bluuebunny/crossref_metadata_2025 huggingface dataset:
Reimagining the Boundaries of the Nation: Politics and the Development of Ideas on Minority Rights
Authors: Deets Stephen
Published: July 2006

The collapse of communism reshaped European debates on minority rights. By the 1980s, the different institutionalizations of turn-of-the-century perspectives created an ideational divide between East and West. Since 1989, Western norms have not simply transferred East, as intellectuals and politicians in the region challenged and reinterpreted the norms in novel ways. Fifteen years later, European minority norms are elaborated in much greater detail than ever before, but consensus on core issues remains elusive. The article first explores the roots of this ideational divide and how recent trafficking of ideas between East and West Europeans has caused both to reexamine their core assumptions on the rights of minority communities, particularly with regards to individualism, collective autonomy, and justice. The second part examines how these controversies over norm interpretation appear in minority policy debates in Eastern Europe, including minority autonomy, education, and the Hungarian Status Law.
Social Contract and Perceived Justice of Workplace Practices to Cope With Financial Crisis
Authors: Aycan Zeynep , Kabasakal Hayat
Published: July 2006

This study examined the influence of type of social contract (i.e., transactional vs. relational) on how organizations responded to financial crisis in Turkey. Moreover, it examined the role of social contracts in moderating the relationship between type of response strategies organizations used and justice perceptions of employees. Participants were 132 full-time employees from 85 different business organizations. Results showed that as the social contract tended to be more transactional, there was less focus on cost-cutting strategies in production, marketing, and financial practices (PMF), whereas when the social contract tended to be more relational, there was less focus on cost-cutting strategies in human resource management practices (HRM). Cost-cutting in PMF areas yielded low procedural justice when employees were in organizations that were high rather than low on transactional contracts, whereas cost-cuttingin HRM areas resulted in low distributive justice when employees were in organizations that were high rather than low on relational contracts.
Perceived Support as a Mediator of the Relationship Between Justice and Trust
Authors: Stinglhamber Florence , Cremer David De , Mercken Liesbeth
Published: July 2006

Using a sample of 212 employees, the authors examined the relationships between employees’ perceptions of procedural and interactional justice and their subsequent trust in their organization and supervisor. Specifically, the authors predicted that the link between procedural justice and trust in organization would be mediated by perceived organizational support (POS), whereas the relationship between interactional justice and trust in supervisor would be mediated by perceived supervisor support (PSS). In line with predictions, the authors found that POS partially mediated the effect of procedural justice on trust in organization and PSS partially mediated the impact of interactional justice on trust in supervisor. These findings suggest that employees develop relationships with their supervisors that are distinct from those relationships they experience with their organization.
The Impact of Gender Similarity, Racial Similarity, and Work Culture on Family-Supportive Supervision
Authors: Foley Sharon , Linnehan Frank , Greenhaus Jeffrey H. , Weer Christy H.
Published: July 2006

This study examines the relationship between demographic similarity in the supervisor-subordinate dyad and family-supportive supervision. The authors found that supervisors provided more family support to subordinates who were similar in either gender or race than to those subordinates who were dissimilar. In addition, family-supportive supervision was highest when subordinates were similar to supervisors in both gender and race. A family-supportive organizational culture was positively related to family-supportive supervision, although contrary to what was predicted, it did not attenuate the effects of gender similarity and racial similarity on family-supportive supervision. Implications of the findings and directions for future research are discussed.
Contextual and Individual Difference Factors Predicting Individuals’ Desire to Provide Upward Feedback
Authors: Kudisch Jeffrey D. , Fortunato Vincent J. , Smith Austin F. R.
Published: July 2006

This study examined the influence of several factors on employees’ desire to provide upward feedback to their supervisors on an impending upward feedback system. Self-report data from 153 university employees indicated that the desire to provide upward feedback related negatively to fear of retaliation and positively to role appropriateness, perceived usefulness, rater self-efficacy, leader-member exchange, knowledge of upward feedback, top management support, coworker support, and feedback-seeking behavior. The authors also found that perceived usefulness mediated the relationships among fear of retaliation, leader-member exchange, top management support, coworker support, and knowledge of upward feedback with desire to provide upward feedback. Theoretical and practical implications are discussed.
Culturally Sensitive Treatment of Metabolic Syndrome in Asian Americans
Authors: Ozawa Cynthia , Alpert Patricia T. , Miller Sally K.
Published: July 2006

Very little is known about the health care needs of Asian Americans and Pacific Islanders (AAPIs). This is not surprising, because AAPIs comprise subgroups that represent more than 20 countries, and research of disease processes among AAPIs is usually not analyzed according to individual subgroups. The purpose of this article is to familiarize the health care professional with the nuances of metabolic syndrome in Asian Americans, utilizing a case study approach to illustrate the importance of providing culturally competent health care.
Agency, Initiative, and Obstacles to Health Among Indigenous Immigrant Women From Oaxaca, Mexico
Authors: McGuire Sr. Sharon
Published: July 2006

