bluuebunny/crossref_metadata_2025 huggingface dataset:
Firearms Availability and Suicide
Authors: Brent David A. , Bridge Jeffrey
Published: July 2003

Case-control studies show an association between firearms in the home and completed suicide, with higher risks associated with loaded guns and handguns in the home. Quasi-experimental studies also show a relationship between greater restrictiveness of gun control laws and lower suicide rates by firearms and overall, although some studies fail to show an effect or show method substitution. A prospective study shows that handgun purchasers have an elevated risk for suicide for up to 6 years after the purchase. Relatively few studies have examined the impact of intervention to encourage families to store guns safely or remove firearms from the home on suicidal outcome.
School Approaches to Youth Suicide Prevention
Authors: Kalafat John
Published: July 2003

Universal and indicated school-based suicide prevention programs are described, including conceptual bases, program components, ineffective approaches, and evaluation outcomes. Controlled evaluations of second-generation programs report positive outcomes, including positive changes in knowledge, attitudes toward suicide, intent to seek help, and reduction of suicidal feelings. Two comprehensive programs reported reduced suicide rates in targeted counties subsequent to program dissemination. Caution is raised concerning variations in program quality. Currently, some model universal and indicated programs show promise and are candidates for more research on mediating and moderating variables and program outcomes.
Suicide in College Students
Authors: Haas Ann Pollinger , Hendin Herbert , Mann J. John
Published: July 2003

Despite substantial attention to the problem of suicide among college students over the past several decades, reports on the extent of the problem have been largely inconclusive. This article reviews the findings of major studies of college suicide, noting how variations in campus and student characteristics, as well as inconsistencies in the way student suicides are defined and measured, have limited comparison of conclusions. Current evidence is reviewed that points to significant mental health problems on college campuses and suggests the need for outreach programs to identify students at risk for suicide and encourage them into treatment. One such program under development by the American Foundation for Suicide Prevention is described in detail. Problems related to its implementation are identified and discussed, notably the reluctance of many university officials to know the actual identities of suicidal students.
Sexual Minority Youth and Suicide Risk
Authors: Russell Stephen T.
Published: July 2003

Numerous studies spanning the past quarter century have used varied designs and methods in multiple settings and have consistently demonstrated that sexual minority youth are among those most likely to report suicidality (suicidal thoughts, plans, and attempts). This article reviews the methodological challenges that have defined and limited research in this area, including issues of sampling, the measurement of sexual minority status, and the measurement of suicide risk. Attention is then given to risk and protective factors for suicide among sexual minority youth. Normative risk and protective factors, those common to all youth, and risk and protective factors unique to sexual minority youth are reviewed. In closing, attention is given to the state of suicide prevention and intervention efforts that target sexual minority youth, along with recommendations for further research.
Cognitive Therapy for Adolescent and Young Adult Suicide Attempters
Authors: Henriques Gregg , Beck Aaron T. , Brown Gregory K.
Published: July 2003

Although there is a large and increasing literature on biological, psychological, and social characteristics of suicidal behavior, there is a relative lack of information dealing specifically with how to treat suicidal adolescents and young adults. A 10-session cognitive intervention for older adolescents and young adults who have attempted suicide is described in detail. A novel element of the therapy is that the treatment can be applied to individuals exhibiting suicidal behavior, regardless of psychiatric diagnosis. Information is provided about how to structure therapy sessions and how therapy progresses through the early, middle, and later stages. New, specific strategies are offered for helping suicidal individuals learn to cope more adaptively with crises and distress.
Media Contagion and Suicide Among the Young
Authors: Gould Madelyn , Jamieson Patrick , Romer Daniel
Published: July 2003

Research continues to demonstrate that vulnerable youth are susceptible to the influence of reports and portrayals of suicide in the mass media. The evidence is stronger for the influence of reports in the news media than in fictional formats. However, several studies have found dramatic effects of televised portrayals that have led to increased rates of suicide and suicide attempts using the same methods displayed in the shows. Recent content analyses of newspapers and films in the United States reveal substantial opportunity for exposure to suicide, especially among young victims. One approach to reducing the harmful effects of media portrayals is to educate journalists and media programmers about ways to present suicide so that imitation will be minimized and help-seeking encouraged. Recently released recommendations for journalists are attached as an appendix. Similar initiatives with the entertainment industry would be highly desirable.
The Sociological and Anthropological Study of Globalization and Localization
Authors: Schuerkens Ulrike
Published: July 2003

This article sketches the development of the topic of globalization and localization within sociology and anthropology during the last 20 years and summarizes research findings. Subsequently, a number of topics for further enquiry are outlined. It is argued that the mapping of global cultural flows is still at an impressionistic stage and will be supplemented by systematic procedures. This will lead - as the contributors to this publication show - to a more differentiated assessment of global cultural homogenization. The article tackles the problems of cultural convergence, non-western globalization and alternative modernities. Cultural exchanges that circumvent `the West' have not yet received sufficient attention. A cross-culturally valid notion of modernity may help in conceptualization. Finally, the question whether humanity is gaining or losing in the globalization process calls for further investigation.
Culture, Identity and Hegemony: The Body in a Global Age
Authors: Langman Lauren
Published: July 2003

