bluuebunny/crossref_metadata_2025_split huggingface dataset:
Toward Ethically Grounded Conflict Interventions: Reevaluating Challenges in the 21st Century
Authors:   Neufeldt,   Fast,   Schirch
Published: October 2003

AbstractThis article explores the dimensions of ethics and accountability among conflict interveners, proposing an ethical framework that builds upon human rights and moral development. The framework consists of three ethical principles: inherent worth and dignity of individuals; community-defined common good; and authentic relationships. To apply these principles, the authors identify two embedded circles of accountability, which derive from the central parties in an intervention: the intervener and the participant. Dividing these groups into ``sending'' and ``receiving'' communities, this article reviews dimensions of accountability within the process of intervention that are related to each of the ethical principles. In operationalizing these principles, the authors suggest possible ethical responses to the challenges of intervention.
In Different Tongues: Making Room for Cultural Differences in the Negotiated Rulemaking Process
Authors:   Polkinghorn,   Pinto
Published: October 2003

AbstractThis article explores the ethical impact of cultural recognition within the regulatory negotiation (reg-neg) process as it is currently being used by federal agencies in the United States. The authors use a blend of theory and practice to explore the ethical necessity, feasibility, and practicality of including cultural guidelines within the reg-neg process. Using the findings from extensive prior research on negotiated rulemaking at the U.S. Environmental Protection Agency (EPA) as a foundation, we illustrate the lessons learned from years of regulatory negotiations conducted by the pioneer of reg-neg. We then show how these lessons have been brought under an umbrella of ``cultural recognition'' within the consensus-based regulatory negotiation being used to improve relations between American Indian nations and the U.S. government. We discuss the ethical and practical implications of incorporating cultural sensitivity into the reg-neg process.
Negotiating a Resolution to the Cyprus Problem: Is Potential European Union Membership a Blessing or a Curse?
Authors:   Sozen,   Yesilada
Published: October 2003

AbstractThis article provides a game theoretic analysis of how the candidacy of Cyprus for European Union (EU) membership presents an important challenge for both the Union's eastern enlargement plans and current international efforts aimed at resolving the Cyprus problem. The conclusions indicate that the Cypriot conflict has entered a very delicate period in its protracted and troublesome history characterized by a deadlock game. Strong domestic and international factors have created the conditions for each side to follow a non-cooperative strategy aimed at unilateral victory rather than a compromise. In this regard, the EU's promise to the Greek Cypriots of membership in the Union, regardless of the settlement of the Cyprus problem, serves as a side payment that enforces non-cooperative strategy. Likewise, Turkey's overwhelming military superiority in the region and its unconditional support for the Turkish Cypriots strengthens the Turkish side's rigid position in the Cyprus negotiations. Under these circumstances, it is argued that an influential third party like the United States is needed to coordinate the efforts of the UN and EU to move the two parties away form a deadlock game. This effort requires a package approach to the issues surrounding the Cyprus problem, the island's membership in the EU, and EU-Turkey relations.
Coalition Diversity and Normative Legitimacy in Human Security Negotiations
Authors: Hampson Fen Osler , Reid Holly 
Published: October 2003

AbstractThis article explores coalition dynamics in the negotiations leading up to the international Anti-personnel Landmines Convention and the Rome Treaty for an International Criminal Court. It discusses how "core" coalitions in the two cases formed and how these coalitions acquired international support and legitimacy. It suggests that multilateral negotiation processes on human security issues reflect a new kind of dynamics in multilateral negotiation processes where successful international coalitions draw strength and legitimacy through numbers and the mobilization of "boundary role" players in civil society and non-governmental organizations. The article also suggests that didactic leadership has a critical role to play in assembling these coalitions and generating the requisite levels of international attention and support to carry human security initiatives forward.
Strategic Simplification: Toward a Theory of Modular Design in Negotiation
Authors: Watkins Michael 
Published: October 2003

AbstractUsing Richard Holbrooke's negotiations in Bosnia as an instructive example, this article examines structural complexity as a barrier to agreement and proposes approaches to "strategic simplification" that are inspired by research on modular design of new products. This article represents an initial step toward development of a broader theory of complexity management in negotiation.
Lymphodepletion in the ApcMin/+ mouse model of intestinal tumorigenesis
Authors: Coletta P. Louise , Müller Albrecht M. , Jones Elena A. , Mühl Bettina , Holwell Sarah , Clarke Deborah , Meade Josephine L. , Cook Graham P. , Hawcroft Gillian , Ponchel Frederique , Lam Wai K. , MacLennan Ken A. , Hull Mark A. , Bonifer Constanze , Markham Alexander F. 
Published: October 2003

