bluuebunny/crossref_metadata_2025 huggingface dataset:
Seasonal Propagation of Sea Level along the Equator in the Atlantic
Authors: Bunge Lucia , Clarke Allan J.
Published: October 2008

In the equatorial Atlantic the sea surface height (SSH) anomaly field is dominated by an annual signal propagating eastward. This signal has been previously interpreted in terms of propagating waves. In this article it is argued that this propagating signal is not a free equatorial Kelvin wave because the phase velocity observed is too small compared to first, second, or third baroclinic mode Kelvin waves, and is not the result of an equatorial forced wave because the zonal wind stress does not show a similar propagation. Rather, it is suggested that the eastward propagation in SSH is due to the sum of two independent modes of variability: one mainly driven by the wind stress curl off the equator, and the other driven by the zonal wind stress along the equator. These two modes are uncorrelated in time and space and therefore can be conveniently separated by an empirical orthogonal function analysis of the equatorial Atlantic sea surface height. The first mode explains 74% of the variance, is one-signed in longitude, and is interpreted as the variability of the warm water volume above the thermocline. The second mode explains 24% of the variance, consists of an east–west tilt along the equator, and is driven by variations of the zonal equatorial wind stress.
Criminality Among Rural Stimulant Users in the United States
Authors: Oser Carrie , Leukefeld Carl , Staton-Tindall Michele , Duvall Jamieson , Garrity Thomas , Stoops William , Falck Russel , Jichuan Wang  , Carlson Robert , Sexton Rocky , Wright Patricia , Booth Brenda
Published: October 2008

Despite the increase in media attention on “meth cooking” in rural areas of the United States, little is known about rural stimulant use—particularly, the criminality associated with stimulant use. Data were collected from community stimulant users in rural Ohio, Arkansas, and Kentucky ( N = 709). Findings from three logistic regression models indicate that younger stimulant users ( M = 32.55, SD = 10.35), those with more convictions, and those who used crack frequently were significantly more likely to have been arrested for committing a substance-related crime, a property crime, or another crime in the 6 months before entering the study. Implications include the need for longitudinal studies to further understand rural stimulant use, as well as increased community and corrections-based drug abuse prevention and treatment interventions for stimulant users who live in rural areas.
Woven in Deeply
Authors: Theoharis George
Published: October 2008

This article comes from an investigation into the identities and leadership traits of seven urban school principals committed to social justice across elementary, middle, and high school levels. These administrators believed that enacting social justice for marginalized students was instrumental in their desire to become school leaders and central to their practice. A qualitative approach combined with principles of autoethnography has guided the research methods. Findings include varied personal experiences that sound their call to leadership and three common leadership traits. These traits are arrogant humility, passionate leadership, and a tenacious commitment to social justice. The article concludes with a metaphor explaining these leaders and their connection with their social justice work.
The Territorial Prior-Residence Effect and Children's Behavior in Social Dilemmas
Authors: Ru Han  , Shu Li  , Shi Jian-Nong
Published: October 2008

Research on territorial behavior has focused on animal populations, and relatively little has dealt with territoriality in humans, except in the area of human sports. This study was an investigation of the prior-residence effect on children's behavior in social dilemmas. The analysis was carried out by means of research designed for preschool children who played a dictator game and an ultimatum game. This study demonstrates the advantages of being on one's own turf. The authors found that children playing in their own classroom obtained more from games than did those playing in their partners' classroom. In contrast, not being in their own classroom and not having the power to dictate in the ultimatum game were seen as an underlying reason why children propose more offers to their partners. The theoretical and practical implications of these findings for the evolution of prosocial behavior are discussed.
Action Programmes of Social Work Organisations
Authors: Bongsprabandh H.R.H. Krommun Narathip
Published: October 2008

Social work representatives from eleven Asian nations participated in the first regional International Federation of Social Workers Conference for Asia, November 6-10, 1967. The theme was "Action Programmes in Social Welfare and their Impact on a Changing Asia." His Royal Highness Krommun Narathip Bongsprabandh opened the Conference with the statement presented here. In addition, the three position papers of the Conference are reproduced in this issue of INTERNATIONAL SOCIAL WORK. One of the background papers for the Confer ence and a report of the work groups appeared in the April 1968 issue of the Journal.
The Social Policy Areas of Marriage and Family, Family Planning, Child Care and Health Care in China
Authors: Roberts Maria
Published: October 2008

The author was recently invited by the Chinese Association for Friendship with Foreign Countries to visit China on a special U.S.-China Relations Tour. One of the most impressive characteristics of the visit was the impact that the social system has upon individuals in China. Consequently, China's human services structure is designed to cooperate in the building of a strong, socialist state. This article is an attempt to briefly discuss four significant social policy areas in the Peoples Republic of China. These policy areas include: marriage and family; family planning; child care, and health care. These particular social policy areas will have a major influence as to whether China will have the domestic resources in order to achieve its goal of the four modernizations (agriculture, industry, national defense and science and technology). For those of us who perceive ourselves as world citizens, China should be of special interest because it now cares for over one-fifth of the total world population.
Problems in the Teaching of Social Policy To Students From Less Developed Countries and the Use of Imaginative Literature
Authors: Reidy Angela
Published: October 2008