The article argues that capitalism has reconstituted itself as a globalized system of transnational corporations and that a universalized, mass-mediated, consumer culture sustains its legitimacy in face of massive redistributions of wealth. The author argues that consumerism and privatized hedonism provide, on one hand, the basis for profits as well as identities that sustain hegemony, and, on the other hand, the ideological control of culture to produce willing consent to the new economic reality. The article shows that a ludic carnival culture of the grotesque has emerged that has fostered a migration of subjectivity from political economy and concerns with the social to lifestyles and identities of inversion and transgression. The author demonstrates his argument by an analysis of rituals of cultural consumption such as football, carnival and extreme forms of bodily adornment: tatoos, piercings and scarification. This `colonization' of the consciousness by the culture industry, mediated through the body, has led to an erosion of political communities and a waning of critical reason.
`Ethnicity is Everywhere': On Globalization and the Transformation of Cultural Identity
Authors: Berking Helmuth
Published: July 2003

This article seeks to discover a possible relationship between processes of globalization and changing modes of constructing cultural identities. After briefly examining the pros and cons related to the widespread thesis of the end of the nation-state, the article describes the spatial reconfiguration of the nation-state focusing on the separation of territoriality, sovereignty and identity. Finally, the author links these spatial reconfigurations with constructions of cultural identities which seem more and more to rely on and play with strategies of ethnicization. The basic presumption is that globalization and ethnicization may be two aspects of the same phenomenon.
Multiple Modernity, Nationalism and Religion: A Global Perspective
Authors: Spohn Willfried
Published: July 2003

The article develops a multiple modernity perspective that attempts to explain the global rise of religious and ethnic nationalism as a result of the contemporary worldwide multiple modernization processes with civilization-specific constellations of nation-state formation, democratization and religious change as well as secularization in the different world regions. For this purpose, the article first re-examines the exceptional case of Europe, showing that also here the dominating forms of secular nationalism entail, in differing combinations, also Christian components. Then a comparative tour through the various non-European civilizations is undertaken from the Americas to the Islamic civilization, Israel, Africa, India and Pakistan as well as Japan and China, demonstrating the varying religious and secular constellations of nationalism and national identity formation. As a result, the contemporary rise of religious and ethnic nationalism is explained as a reaction to the previous authoritarian imposition of the Western European model of state secularism within predominantly religious and multiethnic societies.
Structural Change in Western Africa as a Legacy of European Colonialism: The Labour System in Ghana and the Ivory Coast
Authors: Schuerkens Ulrike
Published: July 2003

In this article, the author analyses the transformation of the labour system in the Ivory Coast and in Ghana. The empirical research was undertaken during two field trips in urban centres (Abidjan and Accra). The transformation of the labour system is shown on a macro- and a micro-level: the structural change of the economy on the one hand, and life-stories of men in their fifties and sixties on the other. This comparative research project shows the symbiosis which resulted from the confrontation of global and local elements. The results demonstrate processes of globalization which took place in urban areas in many social fields, and with a lesser impact in rural areas. In the 1940s and 1950s, a restructuration of the labour system happened which the life-stories of the older men demonstrate. This paradigmatic analysis of transformation processes shows the mixtures, the intertwining and the embedding of these local West African societies in a global history.
Glocalization of Law: Environmental Justice, World Bank, NGOs and the Cunning State in India
Authors: Randeria Shalini
Published: July 2003

This article delineates trajectories of the glocalization of law and maps the changing contours of legal pluralism using empirical material on World Bank financed infrastructure and biodiversity projects in India. The role of international institutions, social movements and NGOs, which challenge the monopoly of the state over the production of law and the definition of the common good, is analysed with reference to conflicts over privatization of natural resources, struggles against forced displacement and loss of livelihood as well as the complaints on behalf of indigenous communities before the World Bank Inspection Panel. It is argued that despite scattered sovereignties in the new architecture of global governance, the state remains a central albeit contested terrain. Its pivotal role in selectively transposing conditionalities, law and policies into the national arena as well as its strategies to avoid accountability are foregrounded against the attempts by civil society actors to use national and international legal platforms to enforce compliance with environmental and human rights standards.
Knowledge between Globalization and Localization: The Dynamics of Female Spaces in Ghana
Authors: Müller Christine
Published: July 2003

