l)
alone showed little mitogenic activity and no
significant effect on MAPK activity. However,
the presence of insulin enhanced both DNA
synthesis and MAPK activation by PDGF. The
enhancing effect of insulin was not seen in cells
treated with PD98059. Insulin was without
effect on PDGF‐stimulated activations of protein kinase B (Akt/PKB) and p70S6K. We conclude
that insulin, at pathophysiologically relevant
concentrations, potentiates the PDGFstimulated
DNA synthesis, at least in part, by
potentiating activation of the MAPK cascade.
These results are consistent with the notion
that hyperinsulinemia is a risk factor for the
development of atherosclerosis.
Novel Form of Adaptation in Mouse Retinal Rods Speeds Recovery of Phototransduction
Authors: Krispel Claudia M. , Chen Ching-Kang , Simon Melvin I. , Burns Marie E.
Published: November 2003

Photoreceptors of the retina adapt to ambient light in a manner that allows them to detect changes in illumination over an enormous range of intensities. We have discovered a novel form of adaptation in mouse rods that persists long after the light has been extinguished and the rod's circulating dark current has returned. Electrophysiological recordings from individual rods showed that the time that a bright flash response remained in saturation was significantly shorter if the rod had been previously exposed to bright light. This persistent adaptation did not decrease the rate of rise of the response and therefore cannot be attributed to a decrease in the gain of transduction. Instead, this adaptation was accompanied by a marked speeding of the recovery of the response, suggesting that the step that rate-limits recovery had been accelerated. Experiments on knockout rods in which the identity of the rate-limiting step is known suggest that this adaptive acceleration results from a speeding of G protein/effector deactivation.