bluuebunny/crossref_metadata_2025 huggingface dataset:
Traumatic Brain Injury in Children and Adolescents: Surveillance for Pituitary Dysfunction
Authors: Norwood Kenneth W. , DeBoer Mark D. , Gurka Matthew J. , Kuperminc Michelle N. , Rogol Alan D. , Blackman James A. , Wamstad Julia B. , Buck Marcia L. , Patrick Peter D.
Published: August 2010

Background. Children who sustain traumatic brain injury (TBI) are at risk for developing hypopituitarism, of which growth hormone deficiency (GHD) is the most common manifestation. Objective. To determine the prevalence of GHD and associated features following TBI among children and adolescents. Study design. A total of 32 children and adolescents were recruited from a pediatric TBI clinic. Participants were diagnosed with GHD based on insufficient growth hormone release during both spontaneous overnight testing and following arginine/glucagon administration. Results. GHD was diagnosed in 5/32 participants (16%). Those with GHD exhibited more rapid weight gain following injury than those without GHD and had lower levels of free thyroxine and follicle-stimulating hormone. Males with GHD had lower testosterone levels. Conclusions. GHD following TBI is common in children and adolescents, underscoring the importance of assessing for GHD, including evaluating height and weight velocities after TBI. Children and adolescents with GHD may further exhibit absence or intermediate function for other pituitary hormones.
Physical Versus Mental Predictors of Mortality Among the Old-Old in Israel: The CALAS Study
Authors: Ben-Ezra Menachem , Shmotkin Dov
Published: August 2010

When risk factors are examined concurrently, they tend to show mixed results in predicting mortality among the old-old. The purpose of this study was to compare a set of physical predictors with a set of mental predictors, all considered as most common and predictive in the literature, to assess their relative dominance in predicting mortality at old-old age. Based on Baltes’s incomplete architecture model and the disablement process, the authors postulated that physical predictors of mortality would diminish the impact of mental predictors of mortality. The database used for this study was the multidimensional survey of the Cross-Sectional and Longitudinal Aging Study conducted from 1989 to 1992 with a follow-up of mortality after 10 years. Participants ( N = 1,369) were drawn from a national sample of the Jewish Israeli population aged 75 to 94. The mean age of the sample was 83.52 ( SD = 5.42). Results of hierarchical Cox regression models showed that besides sociodemographic effects (mainly age, gender, and marital status), physical disability, physician visits, and medication consumption predicted mortality. Mental predictors (cognitive impairment and life evaluation) lost their predictive power when the physical predictors were introduced. Hence, biological and physical risk factors predominated over mental risk factors when examining prediction of mortality among the old-old age population.
Is the Household-Based Convoy a Role-Related Support Network?
Authors: Chen Chaonan , Liao Pei-shan , Lin Hui-lin
Published: August 2010

Based on role theory, a household-based convoy (HbC) was proposed as a support system comprised of four kinds of networks: household types, family, kinship, and friendship. To test the feasibility of the support network concept, data from the 2001 Taiwan Social Change Survey were used to derive a latent structure with four latent classes. These classes consisted of the “prefamily convoy,” “pro-social convoy,” “mature convoy,” and the “extended convoy.” Their network characteristics revealed that the four latent classes corresponded to stages in the family life course. Moreover, these convoy subtypes had differential intergenerational support functions. Respondents from the pre-family and the pro-social convoys were found to provide fewer types of support to their parents but received more types of support from them. The findings also indicate that the household-based convoy is a role-related support network.
Completion of Advance Directives Among Korean American and Non-Hispanic White Older Adults
Authors: Ko Eunjeong , Lee Jaehoon
Published: August 2010

This study examines completion of advance directives, highlighting ethnic differences between Korean and non-Hispanic White older adults in relation to health beliefs and knowledge. In this study, 217 community-dwelling older adults (112 Korean Americans and 105 non-Hispanic Whites) were interviewed using structured questionnaires. As compared to only 5.4% ( n = 6) of Korean American older adults, more than half of non-Hispanic White older adults (59.2%, n = 61) had completed advance directives. Health beliefs, but not knowledge, significantly mediated the relationship between ethnicity and completion of advance directives; Korean Americans had lower levels of health beliefs toward advance care planning than non-Hispanic Whites, and this in turn led to relatively lower rates of completing advance directives. Thus, it is advised that health care practice needs to encompass older adults’ health beliefs, which may be uniquely represented among different ethnic groups.
A Longitudinal Investigation of Work-Family Strains and Gains, Work Commitment, and Subsequent Employment Status Among Partnered Working Mothers
Authors: Mulvaney Matthew K. , McNall Laurel A. , Morrissey Rebecca A.
Published: August 2010