Multi-ethnic, indigenous Mexican immigrants from Oaxaca, the poorest state in Mexico, have engaged in transnational migration to the United States in increasing numbers since the early 1980s and the economic crisis in Mexico. Indigenous women migrants constitute a significant segment of this population, significant to nursing because of their major role in watching over the health of their families. This article reports selected research findings of an exploratory study of the migration and health experiences of Mexican indigenous women from Oaxaca that focus on their strengths while recognizing their vulnerabilities for health problems. Implications for nursing practice and praxis are identified.
Health-Promoting Lifestyle and Diabetes Knowledge in Hispanic American Adults
Authors: Chilton Linda , Hu Jie , Wallace Debra C.
Published: July 2006

This study examined the relationships among demographics, a health-promoting lifestyle, and diabetes knowledge. A descriptive study was conducted in a convenience sample of 40 Hispanic American adults. Participants were recruited from Hispanic churches in the southeastern United States. The Health Promoting Lifestyle Profile II and the Diabetes Knowledge Questionnaire were used to assess participants’ health-promoting lifestyle and diabetes knowledge. Participants had low levels of a health-promoting lifestyle and a strong deficiency in diabetes knowledge. Income was found to be associated with physical activity lifestyle. Age and education were significantly related to diabetes knowledge. This study suggested that community health nurses should assess and educate Hispanic American adults for a health-promoting lifestyle and diabetes knowledge and use appropriate methods of teaching with low-literacy and audiovisual materials to provide culturally specific care to this vulnerable group.
Advances in Conceptualization of Cultural Care and Cultural Competence in Nursing: An Initial Assessment
Authors: Xu Yu , Shelton Deborah , Polifroni E. Carol , Anderson Elizabeth
Published: July 2006

This article reviews advances in conceptualization of cultural care and cultural competence in the nursing literature. First, three evaluative criteria are set forth (i.e., practice, education, and research). Second, the published conceptualizations of cultural care and cultural competence are assessed based on the three criteria. The review suggests that conceptualizations of cultural care and cultural competence have made noted progress in the past few decades both in quantitative and qualitative terms. Based on this initial assessment, areas for further development are suggested to facilitate the continued advances in conceptualization of cultural care and cultural competence in the future.
Cultural Competence and Organizational Change: Lasting Results of an Institutional Linkage
Authors: Doutrich Dawn , Storey Marni
Published: July 2006

This article reports on lasting changes that evolved as a result of a project that linked Washington State University Vancouver (WSU Vancouver) and Clark County Health Department (CCHD) in Washington. Through a federally funded project, WSU Vancouver and CCHD united to improve public health curricular relevance, nursing students' public health practicum experience, cultural competence in the classroom and workplace, and overall interinstitutional collaboration. Lasting changes from the project include (a) a strengthened relationship between WSU Vancouver and CCHD; (b) the development and interactive use of the Welcome to Public Health orientation module based upon narrative themes from the evaluative research that are now available for CCHD public health nurses and new students to public health; and (c) institutionalization of cultural competence throughout the health department and the university, including a collegewide effort toward multicultural transformation in courses and changes in hiring processes in the health department.
A Community and Academic Partnership to Improve Breast Cancer Outcomes for African Americans on Long Island: A Ministry of Health Dissemination
Authors: Schoenfeld Elinor Randi , Davis Margaret V. , Kovach John S. , Mchunguzi Cheryl , Nies Mary A.
Published: July 2006

Communities on Long Island have a widespread interest and a pressing need for approaches to promote early detection and prompt treatment of breast cancer given the overall high rates of morbidity and mortality in the region. African American communities have a special concern given that population's disproportionately high mortality rates from this disease. This article presents a success story for the development of a collaborative network creating a community, government, and academic partnership to address this disparity in African American women on Long Island. The development process utilized focus group and case story methodologies to work with the community to assess needs. Formal educational programs, community events, and a navigational program were then provided to encourage and assist in breast cancer screening and follow-up when needed. Detailed here is a description of the authors’ program development and the far-reaching community impact such a program can have once implemented.
"Securing Space"
Authors: Spierenburg Marja , Wels Harry
Published: July 2006

This article provides a brief history of the use of maps and fences in wildlife conservation. Analysis of the promotional materials of one of the main promoters of Transfrontier Conservation Areas (TFCAs) in southern Africa, the Peace Parks Foundation, reveals the importance of mapping as a planning and promotion tool. These maps, however, appear to be quite silent about the communities that are supposed to benefit from the TFCAs. The fences around wildlife areas are resented by local communities because they prevent them from harvesting natural resources “on the other side.” Local communities also object to the fences because of their symbolic meaning and instrumentality, shown in warfare and policies “to control and divide.” Conservation organizations nowadays use the symbol of the fence to communicate their change in policy toward local communities: stressing the need to move “beyond the fences” by involving local communities in the management of protected areas and using these to promote economic development.
Absence, "Removal," and Everyday Life in the Diasporic City
Authors: Burman Jenny
Published: July 2006

