bluuebunny/crossref_metadata_2025 huggingface dataset:
Translational regulation of vascular endothelial growth factor expression in renal epithelial cells by angiotensin II
Authors: Feliers Denis , Duraisamy Senthil , Barnes Jeffrey L. , Ghosh-Choudhury Goutam , Kasinath Balakuntalam S.
Published: December 2004

ANG II regulates growth factor expression in the kidney. We investigated whether ANG II regulated vascular endothelial growth factor (VEGF) synthesis in proximal tubular epithelial (MCT) cells. ANG II (1 nM) increased VEGF protein expression within 5 min, the effect lasting for 30 min. There was no change in VEGF mRNA levels or mRNA stability, and transcription inhibitors did not affect ANG II-induced VEGF expression. Regulation of VEGF translation was investigated. Polyribosomal analysis revealed selective enrichment of heavy ribosomes (polysomes) with VEGF mRNA transcripts compared with light ribosomes in ANG II-treated cells, although distribution of GAPDH was unaltered. In vitro translation of total RNA from polysomal fractions showed selective increase in VEGF protein synthesis in ANG II-treated cells. Preincubation with LY-294002, a PI 3-kinase inhibitor, or expression of dominant-negative Akt prevented ANG II-stimulated increase in VEGF translation. ANG II increased phosphorylation of eukaryotic initiation factor 4E and its binding protein 4E-BP1, critical events that regulate the initiation phase of protein translation. ANG II failed to increase VEGF mRNA translation in cells stably expressing the phosphorylation mutant of 4E-BP1. Our data illustrate that a rapid increase in VEGF protein expression by ANG II is regulated at the initiation phase of translation of VEGF mRNA in renal epithelial cells. Regulation of VEGF translation by ANG II represents a novel pathway of renal response to injury.
Development of an Inhibitory Interneuronal Circuit in the Embryonic Spinal Cord
Authors: Xu Huaying , Whelan Patrick J. , Wenner Peter
Published: December 2004

Locally projecting inhibitory interneurons play a crucial role in the patterning and timing of network activity. However, because of their relative inaccessibility, little is known about their development or incorporation into circuits. In this study, we characterized the functional onset, neurotransmitters, rostrocaudal spread, and funicular distribution of one such spinal interneuronal circuit during development. The R-interneuron is the avian homologue of the mammalian Renshaw cell. Both cell types receive input from motoneuron recurrent collaterals and make direct connections back onto motoneurons. By stimulating motoneurons projecting in a given ventral root and recording the response in adjacent ventral roots, we demonstrate that the R-interneuron circuit becomes functional between embryonic day 6 (E6) and E7. This ventral root response is observed at E11 and at E14 until it can no longer be detected at E16. Using bath-applied neurotransmitter receptor antagonists, we were able to demonstrate that the circuit is predominately nicotinic and GABAergic from E7.5 to E15. We also found a glutamatergic component to the pathway throughout this developmental period. The R-interneuron projects three or more segments both rostrally and caudally through the ventrolateral funiculus. The distribution of this circuit may become more locally focused between E7.5 and E15.
On the uniform exponential stability of linear time‐delay systems
Authors: de la Sen M. , Luo Ningsu
Published: December 2004

This paper deals with the global uniform exponential stability independent of delay of time‐delay linear and time‐invariant systems subject to point and distributed delays for the initial conditions being continuous real functions except possibly on a set of zero measure of bounded discontinuities. It is assumed that the delay‐free system as well as an auxiliary one are globally uniformly exponentially stable and globally uniform exponential stability independent of delay, respectively. The auxiliary system is, typically, part of the overall dynamics of the delayed system but not necessarily the isolated undelayed
dynamics as usually assumed in the literature. Since there is a great freedom in setting such an auxiliary system, the obtained stability conditions are very useful in a wide class of practical applications.
The Effect of Two Methods of Pomegranate (Punica granatum L) Juice Extraction on Quality During Storage at 4∘C
Authors: Miguel Graça , Dandlen Susana , Antunes Dulce , Neves Alcinda , Martins Denise
Published: December 2004

The effect of two extraction methods of pomegranate juice on its quality and stability was evaluated. The first method consisted of separation of the seeds from fruits and centrifugation. The second method consisted of squeezing fruit halves with an electric lemon squeezer. During a period of 72 hours of cold storage at 4∘C, the juices were evaluated for the presence of sugars, organic acids, and anthocyanins. Delphinidin 3‐glucoside was identified to be the major anthocyanin present at the level of 45–69 mg/L. Among the organic acids, oxalic and tartaric acids dominated. The major sugars detected in pomegranate juice were glucose and sucrose. No significant differences in the content of sugars, organic acids, or anthocyanins in juices obtained through application of the two different extraction methods were detected, with the exception of the drastic decrease of cyanidin 3, 5‐diglucoside level in juice obtained by seed centrifugation. The pH did not show differences between treatments. Titrable acidity and the level of sugars expressed as  ∘Brix decreased after 32 and 15 hours after extraction, respectively, when juice was obtained by centrifuging the seeds.
Anthocyanins and Human Health: An In Vitro Investigative Approach
Authors: Lila Mary Ann
Published: December 2004