AbstractGerm line mutations in the Adenomatous polyposis coli tumor suppressor gene cause a hereditary form of intestinal tumorigenesis in both mice and man. Here we show that in ApcMin/+ mice, which carry a heterozygous germ line mutation at codon 850 of Apc, there is progressive loss of immature and mature thymocytes from approximately 80 days of age with complete regression of the thymus by 120 days. In addition, ApcMin/+ mice show parallel depletion of splenic natural killer (NK) cells, immature B cells, and B progenitor cells in bone marrow due to complete loss of interleukin 7 (IL-7)-dependent B-cell progenitors. Using bone marrow transplantation experiments into wild-type recipients, we have shown that the capacity of transplanted ApcMin/+ bone marrow cells for T- and B-cell development appears normal. In contrast, although the ApcMin/+ bone marrow microenvironment supported short-term reconstitution with wild-type bone marrow, ApcMin/+ animals that received transplants subsequently underwent lymphodepletion. Fibroblast colony-forming unit (CFU-F) colony assays revealed a significant reduction in colony-forming mesenchymal progenitor cells in the bone marrow of ApcMin/+ mice compared with wild-type animals prior to the onset of lymphodepletion. This suggests that an altered bone marrow microenvironment may account for the selective lymphocyte depletion observed in this model of familial adenomatous polyposis. (Blood. 2004;103:1050-1058)
Assessment of removal of human cytomegalovirus from blood components by leukocyte depletion filters using real-time quantitative PCR
Authors: Visconti Micaela Rios , Pennington Joanne , Garner Stephen F. , Allain Jean-Pierre , Williamson Lorna M. 
Published: October 2003

Abstract
To assess removal of cytomegalovirus (CMV) by leukocyte depletion (LD) filters, we developed a spiking model of latent virus using peripheral blood mononuclear cells (PBMCs) infected by coculture with CMV-infected human fibroblasts. Infected PBMCs were purified by dual magnetic column selection and then spiked into whole blood units or buffy coat pools prior to LD by filtration. CMV load and fibroblast contamination were assessed using quantitative CMV DNA real-time PCR and quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) of mRNA encoding the fibroblast-specific splice variant of prolyl-4-hydroxylase, respectively. After correcting for fibroblast-associated CMV, the mean CMV load was reduced in whole blood by LD from 7.42 × 102 to 1.13 copies per microliter (2.8110log reduction) and from 3.8 × 102 to 4.77 copies per microliter (1.910log reduction) in platelets. These results suggest that LD by filtration reduces viral burden but does not completely remove CMV from blood components. (Blood. 2004;103:1137-1139)
Ex vivo depletion of alloreactive cells based on CFSE dye dilution, activation antigen selection, and dendritic cell stimulation
Authors: Godfrey Wayne R. , Krampf Mark R. , Taylor Patricia A. , Blazar Bruce R. 
Published: October 2003

AbstractEliminating alloreactive cells from T-cell populations would enable the transfer of immune function to patients who receive stem cell transplants. However, high-efficiency depletion has proved difficult to achieve. We sought to develop ex vivo approaches for the maximal depletion of alloreactive CD4+ T cells. Using a flow cytometric cell sorting approach after mixed lymphocyte reaction (MLR) culture, we have found that sorted CFSEbright (5-(and-6)-carboxyfluorescein diacetate succinmidyl ester) (nondivided) and activation antigen-negative cells are markedly depleted of alloreactivity. With HLA-mismatched peripheral blood mononuclear cell (PBMC) stimulators we have consistently attained (90%-95%) depletion of alloreactivity. Importantly, when purified matured monocyte-derived dendritic cells (DCs) are used as stimulators, a 100-fold (99%) reduction in alloreactivity was attained, resulting in abrogation of the secondary MLR. Significantly, the CFSEbright CD25- cells recovered from these cultures retained general immunoreactivity, including responses to Candida and cytomegalovirus (CMV) antigens. In addition, a CFSE-based approach was tested and found to be sufficient for graft-versus-host disease (GVHD) prevention in vivo, in a major histocompatibility complex (MHC) class II disparate murine model. This efficient approach to selectively deplete mature alloantigen-specific T cells may permit enhanced immune reconstitution without GVHD. (Blood. 2004;103:1158-1165)
Donor immune reconstitution after liver–small bowel transplantation for multiple intestinal atresia with immunodeficiency
Authors: Gilroy Richard K. , Coccia Peter F. , Talmadge James E. , Hatcher Lori I. , Pirruccello Samuel J. , Shaw Byers W. , Rubocki Ronald J. , Sudan Debra L. , Langnas Alan N. , Horslen Simon P. 
Published: October 2003