This article is concerned with the “removal” (the Canadian government policy word for deportation) of noncitizens rendered suspect in the climate of 9-1-1 Islamophobia, who are detained and/or deported without specific charges, and with the impact of removals on the landscape of a cosmopolitan city such as Montréal. When people are removed, their absence leaves an imprint; the intimates they have left behind restructure their everyday lives around that imprint. But how is the imprint of absence transposed into presence, and how does that presence affect the city as a site that lets flourish or prohibits radical difference and hybridization? The article focuses on the examples of family members of detainees or deportees and antideportation activist networks.
From Cyber to Hybrid
Authors: de Souza e Silva Adriana
Published: July 2006

Hybrid spaces arise when virtual communities (chats, multiuser domains, and massively multi-player online role-playing games), previously enacted in what was conceptualized as cyberspace, migrate to physical spaces because of the use of mobile technologies as interfaces. Mobile interfaces such as cell phones allow users to be constantly connected to the Internet while walking through urban spaces. This article defines hybrid spaces in the light of three major shifts in the interaction between mobile technology and spaces. First, it investigates how the use of mobile technologies as connection interfaces blurs the traditional borders between physical and digital spaces. Second, it argues that the shift from static to mobile interfaces brings social networks into physical spaces. Finally, it explores how urban spaces are reconfigured when they become hybrid spaces. For this purpose, hybrid spaces are conceptualized according to three distinct but overlapping trends: hybrid spaces as connected spaces, as mobile spaces, and as social spaces.
Productive Pleasures
Authors: Martin Randy
Published: July 2006

As ephemeral as the social effects of dance may be, still more elusive are the embodiments of a critical public. The publics so dear to democratic practice so often appear only metonymically in rules that govern speech. Or they may seem to be inchoate yearnings whose only possible realization lies in formal representation. To attend to actual circuits of participation, one needs to account for the practical capacities that allow bodies to gather in public and move toward desirable ends. The imbrication of state and daily life in Cuba makes study of the affinities between formal and informal political domains particularly robust. Contemporary Cuban dance in a variety of venues—proscenium stages, streets, clubs, and houses—is used to grasp how pleasure meets critique where a social economy for corporeal mobilization is in evidence.
Face City
Authors: McGrath Brian
Published: July 2006

Face City examines Bangkok through cinematic “close-ups” and meditative states, conjuring a new, nonorganic city body. The human face is a relatively immobile receptive surface for incoming sensations rather than outgoing action. Facialized, the body is understood as a stable sensory-motor apparatus rather than an assemblage of organs for action. In Thailand, Theravada Buddhist meditation practice has taught practitioners to still their bodies and minds to reach states of attentiveness to sensory-motor chains of stimulation and reaction. The cinematic close-up and meditative attentiveness facializes objects and space. The facialization of the city is staged here in a Vietnam War-era hotel in the heart of Bangkok. The Vietnam War era in Thailand introduced American mass cinema culture and new building types along with thousands of soldiers on rest and recreation. In this new transnational space, Face City became possible, one that intersects America and Thailand as states of mind.
Out of the Dark Room
Authors: Clover Darlene E.
Published: July 2006

Participatory photography places the medium of the camera into the hands of learners to democratize the image-making dynamic and give them the power to show and speak their own realities. This study examines two participatory photography projects in Canada and how they contribute to the lives of disadvantaged women and children. With Through the Eyes of Children, a freestanding, photographic montage was created by 10 homeless children in Victoria, British Columbia. In Toronto, 8 socially disadvantaged women chose photography to explore issues of power and identity in exhibitions of their work and in a calendar,Portraits of Resistance: Celebrating Women's Lives. Although there are limitations to this method of transformative education, the project empowered the photographers to become and be activist artists; see and speak publicly through image, symbol, and metaphor; and creatively address dichotomies, such as that between the private and the public.
Transforming Thinking Amongst British African Caribbeans as an Academically Based Community Service Contribution
Authors: Gordon Gloria
Published: July 2006

This article reports on an ongoing action research project that focusses on the transformation of the British African Caribbean (BAC) lived experience through the strategic use of the educational process to meet their particular needs. The analytical framework that has been developed to achieve this outcome consists of four key academic ideas: academically based community service and transformative learning principles, conscious bicultural competence, Black socialisation, and social quality. Details are provided about the origins of the project idea and the BAC experience, as well as about the research process and its underlying principles. Reflections and comments from group participants help provide an overall picture of how the transformative process of the project was achieved, notwithstanding the challenges faced by both the initiating researcher and the project participants.
Dialogue Meetings as Nonformal Adult Education in a Municipal Context
Authors: Wilhelmson Lena
Published: July 2006