Anthocyanin pigments and associated flavonoids have demonstrated ability to protect against a myriad of human diseases, yet they have been notoriously difficult to study with regard to human health. Anthocyanins frequently interact with other phytochemicals to potentiate biological effects, thus contributions from individual components are difficult to decipher. The complex, multicomponent structure of compounds in a bioactive mixture and the degradation of flavonoids during harsh extraction procedures obscure the precise assignment of bioactivity to individual pigments. Extensive metabolic breakdown after ingestion complicates tracking of anthocyanins to assess absorption, bioavailability, and accumulation in various organs. Anthocyanin pigments and other flavonoids that are uniformly, predictably produced in rigorously controlled plant cell culture systems can be a great advantage for health and nutrition research because they are quickly, easily isolated, lack interferences found in whole fruits, can be elicited to provoke rapid and prolific accumulation, and are amenable to biolabeling so that metabolic fate can be investigated after ingestion.
Caffeoylquinic Acids Generated In Vitro in a High‐Anthocyanin‐Accumulating Sweet potato Cell Line
Authors: Konczak Izabela , Okuno Shigenori , Yoshimoto Makoto , Yamakawa Osamu
Published: December 2004

Accumulation of phenolic compounds has been monitored in a suspension culture of anthocyanin‐accumulating sweet potato cell line grown under the conditions of modified Murashige and Skoog high‐anthocyanin production medium (APM) over a period of 24 days. Tissue samples extracted with 15% acetic acid were analysed using HPLC at a detection wavelength of 326 nm. Among others, the following derivatives of caffeoylquinic acids were detected: 4,5‐dicaffeoylquinic acid, 3,5‐dicaffeoylquinic acid, 3,4‐dicaffeoylquinic acid, and 3,4,5‐tricaffeoylquinic acid. Their total amount reached a maximum of 110 mg/gFW between the 4th and the 15th day of culture growth on APM. The major compound of the phenolic mixture was 3,5‐dicaffeoylquinic acid with maximum accumulation level of 80 mg/100 gFW. The potential effects of targeted phenolic compounds on the nutraceutical qualities of in vitro produced anthocyanin‐rich extracts are discussed.
Sour Cherry (Prunus cerasus L) Anthocyanins as Ingredients for Functional Foods
Authors: Blando Federica , Gerardi Carmela , Nicoletti Isabella
Published: December 2004

In the recent years many studies on anthocyanins have revealed their strong antioxidant activity and their possible use as chemotherapeutics. The finding that sour cherries (Prunus cerasus L) (also called tart cherries) contain high levels of anthocyanins that possess strong antioxidant and anti‐inflammatory properties has attracted much attention to this species. Here we report the preliminary results of the induction of anthocyanin biosynthesis in sour cherry callus cell cultures. The evaluation and characterization of the in vitro produced pigments are compared to those of the anthocyanins found in vivo in fruits of several sour cherry cultivars. Interestingly, the anthocyanin profiles found in whole fruit extracts were similar in all tested genotypes but were different with respect to the callus extract. The evaluation of antioxidant activity, performed by ORAC and TEAC assays, revealed a relatively high antioxidant capacity for the fruit extracts (from 1145 to 2592 μmol TE/100 g FW) and a lower one for the callus extract (688 μmol TE/100 g FW).
To Stretch the Boundary of Secondary Metabolite Production in Plant Cell‐Based Bioprocessing: Anthocyanin as a Case Study
Authors: Zhang Wei , Franco Chris , Curtin Chris , Conn Simon
Published: December 2004

Plant cells and tissue cultures hold great promise for controlled production of a myriad of useful secondary metabolites on demand. The current yield and productivity cannot fulfill the commercial goal of a plant cell‐based bioprocess for the production of most secondary metabolites. In order to stretch the boundary, recent advances, new directions and opportunities in plant cell‐based bioprocessing, have been critically examined for the 10 years from 1992 to 2002. A review of the literature indicated that most of the R&D work was devoted predominantly to studies at an empirical level. A rational approach to molecular plant cell bioprocessing based on the fundamental understanding of metabolic pathways and their regulations is urgently required to stimulate further advances; however, the strategies and technical framework are still being developed. It is the aim of this review to take a step forward in framing workable strategies and technologies for molecular plant cell‐based bioprocessing. Using anthocyanin biosynthesis as a case study, an integrated postgenomic approach has been proposed. This combines the functional analysis of metabolic pathways for biosynthesis of a particular metabolite from profiling of gene expression and protein expression to metabolic profiling. A global correlation not only can thus be established at the three molecular levels, but also places emphasis on the interactions between primary metabolism and secondary metabolism; between competing and/or complimentary pathways; and between biosynthetic and post‐biosynthetic events.
Nature′s Swiss Army Knife: The Diverse Protective Roles of Anthocyanins in Leaves
Authors: Gould Kevin S.
Published: December 2004

