bluuebunny/crossref_metadata_2025 huggingface dataset:
The Feasibility of Computer-Assisted Survey Interviewing in Africa
Authors: Hewett Paul C. , Erulkar Annabel S. , Mensch Barbara S.
Published: July 2004

This article explores the use of an audio computer-assisted self-interviewing (audio-CASI) methodology in a household survey of adolescents in two districts of Kenya. Computer software was developed as part of a research project comparing audio-CASI with traditional methods of interviewing about sensitive behaviors, including sexual initiation, risky sexual behavior, coerced sex, and drug and alcohol use. The article describes the experience of carrying out a household-based study using computers and explores the technical challenges faced by the data-collection teams. Few problems emerged with the computer hardware and software despite the difficult interviewing conditions. The adolescent respondents easily adapted to the computerized interview and were able to complete the survey with minimal assistance. However, the computers were not a completely neutral part of the data-collection process and added to problems encountered during the fieldwork in one of the districts. Unexpected findings regarding respondents’ perceptions of privacy and confidentiality were also observed.
Internet Use in the State Legislature
Authors: Cooper Christopher A.
Published: July 2004

Using a survey of state legislators in Iowa, Georgia, and California, this article examines how often legislators use the Internet as a source for policy information, and which legislators tend to make more frequent use of the Internet to gather information. The author finds that there is tremendous variation as to how often state legislators use the Internet to gather policy information. The author did not find evidence of a digital divide as it pertains to urbanism, or gender. It appears that a digital divide remains, however, between young and old legislators—with younger legislators using the Internet more often— and legislators in California versus legislators in Georgia and Iowa. In the end, it appears that the digital divide in the state legislature is shrinking. As the older generation of legislators retires, the author expects that the Internet will become a more institutionalized part of the information environment of state legislators.
The Effects of Cash, Electronic, and Paper Gift Certificates as Respondent Incentives for a Web-Based Survey of Technologically Sophisticated Respondents
Authors: Birnholtz Jeremy P. , Horn Daniel B. , Finholt Thomas A. , Bae Sung Joo
Published: July 2004

An experiment was conducted to determine the effectiveness of three invitation and incentivecombinations in a web-based survey. A stratified convenience sample of 434 researchers who were target users of a collaboratory for earthquake engineering was randomly divided into three experimental conditions: (a) a $5 bill sent with the survey instructions via first class mail, (b) a $5 gift certificate code to Amazon.com sent with the survey instructions via first-class mail, or (c) a $5 gift certificate code to Amazon.com sent with the survey instructions via e-mail. Overall response was 43%. Results show that $5 bills led to significantly higher response rates than either gift certificate condition (57% for cash vs. 36% for the two gift certificate conditions, [UNKNOWN]2(1) = 9.3, p < .01). This suggests that cash is a superior incentive for an online survey, even with technologically sophisticated respondents. This may be due to the perceived limitations, delayed payoff, or reduced visibility of online gift certificates.
Instrument Effects of Images in Web Surveys
Authors: Witte James C. , Pargas Roy P. , Mobley Catherine , Hawdon James
Published: July 2004

This research note offers cautionary evidence, indicating just how little we know about how respondents react to and complete Web surveys. Researchers using or contemplating a Web-based approach need to be very clear that the line between the phenomena to be measured and the means of measurement is often quite fuzzy. This note uses data from Survey2001 to illustrate this point. Nearly 30,000 respondents completed part or all of Survey2001, which was hosted by the National Geographic Magazine’s Web site and queried individuals on a number of topics related to the impact of information technology on conservation, community and culture.
“Going Forward”: Family Resiliency in Patients on Hemodialysis
Authors: White Nancy , Richter Judith , Koeckeritz Jane , Munch Kristy , Walter Patty
Published: July 2004

Patients with end-stage renal disease (ESRD) on hemodialysis and their families are faced with significant challenges. The purpose of this research was to explore the nature of resiliency in the context of the family with hemodialysis. Naturalistic inquiry was used to elicit descriptions from 15 White patients on hemodialysis and their caregivers about what it was like to live withESRDand how they managed. Being on dialysis provides an understanding of the dialysis experience, strategies and resources represent the role of support systems and resources and the tactics the family uses to maintain and restore the well-being of the family unit, and having a positive life view encompasses the “bonadaptation” of the families as they were able to maintain the integrity of the family unit under extremely adverse conditions and continue “going forward.”
A Feminist Critique of Research on Interracial Family Identity: Implications for Family Health
Authors: Byrd Marcia M. , Garwick Ann W.
Published: July 2004

The focus of this literature review is on family identity formation within a social cultural context for families, couples, and women who are in committed Black-White interracial relationships that include biracial children. This review and synthesis of interdisciplinary literature was limited to U.S. research studies completed between 1990 and 2002. The American racial lens represented the environmental context that this article seeks to capture. Health care providers lack knowledge of this complex mixed-race family identity formation and its implications for healthy interracial families. Family nurses who can assess and intervene in a culturally competent manner will be essential to promoting health and eliminating health disparities for these interracial families of color.
Family Nursing in Scotland
Authors: O’Sullivan Burchard Dorothee J. H. , Claveirole Anne , Mitchell Ruth , Walford Carol , Whyte Dorothy A.
Published: July 2004