The purpose of this study was to examine the influence of the work—family interface on mothers’ commitment to work and the implications of that work commitment for subsequent employment. The study included a sample of employed partnered mothers who participated in the National Institute of Child Health and Human Development Study of Early Child Care and Youth Development, all of whom had given birth at the beginning of the study. Longitudinal analyses were specified to isolate the predictors of change in work commitment during the first 3 years following childbirth. Results indicate that perceived work—family strains were uniquely associated with decreased work commitment whereas perceived work—family gains were uniquely associated with increased work commitment during this period. In addition, greater work commitment during the first 3 years following childbirth was associated with a greater likelihood that the woman would be employed 9 years later. Implications are discussed.
Housing Dependence and Intimate Relationships in the Lives of Low-Income Puerto Rican Mothers
Authors: Lawson Clark Sherri , Burton Linda M. , Flippen Chenoa A.
Published: August 2010

Using longitudinal ethnographic data from the Three-City Study, the authors examined the relationship between 16 low-income Puerto Rican mothers’ housing dependencies and their intimate partner relations. This study traced mothers’ dependent housing arrangements and entrée to marital or cohabiting relationships from their teens through their procurement of independent housing while entering and maintaining intimate partner unions as adults. Findings indicated that various trigger factors led women out of their natal homes and into expedited cohabitation with romantic partners, which frequently resulted in unstable unions in which mothers had little power and autonomy. As mothers became eligible for housing subsidies they obtained housing independent from their male partners, potentially increasing the propensity for greater relationship power. Housing independence, however, was not without problems. Spillover effects, such as shadowing partners, threatened housing stability, and mothers’ independence. The relevance of these findings for future research is discussed.
The Official Knowledge and Adult Education Agents: An Ethnographic Study of the Adult Education Team of a Local Development-Oriented Nongovernmental Organization in the North of Portugal
Authors: Loureiro Armando Paulo Ferreira , Cristóvão Artur Fernando Arêde Correia
Published: August 2010

Nongovernmental organizations, particularly those related to development work (local development-oriented nongovernmental organizations; LDNGO), and their agents have been assuming, in Portugal, an important role in the field of adult education. These organizations develop with the State, at the national level, and with supranational institutions and programs different types of relationships and arrangements, as a result of the activity in such educational arena. This article intends to question, on the basis of an ethnographic study of an adult education team of an LDNGO and using the pedagogical discourse model of Bernstein, the relationship that these agents establish with the official knowledge (pedagogical discourse) emerging from State-dependent intervention bodies. The results of the study shows that, even in strongly prescriptive working contexts, it is possible to develop an active relationship with the official knowledge and make recontextualizing uses of it.
Incidental Neuroimaging Findings in Nonacute Headache
Authors: Graf William D. , Kayyali Husam R. , Abdelmoity Ahmed T. , Womelduff Gloria L. , Williams Arthur R. , Morriss Michael C.
Published: August 2010

We studied the frequency and consequences of incidental neuroimaging findings in 400 otherwise healthy, nonacute pediatric headache patients through a retrospective, cross-sectional analysis. We excluded patients with currently recommended clinical criteria to consider diagnostic neuroimaging. We categorized neuroimaging results as normal, remarkable without clinical action, remarkable with clinical follow-up action, and abnormal. One hundred eighty-five of 400 patients (46%) had neuroimaging. Of these, 78.4% of neuroimaging studies were normal, and none was considered abnormal. Also, 21.5% had remarkable findings in the neuroradiology report. The frequency and types of all incidental findings were generally comparable to previous studies. One third of these patients received further consultation or neuroimaging because of incidental findings. In the evaluation of nonacute pediatric headache, overuse of neuroimaging leads to frequent discovery of incidental findings and increased testing. Individualized health care calls for physician-consumer discussions about current indications for neuroimaging, the general frequency of incidental findings, and potential difficulties in their interpretation.
Longitudinal Research With Sexual Assault Survivors: A Methodological Review
Authors: Campbell Rebecca , Brown Sprague Heather , Cottrill Sara , Sullivan Cris M.
Published: August 2010

Longitudinal research designs are relatively rare in the academic literature on rape and sexual assault despite their tremendous methodological rigor and scientific utility. In the interest of promoting wider use of such methods, we conducted a methodological review of projects that have used prospective longitudinal designs to study the occurrence of sexual victimization throughout the lifespan and/or the process of change during rape recovery ( N = 32 projects). Five questions were examined: (a) What were the substantive foci of these longitudinal studies? (b) How were survivors recruited? (c) What participation rates were typical? (d) How long were participants followed over time and with what success rates? and (e) What incentives were used to increase participation? Most studies focused on postassault sequelae and recruited survivors from hospital emergency departments and other first-response help-seeking sites with highly variable participation rates. Retention rates were comparable across studies (approximately 70%).
Degree of Exposure to Domestic Violence, Psychopathology, and Functional Impairment in Children and Adolescents
Authors: Bayarri Fernàndez Eduard , Ezpeleta Lourdes , Granero Roser , de la Osa Núria , Domènech Josep María
Published: August 2010