AbstractThe syndrome of multiple intestinal atresia with immunodeficiency is a rare, invariably fatal congenital disorder. At 16 months of age, a child with this syndrome underwent liver-small bowel transplantation from a 1-of-6 HLA-matched donor. He acquired full enteral tolerance and normal liver function and has never shown evidence of allograft rejection. After mild graft-versus-host disease developed, studies revealed that more than 99% of his CD3+ lymphocytes and 50% of his CD19+ lymphocytes were of donor origin, whereas granulocytes and monocytes remained of recipient origin. He synthesizes polyclonal immunoglobulin G (IgG), IgA, and IgM and has developed antibodies to cytomegalovirus (CMV) and parainfluenza 3. His T lymphocytes are predominately CD3+CD4-CD8- with T-cell receptor γδ heterodimers and CD3+CD4-CD8+ with CD8αα homodimers, populations consistent with an intraepithelial lymphocyte phenotypic profile. We postulate that he has engrafted a donor intestine-derived immune system and is incapable of rejecting his engrafted organs. (Blood. 2004;103:1171-1174)
CD44: a new means to inhibit acute myeloid leukemia cell proliferation via p27Kip1
Authors: Gadhoum Zeineb , Leibovitch Marie-Pierre , Qi Junyuan , Dumenil Dominique , Durand Laetitia , Leibovitch Serge , Smadja-Joffe Florence 
Published: October 2003

AbstractAcute myeloid leukemia (AML) is sustained by the extensive proliferation of leukemic stem and progenitor cells, which give rise to the population of leukemic blasts with defective differentiation and low proliferative capacity. We have recently shown that ligation of CD44, a cell surface molecule present on AML cells, with specific monoclonal antibodies (mAbs) inhibits their proliferation. However, its mechanism has not been investigated yet. Here, using the NB4 cell line as a model of proliferating human AML cells, and the A3D8 mAb to ligate CD44, we show for the first time that CD44 ligation stabilizes the cyclin-dependent kinase inhibitor p27Kip1 (p27) protein, resulting in increased association with cyclin E/Cdk2 complexes and inhibition of their kinase activity. Moreover, using a p27 antisense vector, we provide direct evidence that p27 is the main mediator of cell growth arrest by CD44. CD44 ligation also leads to p27 accumulation in THP-1, KG1a, and HL60 cell lines and in primary leukemic cells, suggesting that this process is general in AML. Taken together, our present results suggest that CD44 is a new and efficient means to increase the expression of p27 in AML cells. Considering that elevated expression of p27 is a factor of good prognosis in AML, these results provide a new basis for developing CD44-targeted therapy in AML. (Blood. 2004;103:1059-1068)
Single administration of stem cell factor, FLT-3 ligand, megakaryocyte growth and development factor, and interleukin-3 in combination soon after irradiation prevents nonhuman primates from myelosuppression: long-term follow-up of hematopoiesis
Authors: Drouet Michel , Mourcin Frédéric , Grenier Nancy , Leroux Valérie , Denis Josianne , Mayol Jean-François , Thullier Philippe , Lataillade Jean-Jacques , Herodin Francis 
Published: October 2003