The purpose of the article is to trace the development of family nursing in Scotland and to describe the work of the Family Nursing Network Scotland (FNNS) since its inception in 1997. Although the origins of the early work are in child health nursing, the Network aims to support family nursing research, education, and practice across all areas of the discipline. Original research provided the impetus for an examination of family nursing in Scotland. Recent research has focused on the preparation of nursing students in Scotland for family nursing practice. Initiatives by the FNNS have raised awareness and encouraged the practice of family nursing. Future goals for the development of family nursing in Scotland are discussed.
Cultural Criminology:
Authors: Presdee Mike
Published: July 2004

This article will offer a thumbnail sketch of some of the key theoretical antecedents that have underscored the cultural analysis of crime and criminality in both the United States and Britain. It traces the origins of the ‘cultural tradition’, from its beginnings in turn of the 20th-century American sociology to the flowering of radical British criminology with the National Deviancy conferences of the 1960s. It will then move on to consider the contemporary resurgence of cultural criminology and its attempts to once again prioritize the experiences of everyday life within the processes of crime and criminality. It will be argued that this approach offers a more viable and effective account of crime than that currently offered by the dominant discourse of administrative criminology as favoured by Blair’s New Labour approach to bureaucratic Britain.
Boredom, Crime and Criminology
Authors: Ferrell Jeff
Published: July 2004

Under the dehumanizing conditions of modernism, boredom has come to pervade the experience of everyday life. This collective boredom has spawned not only moments of illicit excitement—that is, ephemeral crimes committed against boredom itself—but larger efflorescences of political and cultural rebellion. In the same way, the machinery of modern criminology has organized a vast collectivity of boredom buttressed by rationalized methodologies and analytic abstraction. Against this institutionalized boredom, cultural criminology offers a rebellion of its own, and with it the possibility of intellectual excitement by way of methodological innovation, momentary insight and human engagement.
The Unconventional Methods of Cultural Criminology
Authors: Kane Stephanie C.
Published: July 2004

This essay is about (a) the dilemmas of doing cultural criminology and (b) the importance of reading criminology through culture. Drawing from the author’s research, it presents three tropes of culture-work on crime (village, city street and media), attending to the implications of the observer’s documentary presence. While describing rules, logics and practices that compose the bundle of habits and inventions we call methods, I highlight the ways in which methods are differentially situated within hierarchies of knowledge production and dissemination. I argue that as we become participant observers and analysts in and of these contexts, we commonly transform the narratives we collect into data by linking them to maps in our logistics, epistemologies and rhetoric.
Crime, Edgework and Corporeal Transaction
Authors: Lyng Stephen
Published: July 2004

This article responds to the call by cultural criminologists for a ‘criminology of the skin’ that attends to the embodied pleasures and emotions generated by certain forms of criminal behavior. Drawing on the ‘edgework’ model of voluntary risk taking and a modified version of Jurgen Habermas’s Theory of Communicative Action, I theorize risk taking in criminal endeavors as an activity linked to the embodied social practices of the life-world. Conceptualized in this way, illicit risk taking can be seen to play an important role in crystallizing the ‘criminal erotics’ involved in some types of crime. Standing in opposition to the disembodied system imperatives of late capitalism, criminal edgework represents a form of escape and resistance to the prevailing structures of political and economic power.
Packaging Reality
Authors: Baym Geoffrey
Published: July 2004

This study takes its lead from Schudson’s (1995) insightful suggestion that the power of news lies less in the stories it tells than in the form those stories assume. The form of news directs the journalistic effort to engage with the world, shapes the subsequent narratives of the real, and encodes wider cultural patterns of authority. Yet the form of news is continually changing. To assess the nature of news form in two eras of markedly different journalistic standards, this study explores the patterns of form that structured US network news coverage of Watergate in 1973-74 and the Clinton impeachment of 1998. Specifically examining the format known to the television news business as the package, it charts a turn in news form from the typographic to the televisual and considers the implications of that turn for journalistic authority.
Our News and their News
Authors: Nossek Hillel
Published: July 2004

The theoretical assumption of this paper is that when a foreign news item is defined as ‘ours’, then journalists’ professional practices become subordinate to national loyalty; when an item is ‘theirs’, journalistic professionalism comes into its own. Thus, the article argues that there is an inverse relation between professional news values and the national identity of the journalist and the journal’s editors. Expressed as a rule, we would say that the more ‘national’ the report is, the less ‘professional’ it will be, i.e. the closer the reporters/editors are to a given news event in terms of national interest, the further they are from applying professional news values.

This claim is presented in the form of a flow diagram and is investigated using qualitative content analysis of the coverage of four events in three different countries (the USA, Britain and Israel). The four events, which were all presented as foreign news, were defined as political violence based on an observational definition.