This article discusses the prospects of fostering dialogue-competent behaviour, an important ingredient for supporting learning in discourse. The theory of transformative learning is the theoretical departure for a study of group discussions in a municipal context. A qualitative approach was used; individual interviews and field experiments with dialogue meetings were the main data collection methods. Several conditions and processes were identified as important for learning possibilities in small-group communication: participant perspectives, dialogue competence, discursive power, gender conversational styles, discourse types and prospects for learning, and perspective change. These findings have implications for individual and collective transformative learning. Single individuals could, through their own reflections in, as well as on, group conversation, experience personal transformative learning. Collective transformative learning is seen as an active and explicit transmutation that forges several different perspectives into a new alloy of knowledge. One conclusion is that with some training in dialogue competence, individuals and groups may be more likely to experience transformative learning.
Southern Community Women Teach a New Generation Lessons of Leadership for Social Change
Authors: Williams Isa D.
Published: July 2006

Service-learning can profoundly alter students' perceptions of leadership, often clouded by negative stereotypes of racial and ethnic, gender, and social-class differences that dis-advantage one group while advantaging another. This article presents findings from a 5-year study conducted at a women's college linking program design to students' perceptions of women's leadership for social justice. Before venturing into community organizations, female students complete a preassessment designed to measure definitions and perceptions of leadership. Students then engage in a program design emphasizing discontinuous experiences. Students also read and respond to multiple, often contradictory texts regarding women's leadership and social change while engaging with female community leaders often of differing racial and ethnic and social-class backgrounds. At semester's end, a postassessment is administered. Although the preand postassessments in this study found no change in students' perceptions of gender differences in leadership effectiveness, their definitions of leadership and their perceptions of women's style of leadership evolved consistently with the program's intent.
Teachers and Technology
Authors: Kitchenham Andrew
Published: July 2006

This article reports the findings of a study conducted with 10 teachers who experienced perspective transformations as they learned to use educational technology and integrate it into their classroom teaching. The research used a mixed-methodology approach and combined data from reflective journals, a teacher questionnaire, semistructured interviews, and research field notes. Analysis of these data identified themes related to perspective transformations. Sample participant comments are presented to illustrate the themes and corresponding perspective transformation elements.
Solute transport via the new permeability pathways in Plasmodium falciparum–infected human red blood cells is not consistent with a simple single-channel model
Authors: Staines Henry M. , Ashmore Stephanie , Felgate Hannah , Moore Jessica , Powell Trevor , Ellory J. Clive
Published: July 2006

After infection of a red blood cell (RBC), the malaria parasite, Plasmodium falciparum, increases the permeability of the host's plasma membrane by inducing new permeability pathways (NPPs). Single-channel patch-clamp experiments have shown the presence in infected RBCs of novel anion-selective channel types with low open-state probabilities at positive membrane potentials. These channels have been postulated to form the NPPs. Here, we have used a range of transport techniques to study whether electroneutral solutes use these channels or altered/separate pathways. Transport of the electroneutral solute sorbitol via the NPPs was found to increase by a small but significant amount after gross membrane depolarization. This is inconsistent with transport via a channel with a reduced open-state probability at positive membrane potentials. As has been demonstrated previously for parasite-induced anion currents, sorbitol transport in infected RBCs was found to be sensitive to the presence of bovine serum albumin (BSA). However, it remains to be shown whether the effect is due to serum/BSA altering a single channel type or activating a new pathway. In addition, the study highlights problems that can occur when using different transport techniques to study the NPPs.
Immunostimulatory oligonucleotide-induced metaphase cytogenetics detect chromosomal aberrations in 80% of CLL patients: a study of 132 CLL cases with correlation to FISH, IgVH status, and CD38 expression
Authors: Dicker Frank , Schnittger Susanne , Haferlach Torsten , Kern Wolfgang , Schoch Claudia
Published: July 2006

Compared with fluorescence in situ hybridization (FISH), conventional metaphase cytogenetics play only a minor prognostic role in chronic lymphocytic leukemia (CLL) so far, due to technical problems resulting from limited proliferation of CLL cells in vitro. Here, we present a simple method for in vitro stimulation of CLL cells that overcomes this limitation. In our unselected patient population, 125 of 132 cases could be successfully stimulated for metaphase generation by culture with the immunostimulatory CpG-oligonucleotide DSP30 plus interleukin 2. Of 125 cases, 101 showed chromosomal aberrations. The aberration rate is comparable to the rate detected by parallel interphase FISH. In 47 patients, conventional cytogenetics detected additional aberrations not detected by FISH analysis. A complex aberrant karyotype, defined as one having at least 3 aberrations, was detected in 30 of 125 patients, compared with only one such case as defined by FISH. Conventional cytogenetics frequently detected balanced and unbalanced translocations. A significant correlation of the poor-prognosis unmutated IgVH status with unbalanced translocations and of the likewise poor-prognosis CD38 expression to balanced translocations and complex aberrant karyotype was found. We demonstrate that FISH analysis underestimates the complexity of chromosomal aberrations in CLL. Therefore, conventional cytogenetics may define subgroups of patients with high risk of progression.
Continuous signaling via PI3K isoforms β and γ is required for platelet ADP receptor function in dynamic thrombus stabilization
Authors: Cosemans Judith M. E. M. , Munnix Imke C. A. , Wetzker Reinhard , Heller Regine , Jackson Shaun P. , Heemskerk Johan W. M.
Published: July 2006