"Besides you are dead yourself. You have to realise this. When men decreed you were mad, you were treated as a madman. When they decreed you were dead, Bouna could only take you for a ghost. Whatever you do, Magamou is dead. The crowd has so decided." Malick Fall, The Wound.
Before Escalation: Behavioral and Affective Forecasting in Escalation of Commitment
Authors: Ku Gillian
Published: October 2008

This research examines preinvestment forecasting processes in escalation of commitment, considering two questions: whether individuals are able to accurately predict their behavior and affect in escalation situations and how forecasting processes may be linked to actual escalation. Three experiments demonstrated that individuals underpredicted their escalation and overpredicted their postescalation regret. Two of the experiments also indicated that the less individuals predicted being entrapped, the more they escalated. Counter to expectations, anticipated regret did not predict escalation. The discussion focuses on the theoretical and practical importance of forecasting on escalation and on the importance of understanding both behavioral and affective forecasting effects simultaneously.
“Seizing and Freezing” on a Significant-Person Schema: Need for Closure and the Transference Effect in Social Judgment
Authors: Pierro Antonio , Kruglanski Arie W.
Published: October 2008

Two experimental studies examined the possibility that the need for cognitive closure (NfCC) affects the tendency to exhibit transference effects in social encounters. They reveal that the transference effect is more pronounced when individuals' (dispositional) NfCC is high (vs. low). In Study 1, this effect is demonstrated with respect to the transference of false memories about a newly encountered target person generalized from one's representation of a significant other. In Study 2, it is demonstrated with respect to the transference of both false memories and affective reaction to a new leader based on one's representation of a past leader. The discussion considers the role of motivation in the transference effect in relation to the social cognitive and psychodynamic views of transference.
In Search of Clarity: Self-Esteem and Domains of Confidence and Confusion
Authors: Stinson Danu Anthony , Wood Joanne V. , Doxey Juliana R.
Published: October 2008

To date, research suggests that self-concept clarity is a monolithic construct: Some people have clearly defined self-concepts in all domains, whereas others do not. The authors argued that self-concept clarity is instead multifaceted and varies across trait domains. The authors predicted that social commodities (SCs; e.g., looks, popularity, social skills) would show less self-concept clarity than would communal qualities (CQs; e.g., kindness, warmth, honesty), due to domain differences in observability, ambiguity, and controllability. Results replicated past findings that self-esteem predicts self-concept clarity but also demonstrated that participants' SC self-views were less clear than their CQ self-views. Moreover, people showed greater clarity about traits that were lower in observability and higher in ambiguity and controllability. These findings suggest that everyone, regardless of self-esteem, has self-concept domains of relative confidence and confusion.
The Proverbs of New Public Management
Authors: Meier Kenneth J. , O'Toole Laurence J.
Published: October 2008

The movement for an evidence-based practice of medicine seeks to systematically examine and challenge current practices in that professional field. This article uses the same philosophy to examine an extensive research agenda by Laurence J. O'Toole and Kenneth J. Meier and apply it to public management. Using the New Public Management as a foil, the article examines 10 extant proverbs of public management. The assessment shows the weak support for many such nostrums of public management and illustrates how systematic, theoretically designed quantitative research can inform the practice of public management.
Inclusive Teachers’ Concern and Rejection Toward Their Students
Authors: Cook Bryan G. , Cameron David L.
Published: October 2008

This article reports two related studies. In the first study, concern and rejection ratings of 14 inclusive teachers toward 26 students with disabilities were correlated with teacher—student interactions. Partial correlations, controlling for severity of disability, indicated that instructional-academic interactions corresponded significantly with teachers’ concern ratings and noninstructional-behavioral interactions corresponded significantly with teachers’ rejection ratings. In the second study, the authors compared teachers’ concern and rejection ratings of students with learning disabilities ( n = 77), cognitive disabilities ( n = 44), attention-deficit disorder ( n = 20), behavioral disorders ( n = 19), and no disabilities ( n = 1,153) in 65 inclusive classes using ANOVAs and Scheffe post hoc tests. Students in all disability categories received significantly higher concern ratings than nondisabled students, students with learning disabilities and behavioral disorders received significantly higher rejection ratings than nondisabled students, and students with behavioral disorders received significantly higher rejection ratings than students with cognitive disabilities.
Darfur Refugees in Cairo
Authors: Meffert Susan M. , Marmar Charles R.
Published: October 2008

Hundreds of thousands of Darfur people affected by the Sudanese genocide have fled to Cairo, Egypt, in search of assistance. Collaborating with Africa and Middle East Refugee Assistance (AMERA), the authors conducted a mental health care needs assessment among Darfur refugees in Cairo. Information was collected using individual and focus group interviews to identify gaps in mental health care and develop understandings of emotional and relationship problems. The refugee mental health care system has a piecemeal structure with gaps in outpatient services. There is moderate to severe emotional distress among many Darfur refugees, including symptoms of depression and trauma, and interpersonal conflict, both domestic violence and broader community conflict, elevated relative to pregenocide levels. Given the established relationships between symptoms of depression/traumatic stress and interpersonal violence, improving mental health is important for both preventing mental health decompensation and stemming future cycles of intra- and intergroup conflict.
Relationship Between Type of Trauma Exposure and Posttraumatic Stress Disorder Among Urban Children and Adolescents
Authors: Luthra Rohini , Abramovitz Robert , Greenberg Rick , Schoor Alan , Newcorn Jeffrey , Schmeidler James , Levine Paul , Nomura Yoko , Chemtob Claude M.
Published: October 2008