The theory which is empirically tested and presented in this article can help us to understand the coverage of September 11, 2001 and its aftermath and the wars in Afghanistan and Iraq, and further our understanding of how events were, and still are, covered as foreign news in general, and, in particular, how political violence is covered as foreign news.
Seeing Ghosts
Authors: Klenk Rebecca M.
Published: July 2004

This essay is a narrative meditation on fieldwork and the construction of ethnographic knowledge of lived experience drawn from my fieldwork in rural Kumaon, a region of the Indian Himalaya. It reflects critically upon fieldwork, writing practices, memory, and imagination. This is accomplished through unfolding a specific ethnographic encounter in the context of events which took place in the autumn of 1994, a moment of keen significance in Kumaon because this is when the movement for a separate hill state escalated and became violent. The state of Uttaranchal was established in 2000, but in 1994 agitation for it was fresh and raw. In this essay, a girl and a ghost become entangled during the same time that supporters of the movement come under attack and schools close. Rather than analyzing spirit possession or political culture as such, this essay explores the diverse ways in which women occupying multiple subject positions negotiated, discussed, and imagined the presences of a ghost and of an anthropologist, and of how, in turn, I now construct them.
Talking about Picture Books: The Influence of Maternal Education on Four-Year-Old Children’s Talk with Mothers and Pre-School Teachers
Authors: Torr Jane
Published: July 2004

This study analyses how pre-school children who differ in terms of maternal education respond to and interpret the images and written text in the same two picture books, one informational ( The sleepy book[Zolotow and Bobri, 1960]) and one narrative ( The baby who wouldn’t go to bed[Cooper, 1996]). Twelve children were recorded in their homes interacting with their mothers, and 12 children were recorded in their pre-schools interacting with a teacher. There were systematic differences in the manner in which the children who were interacting with their pre-school teachers responded to the texts compared with the children who were interacting with their mothers. The pre-school teachers provided the children of early school leaving mothers with opportunities to interact with text, which differed from those provided by their mothers. Such differences were not apparent to the same extent for the children of tertiary-educated mothers.
Young Children Interpret the Metafictive in Anthony Browne’s Voices in the Park
Authors: Pantaleo Sylvia
Published: July 2004

Voices in the Park(Browne, 1998) was one of nine picture books I used in a study that explored the nature of Grade 1 children’s literary understanding by examining their verbal responses during storybook read-aloud sessions, and their subsequent written, visual arts, and dramatic responses. This article discusses the Grade 1 students’ responses to and understandings of the metafictive devices in Anthony Browne’s picture book. Although researchers and theorists have written about metafiction, a paucity of research has explored elementary students’ literary understandings of and responses to books with metafictive devices. As well as defining metafiction and identifying various metafictive devices described in the literature, this article contextualizes Browne’s work and the children’s responses in a discussion of metafictive textual practices in postmodern and Radical Change literature.
Human Resource Development as National Policy in India
Authors: Rao T. V.
Published: July 2004

The problem and the solution. Although India took the lead in the Asia Pacific region, setting up a full Ministry of Human Resource Development, the National human resource development concept in India has largely been limited to education and culture. The complexity of the country perhaps makes it difficult to have integrated HRD systems at the national level. Networking and learning from each other among various ministries and institutions and from the corporate sector will, however, go a long way in effectively evolving and implementing NHRD policies.
HRD as National Policy in the Pacific Islands
Authors: Bartlett Kenneth R. , Rodgers Jimmie
Published: July 2004

The problem and the solution. Human resource development (HRD) is a critical issue in the Pacific Islands as the region’s nations and territories are recognizing that they face a challenging task of striking the right balance among population, available resources, and development. National HRD (NHRD) is emerging as a preferred solution for these challenges as the often small and far-flung nations of the South Pacific search for ways of dealing with feeding, housing, employing, and educating growing populations. In this article, an overview of the Pacific Islands region is provided before providing a brief snapshot of the current challenges these nations and territories face and how HRD at the national level is being positioned in response. The uniquely Pacific conceptualization of HRD and its emerging definition are presented before highlighting the role that regional intergovernmental organizations are playing in implementing HRD at the national level.
Human Resource Development: the South African Case
Authors: Lynham Susan A. , Cunningham Peter W.
Published: July 2004

The problem and the solution. Faced by the challenges of the past and by pressure to become increasingly competitive internationally, South Africa has recognized that the education, training, and development of its labor force and citizenry will be instrumental to its long-term economic growth and social well-being. Consequently, an integrated framework of policy and legislation is being implemented to ensure that human resource development is firmly placed on the national agenda.
National Human Resource Development in the United Kingdom
Authors: Lee Monica
Published: July 2004

The problem and the solution. National human resource development (NHRD) in the United Kingdom can be looked at from two intertwined perspectives, namely, initiatives to foster the development of the national workforce alongside the impact these initiatives have on the U.K. conceptualization of HRD. This article looks first at key government initiatives and the roles of providers before discussing some general issues that affect human resource development in the United Kingdom. Despite increasing standardization, the scope of HRD as a subject has changed dramatically during the past few years, and many now see it contributing to the core aspects of the study and practice of organizations and management.
National Human Resource Development: What in the World Is It?
Authors: McLean Gary N.
Published: July 2004