There are discrepancies about whether children who witness and suffer domestic violence (DV) have similar outcomes in terms of psychopathology. This work examines the relationship between different types of exposure to DV and child psychopathology and functional impairment. One hundred and forty-four Spanish children aged from 4 to 17 years and exposed to DV were evaluated using a diagnostic interview and other instruments of psychopathology and functional impairment. The participants were classified in three groups according to the degree of exposure: witness ( n = 72), involved ( n = 52), and victim ( n = 20). According to mothers’ self-reports and mother—child combined information, DV equally affects psychopathology and functional impairment regardless of the degree of the exposure. Children’s self-reports showed a linear trend to present greater psychopathology as a victim than as a witness. The differential effect of exposure to DV measured in this study depended on the informant, which underlines the importance of obtaining information from the children exposed to violence at home.
Prospective Changes in Attributions of Self-Blame and Social Reactions to Women’s Disclosures of Adult Sexual Assault
Authors: Ullman Sarah E. , Najdowski Cynthia J.
Published: August 2010

The present longitudinal study examined relationships between self-blame attributions and social reactions to disclosure in a community sample of adult sexual assault victims ( N = 555). Cross-lagged panel analyses showed that neither characterological self-blame nor behavioral self-blame related to negative social reactions over the 1-year follow-up period. In contrast, characterological but not behavioral self-blame predicted fewer positive reactions over time. Although positive reactions did not reduce self-blame, negative reactions led to greater characterological, but not behavioral, self-blame during the course of the study. Thus, relationships between self-blame and social reactions were not reciprocal but rather quite complex. The effects of victims’ coping strategies and sexual revictimization were also assessed.
“Our Club”: Place-Work and the Negotiation of Collective Belongingness
Authors: Hochschild Thomas R.
Published: August 2010

This research examines the process by which vying social groups negotiate collective belongingness within contested space. At an American Legion veterans’ post, two factions—the Skeet Club and the New Regime—developed strong emotional attachments to the location. The Skeet Club consisted of ineligible townspeople who had illegally gained access to the post through the help of several legitimate members. For Skeet Club members, the post was a beloved social club where strong social bonds had developed over the course of many years. For the New Regime, the post was first and foremost a shrine to honor and assist military veterans. These divergent interpretations resulted in a process the author calls place-work, whereby members of the two factions struggled to establish a definition of the location that would allow their respective groups to feel that “we belong.” The four place-work strategies observed include (1) the presentation of group value, (2) deference to organizational culture, (3) spatial control, and (4) out-group intimidation. Through these strategies, “collective belongingness” was constructed, presented, and maintained as a resource in intergroup conflict. This study builds on the literatures regarding place, emotion, and intergroup conflict.
Climate and anthropogenic factors affecting alluvial fan development during the late Holocene in the central Ebro Valley, northeast Spain
Authors: Constante Ana , Peña José Luis , Muñoz Arsenio , Picazo Jesús
Published: August 2010

The late Holocene in the central Ebro Depression is characterized by a number of morphodynamic stages that affected hillslopes and channels. Climate fluctuations and human activities together caused severe erosion and floods, resulting in alternating stages of accumulation and incision in the valley floors. Seven accumulation levels (N6-N0) correlated with Ebro River fluvial terraces have been identified in the secondary fluvial network of the central Ebro Depression. The main accumulation level (N3) corresponds to a long period of increased hillslope erosion and sedimentation in the valleys, from the Neolithic to the late Roman periods. The accumulation levels are evident throughout the valleys and extend to the valley mouths, where many connect with alluvial fans. The study of several sedimentological profiles, 14C AMS dating, and many archaeological remnants, have enabled detailed assessment of sedimentation characteristics in the alluvial fans and the relationship thereof to the presence of human settlements. Four sedimentation stages have been identified: (i) pre-Bronze Age (> 3800 years BP), (ii) Bronze Age/Iron Age (3800-2500 years BP), (iii) Roman/post-Roman period (2500-1500 years BP), and, (iv) the early Middle Ages, mainly during the Visigothic period (sixth century). The sedimentation dynamics of the alluvial fans are related to: (i) climate variability, (ii) human activities in the watershed, and (iii) the meandering character of the Ebro River, which has lateral displacements that change the local base level of tributaries and fans. Level N3 in the valley floors corresponds to stages i-iii of the alluvial fans, which are mostly related to human-induced transformation of characteristics of the secondary basins, coinciding with enhanced erosion under favorable (warm and humid) climatic conditions. In contrast, the Medieval stage, which corresponds to level N2 in the valleys, was caused by floods during a period of high climatic variability.
Seamless phase II/III designs
Authors: Stallard Nigel , Todd Susan
Published: August 2010

In recent years, there has been a drive to save development costs and shorten time-to-market of new therapies. Research into novel trial designs to facilitate this goal has led to, amongst other approaches, the development of methodology for seamless phase II/III designs. Such designs allow treatment or dose selection at an interim analysis and comparative evaluation of efficacy with control, in the same study. Methods have gained much attention because of their potential advantages compared to conventional drug development programmes with separate trials for individual phases. In this article, we review the various approaches to seamless phase II/III designs based upon the group-sequential approach, the combination test approach and the adaptive Dunnett method. The objective of this article is to describe the approaches in a unified framework and highlight their similarities and differences to allow choice of an appropriate methodology by a trialist considering conducting such a trial.
Age-Based Faultlines and Perceived Productive Energy: The Moderation of Transformational Leadership
Authors: Kunze Florian , Bruch Heike
Published: August 2010