The global turn towards knowledge societies indicates that within contemporary processes of globalization, knowledge has become the major factor of present and future social change. As creators of a special institutionalized frame of interaction, women in Ghana have organized themselves from the rural village to the national level and beyond, by using the worldwide women's web. Within these glocalized links related to different locations of knowledge production, new knowledge repertoires are constantly built up, connecting everyday knowledge with scientific knowledge and with global discourses. The formation of an epistemic culture on development is connected with a critical discourse on gender relations in societal institutions. Women are expanding their spaces by politicizing knowledge, and, on the local level, by bridging old spaces in filling them with new elements aiming at social transformations. The enquiry focuses on the newly evolving spaces of negotiation of knowledge, such as meetings, forums, conferences and networking, which are spaces of knowledge circulation, distribution, articulation and politicization across distances.
Transnational Migration and Development in Postwar Peripheral States: An Examination of Guatemalan and Salvadoran State Linkages with Their Migrant Populations in Los Angeles
Authors: Popkin Eric
Published: July 2003

This article examines politically motivated migration from El Salvador and Guatemala to the US. The author argues that the nature of these countries' insertion into the global economy require these states to devote considerable resources to establish relationships with their respective emigrant populations in the US. The Salvadoran immigrant hometown organizations have become incorporated into home country local development efforts at a higher level than their Guatemalan counterparts due to a more developed organizational structure, higher levels of interaction/collaboration with government officials, and a higher degree of democracy achieved in El Salvador as compared to Guatemala. Both Salvadoran and Guatemalan immigrant organizations gain some leverage over the process of local development and politics in these countries. However, government policies that attempt to channel remittances will contribute little to productive development at the local level in the absence of state-supported macroeconomic policies aimed at reducing socioeconomic disparities in Guatemala and El Salvador.
Particularizing the Global: Reception of Foreign Direct Investment in Slovenia
Authors: Bandelj Nina
Published: July 2003

Exploring the relationship between global forces and local practices, this article examines the reception of global investment flows in an East European transition country, Slovenia. Using content analysis of legal regulations and policies, the article investigates how global pressures impact the official foreign investment policy regime in Slovenia. Examples of foreign investment transactions illustrate economic practice. The analysis shows that yielding to the universalizing pressures of neoliberalism creates convergence in official foreign investment policies. In practice, however, economic actors involved in foreign investment transactions resist and particularize global processes on the basis of their network ties, political alliances and cultural affinities. Overall, the study emphasizes the social and political embeddedness of economic processes and substantiates how the decoupling of formal policies and local practices sustains the coexistence of uniformity and diversity.
Disintegration and Resilience of Agrarian Societies in Africa - the Importance of Social and Genetic Resources: A Case Study on the Reception of Urban War Refugees in the South of Guinea-Bissau
Authors: Temudo Marina Padrão , Schiefer Ulrich
Published: July 2003

The disintegration of African agrarian societies is partly caused by the dissipative economy of development aid and becomes more visible in wartime. The resilience of agrarian societies constitutes thus an important resource for the whole country. Their capacity to maintain stability and a productive agricultural potential can ensure the survival of urban populations driven from the cities in time of war. The potential for reconstruction of these agrarian societies after catastrophes depends on internal - genetic as well as social - resources and on their capacity to mobilize and to integrate external resources. The thesis of this article is that the usual package of emergency relief, rehabilitation and rural development aid does not form the most adequate approach to traumatized societies. The authors show that in the south of Guinea-Bissau during and after the armed conflict, the established interethnic network of rural populations was able to shelter a large number of urban refugees for a considerable time.
Paradise Lost? Social Change and Fa'afafine in Samoa
Authors: Schmidt Johanna
Published: July 2003

Geographically isolated in the centre of the Pacific, Samoa has only recently become fully incorporated into economic and social forms of globalization. The past few decades have seen significant shifts in the construction and expression of gender and sexuality. Among the groups most affected are the fa'afafine, biological males who express feminine gender identities. These transgendered identities were `traditionally' most often enacted through labour, but fa'afafine subjectivities currently incorporate more and more western discourses of gender and sexuality. In this article, the author examines how westernization has resulted in the social marginalization of fa'afafine, but has also allowed access to a wider range of `imagined lives' than previously available. While globalization has inevitably and irrevocably changed the local life-worlds of Samoa, and thus the enactment of fa'afafine identities, the author argues that fa'afafine continue to enact culturally unique identities that incorporate aspects of both western and Samoan gender and sexuality conceptions.
Autochthonous Australian Syncretism
Authors: Morgan George
Published: July 2003

Most Aboriginal Australians now live in cities and towns amid the accoutrements of modernity and the cultural influences of globalization. They practise a way of life very different from that of their ancestors. Nevertheless, the dominant public representations of Aboriginal people and culture are traditional and primordial. Most autochthonous urban dwellers embrace these representations even though they bear little resemblance to their own lives. Stuart Hall and Paul Gilroy have criticized the tendency to reduce ethnicity to an essence or grounding tradition. They advocate viewing ethnic cultures as mixtures combining both residual and contemporary elements. However, many Aboriginal people embrace essentialist collective symbols in order to escape the stigma of `fringe dwelling', of being caught between autochthonous and colonial societies and belonging to neither.
The Changing Meaning of Work: Restructuring in the Former Coalmining Communities of the South Wales Valleys
Authors: Parry Jane
Published: July 2003