Anthocyanins, the pigments responsible for spectacular displays of vermilion in the leaves of deciduous trees, have long been considered an extravagant waste of a plant′s resources. Contemporary research, in contrast, has begun to show that the pigments can significantly influence the way a leaf responds to environmental stress. Anthocyanins have been implicated in tolerance to stressors as diverse as drought, UV‐B, and heavy metals, as well as resistance to herbivores and pathogens. By absorbing high‐energy quanta, anthocyanic cell vacuoles both protect chloroplasts from the photoinhibitory and photooxidative effects of strong light, and prevent the catabolism of photolabile defence compounds. Anthocyanins also mitigate photooxidative injury in leaves by efficiently scavenging free radicals and reactive oxygen species. Far from being a useless by‐product of the flavonoid pathway, these red pigments may in some instances be critical for plant survival.
Multiple Media, Convergent Processes, and Divergent Products: Organizational Innovation in Digital Media Production at a European Firm
Authors: Boczkowski Pablo J. , Ferris José A.
Published: December 2004

This article addresses the intersection of two underexplored themes in studies of cultural production in traditional and digital media: the role of technology in news work and the processes that shape media convergence. The authors analyze organizational innovation in digital media production at GMS, a European firm that operates print and broadcast outlets in several specialized news markets. Between 1994 and 2003, GMS went from a phase of digital media experimentation under-taken by teams located within each existing newsroom, to the creation of a separate unit handling the online content of all print and broadcast newsrooms, to the ongoing integration of news production into a single newsroom per specialized market that generates different products for the various outlets in each market. This analysis illuminates how adopting online technologies has involved shifts in the locus of content creation in a path of increasing convergence in production processes but continued divergence of media products.
Deep Democracy, Thin Citizenship: The Impact of Digital Media in Political Campaign Strategy
Authors: Howard Philip N.
Published: December 2004

Digital media strategies are a crucial component of contemporary political campaigns. Established political elites use database and Internet technologies to raise money, organize volunteers, gather intelligence on voters, and do opposition research. However, they use data-mining techniques that outrage privacy advocates and surreptitious technologies that few Internet users understand. Grassroots political actors and average votersbuild their own digital campaigns, researching public policy options, candidate histories, lobbyist maneuvering, and the finances of big campaigns. I examine the role of digital technologies in the production of contemporary political culture with ethnographic and survey evidence from four election seasons between 1996 and 2002. Democracy is deeper in terms of the diffusion of rich data about political actors, policy options, and the diversity of actors and opinion in the public sphere. Citizenship is thinner in terms of the ease in which people can become politically expressive without being substantively engaged.
Remote Control: The Rise of Electronic Cultural Policy
Authors: Vaidhyanathan Siva
Published: December 2004

Since the early 1990s, the United States has been formulating, executing, and imposing a form of “electronic cultural policy.” This phrase means two things: a state-generated setof policies to encourage or mandate design standards for electronic devices and dictate a particular set of cultural choices; and the cultural choices themselves, which have been embedded in the design and software of electronic goods. The goal of electronic cultural policy has been to encourage and enable “remote control,” shifting decisions over the use of content from the user to the vendor. The intended macro effects of such micro policies are antidemocratic. Their potential has created the possibility of a whole new set of forms of cultural domination by a handful of powerful global institutions. Yet so far, the actual consequences of these policies have been different from those intended, igniting activism and disobedience on a global scale.
Counselor and Client Predictors of the Initial Working Alliance:
Authors: Wei Meifen , Heppner P. Paul
Published: December 2004

One mission of the International Forum section in The Counseling Psychologist is to increase the globalization of counseling psychology (Leong & Ponterotto, 2003). The goals of this study are in line with this mission: (a) to replicate U.S. counseling research on the working alliance to Taiwan by examining clients’perceptions of their counselors’ credibility and (b) to extend the working-alliance literature by examining the role that counselors’problem-solvingstyles play in predicting the initial working alliance. Thirty-one counseling dyads from four counseling centers in Taiwan participated by completing inventories after their first counseling sessions. Results found that (a) clients’ perceptions of their counselors’ credibility and (b) counselors’ perceptions of their problemsolving styles significantly predicted the client-rated, but not the counselor-rated, working alliance. Counseling implications and recommendations for future research are discussed.
Intermediary Organizations as Capacity Builders in Family Educational Involvement
Authors: Lopez M. Elena , Kreider Holly , Coffman Julia
Published: December 2004

Although a substantial literature examines the outcomes of family involvement in education, and the family and school characteristics that support or deter such involvement, we know little about the role of national nonprofit intermediary organizations in family educational involvement. This article argues that intermediary organizations play a crucial role in capacity building for family involvement by providing alternatives to school-centered approaches to family involvement and engaging families with intensive support that schools seldom offer. It examines the functions of intermediary organizations by using a framework of capacity building at the individual, organizational, and relational levels.
Darwinian Grandparenting: Preferential Investment in More Certain Kin
Authors: Laham Simon M. , Gonsalkorale Karen , von Hippel William
Published: December 2004