This article addresses the role of age-based faultlines in relation to the perceived productive energy of work teams and transformational leadership as a potential moderator of this relationship. Based on social identity and social categorization theory, teams that have strong age-based faultlines— defined as age subgroup formation that is reinforced by internal alignment with other demographic characteristics (tenure and sex)—should show a lower level of perceived productive energy than do teams that have weak faultlines. In teams with high levels of perceived transformational leadership, this effect should be reversed. Study hypotheses were tested on a sample of 664 individuals in 72 teams from a multinational company. Results showed a marginally significant negative relationship between age-based faultlines and teams’ productive energy, although the moderation effect of transformational leadership was found to be significant. These results point toward transformational leadership as a promising strategy for overcoming the negative effects of age-based faultlines in team settings.
Modularizing Small Group Theories in Sociology
Authors: Markovsky Barry
Published: August 2010

This article asserts that it is beneficial to formulate theories using methods specifically designed to facilitate and promote integrations. Although it is written using illustrations primarily from sociology, the discussion is relevant to other fields to whatever extent their theories may be deemed informal (i.e., presented without explicitly defined terms, distinct propositions, or logical calculi for deriving hypotheses). Constructing theories in a modular fashion makes the processes of development and explication more efficient, and the products more generally useful. Modules are semiautonomous components designed with sufficient flexibility that they can be assembled into larger combinations which are capable of generating explanations and predictions that individual modules could not manage alone. The general benefits of modularization are demonstrated for a variety of applications, and the argument is made that modularizing our theories would facilitate refinement, integration, and problem solving. Included are several illustrations in which two or more formal theories or parts of theories from the small group literature in sociology are linked in useful ways. More explicit attention to modularizing formal theories from the outset should enhance the potential for easier integrations and solutions to a broader array of substantive problems and applications.
Effects of Intergroup Dialogue: Public School Teachers and Sexual Orientation Prejudice
Authors: Dessel Adrienne B.
Published: August 2010

Prejudice and hate crimes against lesbians and gay men are prevalent throughout the United States. Prejudice in public school settings is particularly problematic for lesbian, gay, and bisexual (LGB) students and LGB parents. Efforts to reduce prejudice for LGB groups have met with limited success. Creating safer and more inclusive school environments is essential. An experimental mixed methods field design tested outcomes of an intergroup dialogue intervention on public school teacher attitudes, feelings, and behaviors toward LGB students and parents. Quantitative results indicate dialogue participation resulted in statistically significant positive changes in attitudes, feelings, and behaviors. Qualitative data analysis confirmed positive changes as a result of dialogue participation.
Managers’ Trait Emotional Intelligence and Group Outcomes: The Case of Group Job Satisfaction
Authors: Zampetakis Leonidas A. , Moustakis Vassilis
Published: August 2010

The purpose of this study is to extend the emerging literature on the effects of managers’ emotional skills on group outcomes. Specifically, the authors propose and test a theoretical model that examines impact of managers’ trait emotional intelligence (EI) on group job satisfaction. Data are based on middle managers and their immediate team members from public service organizations. Results, using Bayesian path analysis, indicate that middle managers’ trait EI has a significant indirect effect on group job satisfaction via group evaluative judgment toward manager’s trait EI. Results advance the emerging literature on the effects of team leader EI on group dynamics in the context where the manager holds legitimate authority.
Effects of Team Size and Work Team Perception on Workplace Commitment: Evidence From 23 Production Teams
Authors: Ogungbamila Bolanle , Ogungbamila Adepeju , Agboola Adetula Gabriel
Published: August 2010

This study investigated the influence of production team size (small vs. large) and employees’ perceptions of their production work teams (negative, neutral, and positive) on their level of workplace commitment.Twenty-three production work teams composed of 205 employees (105 males, 100 females), drawn from two team-based private manufacturing organizations, participated in the study. They responded to the workgroup functioning scale and Buchanan’s organizational commitment scale. Team size had no significant correlation with how employees perceived their production work team and their levels of workplace commitment. The results of the 2 × 3 analysis of variance indicated that production team size had no significant influence on workplace commitment. However, employees who had positive perceptions of their production work teams were significantly more committed to the workplace than were those who held either neutral or negative perceptions.
Factors Influencing People’s Acceptance of Gene Technology: The Role of Knowledge, Health Expectations, Naturalness, and Social Trust
Authors: Connor Melanie , Siegrist Michael
Published: August 2010