Signaling from collagen and G protein–coupled receptors leads to platelet adhesion and subsequent thrombus formation. Paracrine agonists such as ADP, thromboxane, and Gas6 are required for platelet aggregate formation. We hypothesized that thrombi are intrinsically unstable structures and that their stabilization requires persistent paracrine activity and continuous signaling, maintaining integrin αIIbβ3 activation. Here, we studied the disassembly of human and murine thrombi formed on collagen under high shear conditions. Platelet aggregates rapidly disintegrated (1) in the absence of fibrinogen-containing plasma; (2) by blocking or inhibiting αIIbβ3; (3) by blocking P2Y12 receptors; (4) by suppression of phosphoinositide 3-kinase (PI3K) β. In murine blood, absence of PI3Kγ led to formation of unstable thrombi, leading to dissociation of multiplatelet aggregates. In addition, blocking PI3Kβ delayed initial thrombus formation and reduced individual platelet-platelet contact. Similarly without flow, agonist-induced aggregation was reversed by late suppression of P2Y12 or PI3K isoforms, resulting in single platelets that had inactivated αIIbβ3 and no longer bound fibrinogen. Together, the data indicate that continuous outside-in signaling via P2Y12 and both PI3Kβ and PI3Kγ isoforms is required for perpetuated αIIbβ3 activation and maintenance of a platelet aggregate. This novel concept of intrinsic, dynamic thrombus instability gives possibilities for the use of antiplatelet therapy.
Strong selection of virus-specific cytotoxic CD4+ T-cell clones during primary human cytomegalovirus infection
Authors: van Leeuwen Ester M. M. , Remmerswaal Ester B. M. , Heemskerk Mirjam H. M. , ten Berge Ineke J. M. , van Lier Rene A. W.
Published: July 2006

To obtain insight into human CD4+ T cell differentiation and selection in vivo, we longitudinally studied cytomegalovirus (CMV)–specific CD4+ T cells after primary infection. Early in infection, CMV-specific CD4+ T cells have the appearance of interferon γ (IFNγ)–producing T-helper 1 (TH1) type cells, whereas during latency a large population of CMV-specific CD4+CD28– T cells emerges with immediate cytotoxic capacity. We demonstrate that CD4+CD28– T cells could lyse CMV antigen–expressing target cells in a class II–dependent manner. To clarify the clonal relationship between early and late CMV-specific CD4+ T cells, we determined their Vβ usage and CDR3 sequences. The T-cell receptor β (TCRβ) diversity in the early CMV-specific CD4+ T-cell population was high in contrast to the use of a very restricted set of TCRβ sequences in latent infection. T-cell clones found in the late CMV-specific CD4+ T-cell population could not be retrieved from the early CD4+ T-cell population, or were present only at a low frequency. The observation that dominant CMV-specific CD4+ clones during latency were only poorly represented in the acute phase suggests that after the initial control of the virus strong selection and/or priming of novel clones takes place in persistent infections in humans.
Pentraxin 3 protects from MCMV infection and reactivation through TLR sensing pathways leading to IRF3 activation
Authors: Bozza Silvia , Bistoni Francesco , Gaziano Roberta , Pitzurra Lucia , Zelante Teresa , Bonifazi Pierluigi , Perruccio Katia , Bellocchio Silvia , Neri Mariella , Iorio Anna Maria , Salvatori Giovanni , De Santis Rita , Calvitti Mario , Doni Andrea , Garlanda Cecilia , Mantovani Alberto , Romani Luigina
Published: July 2006

Reactivation of latent human cytomegalovirus (HCMV) following allogeneic transplantation is a major cause of morbidity and mortality and predisposes to severe complications, including superinfection by Aspergillus species (spp). Antimicrobial polypeptides, including defensins and mannan-binding lectin, are known to block viral fusion by cross-linking sugars on cell surface. Pentraxin 3 (PTX3), a member of the long pentraxin family, successfully restored antifungal immunity in experimental hematopoietic transplantation. We assessed here whether PTX3 binds HCMV and murine virus (MCMV) and the impact on viral infectivity and superinfection in vivo. We found that PTX3 bound both viruses, reduced viral entry and infectivity in vitro, and protected from MCMV primary infection and reactivation as well as Aspergillus superinfection. This occurred through the activation of interferon (IFN) regulatory factor 3 (IRF3) in dendritic cells via the TLR9/MyD88-independent viral recognition sensing and the promotion of the interleukin-12 (IL-12)/IFN-γ–dependent effector pathway.
Cytogenetics and age are major determinants of outcome in intensively treated acute myeloid leukemia patients older than 60 years: results from AMLSG trial AML HD98-B
Authors: Fröhling Stefan , Schlenk Richard F. , Kayser Sabine , Morhardt Martina , Benner Axel , Döhner Konstanze , Döhner Hartmut ,   for the German-Austrian AML Study Group
Published: July 2006