Studies on grandparental investment have revealed that mothers’ fathers are emotionally closer to their grandchildren than are fathers’ mothers. In the current study, it was hypothesized that this difference is caused by the fact that fathers’ mothers often have the potential to invest in genetically more certain kin (children through their daughters). To test this hypothesis, 787 participants rated their emotional closeness and exposure to their grandparents and indicated whether they had cousins through paternal and maternal aunts and uncles. Results indicated that participants felt closer to mothers’ fathers than fathers’ mothers only when alternate investment outlets for fathers’ mothers were available. Closeness ratings to fathers’ fathers also were reduced when they had grandchildren through their daughters. Exposure to grandparents revealed a similar pattern of findings but did not show the same sensitivity to the presence of more certain kin and did not appear to account for the closeness ratings.
The Impact of Fear Appeals on Processing and Acceptance of Action Recommendations
Authors: de Hoog Natascha , Stroebe Wolfgang , de Wit John B. F.
Published: December 2004

A stage model of processing of fear-arousing communications was tested in an experiment that examined the impact of vulnerability to a severe health risk, the quality of the arguments supporting a protective action recommendation, and the source to which the recommendation was attributed, on processing and acceptance of the recommendation. Argument quality influenced attitudes toward the recommendation (but not intention to act), and this effect was mediated by negative thoughts about the recommendation. Vulnerability influenced intention to act (but not attitudes), and this effect was mediated by perceived threat and positive thoughts about the recommendation. The pattern of findings suggests that although vulnerability to a severe health risk induces biased processing of the recommendation, biased processing is restricted to intentions and does not compromise the evaluation of the recommendation. The theoretical and practical implications of these findings are discussed.
Introduction: Demarcation Socialized: Constructing Boundaries and Recognizing Difference
Authors: Evans Robert
Published: December 2004

Given what we know about the nature of knowledge and scientific work it no longer makes sense to think of scientific knowledge as demarcated from “ordinary” knowledge through its methods or the characteristics of the scientific community. As the social studies of science have shown, boundaries become ambiguous when viewed close up so that science merges with ordinary knowledge. But does this mean that distinctions between knowledge claims rest on nothing more than social conventions, powerful as these might be? The articles in this special issue address this question from a variety of perspectives, while this introduction sets out this broader framework and highlights the themes that unite the individual articles. Our central argument is that although boundary work is difficult, complex, and contingent, it is too important to be left to chance or tradition. We need to rescue expertise from the antiessentialist consensus that there is nothing but attribution.
From Civil Rights to Environmental Rights: Constructions of Race, Community, and Identity in Three African American Newspapers’ Coverage of the Environmental Justice Movement
Authors: Heinz Teresa L.
Published: December 2004

Environmental racism refers to the placement of health-threatening structures such as landfills and factories in areas where the poor and ethnic minorities live. These issues are often ignored by the mainstream environmental movement, which is largely White, male, and middle class. In advocating against discriminatory polluting practices, the environmental justice movement particularly emphasizes the issues of community, identity, and race. This article examines how the coverage of environmental justice in three African American newspapers (The Los Angeles Sentinel, The Chicago Defender, and Detroit’s Michigan Chronicle) articulates these three issues in politically problematic ways that are likewise present in the mainstream media.
Language and National Identity in the Era of Globalization: The Case of English in Switzerland
Authors: Demont-Heinrich Christof
Published: December 2004

This article engages the intersection of language, national identity, nation state, English and discourses of (global) modernization, progress, and the transcendence of the national vis-à-vis an instructive case: Switzerland. It examines the rise of English in multilingual Switzerland and its potential impact on Swiss collective (national) identity. It reflects, as well, on the ways in which English’s spread might influence the ethic of multilingual reciprocity in the Swiss and global contexts. It is contended that despite significant shortcomings, multilingualism has survived and, to a large extent, even thrived in Switzerland precisely because that nation state has legally and normatively codified the protection of linguistic particularism and established multilingualism as a basic component of its national identity. Yet even state-sanctioned and officially codified multilingualisms deeply embedded in national mythology, such as in Switzerland, are potentially threatened by an incessant drive to modernize, globalize, and “Englishize.”
Shameful Mother: Poverty and Prostitution in Seventeenth-Century Milan
Authors: D’Amico Stefano
Published: December 2004

In the spring of 1672, in Milan, Angela Visconti was convicted for having forced her fifteen-year-old daughter, Margherita, into prostitution. The case of Angela and Margherita Visconti demonstrates the ways in which sexuality and prostitution could and often needed to be employed by large strata of poor women to escape misery and to reduce the gap between their standard of living and that of the higher classes. In the life of the lower orders, it did not represent an exceptional and disturbing feature; rather, it was a necessary survival strategy to adopt in particularly difficult periods. The trial also offers intimate insight into how the moral norms of the Counter-Reformation, despite their permeation in all aspects of seventeenth-century society, could be challenged for the pursuit of material benefits.
Doctoral Students and Nursing Research
Authors: Malinski Violet M.
Published: December 2004