The problem and the solution. Recent exploratory research has affirmed the variations in understanding of the meaning of human resource development (HRD) from country to country based on a number of identifiable characteristics of the country. One area identified in the definitions of some countries, which was different from that found in the United States and in some other countries, was a focus on HRD as national policy. The purpose of this issue of ADHR, then, is to explore how HRD is viewed as national policy around the world.
Production and Properties of High-Modulus—High-Tenacity Polypropylene Filaments
Authors: Mukhopadhyay S. , Deopura B. L. , Alagirusamy R.
Published: July 2004

Polypropylene (PP) filaments have become one of the most important industrial filaments. Fibers from advanced Ziegler-Natta and metallocene catalyst-based polypropylene have made inroads in technical textiles. High-modulus—high-tenacity PP filaments have found various uses in industrial applications on the basis of their superior properties and inert nature. The feed parameters as well as the processing variables - all have an important impact on the ultimate properties of PP filament, as has been observed by various researchers. This article critically reviews the production of high-modulus—high-tenacity PP filament along with proposed changes in microstructure leading to the superior mechanical properties. The contribution of crystallite and amorphous orientations, amorphous modulus, crystallinity, taut-tie molecules, and flaws in the shaping of mechanical properties of such filaments have been discussed. The chasm between practical and theoretical values in modulus and tenacity values are still large and a great deal of challenge involved in achieving high draw ratios. In most of the cases, high draw ratios have been achieved with single or multiple steps but with low strain rates and low processing speeds. Majority of the processes are batch processes and limits productivity.
Can Bourdieu’s Critical Theory Liberate us from the Symbolic Violence?
Authors: Kim Kyung-Man
Published: July 2004

Pierre Bourdieu argued that sociologists must go beyond the description of how social agents’ self-understanding of their institution and society is displayed in their interaction, and should offer a critique of current practice so that the social agents can liberate themselves from the grip of the legitimated symbolic domination. In this article, the author hopes to show that Bourdieu’s attempt to establish the epistemologically privileged status of his critique fails on two counts. First, Bourdieu’s reliance on psychoanalysis to prove the epistemologically privileged status of his analysis does not provide us with independent evidence that shows why the lay social agents must ascribe an epistemic authority to him. Second, Bourdieu’s notion of illusio deprives him of the epistemic authority required for the liberation of social agents from the symbolic violence.
Teaching for England: Five Poems
Authors: Perselli Victoria
Published: July 2004

“Teaching for England” consists of five allegorical poems exploring the axes of self to social and political to personal within the life of a teacher, as she struggles to relocate her affective engagement in her work at a time of political and emotional trauma. The poems offer scathing commentary on the technical rationalism that presently dominates mainstream education in the U.K. and the author’s disappointment with New Labor. They represent her attempt to write self-deprecatingly, humorously, and against the grain of this ideology, while simultaneously harboring the possibility for (self) transformation.
Edward Said and the Politics of Worldliness: toward a “Rendezvous of Victory”
Authors: Giroux Henry A.
Published: July 2004

This essay addresses both the nature of what it means to be a public intellectual and the politics such an understanding would entail by examining the work of the late Edward Said. Said embodied both a particular kind of politics and a specific notion of how intellectuals should engage public life. The author takes up these issues by providing a critical commentary on the relevance of Said’s notion of wakefulness and how it both shapes his important consideration of academics as oppositional public intellectuals and his related emphasis on cultural pedagogy and cultural politics. The author concludes by arguing that Said’s work and legacy are crucial to rethinking the nature of academic work and the work of academia within the larger context of a democracy under siege.
Can the United States Correct Itself?
Authors: Pieterse Jan Nederveen
Published: July 2004

Can the United States correct itself? Is the balance of forces such that, short of undergoing a major economic and political crisis, the United States can chart a significantly different course? Domestically this would mean a return to New Deal politics and internationally a return to genuine constructive multilateralism. The answer is negative: growing social inequality, political and corporate unaccountability are structurally entrenched, and public forums to address them hardly exist. A case in point is the military-industrial complex as a major source of distortion in the American economy and politics. Privileging military contracts means that the US economy has become uncompetitive.
The National Security State
Authors: Nelson Cary
Published: July 2004

The current political climate and the upcoming election provide us with both short-term opportunities for critical activism and long-term encouragement to rethink higher education’s role in preparing citizens for participation in a democracy. This is a rare, if brief, opportunity for academics to encourage participation in the political process by writing and speaking. We face real risks of an emerging national security state limiting our freedom of speech and access to education. Long term, we must recognize our failure to produce a critical mass of graduates ready to engage public policy in a reflective and independent fashion. In large measure, education has failed the country. We need to reevaluate our mission and the undergraduate curriculum.
HIV-1-infected dendritic cells up-regulate cell surface markers but fail to produce IL-12 p70 in response to CD40 ligand stimulation
Authors: Smed-Sörensen Anna , Loré Karin , Walther-Jallow Lilian , Andersson Jan , Spetz Anna-Lena
Published: July 2004