This study examines the association between trauma exposure and posttraumatic stress disorder (PTSD) among 157 help-seeking children (aged 8-17). Structured clinical interviews are carried out, and linear and logistic regression analyses are conducted to examine the relationship between PTSD and type of trauma exposure controlling for age, gender, and ethnicity. Confrontation with traumatic news, witnessing domestic violence, physical abuse, and sexual abuse are each significantly associated with PTSD. Witnessing a crime, being the victim of a crime, and exposure to accidents, fire, or disaster are not associated with PTSD. These findings underscore the association between interpersonal violence and childhood PTSD.
Gender Symmetry, Sexism, and Intimate Partner Violence
Authors: Allen Christopher T. , Swan Suzanne C. , Raghavan Chitra
Published: October 2008

This study of a predominantly Hispanic sample of 92 male and 140 female college students examines both gender symmetry in intimate partner violence (IPV) and inconsistent relationships found in previous studies between sexist attitudes and IPV. Results indicate that although comparable numbers of men and women perpetrate and are victimized in their relationships with intimate partners, the path models suggest that women’s violence tends to be in reaction to male violence, whereas men tend to initiate violence and then their partners respond with violence. Benevolent sexism was shown to have a protective effect against men’s violence toward partners. Findings highlight the importance of studying women’s violence not only in the context of men’s violence but also within a broader sociocultural context.
Hospitalization Pattern in a Hospital-based Palliative Care Program: An Example From Saudi Arabia
Authors: Alsirafy Samy A. , Hassan Azza A. , Al-Shahri Mohammad Z.
Published: October 2008

The few palliative care programs available to date in Saudi Arabia are largely hospital-based. Subacute palliative care models have not been developed yet. This retrospective review was conducted to assess the patterns and outcomes of hospital-based palliative care unit admissions in the absence of subacute palliative care models. We reviewed 759 eligible palliative care unit admissions related to 629 cancer patients during a 4-year period. Of all admissions, 66% were hospitalized through the emergency room. The average hospital stay was 24 days. The majority (86%) of patients died in-hospital. These results suggest that end-of-life quality indicators are unlikely to improve depending on hospital-based palliative care models only. To improve palliative care services in Saudi Arabia, other subacute models may need to be considered.
Embryonal and Alveolar Rhabdomyosarcoma of Parameningeal Sites in Adults: A Report of 13 Cases
Authors: Montone Kathleen T. , Barr Frederic G. , Zhang Paul J. , Feldman Michael D. , LiVolsi Virginia A.
Published: October 2008

This study reports 13 adult parameningeal rhabdomyosarcomas. Ages ranged from 18 to 86 years. Nine lesions were alveolar, 3 were embryonal, and 1 could not be further classified. All cases were positive for desmin and/or myogenin and 1 tumor was strongly positive for cytokeratin. PAX3-FKHR or PAX7-FKHR fusion transcripts or FKHR breaks were identified in 5 cases confirming a diagnosis of alveolar rhabdomyosarcoma. Three cases were negative supporting a diagnosis of embryonal rhabdomyosarcoma. A total of 10 patients were treated with chemotherapy and radiation. Three patients are alive with no disease, 3 are alive with disease, 3 died of disease, and 4 patients are lost to follow-up. Adult sinonasal rhabdomyosarcoma is uncommon and should be considered in the differential of sinonasal neoplasms. Disease can occur in the elderly. Desmin and myogenin can aid in the diagnosis but cytokeratin reactivity can be seen and care must be taken not to diagnose carcinoma.
Roles of Oxidants, Nitric Oxide, and Asymmetric Dimethylarginine in Endothelial Function
Authors: Siekmeier Rüdiger , Grammer Tanja , März Winfried
Published: October 2008

Vascular endothelium plays a crucial role in ensuring normal function and morphology of blood vessels, and many risk factors of atherosclerosis act via their effects on endothelial cells. However, endothelial dysfunction is induced by very different pathomechanisms. In principle, it is caused by an impaired bioavailability of nitric oxide (NO) due to an inhibited synthesis (eg, by asymmetric dimethylarginine [ADMA]) or increased consumption of formed NO (by reactive oxygen species [ROS]). ROS can be synthesized in the organism (eg, by different enzymes) or can be administered from the environment (eg, by cigarette smoking), whereas ADMA is the subject of endogenous metabolism only. Many studies have elucidated the system of pathomechanisms and targeted some as potential goals for therapeutic interventions. This review demonstrates roles of ROS, NO, ADMA, endothelin, and estrogen in endothelial function and dysfunction focusing on homocysteinemia and diabetes mellitus and provide examples for the medical treatment of endothelial dysfunction.
Economic Foundation of Human Resource Development: Advancing the Theory and Practice of the Discipline
Authors: Swanson Richard A.
Published: October 2008