Three nurse scholars independently present their views about research appropriate for doctoral students in nursing. Taken together, their individual perspectives provide insights into the diverse range of opinions present in the profession today.
Being a Sibling
Authors: Baumann Steven L. , Dyches Tina Taylor , Braddick Marybeth
Published: December 2004

The purpose of this descriptive exploratory study was to explore the meaning of being a sibling using Parse’s human becoming perspective. Twelve children between 5 and 15 years of age with a younger sibling with a cleft lip and palate or Down Syndrome participated. Through semi-structured interviews and the use of art, children talked about their experiences. Major themes portrayed the complex and paradoxical nature of being a sibling. The themes also revealed that having a sibling with special circumstances includes some unique opportunities and challenges. The finding of this study is the descriptive statement, being a sibling is an arduous charge to champion close others amid restricting-enhancing commitments while new endeavors give rise to new possibilities. Implications for nursing are discussed in the context of understanding being a sibling.
Anticoagulation Monitoring
Authors: Smythe Maureen A. , Caffee Anne
Published: December 2004

Optimal management of anticoagulant therapy requires an understanding of the laboratory tests often employed to guide therapy. The activated partial thromboplastin time (aPTT) can detect abnormalities in the intrinsic and common clotting pathways. Despite numerous limitations in the aPTT test, it remains the gold standard for monitoring unfractionated heparin and direct thrombin inhibitor therapy. The aPTT can be performed in the central laboratory or at the bedside (point of care [POC] testing). The activated clotting time (ACT) is a POC test that is routinely employed to monitor high-dose heparin during invasive and surgical procedures. The ACT therapeutic range will depend on the specific procedure or surgery being performed. Heparin levels are becoming more routinely available and are used to establish the aPTT therapeutic range for heparin therapy as well as for direct monitoring of heparin and low-molecular-weight heparin therapy. The international normalized ratio (INR) is the gold standard for monitoring warfarin patients. The target INR depends on the indication for anticoagulation. POC monitoring for warfarin is becoming increasingly used. Clinicians should have a thorough understanding of the benefits as well as the limitations of warfarin POC monitoring.
Therapeutic Update on the Prevention and Treatment of Venous Thromboembolism
Authors: McGuire Mike , Dobesh Paul P.
Published: December 2004

Venous thromboembolism (VTE) is a common condition that increases in incidence with age and risk factors. Therapies for VTE are aimed at either preventing the disease in high-risk individuals or treating patients who have developed VTE. Assessing risk and aggressively using the recommended therapies is primacy in preventing VTE in surgical and medical patients. Risk of VTE in medical patients has become more defined in recent years, and prophylaxis in this group can prevent scores of iatrogenic VTE. Treatment of VTE has evolved in the past decade from a condition that required hospitalization for 5 to 7 days to a disease state that can be conveniently and safely treated on an outpatient basis, largely due to the advent of low-molecular-weight heparins and patient self-directed treatment.
Parents’ Refusal of Medical Treatment for Cultural or Religious Beliefs: An Ethnographic Study of Health Care Professionals’ Experiences
Authors: Linnard-Palmer Luanne , Kools Susan
Published: December 2004

Pediatric nurses working in acute care settings serving religious and culturally diverse families may encounter parents whose beliefs influence treatment decisions. Previous literature describes how these complex situations lead to emotional distress and strained relationships between health care provider and family members. An ethnographic study was conducted to investigate the impact of parental treatment refusal on the bedside interactions between pediatric nurses and parents. Twenty in-depth interviews with nurses were conducted, and extensive field notes were taken during data collection. Emotional feelings associated with possible loss of guardianship and subsequent mandated treatment, the impact of the situation on the nurses’ health and stress levels, and functional status were all explored. Three themes were identified following interpretive narrative analysis of transcriptions and field notes: weathering the storm of moral conflict, closeness and involvement versus distance and retreat, and battles between the supportive and oppositional groups. The findings of the study lead to a deeper understanding of the complexities of the ethical dilemma surrounding treatment refusal in pediatrics.
Using a Collaboratory Model to Translate Social Work Research Into Practice and Policy
Authors: Allen-Meares Paula , Hudgins Cynthia A. , Engberg Mark E. , Lessnau Barbara
Published: December 2004

Objective: The purpose of this article was to examine how an initiative of 10 collaborative projects focused on children and youth have applied principles of participatory research, collaboratories, and technological solutions. Method: The study analyzed multiple forms of qualitative data, including semiannual formative evaluations and semistructured interviews of participating partners. Results: Both the collaborative method and the infusion of technology were central to the functioning of collaboratory projects and, ultimately, the translation from research to practice and policy. The community-based participatory nature of the research projects resulted in applicable findings that were credible with people affected by the issues studied. Conclusions: The present study suggests that when there is steadfast commitment on the part of a diverse group of partners, even simple applications of technology can make a difference.
Victims Twice Over: Perceptions and Experiences of Injured Workers
Authors: Beardwood Barbara A. , Kirsh Bonnie , Clark Nancy J.
Published: December 2004