This article examines how industrial restructuring has effected social transformation in terms of the type and meaning of work in the post-closure context of the South Wales Valleys. A conceptual framework is developed which considers a range of experiences within and outside the paid labour market. This theorizes social movement and stasis, and analyses the resources and priorities invoked in pursuing different types of work. Restructuring has weakened occupation's role as a primary means of social cohesion in former coalmining communities, and labour market experiences have become more diffuse and dynamic. It is argued that while paid work remains important to some individuals, this overlooks the experiences of those excluded from or constrained in their economic activity. In order to understand these social solidarities it is necessary to employ less restrictive definitions of work, and examine the meaningful labour embedded in a more interconnected set of relationships and structures.
Mobilization and Change in a Trade Union Setting: Environment, Structures and Action
Authors: Foley Janice R.
Published: July 2003

This case study, based on data collected from archival and interview sources, describes the variable efficacy over a 24-year period of a union-based women's committee. A theoretical model was developed that identified environmental factors, union and committee structures, and committee characteristics as variables that might affect the committee's effectiveness. Outcomes of three types were considered: structural changes that would benefit women, increased female participation in union decision making, and improved clauses in the collective agreement especially relevant to women. The study shows that while environmental factors and formal structures play an important role in achieving mobilization and change, the actions of the Social Movement Organization (SMO) itself, and of all the parties potentially affected by the SMO, are equally critical. The social movement literature complements the industrial relations and feminist organizational literatures in explaining the processes involved in successful collective action.
Apprenticeship in the `Golden Age': Were Youth Transitions Really Smooth and Unproblematic Back Then?
Authors: Vickerstaff Sarah A.
Published: July 2003

This article challenges the taken-for-granted orthodoxy of contemporary youth studies that young people's transitions from school to work have become extended and fragmented in comparison to those of people who left school in the period 1945-75. It is argued that the characterization of the earlier period as a `golden age' of smooth, unproblematic, one-step transitions from school into the labour market misrepresents the experiences of people in that period and in particular, fails to understand the specificity of the apprenticeship model of transition which was experienced by around 35 percent of the male school-leaving age cohort. The discussion examines the experience of people in the period 1945-75 by reference to 30 interviews undertaken by the author with people who did apprenticeships in a variety of trades.
Trolley Dolly or Skilled Emotion Manager? Moving on from Hochschild's Managed Heart
Authors: Bolton Sharon C. , Boyd Carol
Published: July 2003

This article examines emotion in organizations and the emotion management skills organizational actors possess. While Hochschild's (1983) seminal work on emotional labour is perhaps one of the greatest contributions to our understanding of emotion in organizations, this article challenges key tenets of Hochschild's thesis and goes on to offer an evolved analysis of emotional labour and alternative conceptualizations of organizational emotionality. Using comparable data, this article depicts airline cabin crews as skilled emotion managers who are able to juggle and synthesize different types of emotion work dependent on situational demands. In addition, the capacity for cabin crews to resist and modify the demands of management and customers acts to further contradict Hochschild's claim regarding the `transmutation' of feelings.
Motherhood, Paid Work and Partnering: Values and Theories
Authors: Duncan Simon , Edwards Rosalind , Reynolds Tracey , alldred Pam
Published: July 2003

The male breadwinner model, which dominated both policy assumptions and social ideals in the post-war welfare state, is increasingly being supplanted by an adult worker family model. In this new model, both men and women are assumed to be primarily workers in the labour market, who as fathers and mothers pool their earned income in supporting children. In this article we assess this assumption. First, we examine the gendered moral rationalities of particular social groups of partnered mothers, defined in terms of class, conventionality, ethnicity and sexuality, about how mothering is combined with paid work, and how time and labour is allocated with their partners. Second, in the light of this empirical research, we examine three leading approaches to understanding change and decision making in families - new household economics, individualization in late modernity, and `post-modern moral negotiation'. We conclude that both the empirical and theoretical assumptions of the adult worker model are severely limited.
Women, Work and Equal Opportunities in Post-Communist Transition
Authors: Pollert Anna
Published: July 2003

This article examines gender, work and equal opportunities (EO) in five central eastern European (CEE) candidates to an enlarged European Union (EU): the Czech Republic, Hungary, Poland, Slovenia and Slovakia. It demonstrates how capitalist transition has eroded women's Communist economic and social legacy, and considers implications for EO of the EU enlargement process. Analysis of decline begins with an outline of women's position under Communism, showing both similarities in gender inequality to those of capitalism, but also significant differences and advances. Post-transition is then examined in terms of the UN Gender Development Index, women's loss of social support, their decline in labour force participation and changes in employment and political representation. A limitation in available data is lack of information on unregulated employment and informal work - both major developments in CEE. The objective picture is then set against subjective responses to change - a key factor in gender EO prospects. Finally, developments in EO monitoring and enforcement agencies are reviewed, with the conclusion drawing these levels of enquiry together to assess the possibilities of EU enlargement as a spur to greater commitment to gender equality in CEE.
`Perdóneme que se lo diga, pero vuelve usted a faltar a la verdad, señor González': Form and Function of Politic Verbal Behaviour in Face-to-Face Spanish Political Debates
Authors: Blas-Arroyo José Luis
Published: July 2003