The problem and the Solution . Economics theory, together with systems and psychological theories, is considered the core theories integrated to create the foundation for the human resource development discipline. Few human resource development scholars have explored the full potential of the economics and its implications for human resource development theory, research, and practice.This article presents a rationale for focusing on economics and an introduction to selected specific economic theories relevant to human resource development.
Development Economics: A Foundation for HRD Policy Studies in Developing Countries
Authors: Wang Greg G. , Korte Russell F. , Sun Judy Y.
Published: October 2008

The problem and the solution . Theoretical work in development economics has had a significant impact on the development process of nations, including national policies for human resource development (HRD) in developing countries.As an important component of an overall economic development system, HRD can benefit from the insights provided by development economics—especially in developing countries. At the national policy level, HRD should identify and pursue opportunities for economic development by engaging in policy analysis and comparative studies, as well as contributing to policy recommendations and implementation based on development economics.
Economics: Opportunity and Challenges for Human Resource Development
Authors: Allen W. Clayton , Fischer Mary , Swanson Richard A.
Published: October 2008

The problem and the solution. Given the many organizational problems human resource development is expected to help solve and the many tools offered by economics, foundational direction for action can have high utility. This article concludes this issue by discussing the opportunity and challenges facing human resource development scholars and practitioners in integrating economics foundations into its theory building, research, and practice along with the potential gains.
Toward a Human Capital Measurement Methodology
Authors: Bassi Laurie J. , McMurrer Daniel P.
Published: October 2008

The problem and the solution. Measuring the impact of human capital and investments made in it has been an ongoing challenge for the field of human resource development (HRD).This study reports on an intensively researched, rigorous measurement methodologies designed to address this challenge.This article presents the process by which the methodology was developed, from foundational economic logic to analysis and validation.The resulting Human Capital Capability Scorecard approach allows organizations to comprehensively measure 69 different human capital items and link them to organizational performance.The implications for HRD theory building and related public policy issues are also discussed.
Human Capital and Screening Theories: Implications for Human Resource Development
Authors: Dobbs Rita L. , Sun Judy Y. , Roberts Paul B.
Published: October 2008

The problem and the solution. Human capital theory is a well-accepted foundation of human resources development (HRD) research and practices. Screening theory is equally foundational to HRD. This article presents and compares the two seemingly contrasting theories in economics. The origins, evolution, and current states of research on both theories are explored. The focus of the article is to identify their foundational role in, and implications for, HRD research and practice.The article shows that the two theories are complementary and have important implications for HRD theory building, research, and practices.
Comparison of Monoscopic Insertable, Remotely Controlled Imaging Device With a Standard Laparoscope in a Porcine Model
Authors: Hogle Nancy J. , Tie Hu  , Allen Peter K. , Fowler Dennis L.
Published: October 2008

Laparoscopic imaging has remained relatively unchanged since the introduction of the rod—lens system. The intent here is to improve imaging by designing and building sensors and effectors placed directly into the body and controlled remotely. An 11-mm monoscopic insertable pan/tilt endoscopic imaging device with an integrated light source was studied. In vivo testing included simulated appendectomy, nephrectomy, suturing, and running the bowel in a porcine model (n = 6). Subjective impression and time for each procedure were compared using each imaging modality. The insertable imaging device seemed easier and more intuitive to use than a standard laparoscope. Time to perform procedures was better than or equivalent to a standard laparoscope. The insertable camera was subjectively preferred, and times for completion of complex tasks were shorter using the insertable camera. The insertable imaging device has the potential to be an integral part of surgical system platforms.
Operative Time and Other Outcomes of the Electrothermal Bipolar Vessel Sealing System (LigaSure™) Versus Other Methods for Surgical Hemostasis: A Meta-Analysis
Authors: Macario Alex , Dexter Franklin , Sypal Jennifer , Cosgriff Ned , Heniford B. Todd
Published: October 2008

A meta-analysis was performed of 29 prospective, randomized trials (published January 1, 2000, to August 14, 2007) comparing an electrothermal bipolar vessel sealing system (EBVS-LigaSure™, Covidien) (total n = 1107 patients) with either clamping with suture ligation/ electrocauterization (n = 1079 patients) or ultrasonic energy (eg, Harmonic Scalpel®, Johnson & Johnson). Hemorrhoidectomy (12 articles), hysterectomy (4 articles), and thyroidectomy (3 articles) were the most common procedures. For 15 of 26 studies reporting standard deviations, the normalized mean operative time reduction for EBVS equaled 28% (95% confidence interval [CI] 18%-39%, P < .0001) compared with conventional surgical hemostasis. Operative time was reduced with EBVS in 24 of 26 studies ( P < .0001). EBVS was associated with 43 mL (95% CI 14-73 mL, P = .0021) less blood loss, fewer complications (odds ratio 0.66, 95% CI 0.47-0.92, P = .02), and mean reduction in postoperative pain of 2.8 units (95% CI 1.5-4.1, P < .0001). Five studies used ultrasonic energy as the comparator, but none reported standard deviation so data could not be pooled.
Bone Anchor Mesh Fixation for Complex Laparoscopic Ventral Hernia Repair
Authors: Yee J.A. , Harold K.L. , Cobb W.S. , Carbonell A.M.
Published: October 2008