The authors discuss the qualitative component of a participatory research project conducted in Toronto, Ontario, between 1999 and 2001. Injured workers, who were trained as peer researchers, conducted one-time, semistructured interviews with other injured workers (N = 17) and helped with inductive coding and analyzing the interview transcripts. The qualitative research group consisted of seven peer researchers, four academic researchers, and a community legal worker. The group recruited interviewees by advertising on bulletin boards and in newsletters and newspapers, and selected a diverse group of interviewees who had encountered problems with the return-to-work process. Interviewees believed that the process victimizes them and renders them powerless and dependent on others. Furthermore, they considered that health professionals and bureaucrats impede their rehabilitation. The authors suggest that injured workers should be included in the decision-making process of rehabilitation and rebuilding their lives.
Gestational Diabetes: The Meaning of an At-Risk Pregnancy
Authors: Evans Marilyn K. , O’Brien Beverley
Published: December 2004

Being diagnosed with gestational diabetes (GDM) is coupled with the implication that the woman and her fetus are at risk. In this study, the authors use a hermeneutic phenomenological approach to gain an in-depth understanding of GDM as pregnant women meaningfully experience it. They conducted conversational interviews with 12 women who were diagnosed with and being treated for diabetes in pregnancy. Data analysis involved a reflective process consistent with the guidelines of thematic analysis. Four themes identified as characteristic of the women’s pregnancy experience were Living a Controlled Pregnancy, Balancing, Being a Responsible Mother, and Being Transformed. The findings challenge health care professionals to discuss openly and reassess their present models of care for pregnant women and their families.
Profiling the Hospital-Based Psychiatric Registered Nurse Workforce
Authors: Hanrahan Nancy P. , Gerolamo Angela M.
Published: December 2004

BACKGROUND: Registered nursing is a core profession staffing psychiatric hospitals. However, strategic planning to address a critical national workforce shortage of registered nurses has not included psychiatric registered nurses. The lack of information thwarts policy decisions to adequately staff registered nurses for safe and effective psychiatric inpatient environments. OBJECTIVE: This study describes and compares demographic, educational, and employment characteristics of hospital-based psychiatric nurses with nonpsychiatric nurses at the national level. It is hypothesized that significant differences between psychiatric and nonpsychiatric nurses exist, requiring special planning for recruitment and retention of psychiatric registered nurses. DESIGN: A weighted sample of 1,113,277 hospital-based registered nurses was identified from the 2000 National Sample Survey of Registered Nurses. Of these, 33,891 hospital-based psychiatric nurses were identified. RESULTS: Hospital-based psychiatric nurses are older, with a significantly lower proportion of younger entrants into the field. They are more diverse in race, education, gender, and marital status than nonpsychiatric nurses. Psychiatric nurses are also more likely than nonpsychiatric nurses to have an associate degree in nursing with a previous bachelor’s degree in another field. They have a higher rate of job turnover than nonpsychiatric nurses and have a slightly lower gross annual salary. CONCLUSION: Evidence suggests that psychiatric nurses will age out of the workforce faster than nonpsychiatric nurses. It is imperative that resources for the recruitment and retention of registered nurses be directed toward the psychiatric nurse workforce.
Inflammation and Wound Healing: The Role of Bacteria in the Immuno-Regulation of Wound Healing
Authors: Jones Stuart G. , Edwards Ruth , Thomas David W.
Published: December 2004

Wound healing is a sequence of complex events, an imbalance of which can result in a failure of the wound to heal, with significant implications for patients and health care services alike. Although the exact mechanism that underlies these events is not fully understood, inflammatory processes and the innate immune system play a vital role, not only in normal wound healing but also in the pathophysiology of delayed wound healing. These defense mechanisms are affected by underlying disease states and medical conditions, for example, diabetes, venous insufficiency, and the inflammation associated with acute trauma. Importantly, however, these processes are also modulated in health by bacteria within the wound. This article examines the role of the mediators of inflammation involved in the wound-healing process and discusses the function of these mediators when normal healing fails. The reaction of the wound to bacterial contamination and the effect of bacteria on wound healing are also discussed.
Dexamethasone resistance in B-cell precursor childhood acute lymphoblastic leukemia occurs downstream of ligand-induced nuclear translocation of the glucocorticoid receptor
Authors: Bachmann Petra S. , Gorman Rosemary , MacKenzie Karen L. , Lutze-Mann Louise , Lock Richard B.
Published: December 2004