Abstract
Preservation of hematopoietic stem and progenitor cell survival is required for recovery from radiation-induced myelosuppression. We recently showed that short-term injection of antiapoptotic cytokine combinations into mice soon after lethal gamma irradiation promoted survival. The present study investigated the hematopoietic response of cynomolgus monkeys to a single dose of stem cell factor, FLT-3 ligand, megakaryocyte growth and development factor, and interleukin-3 in combination (4F, each factor given intravenously at 50 μg/kg) administered 2 hours after 5-Gy gamma irradiation. Treated monkeys (n = 4) experienced no thrombocytopenia. Only 1 in 4 displayed a transient period of neutropenia (neutrophil [ANC] count &lt; 0.5 × 109/L), whereas all irradiated controls (n = 4) experienced neutropenia (5-12 days) and thrombocytopenia (platelet [PLT] count &lt; 20 × 109/L, 5-31 days). Treated animals exhibited an impressive 2-wave PLT response that peaked at days 8 and 22 after total body irradiation (TBI). Areas under the curve (AUC) of PLTs, ANCs, white blood cells (WBCs), and red blood cells (RBCs) between days 0 and 90 were significantly higher in treated animals than in controls. Humeral bone marrow–derived clonogenic activity was significantly spared at 24 hours and 4 days after TBI in treated monkeys. No apparent impairment of the hematopoietic status and stem cell pool, in terms of long-term culture–initiating cells (LTC-ICs) and side population (SP) cells, was observed after 15 months. These results strongly suggest that the 4F cytokine combination, as a single dose regimen, could act as an emergency treatment for nuclear accident or terrorism victims.
The natural history of respiratory syncytial virus infection in cancer and transplant patients: implications for management
Authors: Anaissie Elias J. , Mahfouz Tahsine H. , Aslan Turan , Pouli Anastasia , Desikan Rahman , Fassas Athanasios , Barlogie Bart 
Published: October 2003

AbstractRespiratory syncytial virus (RSV) has been reported to cause severe morbidity and mortality among cancer patients receiving chemotherapy with or without autologous peripheral blood stem cell transplantation (APBSCT). However, little is known about the natural history of this infection in these patients, and current standard practice, aerosolized ribavirin plus intravenous immunoglobulin (IVIG), is extremely expensive, difficult to use, and not supported by controlled clinical trials. The purpose of this observational study was to determine the frequency, seasonality, morbidity, and mortality of RSV infection in a group of cancer patients receiving cytotoxic chemotherapy with neither ribavirin nor IVIG treatment. During the period of October 3, 1997, through October 14, 1998, 190 cancer patients (median age, 58 years; 71 women) underwent viral nasopharyngeal washing prior to chemotherapy. Multiple myeloma (MM) accounted for most patients (147, 77%). RSV was recovered from cultures taken from 71 patients (37%) throughout the year, although more frequently during fall and winter seasons (P &lt; .001) than spring and summer. Serious respiratory complications developed in 19 (27%) of 71 RSV-positive patients versus 24 (20%) of 119 patients whose RSV cultures were negative (P = .384). The presence of renal failure or increased lactate dehydrogenase (LDH) prior to chemotherapy and the development of mucositis were the only predictive factors for severe respiratory complications. Recovery of RSV from nasopharyngeal washings among cancer patients is common, occurs throughout the year, and does not appear to increase serious morbidity or mortality. RSV infection may not necessarily be a contraindication for APBSCT or an indication for therapy with aerosolized ribavirin and IVIG.
An amino acid polymorphism in von Willebrand factor correlates with increased susceptibility to proteolysis by ADAMTS13
Authors: Bowen Derrick John , Collins Peter William 
Published: October 2003

AbstractThe hypothesis that increased ADAMTS13 (a disintegrin and metalloprotease with thrombospondin repeats) activity or increased susceptibility of von Willebrand factor (VWF) to proteolysis by ADAMTS13 may underlie type I von Willebrand disease (VWD) in some patients was investigated. Plasma from 4 patients with type I VWD was cryoprecipitated. ADAMTS13 activity in the VWF-poor cryodepleted fraction was assessed by incubation with purified VWF; susceptibility to proteolysis of the VWF in the VWF-rich cryoprecipitate was assessed by incubation with a normal, group O cryodepleted plasma. ADAMTS13 activity was similar in all 4 type I VWD cryodepleted plasmas and comparable to a normal control plasma. In contrast, the VWF of one patient showed increased susceptibility to proteolysis by ADAMTS13. Investigation of additional family members indicated that increased susceptibility was heritable, but it did not track uniquely with type I VWD. Sequence analysis of VWF exon 28 indicated that increased susceptibility to proteolysis tracked with the “G” allele of the A/G polymorphism at position 24/1282, encoding the amino acid polymorphism Tyr/Cys1584 (“G” = Cys1584). A prospective study of 200 individuals yielded 2 Tyr/Cys1584 heterozygotes; for both, plasma VWF showed increased susceptibility to proteolysis. The finding that an amino acid polymorphism in VWF may influence susceptibility to ADAMTS13 has potentially significant implications in diverse areas. (Blood. 2004;103:941-947)
The effect of human tissue factor pathway inhibitor-2 on the growth and metastasis of fibrosarcoma tumors in athymic mice
Authors: Chand Hitendra Singh , Du Xin , Ma Duan , Inzunza Hector David , Kamei Shintaro , Foster Donald , Brodie Steven , Kisiel Walter 
Published: October 2003