Following some previous lines of thought held by the author on the role of politeness and related phenomena in face-to-face electoral debates, this article deals with a series of linguistic devices frequently used by participants in this adversarial genre, and commonly characterized as mitigated aggression, in order to determine their main strategic values in the context of both current politics and the mass media spectacle. By making use of a methodology which combines both qualitative and quantitative analysis, it is demonstrated that the meaning and context in which these resources appear in electoral debate often contradict their literal meaning, and hence weaken the moderating function which is operative in non-adversarial genres. This, as well as other structural facts discussed in the article, allows us to understand some apparent contradictions in the fact that more aggressive participants could make the greatest use of both polite and impolite strategies; or that apparently polite strategies appear mainly in the core phases of the debate where aggressiveness and rudeness are the norm, and much less in the peripheral parts, where the dialectic war tones down.
`A Phantom Menace and the New Apartheid': The Social Construction of Asylum-Seekers in the United Kingdom
Authors: Lynn Nick , Lea Susan
Published: July 2003

A succession of well-publicized incidents in Britain, and elsewhere, has highlighted the dilemma of refugees and seekers of asylum. A number of desperate human tragedies allied to some very dubious institutional practices and decisions have been a cause for concern. Drawing upon that vast corpus of information we call `common knowledge', together with other more exclusive sources of knowledge, British national newspapers and their readers, among others, are involved in the social construction of asylum-seekers. Ideas of citizenship, identity and Nation-hood are employed within a variety of discursive and rhetorical strategies that form part of an `elite' discourse, one that contributes to a `new Apartheid'. This article presents a discursive and rhetorical analysis of letters written to British national newspapers by members of the public. Asylum-seekers find themselves [re]positioned and contrasted with a variety of other social groups in such a way as to justify disregarding some of the central tenets of British democracy. Dissenting voices and a `counter' discourse are evident although very much a minority. It is argued that applied discursive work is necessary to bolster resistance and deconstruct the `new Apartheid'.
Branding and Discourse: The Case of Cosmopolitan
Authors: Machin David , Thornborrow Joanna
Published: July 2003

Like fast food and fizzy drinks, discourses are globally marketed by powerful multinational corporations. In this article we look at discourses about women which are distributed around the planet by the 44 different national versions of Cosmopolitan. These versions are localized, but still transmit the Cosmo brand, resulting in similarities between the versions. We apply a multimodal discourse analytic approach to understand this global branding, the type of analysis which is lacking in existing accounts of globalization, and ask, what exactly does remain the same across the localized versions? What this article offers is not an analysis of the magazine per se, but an analysis of the discourses that underpin it. We show how the magazine creates a fantasy world through the use of low modality images, which allow a particular kind of agency, mainly sex, to signify power. The multimodal realizations of Cosmo discourse enable women to signify their alignment with the Cosmo world through such things as the cafes they frequent, the clothes they wear and the way that they dance. Cosmo presents these not as real, but as playful fantasies, something which existing literature on women's magazines has missed. In these fantasies, women act alone and rely on acts of seduction and social manoeuvreing, rather than on intellect, to act in and on the world.
Communities of Practice at Work: Gender, Facework and the Power of Habitus at an All-Female Police Station and a Feminist Crisis Intervention Center in Brazil
Authors: Ostermann Ana Cristina
Published: July 2003

This article investigates discursive practices and their relations to gender, facework and workplace in two all-female institutions that address violence against women in Brazil. By investigating 26 audio-taped interactions with victims of domestic violence at an all-female police station and a feminist activist crisis intervention center, this study contributes to the understanding of intragender differences. The findings suggest that gender does not predict interactional patterns; instead these interactional patterns are best understood as reflecting the gendered communities of practice from which the professionals are drawn. Police officers attend less to the victims' needs by providing minimal feedback when the victims report their problems. They are four times more likely than feminists to provide non-responses to the victims' turns, as well as four times more likely to change topics in their responses to the victims' turns. The linguistic and ethnographic findings suggest that the more cooperative strategies used by the feminists are not as `valuable' for police officers in the symbolic market of their habitus. In the police system, a more affiliative way of relating to the female clientele seems to work against the female police officers and their aims, by reifying the essentialist ideology that affiliative interactions are `natural' to women, or that is all females can offer in the police system.
Ideological Imagination: Intertextual and Correlational Metaphors in Political Discourse
Authors: Zinken Jörg
Published: July 2003