Dendritic cells (DCs) are antigen-presenting cells with the capacity to prime naive T cells for efficient cellular responses against pathogens such as HIV-1. DCs are also susceptible to HIV-1 infection, which may impair their ability to induce immunity. Here, we examined the ability of HIV-1-infected, in vitro-derived DCs to respond to CD40 ligand (CD40L) stimulation with the aim to study events during early HIV-1 infection. HIV-1BaL-infected p24+ DCs were detected after only 3 days of exposure to highly concentrated virus. We show that HIV-1-infected DCs up-regulated costimulatory molecules, but were skewed in their production of effector cytokines in response to CD40L stimulation. CD40L stimulation induced significant secretion of tumor necrosis factor α (TNFα) and interleukin 12 (IL-12) p70 from both HIV-1-exposed and unexposed DCs. Intracellular stainings of HIV-1-exposed DCs revealed that TNFα could be detected in both the p24- and p24+ DCs, but IL-12 p70 could be found only in the p24- DCs. Thus, although p24+ DCs showed a mature phenotype similar to p24- DCs after CD40L stimulation, they appeared to have an impaired cytokine profile. These observations suggest that HIV-1 infection disables DC function, a phenomenon that may be relevant for optimal induction of HIV-1-specific immune responses. (Blood. 2004;104:2810-2817)
Imatinib mesylate (STI571) for treatment of children with Philadelphia chromosome-positive leukemia: results from a Children's Oncology Group phase 1 study
Authors: Champagne Martin A. , Capdeville Renaud , Krailo Mark , Qu Wenchun , Peng Bin , Rosamilia Marianne , Therrien Martine , Zoellner Ulrike , Blaney Susan M. , Bernstein Mark
Published: July 2004

The purpose of this study was to determine dose-limiting toxicities and pharmacokinetics of imatinib in children with refractory or recurrent Philadelphia chromosome-positive (Ph+) leukemias. Oral imatinib was administered daily at dose levels ranging from 260 to 570 mg/m2. Plasma pharmacokinetic studies were performed on days 1 and 8 of course 1. There were 31 children who received 479 courses of imatinib. The most common toxicities encountered, which occurred in less than 5% of courses, were grade 1 or 2 nausea, vomiting, fatigue, diarrhea, and reversible increases in serum transaminases. One patient at the 440-mg/m2 dose level had dose-limiting weight gain. There were no other first-course dose-limiting toxicities. A maximum tolerated dosage was not defined. Among 12 chronic myeloid leukemia (CML) patients evaluable for cytogenetic response, 10 had a complete response and 1 had a partial response. Among 10 acute lymphoblastic leukemia (ALL) patients evaluable for morphologic response, 7 achieved an M1 and 1 achieved an M2 bone marrow. We observed marked interpatient variability in the pharmacokinetic parameters. In conclusion, we found that daily oral imatinib is well tolerated in children at doses ranging from 260 to 570 mg/m2. Doses of 260 and 340 mg/m2 provide systemic exposures similar to those of adults who are treated with daily doses of 400 and 600 mg, respectively. (Blood. 2004;104:2655-2660)
CD8+ cytotoxic T lymphocytes isolated from allogeneic healthy donors recognize HLA class Ia/Ib–associated renal carcinoma antigens with ubiquitous or restricted tissue expression
Authors: Dörrschuck Andreas , Schmidt Andrea , Schnürer Elke , Glückmann Matthias , Albrecht Christian , Wölfel Catherine , Lennerz Volker , Lifke Alexander , Di Natale Carmela , Ranieri Elena , Gesualdo Loreto , Huber Christoph , Karas Michael , Wölfel Thomas , Herr Wolfgang
Published: July 2004

Allogeneic hematopoietic stem cell transplantation can induce considerable tumor remissions in metastatic renal-cell carcinoma (RCC) patients. The precise effector mechanisms mediating these graft-versus-tumor reactions are unknown. We studied RCC-directed CD8+ T-cell responses in blood lymphocytes of healthy individuals matched with established RCC cell lines for HLA-class I. In 21 of 22 allogeneic mixed lymphocyte/tumor-cell cultures (MLTCs), RCC-reactive cytotoxic T-lymphocytes (CTLs) were readily obtained. From MLTCs, 121 CD8+ CTL clones with memory phenotype were isolated. Their anti–RCC reactivity was restricted by multiple classical HLA-Ia molecules, in particular by HLA-A2, -A3, -B7, -B44, -Cw7, and by a nonclassical HLA-Ib determinant. Extensive cross-reactivity analyses on a broad target panel identified CTLs that recognize antigens with expression restricted to renal tissue or to renal and colon tumors. Other CTLs were directed against antigens with broader tissue distribution being expressed in various epithelial and nonepithelial tumors or, additionally, in hematopoietic cells. With microcapillary liquid chromatography and matrix-assisted laser desorption ionization time-of-flight (MALDI-TOF)/TOF mass spectrometry, we identified the HLA-A*0301-associated nonpolymorphic peptide KLPNSVLGR encoded by the ubiquitously expressed Eps15 homology domain–containing 2 gene as a CTL target. Defining human RCC antigens recognized by alloreactive CTLs may allow to improve the specificity and efficiency of allogeneic cell therapy (eg, specific donor-lymphocyte infusions or vaccination) in metastatic RCC patients.
Effect of vitamin K intake on the stability of oral anticoagulant treatment: dose-response relationships in healthy subjects
Authors: Schurgers Leon J. , Shearer Martin J. , Hamulyák Karly , Stöcklin Elisabeth , Vermeer Cees
Published: July 2004