This article aims to examine which factors influence people’s perception of gene technology. Data come from a mail survey in the German speaking part of Switzerland ( N = 830). Principal component analyses for acceptance, risks, and benefits of 12 gene technology applications resulted in two factors: one related to medical applications and the other to nonmedical applications. Results showed that three different types of knowledge did not substantially influence perceived risks or perceived benefits of gene technology. Overall results suggest that the experiential system and not the analytical system determines lay people’s perception of gene technology.
Gender Differences in Scientists’ Public Outreach and Engagement Activities
Authors: Crettaz von Roten Fabienne
Published: August 2010

Science communication research has tended to focus on the perceptions of the public and has often neglected the views of scientists. This article analyzes public outreach and engagement attitudes and activities of women scientists; it is based on a case study conducted in Switzerland. The survey results found that attitudes toward public outreach and engagement activities are the same among men and women scientists, but that activities are done significantly more often by men scientists than by women scientists. A multivariate analysis showed that there is a gender difference in the level of activities even after the effects of position, age, and faculty are removed. Because public outreach and engagement activities may be due to either scientists’ initiatives or media initiatives, the author analyzed media contacts. The media contact women scientists less often than men scientists—and this independently of position, age, and faculty. When comparing men’s and women’s improvements for public outreach and engagement, this study found significant differences that can be used to tailor incentives for each group of scientists.
Evaluation of an Automated von Willebrand Factor Activity Assay in von Willebrand Disease
Authors: Trossaërt Marc , Ternisien Catherine , Lefrancois Armelle , Llopis Laura , Goudemand Jenny , Sigaud Marianne , Fouassier Marc , Caron Claudine
Published: August 2010

We evaluated the use of the turbidimetric HemosIL von Willebrand Factor (VWF) Activity assay (VWF:Act) on the STA-R automated coagulometer (Stago, Asnières, France) for the diagnosis of von Willebrand disease (VWD). For this, we prospectively screened 268 patients. As a second part, we retrospectively assayed 111 patients with well-defined VWD subtype. In the first prospective study, we demonstrate that in most cases of VWD, VWF ristocetin cofactor activity (VWF:RCo) and VWF:Act are highly correlated but that they both cannot be considered a good screening assay when used alone, since they could miss about 25% of VWF abnormalities. However, the association of VWF:Act analysis and the Platelet Function Analyzer-100 (PFA-100) test constitutes an excellent screening strategy. In our second retrospective study concerning VWD subtypes, VWF:RCo and VWF:Act were well correlated but could be very discrepant, especially for some cases of type 2M VWD. We consider that VWF:RCo remains the “reference assay” for VWD subtype classification.
Vocabulary skills of Spanish—English bilinguals: impact of mother—child language interactions and home language and literacy support
Authors: Quiroz Blanca G. , Snow Catherine E. , Jing Zhao
Published: August 2010

Quantity and quality of home language use as well as home literacy resources are positively related to vocabulary knowledge among children growing up monolingually (De Temple & Snow, 2003; Juel, 1988; Snow, Burns, & Griffin, 1998; Stanovich, 1986). While the presence of interactive features associated with good vocabulary outcomes have been reported in Latino families (Jiménez, Filippini, & Gerber, 2006; Teale, 1986) no prospective studies relating those features to vocabulary outcomes in either Spanish or English have been carried out with Latino children. In particular, it is unclear whether interactions facilitate vocabulary across languages, or only for the language in which they occur. In this study, home factors (immigration history, home language use, home literacy resources) and the interactive language of 50 mother—child dyads sharing a picture-book were analyzed as predictors of the children’s vocabulary outcomes. The children were aged 4—5 and all were attending a Head Start program at the time of the study. Frequency of reading to the child by an adult other than the
Non-permanent Inferior Vena Cava Filters for Prophylaxis and Treatment of Lower Limb Venous Thromboembolisme
Authors: Hiromatsu Shinichi , Nata Shinichi , Ohno Tomokazu , Shintani Yusuke , Kanaya Kurando , Sakashita Hideki , Fukunaga Shuji , Aoyagi Shigeaki
Published: August 2010

Objectives: The purpose of this study was to evaluate and compare our recent clinical experience with temporary inferior vena cava (IVC) filters (TF) and retrievable IVC filters (RF). Materials and methods: Patients who received TF or RF implantation between October 2002 and May 2009 were studied. The early clinical outcomes between the 2 groups were compared.

Results: Nonpermanent IVC filters were placed in 119 patients (34 in TF and 85 in RF). Retrieval of RF and removal of TF were successful in 98.7% and 100%, respectively. The incidence of filter-related complications for TF was significantly higher than for RF (26.5% vs 3.5%; P = .0004). However, no symptomatic pulmonary embolism (PE) was observed during filter placement.