This article explores the role that metaphors play in the ideological interpretation of events. Research in cognitive linguistics has brought rich evidence of the enormous influence that body experience has on (metaphorical) conceptualization. However, the role of the cultural net in which an individual is embedded has mostly been neglected. As a step towards the integration of cultural experience into the experientialist framework in cognitive metaphor research I propose to differentiate two ideal types of motivation for metaphor: correlation and intertextuality. Evidence for the important role that intertextual metaphors play in ideological discourse comes from an analysis of Polish newspaper discourse on the tenth anniversary of the end of communism.
Overexpression of P-glycoprotein in K562 cells does not confer resistance to the growth inhibitory effects of imatinib (STI571) in vitro
Authors: Ferrao Petranel T. , Frost Michelle J. , Siah Shoo-Peng , Ashman Leonie K.
Published: July 2003

Elevated expression of multidrug efflux pumps such as P-glycoprotein (Pgp) have been associated with resistance to cytotoxic drugs used in the treatment of leukemias and other cancers. Imatinib mesylate (STI-571 or Gleevec) is a potent inhibitor of the BCR/ABL and c-KIT tyrosine kinases. It has displayed considerable efficacy in treatment of patients with Philadelphia-positive acute lymphoblastic leukemia and chronic myelogenous leukemia and those with gastrointestinal stromal tumors (GISTs). However, recently imatinib-resistant relapse has emerged as a significant problem. Although a major cause of resistance appears to be point mutation in the kinase domain of the target enzyme, the potential contribution of elevated multidrug efflux activity has not been systematically evaluated. The imatinib-sensitive human leukemic cell line K562, which is dependent on the activity of BCR/ABL for survival and growth, provides a convenient system for evaluating modulation of drug activity. By expressing Pgp at high levels in these cells, we have demonstrated that this pump provides minimal protection against cell growth inhibition and apoptosis induced by imatinib. In contrast, overexpression of Bcl-xL, which blocks apoptosis, resulted in partial protection against the drug. We conclude that Pgp up-regulation is not likely to be a significant contributor to imatinib resistance. (Blood. 2003;102:4499-4503)
The human anti-CD30 antibody 5F11 shows in vitro and in vivo activity against malignant lymphoma
Authors: Borchmann Peter , Treml John F. , Hansen Hinrich , Gottstein Claudia , Schnell Roland , Staak Oliver , Zhang Hui-fen , Davis Thomas , Keler Tibor , Diehl Volker , Graziano Robert F. , Engert Andreas
Published: July 2003

CD30 is a promising target for antibody-based immunotherapy of Hodgkin lymphoma (HL) and anaplastic large cell lymphoma. To overcome the limitations from currently available murine anti-CD30 monoclonal antibodies (mAbs), a new fully human anti-CD30 antibody was generated. Binding properties were evaluated by recombinant CD30 capture enzyme-linked immunosorbent assay (ELISA) and fluorescence-activated cell-sorter (FACS) flow cytometry. Activity of this new mAb was assessed in vitro using growth inhibition and antibody-dependent cellular cytotoxicity (ADCC) assays on several cell lines. In vivo activity was determined in a solid as well as in a disseminated xenografted model of HL in severe combined immunodeficiency (SCID) mice. The mAb 5F11 showed specific binding to CD30 (cluster A). The ADCC assays indicated dose-dependent lysis of L540 cells when 5F11 was combined with human effector cells. Upon cross-linking in vitro, 5F11 inhibited the growth of CD30-expressing cell lines. In vivo, treatment with 5F11 induced a marked growth delay or even a complete regression of established xenografted HL in SCID mice. In the disseminated HL model, a high proportion of 5F11-treated mice experienced long-term survival. The new human anti-CD30 monoclonal antibody 5F11 shows promise as a means of CD30-targeted immunotherapy of malignant lymphomas. Based on these results, a clinical phase 1 study in patients with refractory CD30+ lymphoma has been initiated. (Blood. 2003;102:3737-3742)
Nodular lymphocyte-predominant Hodgkin lymphoma with nodules resembling T-cell/histiocyte-rich B-cell lymphoma: differential diagnosis between nodular lymphocyte-predominant Hodgkin lymphoma and T-cell/histiocyte-rich B-cell lymphoma
Authors: Boudová Ludmila , Torlakovic Emina , Delabie Jan , Reimer Peter , Pfistner Beate , Wiedenmann Sabine , Diehl Volker , Müller-Hermelink Hans-Konrad , Rüdiger Thomas
Published: July 2003

Nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) and T-cell/histiocyte-rich B-cell lymphoma (T/HRBCL) are distinct tumors and are treated differently. They are linked by a morphologic and probably a biologic continuum, which renders the differential diagnosis difficult. To develop criteria to distinguish the entities along the morphologic continuum, we correlated the lymph node architecture and immunophenotype of both tumor cells and reactive components of 235 neoplasms in the spectrum of NLPHL and T/HRBCL with clinical data. Two hundred and eighteen cases fitted the World Health Organization (WHO) criteria of NLPHL (139) or T/HRBCL (79). While tumor cells in both entities were immunophenotypically similar, background composition differed: in NLPHL small B cells and CD3+CD4+CD57+ T cells were common, whereas in T/HRBCL, CD8+ cytotoxic T cells and histiocytes dominated. Follicular dendritic cells (FDCs) formed expanded meshworks in NLPHL, whereas they were absent in T/HRBCL. Seventeen cases represented a gray zone: within FDC meshworks, neoplastic B cells resided in a background depleted of small B cells but rich in T cells and histiocytes. Tumor cells either were loosely scattered or formed clusters, thus resembling areas of either T/HRBCL or inflammatory diffuse large BCL (DLBCL) within the nodules. Patients with these NLPHLs with T-cell/histiocyte-rich nodules presented at a high stage and with B symptoms, as in T/HRBCL, but had an excellent survival, as in NLPHL. This morphologic pattern suggests a biologic continuum between NLPHL and T/HRBCL. (Blood. 2003;102:3753-3758)
Inhibition of C5a-induced inflammation with preserved C5b-9-mediated bactericidal activity in a human whole blood model of meningococcal sepsis
Authors: Sprong Tom , Brandtzaeg Petter , Fung Michael , Pharo Anne M. , Høiby E. Arne , Michaelsen Terje E. , Aase Audun , van der Meer Jos W. M. , van Deuren Marcel , Mollnes Tom E.
Published: July 2003

The complement system plays an important role in the initial defense against Neisseria meningitidis. In contrast, uncontrolled activation in meningococcal sepsis contributes to the development of tissue damage and shock. In a novel human whole blood model of meningococcal sepsis, we studied the effect of complement inhibition on inflammation and bacterial killing. Monoclonal antibodies (mAbs) blocking lectin and alternative pathways inhibited complement activation by N meningitidis and oxidative burst induced in granulocytes and monocytes. Oxidative burst was critically dependent on CD11b/CD18 (CR3) expression but not on Fcγ-receptors. Specific inhibition of C5a using mAb 137-26 binding the C5a moiety of C5 before cleavage prohibited CR3 up-regulation, phagocytosis, and oxidative burst but had no effect on C5b-9 (TCC) formation, lysis, and bacterial killing. An mAb-blocking cleavage of C5, preventing C5a and TCC formation, showed the same effect on CR3, phagocytosis, and oxidative burst as the anti-C5a mAb but additionally inhibited TCC formation, lysis, and bacterial killing, consistent with a C5b-9-dependent killing mechanism. In conclusion, the anti-C5a mAb 137-26 inhibits the potentially harmful effects of N meningitidis-induced C5a formation while preserving complement-mediated bacterial killing. We suggest that this may be an attractive approach for the treatment of meningococcal sepsis. (Blood. 2003;102:3702-3710)
Expression of the IRTA1 receptor identifies intraepithelial and subepithelial marginal zone B cells of the mucosa-associated lymphoid tissue (MALT)
Authors: Falini Brunangelo , Tiacci Enrico , Pucciarini Alessandra , Bigerna Barbara , Kurth Julia , Hatzivassiliou Georgia , Droetto Sara , Galletti Barbara Verducci , Gambacorta Marcello , Orazi Attilio , Pasqualucci Laura , Miller Ira , Küppers Ralf , Dalla-Favera Riccardo , Cattoretti Giorgio
Published: July 2003

IRTA1 (immunoglobulin superfamily receptor translocation-associated 1) is a novel surface B-cell receptor related to Fc receptors, inhibitory receptor superfamily (IRS), and cell adhesion molecule (CAM) family members and we mapped for the first time its distribution in human lymphoid tissues, using newly generated specific antibodies. IRTA1 was selectively and consistently expressed by a B-cell population located underneath and within the tonsil epithelium and dome epithelium of Peyer patches (regarded as the anatomic equivalents of marginal zone). Similarly, in mucosa-associated lymphoid tissue (MALT) lymphomas IRTA1 was mainly expressed by tumor cells involved in lympho-epithelial lesions. In contrast, no or a low number of IRTA1+ cells was usually observed in the marginal zone of mesenteric lymph nodes and spleen. Interestingly, monocytoid B cells in reactive lymph nodes were strongly IRTA1+. Tonsil IRTA1+ cells expressed the memory B-cell marker CD27 but not mantle cell-, germinal center-, and plasma cell-associated molecules. Polymerase chain reaction (PCR) analysis of single tonsil IRTA1+ cells showed they represent a mixed B-cell population carrying mostly mutated, but also unmutated, IgV genes. The immunohistochemical finding in the tonsil epithelial areas of aggregates of IRTA1+ B cells closely adjacent to plasma cells surrounding small vessels suggests antigen-triggered in situ proliferation/differentiation of memory IRTA1+ cells into plasma cells. Collectively, these results suggest a role of IRTA1 in the immune function of B cells within epithelia. (Blood. 2003;102: 3684-3692)
Long-term follow-up of IgM monoclonal gammopathy of undetermined significance
Authors: Kyle Robert A. , Therneau Terry M. , Rajkumar S. Vincent , Remstein Ellen D. , Offord Janice R. , Larson Dirk R. , Plevak Matthew F. , Melton L. Joseph
Published: July 2003