To assess the prognostic impact of cytogenetics in elderly patients with acute myeloid leukemia (AML) receiving intensive induction and consolidation treatment according to a single protocol specifically designed for patients above age 60, pretreatment samples from 361 patients registered for the AML HD98-B trial of the German-Austrian AML Study Group were analyzed by chromosome banding and fluorescence in situ hybridization, and cytogenetic findings were correlated with outcome. Using a proportional hazards model with backward selection, 3 prognostic subgroups were identified based on the influence of cytogenetic abnormalities on overall survival (OS): low-risk, t(15;17), and inv(16) in 25 of 361 patients (7%); standard-risk, normal karyotype, t(8;21), t(11q23), +8 within a noncomplex karyotype, and +11 within a noncomplex karyotype in 208 of 361 patients (58%); high-risk, all other aberrations in 128 of 361 patients (35%). On multivariate analysis, high-risk cytogenetics (hazard ratio [HR], 2.24) and age above 70 years (HR, 2.34) were independent prognostic factors affecting OS, and stratification according to these parameters demonstrated that a large subgroup of patients (55%), characterized by age 70 or older or high-risk cytogenetics, or both, had very unfavorable treatment results despite intensive chemotherapy. Thus, karyotype and age are major determinants of outcome in elderly patients with AML.
A randomized phase 2 study of lenalidomide therapy for patients with relapsed or relapsed and refractory multiple myeloma
Authors: Richardson Paul G. , Blood Emily , Mitsiades Constantine S. , Jagannath Sundar , Zeldenrust Steven R. , Alsina Melissa , Schlossman Robert L. , Rajkumar S. Vincent , Desikan K. Raman , Hideshima Teru , Munshi Nikhil C. , Kelly-Colson Kathleen , Doss Deborah , McKenney Mary L. , Gorelik Svetlana , Warren Diane , Freeman Andrea , Rich Rebecca , Wu Anfang , Olesnyckyj Marta , Wride Kenton , Dalton William S. , Zeldis Jerome , Knight Robert , Weller Edie , Anderson Kenneth C.
Published: July 2006

This multicenter, open-label, randomized phase 2 study evaluated 2 dose regimens of lenalidomide for relapsed, refractory myeloma. Seventy patients were randomized to receive either 30 mg once-daily or 15 mg twice-daily oral lenalidomide for 21 days of every 28-day cycle. Patients with progressive or stable disease after 2 cycles received dexamethasone. Analysis of the first 70 patients showed increased grade 3/4 myelo-suppression in patients receiving 15 mg twice daily (41% versus 13%, P = .03). An additional 32 patients received 30 mg once daily. Responses were evaluated according to European Group for Blood and Marrow Transplantation (EBMT) criteria. Overall response rate (complete, partial, or minor) to lenalidomide alone was 25% (24% for once-daily and 29% for twice-daily lenalidomide). Median overall survival in 30-mg once-daily and twice-daily groups was 28 and 27 months, respectively. Median progression-free survival was 7.7 months on once-daily versus 3.9 months on twice-daily lenalidomide (P = .2). Dexamethasone was added in 68 patients and 29% responded. Time to first occurrence of clinically significant grade 3/4 myelosuppression was shorter in the twice-daily group (1.8 vs 5.5 months, P = .05). Significant peripheral neuropathy and deep vein thrombosis each occurred in only 3%. Lenalidomide is active and well tolerated in relapsed, refractory myeloma, with the 30-mg once-daily regimen providing the basis for future studies as monotherapy and with dexamethasone.
Hematopoietic origin of fibroblasts/myofibroblasts: its pathophysiologic implications
Authors: Ogawa Makio , LaRue Amanda C. , Drake Christopher J.
Published: July 2006

Tissue fibroblasts/myofibroblasts play a key role in growth factor secretion, matrix deposition, and matrix degradation, and therefore are important in many pathologic processes. Regarding the origin of tissue fibroblasts/myofibroblasts, a number of recent in vivo transplantation studies have suggested the bone marrow as the source of fibroblasts/myofibroblasts in liver, intestine, skin, and lung. Because bone marrow cells are thought to contain 2 types of stem cells (ie, hematopoietic stem cells [HSCs] and mesenchymal stem cells), it is important to determine which type of stem cells is the source of fibroblasts/myofibroblasts. To address this issue, we have carried out a series of studies of tissue reconstitution by single HSCs. By transplanting clones derived from single HSCs expressing transgenic enhanced green fluorescent protein, we found that fibroblasts/myofibroblasts in many organs and tissues are derived from HSCs. This brief note summarizes these findings and discusses clinical and experimental perspectives generated by this newly identified differentiation pathway of HSCs.
Newly identified c-KIT receptor tyrosine kinase ITD in childhood AML induces ligand-independent growth and is responsive to a synergistic effect of imatinib and rapamycin
Authors: Corbacioglu Selim , Kilic Mehtap , Westhoff Mike-Andrew , Reinhardt Dirk , Fulda Simone , Debatin Klaus-Michael
Published: July 2006