Oral anticoagulants exert their effect by blocking the utilization of vitamin K, yet little is known about competitive aspects of their interaction with dietary vitamin K. We carried out systematic dose-response studies in healthy volunteers who had been stably anticoagulated and maintained on their individualized doses for 13 weeks. First, we studied the response to weekly incremental doses (50 μg-500 μg) of vitamin K1 supplements (K1) taken daily for 7 days. The threshold K1 dose causing a statistically significant lowering of the INR was 150 μg/day. In 25% of the participants the INR change was regarded as clinically relevant at a vitamin K intake of 150 μg/day. Circulating undercarboxylated osteocalcin did not decrease until 300 μg K1/day compared with 100 μg K1/day for undercarboxylated FII, suggesting differential antidotal effects on bone and hepatic γ-carboxylation. Next, we tested the response to vitamin K-rich food items. The short-lived response after meals of spinach and broccoli suggested an inefficient bioavailability from these 2 sources. We conclude that short-term variability in intake of K1 is less important to fluctuations in the international normalized ratio (INR) than has been commonly assumed and that food supplements providing 100 μg/day of vitamin K1 do not significantly interfere with oral anticoagulant therapy. (Blood. 2004;104:2682-2689)
Menopausal Increases in Pulsatile Gonadotropin-Releasing Hormone Release in a Nonhuman Primate (Macaca mulatta)
Authors: Gore Andrea C. , Windsor-Engnell Bret M. , Terasawa Ei
Published: July 2004

Reproductive function in all vertebrates is controlled by the circhoral release of the neuropeptide, GnRH, into the portal capillary system leading to the anterior pituitary. Despite its primary role in sexual maturation and the maintenance of adult reproductive function, changes in the concentrations and pattern of GnRH release have not yet been reported in any primate species during the menopausal transition and postmenopause. Such knowledge is essential for ascertaining both the mechanisms for, and consequences of, the menopausal process. Here we used a push-pull perfusion method to measure and compare the parameters of pulsatile GnRH release in adult rhesus monkeys at 8.4 ± 1.5 yr (young adult females, early follicular phase, n = 6) and 28.8 ± 0.3 yr (aged females, n = 4, of which two monkeys were in the menopausal transition, and two were postmenopausal). Our results demonstrate that: 1) GnRH release is pulsatile in both young and aged monkeys; 2) mean concentrations of GnRH increase during reproductive aging; and 3) GnRH pulse frequency does not differ between aged monkeys and young monkeys in the early follicular phase. We conclude that not only do GnRH neurons have the continued capacity to release GnRH in a pulsatile manner but also they can do so with enhanced GnRH levels in aged primates. To our knowledge, this is the first direct demonstration of elevated pulsatile GnRH concentrations in a primate species during reproductive senescence, a result that may have implications for menopausal symptoms.
Central Administration of Ghrelin and Agouti-Related Protein (83–132) Increases Food Intake and Decreases Spontaneous Locomotor Activity in Rats
Authors: Tang-Christensen Mads , Vrang Niels , Ortmann Sylvia , Bidlingmaier Martin , Horvath Tamas L. , Tschöp Matthias
Published: July 2004

Ghrelin was recently identified as an endogenous ligand of the GH secretagogue receptor. The novel peptide hormone is produced by gastric A-like cells, and circulating levels rise before feeding, suggestive of ghrelin as an endogenous hunger factor. ghrelin stimulates food intake and promotes adiposity after peripheral or central administration, likely by activating hypothalamic neurons expressing the orexigenic neuropeptides neuropeptide Y (NPY) and agouti-related protein (AGRP). To examine whether ghrelin-induced feeding resembles NPY and AGRP [AGRP fragment (83–132)] induced orexia, we compared the short- and long-term orexigenic capacity of the three peptides. A single intracerebroventricular injection of ghrelin (0.2, 1.0, and 5.0 μg) increased food intake in a dose-dependent manner. A prolonged and uncompensated increase in feeding was seen after the highest dose of ghrelin. The prolonged effects on feeding (+72 h) closely resembled those of AGRP (83–132) but not NPY. Surprisingly, ghrelin injections reduced overall locomotor activity by 20% during the first 24-h observation period. AGRP (83–132) had similar effects on locomotor behavior, whereas NPY had no effect. In summary, ghrelin causes long-term increases of food intake and, like AGRP, plays a previously unknown role as a suppressor of spontaneous physical activity. Expanding the current model of food intake control to include mechanisms regulating physical activity may promote our understanding of two major etiological factors causing obesity.
Down-Regulated Expression of A Disintegrin and Metalloproteinase with Thrombospondin-Like Repeats-1 by Progesterone Receptor Antagonist Is Associated with Impaired Expansion of Porcine Cumulus-Oocyte Complexes
Authors: Shimada Masayuki , Nishibori Masahide , Yamashita Yasuhisa , Ito Junya , Mori Takahide , Richards JoAnne S.
Published: July 2004