Background: Laparoscopic ventral hernia repair (LVHR) has gained wide acceptance by both surgeons and patients, but hernias that approach a bony prominence are more complex due to the difficulty of proper fixation. This study was conducted to evaluate the use of bone anchor mesh fixation for complex LVHR. Methods: A prospective study of patients having complex LVHR with bone anchors was conducted using patients from 2 academic institutions between July 2003 and December 2007. Patient demographic data, characteristics of the hernia, operative details, and postoperative outcomes were recorded. Results: A total of 30 patients who had LVHR using bone anchors were evaluated (20 women, 10 men; mean age 60.9 years, range 41-83 years). In all, 17 suprapubic and 13 lateral hernias were included, requiring a mean of 2.8 and 3.2 bone anchors, respectively. The average hernia defect was 263 cm2 (range 35-690 cm2), and the average mesh size was 663 cm2 (range 255-1360 cm2). Mean operative time was 218 minutes (range 98-420 minutes), with an estimated blood loss of 46 mL (range 10-100 mL). The average length of stay was 5.2 days (range 1-26 days). Seven patients (23.3%) developed postoperative complications, and 1 patient in this study died (mortality 3.3%). During follow-up of 13.2 months (range 1-26 months), 2 patients (6.7%) developed a recurrent hernia. Conclusions: Bone anchors can be used successfully in the laparoscopic repair of complex ventral hernias, particularly with suprapubic and lateral hernias that approach a bony prominence. The complication rate is acceptable, with a short hospital stay and low recurrence rate.
Metastatic Bone Involvement of the Hallux Distal Phalanx and Cuboid in an Elderly Patient With Non-Hodgkin Lymphoma
Authors: Allman Lara M.
Published: October 2008

Non-Hodgkin lymphoma metastasis to bone is a rare occurrence in the lower extremity. There have been very few reported cases. Bone metastasis, when it occurs, usually affects the axial skeleton. This article presents a case of Waldenström macroglobulinemia, a variant of non-Hodgkin lymphoma, with metastasis to the right hallux distal phalanx and left cuboid, as well as cutaneous lesions of the right foot. The patient received radiation treatments to each involved area with complete resolution of symptoms and tumor.
Charcot-Marie-Tooth Disease
Authors: Casasnovas Carlos , Cano Luis Miguel , Albertí Antonia , Céspedes Maria , Rigo Gillem
Published: October 2008

Charcot-Marie-Tooth disease (CMT) or hereditary motor and sensory neuropathy constitutes a genetically heterogeneous group of diseases that affect the peripheral nervous system. CMT is characterized by degeneration or abnormal development of the peripheral nerve and is transmitted with different genetic patterns. In most cases, the disease starts in infancy. Its symptoms, among others, are an awkward gait; muscular atrophy of the 4 extremities, particularly distally; and foot deformities, such as cavus foot. People with CMT have an altered gait; most have a high stepping gait and frequently trip or fall. CMT disease can be classified according to the pattern of inheritance (autosomal dominant, autosomal recessive, or X-linked), electrophysiological findings (evidence of demyelination or axonal degeneration), or the mutated gene that causes the disease. This classification of CMT is complex and continually updated as new genes and mutations are found. CMT should be suspected in any patient with cavus foot, particularly if other members of the family have been diagnosed with the disease. Treatment decisions must be individualized and based on a clear history, careful examination, and well-defined patient goals.
TGF-β as a candidate bone marrow niche signal to induce hematopoietic stem cell hibernation
Authors: Yamazaki Satoshi , Iwama Atsushi , Takayanagi Shin-ichiro , Eto Koji , Ema Hideo , Nakauchi Hiromitsu
Published: October 2008

Hematopoietic stem cells (HSCs) reside in a bone marrow niche in a nondividing state from which they occasionally are aroused to undergo cell division. Yet, the mechanism underlying this unique feature remains largely unknown. We have recently shown that freshly isolated CD34−KSL hematopoietic stem cells (HSCs) in a hibernation state exhibit inhibited lipid raft clustering. Lipid raft clustering induced by cytokines is essential for HSCs to augment cytokine signals to the level enough to re-enter the cell cycle. Here we screened candidate niche signals that inhibit lipid raft clustering, and identified that transforming growth factor-β (TGF-β) efficiently inhibits cytokine-mediated lipid raft clustering and induces HSC hibernation ex vivo. Smad2 and Smad3, the signaling molecules directly downstream from and activated by TGF-β receptors were specifically activated in CD34−KSL HSCs in a hibernation state, but not in cycling CD34+KSL progenitors. These data uncover a critical role for TGF-β as a candidate niche signal in the control of HSC hibernation and provide TGF-β as a novel tool for ex vivo modeling of the HSC niche.
Stroma-dependent apoptosis in clonal hematopoietic precursors correlates with expression of PYCARD
Authors: Mhyre Andrew J. , Marcondes A. Mario , Spaulding Emily Y. , Deeg H. Joachim
Published: October 2008