Conclusion: TF and RF provided similar protection from PE. We prefer RF because they can be left in permanently if it is impossible to remove or retrieve the filter for some reason.
Group Visits and Chronic Disease Management in Adults: A Review
Authors: Brennan Julie , Hwang Do , Phelps Kevin
Published: August 2010

Chronic disease management using the traditional 15-minute appointment is exceptionally challenging and arguably inadequate to provide comprehensive, prospective, patient-centered primary care. A model of care designed to promote patient education, patient self-management, and improved access to their physicians and other health care providers is needed. Group visits have been identified as one model that allows physicians to deliver extensive patient education and self-management instruction while enhancing financial productivity. A thorough review of the literature on group visits was performed. Fairly consistent results from level I and II quality of evidence from a revised Strength of Recommendation Taxonomy (SORT) rating system indicate that patients who attended group visits demonstrated improved standards of care, improved quality of life, greater patient and physician satisfaction, lower rates of hospitalization and emergency department utilization, and reduced specialty costs. Discrepancies from the literature review include body mass index, hemoglobin A1C, blood pressure, and lipids. Overall, group visits appear to provide an effective and complementary strategy to traditional primary care in dealing with the complexities of providing chronic disease management in an increasing complex and aging population.
Monocyte-bound PF4 in the pathogenesis of heparin-induced thrombocytopenia
Authors: Rauova Lubica , Hirsch Jessica D. , Greene Teshell K. , Zhai Li , Hayes Vincent M. , Kowalska M. Anna , Cines Douglas B. , Poncz Mortimer
Published: August 2010

Heparin-induced thrombocytopenia (HIT) is a life- and limb-threatening thrombotic disorder that develops after exposure to heparin, often in the setting of inflammation. We have shown previously that HIT is associated with antibodies to complexes that form between platelet factor 4 and glycosaminoglycan (GAG) side chains on the surface of platelets. However, thrombosis can occur in the absence of thrombocytopenia. We now show that platelet factor 4 binds to monocytes and forms antigenic complexes with their surface GAG side chains more efficiently than on platelets likely due to differences in GAG composition. Binding to monocytes is enhanced when the cells are activated by endotoxin. Monocyte accumulation within developing arteriolar thrombi was visualized by situ microscopy. Monocyte depletion or inactivation in vivo attenuates thrombus formation induced by photochemical injury of the carotid artery in a modified murine model of HIT while paradoxically exacerbating thrombocytopenia. These studies demonstrate a previously unappreciated role for monocytes in the pathogenesis of arterial thrombosis in HIT and suggest that therapies targeting these cells might provide an alternative approach to help limit thrombosis in this and possibly other thrombotic disorders that occur in the setting of inflammation.
Bone morphogenetic protein receptor II regulates pulmonary artery endothelial cell barrier function
Authors: Burton Victoria J. , Ciuclan Loredana I. , Holmes Alan M. , Rodman David M. , Walker Christoph , Budd David C.
Published: August 2010

Mutations in bone morphogenetic protein receptor II (BMPR-II) underlie most heritable cases of pulmonary arterial hypertension (PAH). However, less than half the individuals who harbor mutations develop the disease. Interestingly, heterozygous null BMPR-II mice fail to develop PAH unless an additional inflammatory insult is applied, suggesting that BMPR-II plays a fundamental role in dampening inflammatory signals in the pulmonary vasculature. Using static- and flow-based in vitro systems, we demonstrate that BMPR-II maintains the barrier function of the pulmonary artery endothelial monolayer suppressing leukocyte transmigration. Similar findings were also observed in vivo using a murine model with loss of endothelial BMPR-II expression. In vitro, the enhanced transmigration of leukocytes after tumor necrosis factor α or transforming growth factor β1 stimulation was CXCR2 dependent. Our data define how loss of BMPR-II in the endothelial layer of the pulmonary vasculature could lead to a heightened susceptibility to inflammation by promoting the extravasation of leukocytes into the pulmonary artery wall. We speculate that this may be a key mechanism involved in the initiation of the disease in heritable PAH that results from defects in BMPR-II expression.
Gene Expression Browser: large-scale and cross-experiment microarray data integration, management, search & visualization
Authors: Zhang Ming , Zhang Yudong , Liu Li , Yu Lijuan , Tsang Shirley , Tan Jing , Yao Wenhua , Kang Manjit S , An Yongqiang , Fan Xingming
Published: August 2010

Background

In the last decade, a large amount of microarray gene expression data has been accumulated in public repositories. Integrating and analyzing high-throughput gene expression data have become key activities for exploring gene functions, gene networks and biological pathways. Effectively utilizing these invaluable microarray data remains challenging due to a lack of powerful tools to integrate large-scale gene-expression information across diverse experiments and to search and visualize a large number of gene-expression data points.

Results

Gene Expression Browser is a microarray data integration, management and processing system with web-based search and visualization functions. An innovative method has been developed to define a treatment over a control for every microarray experiment to standardize and make microarray data from different experiments homogeneous. In the browser, data are pre-processed offline and the resulting data points are visualized online with a 2-layer dynamic web display. Users can view all treatments over control that affect the expression of a selected gene via Gene View, and view all genes that change in a selected treatment over control via treatment over control View. Users can also check the changes of expression profiles of a set of either the treatments over control or genes via Slide View. In addition, the relationships between genes and treatments over control are computed according to gene expression ratio and are shown as co-responsive genes and co-regulation treatments over control.