Glucocorticoids are among the most effective agents used in the treatment of childhood acute lymphoblastic leukemia (ALL), and patient response to treatment is an important determinant of long-term outcome. Despite its clinical significance, the molecular basis of glucocorticoid resistance in lymphoid malignancies is still poorly understood. We have recently developed a highly clinically relevant experimental model of childhood ALL, in which primary childhood ALL biopsies were established as xenografts in nonobese diabetic/severe combined immunodeficient (NOD/SCID) mice. The in vivo and in vitro responses of a panel of these xenografts to the glucocorticoid, dexamethasone, reflected the outcome of the patients from whom they were derived. In this report we show that glucocorticoid resistance in B-cell precursor (BCP) ALL xenografts was not due to down-regulation of the glucocorticoid receptor (GR) nor to defective ligand binding of the GR. Moreover, dexamethasone-induced GR translocation from the cytoplasm to the nucleus was comparable in all xenografts. However, glucocorticoid resistance was associated with profoundly attenuated induction of the BH3-only proapoptotic protein, Bim, when xenograft cells were exposed to dexamethasone. These results show that dexamethasone resistance in BCP ALL xenografts occurs downstream of ligand-induced nuclear translocation of the GR, but upstream of Bim induction.
Inhibiting primary effusion lymphoma by lentiviral vectors encoding short hairpin RNA
Authors: Godfrey Andrew , Anderson John , Papanastasiou Antigoni , Takeuchi Yasu , Boshoff Chris
Published: December 2004

We use lentiviral-delivered RNA interference (RNAi) to inhibit the growth of a model of primary effusion lymphoma (PEL) in vitro and in vivo. RNAi is a phenomenon allowing the sequence-specific targeting and silencing of exogenous and endogenous gene expression and is being applied to inhibit viral replication both in vitro and in vivo. We show that silencing of genes believed to be essential for the Kaposi sarcoma-associated herpesvirus (KSHV) latent life cycle (the oncogenic cluster) has a varied effect in PEL cell lines cultured in vitro, however, concomitant silencing of the viral cyclin (vcyclin) and viral FLICE (Fas-associating protein with death domain-like interleukin-1β-converting enzyme) inhibitory protein (vFLIP) caused efficient apoptosis in all PEL lines tested. We demonstrate that in a murine model of PEL, lentiviral-mediated RNA interference both inhibits development of ascites and can act as a treatment for established ascites. We also show that the administered lentiviral vectors are essentially limited to the peritoneal cavity, which has advantages for safety and dosage in a therapeutic setting. This shows the use of lentiviral-mediated RNA interference in vivo as a potential therapeutic against a virally driven human cancer.
Hematopoietic cells regulate the angiogenic switch during tumorigenesis
Authors: Okamoto Rika , Ueno Masaya , Yamada Yoshihiro , Takahashi Naoko , Sano Hideto , Suda Toshio , Takakura Nobuyuki
Published: December 2004

Hematopoietic cells (HCs) promote blood vessel formation by producing various proangiogenic cytokines and chemokines and matrix metalloproteinases. We injected mouse colon26 colon cancer cells or human PC3 prostate adenocarcinoma cells into mice and studied the localization of HCs during tumor development. HCs were distributed in the inner tumor mass in all of the tumor tissues examined; however, the localization of HCs in the tumor tissue differed depending on the tumor cell type. In the case of colon26 tumors, as the tumor grew, many mature HCs migrated into the tumor mass before fine capillary formation was observed. On the other hand, although very few HCs migrated into PC3 tumor tissue, c-Kit+ hematopoietic stem/progenitor cells accumulated around the edge of the tumor. Bone marrow suppression induced by injection of anti–c-Kit neutralizing antibody suppressed tumor angiogenesis by different mechanisms according to the tumor cell type: bone marrow suppression inhibited the initiation of sprouting angiogenesis in colon26 tumors, while it suppressed an increase in the caliber of newly developed blood vessels at the tumor edge in PC3 tumors. Our findings suggest that HCs are involved in tumor angiogenesis and regulate the angiogenic switch during tumorigenesis.
Psychosocial research on systemic lupus erythematosus: a literature review
Authors: Seawell A H , Danoff-Burg S
Published: December 2004

This article is the first to review published research on psychosocial factors and behavioral interventions related to systemic lupus erythematosus (SLE). The first section presents descriptive studies, followed by studies that investigate psychosocial factors as predictor and outcome variables. These studies demonstrate that the consideration of psychosocial factors is critical to understanding the disease experience of persons with SLE. Next, studies of behavioral interventions are presented, leading to the conclusion that randomized controlled trials are essential yet rare. The final section highlights limitations of the extant literature and suggests directions for future research and recommendations for clinicians.
Multiple arterial thromboses in a patient with primary antiphospholipid syndrome receiving a bromocriptine therapy
Authors: Dargaud Y , Pariset C , Pinede L , Rugeri L , Mohammedi I , Trzeciak C , Negrier C , Ninet J
Published: December 2004

We report a patient with a previously known primary antiphospholipid syndrome who had life threatening multiple arterial thromboses. The patient experienced a myocardial infarction with intraventricular thrombi under bromocriptine therapy in the puerperium, despite prophylactic low molecular weight heparin therapy. In this patient, no microvascular involvement was identified, thus eliminating the diagnosis of catastrophic antiphospholipid syndrome. Arterial thromboses may be explained by peripheral emboli originating from the intraventricular thrombi. This case emphasizes the necessity of a careful evaluation of the risk-benefit balance of bromocriptine therapy in patients with arterial risk factors. It also emphasizes the need for a correct diagnosis of catastrophic antiphospholipid syndrome allowing to limit the prescription of aggressive therapies.
Mitofusin 1 and 2 play distinct roles in mitochondrial fusion reactions via GTPase activity
Authors: Ishihara Naotada , Eura Yuka , Mihara Katsuyoshi
Published: December 2004