AbstractHuman tissue factor pathway inhibitor-2 (TFPI-2) is a matrix-associated Kunitz inhibitor that inhibits the plasmin- and trypsin-mediated activation of zymogen matrix metalloproteinases involved in tumor progression, invasion, and metastasis. To directly assess its role in tumor growth and metastasis in vivo, we stably transfected HT-1080 fibrosarcoma cells expressing either fully active wild-type human TFPI-2 (WT) or inactive R24Q TFPI-2 (QT) and examined their ability to form tumors and metastasize in athymic mice in comparison to mock-transfected cells (MT). MT and QT fibrosarcoma tumors grew 2 to 3 times larger than WT tumors. Tumor metastasis was confined to the lung and was observed in 75% of mice treated with either MT or QT cells, whereas only 42% of mice treated with WT cells developed lung metastases. Real-time quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) analyses of each tumor group revealed 3- to 6-fold lower levels of murine vascular endothelial growth factor gene expression in WT tumors in relation to either MT or QT tumors. Comparative tumor gene expression analysis revealed that several human genes implicated in oncogenesis, invasion, metastasis, apoptosis, and angiogenesis had significantly altered levels of expression in WT tumors. Our collective data demonstrate that secretion of inhibitory TFPI-2 by a highly metastatic tumor cell markedly inhibits its growth and metastasis in vivo by regulating pericellular extracellular matrix (ECM) remodeling and angiogenesis. (Blood. 2004;103:1069-1077)
Bifunctional role for VEGF-induced heme oxygenase-1 in vivo: induction of angiogenesis and inhibition of leukocytic infiltration
Authors: Bussolati Benedetta , Ahmed Asif , Pemberton Helen , Landis R. Clive , Di Carlo Francesco , Haskard Dorian O. , Mason Justin C. 
Published: October 2003

AbstractHeme-oxygenases (HOs) catalyze the conversion of heme into carbon monoxide and biliverdin. HO-1 is induced during hypoxia, ischemia/reperfusion, and inflammation, providing cytoprotection and inhibiting leukocyte migration to inflammatory sites. Although in vitro studies have suggested an additional role for HO-1 in angiogenesis, the relevance of this in vivo remains unknown. We investigated the involvement of HO-1 in angiogenesis in vitro and in vivo. Vascular endothelial growth factor (VEGF) induced prolonged HO-1 expression and activity in human endothelial cells and HO-1 inhibition abrogated VEGF-driven angiogenesis. Two murine models of angiogenesis were used: (1) angiogenesis initiated by addition of VEGF to Matrigel and (2) a lipopolysaccharide (LPS)–induced model of inflammatory angiogenesis in which angiogenesis is secondary to leukocyte invasion. Pharmacologic inhibition of HO-1 induced marked leukocytic infiltration that enhanced VEGF-induced angiogenesis. However, in the presence of an anti-CD18 monoclonal antibody (mAb) to block leukocyte migration, VEGF-induced angiogenesis was significantly inhibited by HO-1 antagonists. Furthermore, in the LPS-induced model of inflammatory angiogenesis, induction of HO-1 with cobalt protoporphyrin significantly inhibited leukocyte invasion into LPS-conditioned Matrigel and thus prevented the subsequent angiogenesis. We therefore propose that during chronic inflammation HO-1 has 2 roles: first, an anti-inflammatory action inhibiting leukocyte infiltration; and second, promotion of VEGF-driven noninflammatory angiogenesis that facilitates tissue repair.