Conclusion

Gene Expression Browser is composed of a set of software tools, including a data extraction tool, a microarray data-management system, a data-annotation tool, a microarray data-processing pipeline, and a data search & visualization tool. The browser is deployed as a free public web service (http://www.ExpressionBrowser.com) that integrates 301 ATH1 gene microarray experiments from public data repositories (viz. the Gene Expression Omnibus repository at the National Center for Biotechnology Information and Nottingham Arabidopsis Stock Center). The set of Gene Expression Browser software tools can be easily applied to the large-scale expression data generated by other platforms and in other species.
Retinoic acid accelerates downregulation of the Xist repressor, Oct4, and increases the likelihood of Xist activation when Tsix is deficient
Authors: Ahn Janice Y , Lee Jeannie T
Published: August 2010

Background

Imbalances in X-linked gene dosage between the sexes are resolved by transcriptionally silencing one of two X-chromosomes in female cells of the early mammalian embryo. X-inactivation is triggered by expression of the non-coding Xist gene. In turn, Xist is dually regulated by the antisense Tsix RNA and by the Oct4 pluripotency factor. Although there is general agreement that Tsix is an inhibitor of Xist, some laboratories have observed ectopic Xist induction in differentiating male ES cells when Tsix is mutated, whereas we have not observed significant changes in Xist. These observational differences have led to fundamentally diverse models of X-chromosome counting. Here, we investigate if different methods of cell differentiation and use of all -trans retinoic acid (RA) could be causative factors and how they might impact Xist expression.

Results

We compared suspension and cell-adhesion cultures in the presence or absence of RA and find that RA significantly impacts Xist expression in Tsix-mutant male cells. Whereas the standard embryoid body method infrequently leads to ectopic Xist expression, adding RA generates a significant number of Xist-positive male cells. However, while normal Xist clouds in wild-type female cells are robust and well-circumscribed, those found in the RA-treated mutant males are loosely dispersed. Furthermore, ectopic Xist expression does not generally lead to complete gene silencing. We attribute the effect of RA on Xist to RA's repressive influence on Oct4, a pluripotency factor recently shown to regulate Tsix and Xist. RA-treated ES cells exhibit accelerated decreases in Oct4 RNA levels and also display accelerated loss of binding to Xist intron 1. When Tsix is deficient, the faster kinetics of Oct4 loss tip the equilibrium towards Xist expression. However, the aberrant Xist clusters are unlikely to explain elevated cell death, as X-linked silencing does not necessarily correlate with the qualitatively aberrant Xist clusters.

Conclusions

We conclude that RA treatment leads to premature downregulation of Oct4 and partial derepression of Xist irrespective of X-chromosome counting. RA-induced Xist clusters in male cells do not result in global or stable silencing, and excess cell death is not observed. These data and RA's known pleiotropic effects on ES transcription networks suggest that RA differentation bypasses normal X-inactivation controls and should be used judiciously. We propose that the likelihood of Xist expression is determined by a balance of multiple Xist activators and repressors, and that levels of Oct4 and Tsix are crucial toward achieving this balance.
Surveillance of pyrazinamide susceptibility among multidrug-resistant Mycobacterium tuberculosis isolates from Siriraj Hospital, Thailand
Authors: Jonmalung Jirarut , Prammananan Therdsak , Leechawengwongs Manoon , Chaiprasert Angkana
Published: August 2010

Background

Susceptibility testing of pyrazinamide (PZA) against Mycobacterium tuberculosis is difficult to perform because the acidity of culture medium that is required for drug activity also inhibits the growth of bacteria. In Thailand, very limited information has been generated on PZA resistance, particularly among multidrug-resistant tuberculosis (MDR-TB) isolated from Thailand. Only two studies on PZA susceptibility among Thai M. tuberculosis strains have been reported; one used a pyrazinamidase assay, and the other used the BACTEC 460 TB for PZA susceptibility testing. In this study, we determined the percentage of strains possessing pyrazinamide resistance among pan-susceptible M. tuberculosis and MDR-TB isolates by using the pyrazinamidase assay, BACTEC MGIT 960 PZA method and pncA sequencing, and assessed the correlation in the data generated using these methods. The type and frequency of mutations in pncA were also determined.

Results

Overall, 150 M. tuberculosis isolates, consisting of 50 susceptible and 100 MDR-TB isolates, were tested for PZA susceptibility by BACTEC MGIT 960 PZA, the pyrazinamidase assay and pncA sequencing. The study indicated PZA resistance in 6% and 49% of susceptible and MDR-TB isolates, respectively. In comparison to the BACTEC MGIT 960 PZA, the PZase assay showed 65.4% sensitivity and 100% specificity, whereas pncA sequencing showed 75% sensitivity and 89.8% specificity. Twenty-four mutation types were found in this study, with the most frequent mutation (16%) being His71Asp. Of these mutations, eight have not been previously described. The Ile31Ser and Ile31Thr mutations were found both in PZA susceptible and resistant isolates, suggesting that mutation of this codon might not play a role on PZA resistance.