Little effort has been made to quantitate adverse outcomes of monoclonal gammopathy of undetermined significance (MGUS) of the immunoglobulin M (IgM) class, which progresses to lymphoma or Waldenström macroglobulinemia, whereas IgA and IgG MGUS progress to multiple myeloma, primary amyloidosis (AL), or a related plasma cell disorder. From 1960 to 1994, IgM MGUS was diagnosed in 213 patients in southeastern Minnesota. The end point was progression to lymphoma or a related disorder, as assessed with the Kaplan-Meier method. The 213 patients were followed up for 1567 person-years (median, 6.3 years per patient). Lymphoma developed in 17 patients (relative risk [RR], 14.8), Waldenström macroglobulinemia in 6 (RR, 262), primary amyloidosis in 3 (RR, 16.3), and chronic lymphocytic leukemia in 3 (RR, 5.7). The relative risk of progression was 16-fold higher in the patients with IgM MGUS than in the white population of the Iowa Surveillance, Epidemiology, and End Results Program. Cumulative incidence of progression was 10% at 5 years, 18% at 10 years, and 24% at 15 years. On multivariate analysis, the serum monoclonal protein and serum albumin concentrations at diagnosis were the only risk factors for progression to lymphoma or a related disorder. Risk for progression to lymphoma or a related disorder at 10 years after the diagnosis of MGUS was 14% with an initial monoclonal protein concentration of 0.5 g/dL or less, 26% with 1.5 g/dL, 34% for 2.0 g/dL, and 41% for more than 2.5 g/dL. (Blood. 2003;102:3759-3764)
Lipid raft-associated protein sorting in exosomes
Authors: de Gassart Aude , Géminard Charles , Février Benoit , Raposo Graça , Vidal Michel
Published: July 2003

Exosomes are small membrane vesicles secreted by cells upon fusion of multivesicular endosomes with the cell surface. The mechanisms underlying the specific sorting of proteins in exosomal membranes are far from being unraveled. We demonstrate here, using different cells, that some molecules are released in the extracellular medium via their association with lipid raft domains of the exosomal membrane. Various typical raft-associated molecules could be detected by immunoblot in exosomes and Triton X-100-insoluble fractions isolated from exosomes of different origins. Partial localization of major histocompatibility complex (MHC) class II molecules with detergent-resistant fractions isolated from Daudi-secreted exosomes was demonstrated by immunoblot and confirmed by electron microscopy colocalization of MHC class II molecules and ganglioside GM1. Moreover, we found that exosome-associated Lyn (1) had a lower molecular weight compared with Lyn detected in cell-isolated detergent-resistant domains, (2) was absent from the Triton X-100-insoluble fraction isolated from exosomes, and (3) had lost its partitioning capacity in Triton X-114. Exosomal Lyn is probably cleaved by a caspase-3-like activity contained in secreted vesicles. All together, the data highlight the presence of lipid microdomains in exosomal membranes and suggest their participation in vesicle formation and structure, as well as the direct implication of exosomes in regulatory mechanisms. (Blood. 2003;102:4336-4344)
Prognostic value of apoptotic cells and infiltrating neutrophils in graft-versus-host disease of the gastrointestinal tract in humans: TNF and Fas expression
Authors: Socié Gérard , Mary Jean-Yves , Lemann Marc , Daneshpouy Marjan , Guardiola Philippe , Meignin Véronique , Ades Lionel , Esperou Hélène , Ribaud Patricia , Devergie Agnès , Gluckman Eliane , Ameisen Jean-Claude , Janin Anne
Published: July 2003

The gastrointestinal (GI) tract is a major target in graft-versus-host disease (GvHD). In rodents both tumor necrosis factor (TNF) and Fas-dependent apoptosis have been shown to play a major role in GvHD lesions, but data in humans on TNF and Fas in situ expression are scarce. More recently, the role of non-T cells as GvHD effectors has also been suggested in experimental models. Here we report a detailed quantitative pathologic analysis in 95 patients who underwent gastroduodenal biopsy. This analysis included characterization and quantification of the cellular infiltrate, TNF, TNF receptors, and Fas in situ expression analyses and quantification of apoptotic cell numbers. TNF was expressed in all biopsies and it was highly specific for acute GvHD. In multivariate analysis, including pathologic factors only, increased early transplantrelated mortality (TRM) was associated with the presence of more than 20 neutrophils per field. Factors affecting early and late TRM were then assessed by multivariate analyses including both pathologic and clinical factors. Increased day-90 TRM was associated with the presence of more than 5 apoptotic bodies per field within the cellular infiltrate, and with stage II or higher acute liver GvHD. One-year TRM associated with the same 2 factors and with chronic GvHD.