The role of the marrow microenvironment in the pathophysiology of myelodysplastic syndromes (MDSs) remains controversial. Using stromal/hematopoietic cell cocultures, we investigated the effects of stroma-derived signals on apoptosis sensitivity in hematopoietic precursors. The leukemia-derived cell line KG1a is resistant to proapoptotic ligands. However, when cocultured with the human stromal cell line HS5 (derived from normal marrow) and exposed to tumor necrosis factor-α (TNF-α), KG1a cells showed caspase-3 activation and induction of apoptosis. Apoptosis was contact dependent. Identical results were obtained in coculture with primary stroma. Gene-expression profiling of KG1a cells identified coculture-induced up-regulation of various genes involved in apoptosis, including PYCARD. Suppression of PYCARD expression in KG1a by miRNA interfered with apoptosis. Knockdown of the TNF receptor 1 (TNFR1) or TNFR2 in HS5 cells had no effect. However, knockdown of R1 in KG1a cells prevented TNF-α–induced apoptosis, while apoptosis was still induced by TNF-α–related apoptosis-inducing ligand. Primary CD34+ cells from MDS marrow, when cocultured with HS5 and TNF-α, also underwent apoptosis. In contrast, no apoptosis was observed in CD34+ cells from the marrow of healthy donors. These data indicate that stroma may convey not only protective effects on hematopoietic cells, but, dependent upon the milieu, may also facilitate apoptosis.
Capture and transfer of HIV-1 particles by mature dendritic cells converges with the exosome-dissemination pathway
Authors: Izquierdo-Useros Nuria , Naranjo-Gómez Mar , Archer Jacob , Hatch Steven C. , Erkizia Itziar , Blanco Julià , Borràs Francesc E. , Puertas Maria Carmen , Connor John H. , Fernández-Figueras Maria Teresa , Moore Landon , Clotet Bonaventura , Gummuluru Suryaram , Martinez-Picado Javier
Published: October 2008

Exosomes are secreted cellular vesicles that can be internalized by dendritic cells (DCs), contributing to antigen-specific naive CD4+ T-cell activation. Here, we demonstrate that human immunodeficiency virus type 1 (HIV-1) can exploit this exosome antigen-dissemination pathway intrinsic to mature DCs (mDCs) for mediating trans-infection of T lymphocytes. Capture of HIV-1, HIV-1 Gag-enhanced green fluorescent protein (eGFP) viral-like particles (VLPs), and exosomes by DCs was up-regulated upon maturation, resulting in localization within a CD81+ compartment. Uptake of VLPs or exosomes could be inhibited by a challenge with either particle, suggesting that the expression of common determinant(s) on VLP or exosome surface is necessary for internalization by mDCs. Capture by mDCs was insensitive to proteolysis but blocked when virus, VLPs, or exosomes were produced from cells treated with sphingolipid biosynthesis inhibitors that modulate the lipid composition of the budding particles. Finally, VLPs and exosomes captured by mDCs were transmitted to T lymphocytes in an envelope glycoprotein-independent manner, underscoring a new potential viral dissemination pathway.
“Vitamin hypothesis”: explanation for allergy increase?
Authors: Bischoff Stephan C.
Published: October 2008

In this issue of Blood, Spiegl and colleagues show that basophils express retinaldehyde dehydrogenase-2 and thus are a new and unique cellular source of RA, known to be an important regulator of immune-cell functions.
Is more better in myeloma?
Authors: Tricot Guido
Published: October 2008

Rosiñol and colleagues report the results of a Spanish PETHEMA trial in this issue of Blood. Their study was an attempt to address the role of additional intensive treatments for patients failing to achieve a complete or nearly complete remission after a single autologous transplantation.
Anti-leukemia activity of alloreactive NK cells in KIR ligand-mismatched haploidentical HSCT for pediatric patients: evaluation of the functional role of activating KIR and redefinition of inhibitory KIR specificity
Authors: Pende Daniela , Marcenaro Stefania , Falco Michela , Martini Stefania , Bernardo Maria Ester , Montagna Daniela , Romeo Elisa , Cognet Céline , Martinetti Miryam , Maccario Rita , Mingari Maria Cristina , Vivier Eric , Moretta Lorenzo , Locatelli Franco , Moretta Alessandro
Published: October 2008

We analyzed 21 children with leukemia receiving haploidentical hematopoietic stem cell transplantation (haplo-HSCT) from killer immunoglobulin (Ig)–like receptors (KIR) ligand-mismatched donors. We showed that, in most transplantation patients, variable proportions of donor-derived alloreactive natural killer (NK) cells displaying anti-leukemia activity were generated and maintained even late after transplantation. This was assessed through analysis of donor KIR genotype, as well as through phenotypic and functional analyses of NK cells, both at the polyclonal and clonal level. Donor-derived KIR2DL1+ NK cells isolated from the recipient displayed the expected capability of selectively killing C1/C1 target cells, including patient leukemia blasts. Differently, KIR2DL2/3+ NK cells displayed poor alloreactivity against leukemia cells carrying human leukocyte antigen (HLA) alleles belonging to C2 group. Unexpectedly, this was due to recognition of C2 by KIR2DL2/3, as revealed by receptor blocking experiments and by binding assays of soluble KIR to HLA-C transfectants. Remarkably, however, C2/C2 leukemia blasts were killed by KIR2DL2/3+ (or by NKG2A+) NK cells that coexpressed KIR2DS1. This could be explained by the ability of KIR2DS1 to directly recognize C2 on leukemia cells. A role of the KIR2DS2 activating receptor in leukemia cell lysis could not be demonstrated. Altogether, these results may have important clinical implications for the selection of optimal donors for haplo-HSCT.
Phospholipase D1 is specifically required for regulated secretion of von Willebrand factor from endothelial cells
Authors: Disse Jennifer , Vitale Nicolas , Bader Marie-France , Gerke Volker
Published: October 2008