Conclusions

Our findings suggest that phenotypic susceptibility testing is still essential for the detection of PZA resistance, especially for MDR-TB isolates. Some mutations were not associated with resistance and could lead to misinterpretation of the genotypic methods. This information could be helpful for clinicians in managing tuberculosis patients and frequencies, and the types of pncA mutations should offer baseline information on PZA resistance.
Effects of cellular iron deficiency on the formation of vascular endothelial growth factor and angiogenesis.
Authors: Eckard Jonathan , Dai Jisen , Wu Jing , Jian Jinlong , Yang Qing , Chen Haobin , Costa Max , Frenkel Krystyna , Huang Xi
Published: August 2010

Background

Young women diagnosed with breast cancer are known to have a higher mortality rate from the disease than older patients. Specific risk factors leading to this poorer outcome have not been identified. In the present study, we hypothesized that iron deficiency, a common ailment in young women, contributes to the poor outcome by promoting the hypoxia inducible factor-1α (HIF-1α and vascular endothelial growth factor (VEGF) formation. This hypothesis was tested in an in vitro cell culture model system.

Results

Human breast cancer MDA-MB-231 cells were transfected with transferrin receptor-1 (TfR1) shRNA to constitutively impair iron uptake. Cellular iron status was determined by a set of iron proteins and angiogenesis was evaluated by levels of VEGF in cells as well as by a mouse xenograft model. Significant decreases in ferritin with concomitant increases in VEGF were observed in TfR1 knockdown MDA-MB-231 cells when compared to the parental cells. TfR1 shRNA transfectants also evoked a stronger angiogenic response after the cells were injected subcutaneously into nude mice. The molecular mechanism appears that cellular iron deficiency elevates VEGF formation by stabilizing HIF-1α. This mechanism is also true in human breast cancer MCF-7 and liver cancer HepG2 cells.

Conclusions

Cellular iron deficiency increased HIF-1α, VEGF, and angiogenesis, suggesting that systemic iron deficiency might play an important part in the tumor angiogenesis and recurrence in this young age group of breast cancer patients.
Kinetics of angiogenic changes in a new mouse model for hepatocellular carcinoma
Authors: Heindryckx Femke , Mertens Koen , Charette Nicolas , Vandeghinste Bert , Casteleyn Christophe , Van Steenkiste Christophe , Slaets Dominique , Libbrecht Louis , Staelens Steven , Starkel Peter , Geerts Anja , Colle Isabelle , Van Vlierberghe Hans
Published: August 2010

Background

The increasing incidence of hepatocellular carcinoma in Western countries has led to an expanding interest of scientific research in this field. Therefore, a vast need of experimental models that mimic the natural pathogenesis of hepatocellular carcinoma (HCC) in a short time period is present. The goal of our study was (1) to develop an efficient mouse model for HCC research, in which tumours develop in a natural background of fibrosis and (2) to assess the time-dependent angiogenic changes in the pathogenesis of HCC.

Methods

Weekly intraperitoneal injections with the hepatocarcinogenic compound N-nitrosodiethylamine was applied as induction method and samples were taken at several time points to assess the angiogenic changes during the progression of HCC.

Results

The N-nitrosodiethylamine-induced mouse model provides well vascularised orthotopic tumours after 25 weeks. It is a representative model for human HCC and can serve as an excellent platform for the development of new therapeutic targets.
Studies on antidyslipidemic effects of Morinda citrifolia (Noni) fruit, leaves and root extracts
Authors: Mandukhail Saf-ur Rehman , Aziz Nauman , Gilani Anwarul-Hassan
Published: August 2010

Background

The objective of present study was to provide the pharmacological basis for the medicinal use ofMorinda citrifoliaLinn in dyslipidemia using the aqueous-ethanolic extracts of its fruits (Mc.Cr.F), leaves (Mc.Cr.L) and roots (Mc.Cr.R).

Results

Mc.Cr.F, Mc.Cr.L and Mc.Cr.R showed antidyslipidemic effects in both triton (WR-1339) and high fat diet-induced dyslipidemic rat models to variable extents. All three extracts caused reduction in total cholesterol and triglyceride levels in triton-induced dyslipidemia. In high fat diet-induced dyslipidemia all these extracts caused significant reduction in total cholesterol, triglyceride, low density lipoprotein-cholesterol (LDL-C), atherogenic index and TC/HDL ratio. Mc.Cr.R extract also caused increase in high density lipoprotein-cholesterol (HDL-C). The Mc.Cr.L and Mc.Cr.R reduced gain in body weight with a reduction in daily diet consumption but Mc.Cr.F had no effect on body weight and daily diet consumption.

Conclusions

These data indicate that the antidyslipidemic effect of the plant extracts was meditated through the inhibition of biosynthesis, absorption and secretion of lipids. This may be possibly due partly to the presence of antioxidant constituents in this plant. Therefore, this study rationalizes the medicinal use ofMorinda citrifoliain dyslipidemia.