The mammalian homologues of yeast and Drosophila Fzo, mitofusin (Mfn) 1 and 2, are both essential for mitochondrial fusion and maintenance of mitochondrial morphology. Though the GTPase domain is required for Mfn protein function, the molecular mechanisms of the GTPase-dependent reaction as well as the functional division of the two Mfn proteins are unknown. To examine the function of Mfn proteins, tethering of mitochondrial membranes was measured in vitro by fluorescence microscopy using green fluorescence protein- or red fluorescent protein-tagged and Mfn1-expressing mitochondria, or by immunoprecipitation using mitochondria harboring HA- or FLAG-tagged Mfn proteins. These experiments revealed that Mfn1-harboring mitochondria were efficiently tethered in a GTP-dependent manner, whereas Mfn2-harboring mitochondria were tethered with only low efficiency. Sucrose density gradient centrifugation followed by co-immunoprecipitation revealed that Mfn1 produced oligomerized ∼250 kDa and ∼450 kDa complexes in a GTP-dependent manner. The ∼450 kDa complex contained oligomerized Mfn1 from distinct apposing membranes (docking complex), whereas the ∼250 kDa complex was composed of Mfn1 present on the same membrane or in the membrane-solubilized state (cis complex). These results were also confirmed using blue-native PAGE. Mfn1 exhibited higher activity for this reaction than Mfn2. Purified recombinant Mfn1 exhibited ∼eightfold higher GTPase activity than Mfn2. These findings indicate that the two Mfn proteins have distinct activities, and suggest that Mfn1 is mainly responsible for GTP-dependent membrane tethering.
Importin β is transported to spindle poles during mitosis and regulates Ran-dependent spindle assembly factors in mammalian cells
Authors: Ciciarello Marilena , Mangiacasale Rosamaria , Thibier Catherine , Guarguaglini Giulia , Marchetti Enzo , Di Fiore Barbara , Lavia Patrizia
Published: December 2004

Spatial control is a key issue in cell division. The Ran GTPase regulates several fundamental processes for cell life, largely acting through importin molecules. The best understood of these is protein import through the nuclear envelope in interphase, but roles in mitotic spindle assembly are also established. In mammalian cells, in which centrosomes are major spindle organizers, a link is emerging between the Ran network, centrosomes and spindle poles. Here, we show that, after nuclear envelope breakdown, importin β is transported to the spindle poles in mammalian cells. This localization is temporally regulated from prometaphase until anaphase, when importin β dissociates from poles and is recruited back around reforming nuclei. Importin β sediments with mitotic microtubules in vitro and its accumulation at poles requires microtubule integrity and dynamics in vivo. Furthermore, RNA interference-dependent inactivation of TPX2, the major Ran-dependent spindle organizer, abolishes importin β accumulation at poles. Importin β has a functional role in spindle pole organization, because overexpression yields mitotic spindles with abnormal, fragmented poles. Coexpression of TPX2 with importin β mitigates these abnormalities. Together, these results indicate that the balance between importins and spindle regulators of the TPX2 type is crucial for spindle formation. Targeting of TPX2/importin-β complexes to poles is a key aspect in Ran-dependent control of the mitotic apparatus in mammalian cells.
Long-term culture of hepatic progenitors derived from mouse Dlk+ hepatoblasts
Authors: Tanimizu Naoki , Saito Hiroki , Mostov Keith , Miyajima Atsushi
Published: December 2004

We previously demonstrated that hepatoblasts can be isolated from mouse fetal liver based on the expression of delta-like leucine zipper kinase (Dlk), also known as Pref-1. Each Dlk+ hepatoblast forms a colony containing both albumin+ hepatocytes and cytokeratin 19+ (CK19) cholangiocytic cells on either type IV collagen or laminin. Here we show that extracellular matrices (ECMs) significantly affect the growth of Dlk+ cells. Dlk+ cells vigorously proliferated on type IV collagen-coated dishes in the presence of EGF and HGF during the first 5 days, but their proliferative capability declined thereafter. Dlk+ cells also proliferated on laminin-coated plates and some colonies continued to expand even beyond one month after plating. These hepatic progenitor cells proliferating on laminin (HPPL) efficiently proliferated even after replating. Moreover, they were induced to differentiate into hepatocytes and cholangiocytes by overlaying Engelbreth-Holm-Swarm sarcoma (EHS) gel and by embedding in type I collagen gel, respectively. HPPL acquired the metabolic functions of accumulating polysaccharides and detoxifying ammonium ions after hepatic differentiation. Surprisingly, HPPL expressed pancreatic genes such as Pdx1 when dexamethasone was depleted from the culture medium. Therefore, the long-term culture of hepatoblasts on laminin produces multi-potential hepatic progenitors, which possess a strong proliferative capability, differentiate into both hepatocytes and cholangiocytes, and potentially give rise to pancreatic cells.