ADAMTS-1, a member of the A disintegrin and metalloproteinase family of proteases, is expressed in rodent follicles via progesterone receptor (PR)-dependent pathways. However, the functional relationship between ADAMTS-1 expression and PR has not been studied extensively in other species. In the present study, we investigated the time-dependent changes in ADAMTS-1 expression in cumulus cells of porcine cumulus-oocyte complexes (COCs), and the roles of ADAMTS-1 in cumulus expansion during in vitro maturation of oocytes. ADAMTS-1 message was not detected in cumulus cells at the time of collection from the follicles. In response to gonadotropins, ADAMTS-1 mRNA was dramatically up-regulated and reached a maximum at 20 h. The level of mature ADAMTS-1 protein increased in a time-dependent manner with a maximum level at 40 h. The induction of ADAMTS-1 mRNA and protein was significantly decreased by the addition of PR antagonist RU486 to the cultures. However, RU486 did not affect the expression of ADAMTS-4 or factors that had been reported to be required for COC expansion (TSG-6, versican, HA synthase-2). COCs cultured with FSH and LH for 40 h exhibited prominent cumulus expansion. The expansion was reduced significantly by the addition of either RU486 or Galardin, a broad-spectrum matrix metalloproteinase inhibitor. These results suggest that the expression and induction of ADAMTS-1 through receptor-mediated action of progesterone in cumulus cells is one of the essential requirements for gonadotropin-regulated cumulus expansion of porcine COCs.
A Tumor Suppressor Role for Thyroid Hormone β Receptor in a Mouse Model of Thyroid Carcinogenesis
Authors: Kato Yasuhito , Ying Hao , Willingham Mark C. , Cheng Sheue-Yann
Published: July 2004

We have created a knockin mutant mouse by targeting a mutation (PV) into the thyroid hormone receptor β gene (TRβPV mouse). TRβPV/PV mice, but not TRβPV/+ mice, spontaneously develop follicular thyroid carcinoma. To identify other genetic changes in the TRβ gene that could also induce thyroid carcinoma, we crossed TRβPV mice with TRβ−/− mice. As TRβPV/− mice (mutation of one TRβ allele in the absence of the other wild-type allele) aged, they also spontaneously developed follicular thyroid carcinoma through the pathological progression of hyperplasia, capsular and vascular invasion, anaplasia, and eventually metastasis to the lung, but not to the lymph nodes. The pathological progression of thyroid carcinoma in TRβPV/− mice was indistinguishable from that in TRβPV/PV mice. Analyses of the expression patterns of critical genes indicated activation of the signaling pathways mediated by TSH, peptide growth factors (epidermal growth factor and fibroblast growth factor), TGF-β, TNF-α, and nuclear factor-κB, and also suggested progressive repression of the pathways mediated by the peroxisome proliferator-activated receptor γ. The patterns in the alteration of these signaling pathways are similar to those observed in TRβPV/PV mice during thyroid carcinogenesis. These results indicate that in the absence of a wild-type allele, the mutation of one TRβ allele is sufficient for the mutant mice to spontaneously develop follicular thyroid carcinoma. These results provide, for the first time, in vivo evidence to suggest that the TRβ gene could function as a tumor suppressor gene. Importantly, these findings present the possibility that TRβ could serve as a novel therapeutic target in thyroid cancer.
Dibutyryl Cyclic Adenosine Monophosphate Restores the Ability of Aged Leydig Cells to Produce Testosterone at the High Levels Characteristic of Young Cells
Authors: Chen Haolin , Liu June , Luo Lindi , Zirkin Barry R.
Published: July 2004

The wealth of knowledge about the function and regulation of adult Leydig cells, the cells within the mammalian testis that produce testosterone, make these cells ideal for studying principles and mechanisms of aging. A hallmark of mammalian aging is decreased serum testosterone concentration. In the Brown Norway rat, this has been shown to be associated with the reduced ability of aged Leydig cells to produce testosterone in response to LH. Herein, we demonstrate that culturing the aged cells with dibutyryl cAMP, a membrane-permeable cAMP agonist that bypasses the LH receptor-adenlyly cyclase cascade, restores testosterone production to levels comparable to those of young cells and also restores steroidogenic acute regulatory protein and P450scc, the proteins involved in the rate-limiting steps of steroidogenesis. These results strongly suggest that signal transduction deficits are responsible for reduced steroidogenesis by aged Leydig cells and that bypassing signal transduction reverses the steroidogenic decline by the aged cells.
Identification of Tissue-Restricted Transcripts in Human Islets
Authors: Maffei Antonella , Liu Zhuoru , Witkowski Piotr , Moschella Federica , Pozzo Giovanna Del , Liu Eric , Herold Kevan , Winchester Robert J. , Hardy Mark A. , Harris Paul E.
Published: July 2004