Activating mutations of c-KIT lead to ligand-independent growth. Internal tandem duplications (ITDs) of exon 11, which encodes the juxtamembrane domain (JMD), are constitutively activating mutations found in 7% of gastrointestinal stromal tumors (GISTs) but have not been described in childhood acute myeloid leukemia (AML). DNA and cDNA from 60 children with AML were screened by polymerase chain reaction (PCR) for mutations of the JMD. A complex ITD (kit cITD) involving exon 11 and exon 12 was identified with a relative frequency of 7% (4/60). The human kit cITDs were inserted into the murine c-Kit backbone and expressed in Ba/F3 cells. KIT cITD induced factorindependent growth and apoptosis resistance, and exhibited constitutive autophosphorylation. KIT cITD constitutively activated the PI3K/AKT pathway and phosphorylated STAT1, STAT3, STAT5, and SHP-2. Imatinib (IM) or rapamycin (Rap) led to complete inhibition of growth, with IC50 values at nanomolar levels. IM and Rap synergistically inhibited growth and surmounted KIT cITD-induced apoptosis resistance. IM but not LY294002 inhibited phosphorylation of STAT3 and STAT5, suggesting aberrant cross talk between PI3K- and STAT-activating pathways. The findings presented may have immediate therapeutic impact for a subgroup of childhood AML-expressing c-KIT mutations.
EphB2 and EphB4 receptors forward signaling promotes SDF-1–induced endothelial cell chemotaxis and branching remodeling
Authors: Salvucci Ombretta , de la Luz Sierra Maria , Martina Jose A. , McCormick Peter J. , Tosato Giovanna
Published: July 2006

The complex molecular mechanisms that drive endothelial cell movement and the formation of new vessels are poorly understood and require further investigation. Eph receptor tyrosine kinases and their membrane-anchored ephrin ligands regulate cell movements mostly by cell–cell contact, whereas the G-protein–coupled receptor CXCR4 and its unique SDF-1 chemokine ligand regulate cell movement mostly through soluble gradients. By using biochemical and functional approaches, we investigated how ephrinB and SDF-1 orchestrate endothelial cell movement and morphogenesis into capillary-like structures. We describe how endogenous EphB2 and EphB4 signaling are required for the formation of extracellular matrix–dependent capillary-like structures in primary human endothelial cells. We further demonstrate that EphB2 and EphB4 activation enhance SDF-1–induced signaling and chemotaxis that are also required for extracellular matrix–dependent endothelial cell clustering. These results support a model in which SDF-1 gradients first promote endothelial cell clustering and then EphB2 and EphB4 critically contribute to subsequent cell movement and alignment into cord-like structures. This study reveals a requirement for endogenous Eph signaling in endothelial cell morphogenic processes, uncovers a novel link between EphB forward signaling and SDF-1–induced signaling, and demonstrates a mechanism for cooperative regulation of endothelial cell movement.
Tumor suppressor p16 methylation in multiple myeloma: biological and clinical implications
Authors: Gonzalez-Paz Natalia , Chng Wee J. , McClure Rebecca F. , Blood Emily , Oken Martin M. , Ness Brian Van , James C. David , Kurtin Paul J. , Henderson Kimberly , Ahmann Gregory J. , Gertz Morie , Lacy Martha , Dispenzieri Angela , Greipp Philip R. , Fonseca Rafael
Published: July 2006

The biological and clinical implications of p16 gene methylation in multiple myeloma (MM) are still unclear despite previous studies. In this comprehensive study, using methylation-specific PCR (MS-PCR), we show that p16 methylation is relatively common and occurs in monoclonal gammopathy of undetermined significance (MGUS; n = 17), smoldering multiple myeloma (SMM; n = 40), and MM (n = 522) at a prevalence of 24%, 28%, and 34%, respectively. However, p16 methylation does not appear to affect gene expression level. In a large cohort of patients with long-term follow-up information (n = 439), there was no difference in overall survival between patients with or without p16 methylation. We also found no association between p16 methylation and the main cytogenetic categories, although it was more common among patients with 17p13.1 deletions (p53 locus), a genetic progression event in MM. In addition, p16 methylation has no apparent effect on the cycle because there was also no difference in the plasma cell labeling index (a direct measurement of proliferation) between patients with and without p16 methylation. Our results question a major role for p16 methylation in the oncogenesis of the PC neoplasm, and we now believe p16 methylation may be a marker for overall epigenetic changes associated with disease progression, with no obvious direct biological or clinical consequences.
Upper airway dynamics during negative expiratory pressure in apneic and non-apneic awake snorers
Authors: Ferretti A , Giampiccolo P , Redolfi S , Mondini S , Cirignotta F , Cavalli A , Tantucci C
Published: July 2006

Background

The ability of negative expiratory pressure (NEP) technique to differentiate between awake snorers with and without obstructive sleep apnea-hypopnea (OSAH) was investigated.

Methods

Forty-eight subjects with sleep disordered breathing (SDB) and 7 healthy subjects, as non-snorer controls, underwent the NEP application of -5 and -7 cmH2O in the seated and supine position during wakefulness, after performing a sleep study. The upper airway collapsibility was assessed by computing the volume exhaled during the first 0.5 sec. (V,NEP0.5) and 1 sec. (V,NEP1) following the NEP start.