Endothelial cells regulate thrombosis, hemostasis, and inflammatory responses by supplying the vasculature with several factors that include procoagulant von Willebrand factor (VWF) and fibrinolytic tissue-type plasminogen activator (tPA). Both proteins can be secreted in a Ca2+-regulated manner after endothelial activation but exhibit opposing physiologic effects. In search for factors that could modulate endothelial responses by selectively affecting the secretion of procoagulant or anticoagulant proteins, we identify here phospholipase D1 (PLD1) as a specific regulator of VWF secretion. PLD1 is translocated to the plasma membrane upon stimulation of endothelial secretion, and this process correlates with the generation of phosphatidic acid (PA) in the plasma membrane. Histamine-evoked secretion of VWF, but not tPA, is inhibited by blocking PLD-mediated production of PA, and this effect can be attributed to PLD1 and not PLD2. Thus, different mechanisms appear to control the agonist-induced secretion of VWF and tPA, with only the former requiring PLD1.
Shear activates platelet-derived latent TGF-β
Authors: Miyazono Kohei
Published: October 2008

Although platelets are a rich source of latent TGF-β it has not been determined how platelet-derived latent TGF-β is activated in vivo. In this issue of Blood, Ahamed and colleagues report that shear and stirring efficiently activate the latent TGF-β.
PRELI is a mitochondrial regulator of human primary T-helper cell apoptosis, STAT6, and Th2-cell differentiation
Authors: Tahvanainen Johanna , Kallonen Teemu , Lähteenmäki Hanna , Heiskanen Kaisa M. , Westermarck Jukka , Rao Kanury V. S. , Lahesmaa Riitta
Published: October 2008

The identification of novel factors regulating human T helper (Th)–cell differentiation into functionally distinct Th1 and Th2 subsets is important for understanding the mechanisms behind human autoimmune and allergic diseases. We have identified a protein of relevant evolutionary and lymphoid interest (PRELI), a novel protein that induces oxidative stress and a mitochondrial apoptosis pathway in human primary Th cells. We also demonstrated that PRELI inhibits Th2-cell development and down-regulates signal transducer and activator of transcription 6 (STAT6), a key transcription factor driving Th2 differentiation. Our data suggest that calpain, an oxidative stress–induced cysteine protease, is involved in the PRELI-induced down-regulation of STAT6. Moreover, we observed that a strong T-cell receptor (TCR) stimulus induces expression of PRELI and inhibits Th2 development. Our results suggest that PRELI is involved in a mechanism wherein the strength of the TCR stimulus influences the polarization of Th cells. This study identifies PRELI as a novel factor influencing the human primary Th-cell death and differentiation.
Effects of eradication of Helicobacter pylori infection in patients with immune thrombocytopenic purpura: a systematic review
Authors: Stasi Roberto , Sarpatwari Ameet , Segal Jodi B. , Osborn John , Evangelista Maria Laura , Cooper Nichola , Provan Drew , Newland Adrian , Amadori Sergio , Bussel James B.
Published: October 2008

Whether the eradication of Helicobacter pylori infection can increase the platelet count in patients with immune thrombocytopenic purpura (ITP) is still a controversial issue. To provide evidence-based guidance, we performed a systematic review of the literature published in English, selecting articles reporting 15 or more total patients. We identified 25 studies including 1555 patients, of whom 696 were evaluable for the effects of H pylori eradication on platelet count. The weighted mean complete response (platelet count ≥ 100 × 109/L) and overall response (platelet count ≥ 30 × 109/L and at least doubling of the basal count) were 42.7% (95% confidence interval [CI], 31.8%-53.9%) and 50.3% (95% CI, 41.6%-59.0%), respectively. In 222 patients with a baseline platelet count less than 30 × 109/L, the complete response rate was 20.1% (95% CI, 13.5%-26.7%) and the overall response rate was 35.2% (95% CI, 28.0%-42.4%). The response rate tended to be higher in countries with a high background prevalence of H pylori infection and in patients with milder degrees of thrombocytopenia. These findings suggest that the detection and eradication of H pylori infection should be considered in the work-up of patients with seemingly typical ITP.
MGUS: not so benign after all
Authors: Kovacs Michael J.
Published: October 2008

In this issue of Blood, Kristinsson and colleagues provide evidence that MGUS is a risk factor for the development of DVT.
The hematopoiesis paradigm: clarity or ambiguity?
Authors: Rathinam Chozhavendan , Flavell Richard A.
Published: October 2008

For several years, the lineage differentiation program of HSCs was believed to be well organized and unidirectional. However, data from recent studies question the commitment of lineage-restricted progenitors to a single lineage. Now, interesting work by Welner and colleagues presented in this issue of Blood suggests that the lineage differentiation pathways may be more complicated than initially thought.
E-selectin prefers fatty-sweet receptors on rolling neutrophils
Authors: Simon Scott I.
Published: October 2008