The purpose of our study was to identify transcripts specific for tissue-restricted, membrane-associated proteins in human islets that, in turn, might serve as markers of healthy or diseased islet cell masses. Using oligonucleotide chips, we obtained gene expression profiles of human islets for comparison with the profiles of exocrine pancreas, liver, and kidney tissue. As periislet presence of type 1 interferon is associated with the development of type 1 diabetes, the expression profile of human islets treated ex vivo with interferon-α2β (IFNα2β) was also determined. A set of genes encoding transmembrane- or membrane-associated proteins with novel islet-restricted expression was resolved by determining the intersection of the islet set with the complement of datasets obtained from other tissues. Under the influence of IFNα2β, the expression levels of transcripts for several of the identified gene products were up- or down-regulated. One of the islet-restricted gene products identified in this study, vesicular monoamine transporter type 2, was shown to bind [3H]dihydrotetrabenazine, a ligand with derivatives suitable for positron emission tomography imaging. We report here the first comparison of gene expression profiles of human islets with other tissues and the identification of a target molecule with possible use in determining islet cell masses.
Plasma Membrane Estrogen Receptors Exist and Functions as Dimers
Authors: Razandi Mahnaz , Pedram Ali , Merchenthaler Istvan , Greene Geoffrey L. , Levin Ellis R.
Published: July 2004

A small pool of estrogen receptors (ERα and -β) localize at the plasma membrane and rapidly signal to affect cellular physiology. Although nuclear ERs function mainly as homodimers, it is unknown whether membrane-localized ER exists or functions with similar requirements. We report that the endogenous ER isoforms at the plasma membrane of breast cancer or endothelial cells exist predominantly as homodimers in the presence of 17β-estradiol (E2). Interestingly, in endothelial cells made from ERα /ERβ homozygous double-knockout mice, membrane ERα or ERβ are absent, indicating that the endogenous membrane receptors derive from the same gene(s) as the nuclear receptors. In ER-negative breast cancer cells or Chinese hamster ovary cells, we expressed and compared wild-type and dimer mutant mouse ERα. Only wild-type ERα supported the ability of E2 to rapidly activate ERK, cAMP, and phosphatidylinositol 3-kinase signaling. This resulted from E2 activating Gsα and Gqα at the membrane in cells expressing the wild-type, but not the dimer mutant, ERα. Intact, but not dimer mutant, ERα also supported E2-induced epidermal growth factor receptor transactivation and cell survival. We also confirmed the requirement of dimerization for membrane ER function using a second, less extensively mutated, human ERα. In summary, endogenous membrane ERs exist as dimers, a structural requirement that supports rapid signal transduction and affects cell physiology.
A unique visual pigment expressed in green, red and deep-red receptors in the eye of the small white butterfly,Pieris rapae crucivora
Authors: Wakakuwa Motohiro , Stavenga Doekele G. , Kurasawa Masumi , Arikawa Kentaro
Published: July 2004

The full primary structure of a long-wavelength absorbing visual pigment of the small white butterfly, Pieris rapae crucivora, was determined by molecular cloning. In situ hybridization of the opsin mRNA of the novel visual pigment (PrL) demonstrated that it is expressed in the two distal photoreceptor cells (R3 and R4) as well as in the proximal photoreceptors(R5–8) in all three types of ommatidia of the Pieris eye. The main, long-wavelength band of the spectral sensitivities of the R3 and R4 photoreceptors is well described by the absorption spectrum of a visual pigment with absorption maximum at 563 nm; i.e. PrL is a visual pigment R563. The spectral sensitivities of R5–8 photoreceptors in ommatidial type I and III peak at 620 nm and those in type II ommatidia peak at 640 nm. The large shifts of the spectral sensitivities of the R5–8 photoreceptors with respect to the absorption spectrum of their visual pigment can be explained with the spectral filtering by pale-red (PR) and deep-red (DR)screening pigments that are concentrated in clusters of granules near the rhabdom boundary. The peak absorbance of the two spectral filters appears to be approximately 1 (PR) and 2 (DR).
Habitat-dependent transmission of male advertisement calls in bladder grasshoppers (Orthoptera; Pneumoridae)
Authors: Couldridge Vanessa C. K. , van Staaden Moira J.
Published: July 2004

It has been hypothesized that the physical properties of the environment exert selection pressure on long-range acoustic communication signals to match the local habitat by promoting signal characteristics that minimize excess attenuation and distortion. We tested this in a unique family of bladder grasshoppers notable for producing a signal with a 2 km maximum transmission distance. In direct performance comparisons, male advertisement calls of seven species were broadcast through four vegetation biomes – forest, fynbos,savanna and succulent karoo. The calls of species native to forest and fynbos biomes propagated with lower levels of distortion over distance in their respective habitats relative to those of non-native species, while fynbos species also performed best in the remaining two habitats. In addition, both forest and fynbos species had low levels of signal attenuation over distance in all environments. The fynbos biome was characterized by high inconsistency in signal degradation, while the forest biome had the highest levels of environmental noise. Innate habitat characteristics, leading to comparatively limited acoustic communication distances in the forest and fynbos relative to the savanna and succulent karoo, may therefore explain the need for a higher quality of signal transmission in grasshoppers inhabiting the former two environments.