Results

Patients with severe (AHI ≥ 30) (n = 19) and mild-to-moderate (AHI <30 and >5) (n = 15) OSAH had lower V,NEP0.5 (340 ± 88 ml) as compared to snorers (AHI ≤ 5) (n = 14) (427 ± 101 ml; p < 0.01) and controls (n = 7) (492 ± 69 ml; p < 0.001) in the supine position with NEP -5 cmH2O. Less significant differences among the different groups were observed for V,NEP0.5 in the seated position with NEP -5 cmH2O and in both positions with NEP -7 cmH2O (only OSAH patients vs controls, p < 0.001). Similar results were obtained for V,NEP1 in either position by using both NEP -5 cmH2O and -7 cmH2O. In spite of this, a substantial overlapping of V,NEP0.5 and V,NEP1 between snorers and OSAH patients did not allow to identify a reliable diagnostic cut-off level. An inverse correlation with AHI was found for V,NEP0.5 in the supine position with NEP -5 cmH2O (rs = -0.46, p < 0.05) in severe OSAH patients.

Conclusion

The awake OSAH patients exhibit values of V,NEP0.5 and V,NEP1 lesser than those of awake snorers. The NEP technique, however, appears to have a limited usefulness as clinical tool for routine screening of the OSAH patients during wakefulness.
Structure alignment based on coding of local geometric measures
Authors: Chang Peter L , Rinne Andrew W , Dewey T Gregory
Published: July 2006

Background

A structure alignment method based on a local geometric property is presented and its performance is tested in pairwise and multiple structure alignments. In this approach, the writhing number, a quantity originating from integral formulas of Vassiliev knot invariants, is used as a local geometric measure. This measure is used in a sliding window to calculate the local writhe down the length of the protein chain. By encoding the distribution of writhing numbers across all the structures in the protein databank (PDB), protein geometries are represented in a 20-letter alphabet. This encoding transforms the structure alignment problem into a sequence alignment problem and allows the well-established algorithms of sequence alignment to be employed. Such geometric alignments offer distinct advantages over structural alignments in Cartesian coordinates as it better handles structural subtleties associated with slight twists and bends that distort one structure relative to another.

Results

The performance of programs for pairwise local alignment (TLOCAL) and multiple alignment (TCLUSTALW) are readily adapted from existing code for Smith-Waterman pairwise alignment and for multiple sequence alignment using CLUSTALW. The alignment algorithms employed a blocked scoring matrix (TBLOSUM) generated using the frequency of changes in the geometric alphabet of a block of protein structures. TLOCAL was tested on a set of 10 difficult proteins and found to give high quality alignments that compare favorably to those generated by existing pairwise alignment programs. A set of protein comparison involving hinged structures was also analyzed and TLOCAL was seen to compare favorably to other alignment methods. TCLUSTALW was tested on a family of protein kinases and reveal conserved regions similar to those previously identified by a hand alignment.

Conclusion

These results show that the encoding of the writhing number as a geometric measure allow high quality structure alignments to be generated using standard algorithms of sequence alignment. This approach provides computationally efficient algorithms that allow fast database searching and multiple structure alignment. Because the geometric measure can employ different window sizes, the method allows the exploration of alignments on different, well-defined length scales.
Interaction between Mycobacterium avium subsp. paratuberculosis and environmental protozoa
Authors: Whan Lynne , Grant Irene R , Rowe Michael T
Published: July 2006

Background

Interactions between Mycobacterium avium subsp. paratuberculosis (Map) and free-living protozoa in water are likely to occur in nature. The potential impact of ingestion of Map by two naturally occurring Acanthamoeba spp. on this pathogen's survival and chlorine resistance was investigated.

Results

Between 4.6 and 9.1% of spiked populations of three Map strains (NCTC 8578, B2 and ATCC 19698), which had been added at a multiplicity of infection of 10:1, were ingested by Acanthamoeba castellanii CCAP 1501/1B and A. polyphaga CCAP 1501/3B during co-culture for 3 h at 25°C. Map cells were observed to be present within the vacuoles of the amoebae by acid-fast staining. During extended co-culture of Map NCTC 8578 at 25°C for 24 d with both A. castellanii and A. polyphaga Map numbers did not change significantly during the first 7 days of incubation, however a 1–1.5 log10 increase in Map numbers was observed between days 7 and 24 within both Acanthamoeba spp. Ingested Map cells were shown to be more resistant to chlorine inactivation than free Map. Exposure to 2 μg/ml chlorine for 30 min resulted in a log10 reduction of 0.94 in ingested Map but a log10 reduction of 1.73 in free Map (p < 0.001).

Conclusion

This study demonstrated that ingestion of Map by and survival and multiplication of Map within Acanthamoeba spp. is possible, and that Map cells ingested by amoebae are more resistant to inactivation by chlorine than free Map cells. These findings have implications with respect to the efficacy of chlorination applied to Map infected surface waters.