In this issue of Blood, Nimrichter and colleagues have defined the structure and function of distinct E-selectin ligands on the plasma membrane of neutrophils. They demonstrate that as few as 60 receptors/μm2 of these sialylated and fucosylated glycolipids facilitate neutrophil capture and rolling at sites of acute inflammation.
Differentiation syndrome in patients with acute promyelocytic leukemia treated with all-trans retinoic acid and anthracycline chemotherapy: characteristics, outcome, and prognostic factors
Authors: Montesinos Pau , Bergua Juan M. , Vellenga Edo , Rayón Chelo , Parody Ricardo , de la Serna Javier , León Angel , Esteve Jordi , Milone Gustavo , Debén Guillermo , Rivas Concha , González Marcos , Tormo Mar , Díaz-Mediavilla Joaquín , González Jose D. , Negri Silvia , Amutio Elena , Brunet Salut , Lowenberg Bob , Sanz Miguel A.
Published: October 2008

Differentiation syndrome (DS) can be a life-threatening complication in patients with acute promyelocytic leukemia (APL) undergoing induction therapy with all-trans retinoic acid (ATRA). Detailed knowledge about DS has remained limited. We present an analysis of the incidence, characteristics, prognostic factors, and outcome of 739 APL patients treated with ATRA plus idarubicin in 2 consecutive trials (Programa Español de Tratamientos en Hematología [PETHEMA] LPA96 and LPA99). Overall, 183 patients (24.8%) experienced DS, 93 with a severe form (12.6%) and 90 with a moderate form (12.2%). Severe but not moderate DS was associated with an increase in mortality. A bimodal incidence of DS was observed, with peaks occurring in the first and third weeks after the start of ATRA therapy. A multivariate analysis indicated that a WBC count greater than 5 × 109/L and an abnormal serum creatinine level correlated with an increased risk of developing severe DS. Patients receiving systematic prednisone prophylaxis (LPA99 trial) in contrast to those receiving selective prophylaxis with dexamethasone (LPA96 trial) had a lower incidence of severe DS. Patients developing severe DS showed a reduced 7-year relapse-free survival in the LPA96 trial (60% vs 85%, P = .003), but this difference was not apparent in the LPA99 trial (86% vs 88%).
Placenta growth factor induces 5-lipoxygenase–activating protein to increase leukotriene formation in sickle cell disease
Authors: Patel Nitin , Gonsalves Caryn S. , Yang Minyang , Malik Punam , Kalra Vijay K.
Published: October 2008

Individuals with sickle cell disease (SCD) have increased inflammation, a high incidence of airway hyperreactivity (AH), and increased circulating leukotrienes (LT). We show that expression of 5-lipoxygenase and 5-lipoxygenase activating protein (FLAP), key catalytic molecules in the LT pathway, were significantly increased in peripheral blood mononuclear cells (MNCs) in patients with SCD, compared with healthy controls. Placenta growth factor (PlGF), elaborated from erythroid cells, activated MNC and THP-1 monocytic cells to induce LT production. PlGF-mediated increased FLAP mRNA expression occurred via activation of phosphoinositide-3 (PI-3) kinase, nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, and hypoxia inducible factor-1α (HIF-1α). HIF-1α small interfering RNA (siRNA) reduced PlGF-induced FLAP expression. FLAP promoter-driven luciferase constructs demonstrated that PlGF-mediated luciferase induction was abrogated upon mutation of HIF-1α response element (HRE), but not the nuclear factor-κB (NF-κB) site in the FLAP promoter; a finding confirmed by chromatin immunoprecipitation (ChIP) analysis. PlGF also increased HIF-1α binding to the HRE in the FLAP promoter. Therefore, it is likely that the intrinsically elevated levels of PlGF in SCD subjects contribute to increased LT, which in turn, mediate both inflammation and AH. Herein, we identify a mechanism of increased LT in SCD and show HIF-1α as a hypoxia-independent target of PlGF. These studies provide new avenues to ameliorate these complications.
Why is CLL refractory to bortezomib?
Authors: Wickremasinghe Ranmohan Gitendra
Published: October 2008

In this issue of Blood, Liu and colleagues present evidence that flavonoids present in plasma may compromise the ability of the proteasome inhibitor bortezomib to induce apoptosis of CLL cells.
The origins of the identification and isolation of hematopoietic stem cells, and their capability to induce donor-specific transplantation tolerance and treat autoimmune diseases
Authors: Weissman Irving L. , Shizuru Judith A.
Published: October 2008

Advances in the understanding of the cells of the hematopoietic system have provided a rich basis for improving clinical hematopoietic cell transplants; finding and using proteins and molecules to amplify or suppress particular blood cell types; understanding the stepwise progression of preleukemic stages leading first to chronic myeloid disorders, then the emergence of acute blastic leukemias; and treating malignant and nonmalignant diseases with cell subsets. As a result of intense scientific investigation, hematopoietic stem cells (HSCs) have been isolated and their key functional characteristics revealed—self-renewal and multilineage differentiation. These characteristics are now found to be present in all tissue/organ stem cell studies, and even in the analysis of pluripotent embryonic, nuclear transfer, and induced pluripotent stem cells. Studies on HSC have identified hematopoiesis as one of the best systems for studying developmental cell lineages and as the best for understanding molecular changes in cell fate decision-making and for finding preclinical and clinical platforms for tissue and organ replacement, regeneration, and oncogenesis. Here we review the steps, from our viewpoint, that led to HSC isolation and its importance in self-nonself immune recognition.