bluuebunny/crossref_metadata_2025 huggingface dataset:
Wilms’ Tumor 1–Associating Protein Regulates the Proliferation of Vascular Smooth Muscle Cells
Authors: Small Theodore W. , Bolender Zuzana , Bueno Clara , O’Neil Caroline , Nong Zengxuan , Rushlow Walter , Rajakumar Nagalingham , Kandel Christopher , Strong Jennifer , Madrenas Joaquin , Pickering J. Geoffrey
Published: November 2006

Smooth muscle cells (SMCs) are called on to proliferate during vascular restructuring but must return to a nonproliferative state if remodeling is to appropriately terminate. To identify mediators of the reacquisition of replicative quiescence, we undertook gene expression screening in a uniquely plastic human SMC line. As proliferating SMCs shifted to a contractile and nonproliferative state, expression of TIMP-3, Axl, and KIAA0098 decreased whereas expression of complement C1s, cathepsin B, cellular repressor of E1A-activated genes increased. Wilms’ tumor 1-associating protein (WTAP), a nuclear constituent of unknown function, was also upregulated as SMCs became nonproliferative. Furthermore, WTAP in the intima of injured arteries was substantially upregulated in the late stages of repair. Introduction of WTAP complementary DNA into human SMCs inhibited their proliferation, with a corresponding decrease in DNA synthesis and an increase in apoptosis. Knocking down endogenous WTAP increased SMC proliferation, because of increased DNA synthesis and G
1
/S phase transition, together with reduced apoptosis. WTAP was found to associate with the Wilms’ tumor-1 protein in human SMCs and WTAP overexpression inhibited the binding of WT1 to an oligonucleotide containing a consensus WT1 binding site, whereas WTAP knockdown accentuated this interaction. Expression of the WT1 target genes, amphiregulin and Bcl-2, was suppressed in WTAP-overexpressing SMCs and increased in WTAP-deficient SMCs. Moreover, exogenous amphiregulin rescued the antiproliferative effect of WTAP. These findings identify WTAP as a novel regulator of the cell cycle and cell survival and implicate a WTAP-WT1 axis as a novel pathway for controlling vascular SMC phenotype.
Upregulation of Heat Shock Transcription Factor 1 Plays a Critical Role in Adaptive Cardiac Hypertrophy
Authors: Sakamoto Masaya , Minamino Tohru , Toko Haruhiro , Kayama Yosuke , Zou Yunzeng , Sano Masanori , Takaki Eiichi , Aoyagi Teruhiko , Tojo Katsuyoshi , Tajima Naoko , Nakai Akira , Aburatani Hiroyuki , Komuro Issei
Published: November 2006

Exercise-induced cardiac hypertrophy has been reported to have better prognosis than pressure overload-induced cardiac hypertrophy. Cardiac hypertrophy induced by exercise was associated with less cardiac fibrosis and better systolic function, suggesting that the adaptive mechanisms may exist in exercise-induced hypertrophy. Here, we showed a critical role of heat shock transcription factor 1 (HSF1), an important transcription factor for heat shock proteins, in the adaptive mechanism of cardiac hypertrophy. We examined expression of 8800 genes in the heart of exercise-induced hypertrophy model using DNA chip technique and compared with pressure overload-induced hypertrophy. Expression of HSF1 and its target molecule heat shock proteins was significantly upregulated in the heart by exercise but not by chronic pressure overload. Constitutive activation of HSF1 in the heart significantly ameliorated death of cardiomyocytes and cardiac fibrosis and thereby prevented cardiac dysfunction as well as hypertrophy induced by chronic pressure overload. Conversely, decreased activity of HSF1 in the heart promoted cardiac dysfunction in response to exercise, a load that normally leads to adaptive hypertrophy with preserved systolic function. Likewise, cardiac function was significantly impaired from the early phase of pressure overload, when HSF1 activation was inhibited. These results suggest that HSF1 plays a critical role in the transition between adaptive and maladaptive hypertrophy.
Can Pulse Oximetry or a Bedside Swallowing Assessment Be Used to Detect Aspiration After Stroke?
Authors: Ramsey Deborah J. C. , Smithard David G. , Kalra Lalit
Published: November 2006

Background and Purpose—Desaturation during swallowing may help to identify aspiration in stroke patients. This study investigated pulse oximetry, bedside swallowing assessment (BSA), and videofluoroscopy as tests for detecting aspiration after stroke.

Methods—Swallowing was assessed in 189 stroke patients (mean±SD age, 70.9±12.3 years) within 5 days of symptom onset with a modified BSA (water replaced by radio-opaque contrast agent, followed by chest radiography to detect aspiration). Simultaneous pulse oximetry recorded the greatest desaturation from baseline for 10 minutes from modified BSA onset. Videofluoroscopy was undertaken in 54 (28%) patients.

Results—Modified BSA showed a safe swallow in 98 (51.9%), unsafe swallow in 85 (45.0%), and silent aspiration in 6 (3.2%) patients. During swallowing, desaturation by >2% occurred in 27 (27.6%) and by >5% in 3 (3.1%) of the 98 safe-swallow patients on modified BSA. Of the 85 unsafe-swallow patients, only 28 (32.9%) desaturated by >2% and 6 (7.1%) by >5%. Desaturation did not occur in any of the 6 silent aspirators. With the modified BSA to detect aspiration, sensitivity and specificity, respectively, were 0.31 and 0.72 for desaturation >2% and 0.07 and 0.97 for desaturation >5%. By videofluoroscopy, sensitivity and specificity for detecting aspiration were 0.47 and 0.72 for modified BSA, 0.33 and 0.62 for desaturation >2%, and 0.13 and 0.95 for desaturation >5%. Combining a failed modified BSA with desaturation >2% or >5% did not significantly improve predictive values.

Conclusions—Modified BSA and pulse oximetry during swallowing, whether alone or in combination, showed inadequate sensitivity, specificity, and predictive values for detection of aspiration compared with videofluoroscopy in stroke patients.
New Insight Into the Association of Apolipoprotein E Genetic Variants With Carotid Plaques and Intima-Media Thickness
Authors: Debette Stéphanie , Lambert Jean-Charles , Gariépy Jérôme , Fievet Nathalie , Tzourio Christophe , Dartigues Jean-Françoise , Ritchie Karen , Dupuy Anne-Mary , Alpérovitch Annick , Ducimetière Pierre , Amouyel Philippe , Zureik Mahmoud
Published: November 2006

Background and Purpose—

Carotid plaques and elevated carotid artery intima-media thickness (IMT) are major predictors of vascular morbidity and mortality. Our aim was to test their association with 2 polymorphisms of the apolipoprotein E (
apoE
) gene, ε and -219G/T.

Methods—

The study was performed on 5856 subjects aged ≥65 years recruited from the French population for the Three-City Study. Carotid ultrasound examination included an assessment of atherosclerotic plaques in the extracranial carotid arteries and a measurement of IMT in the common carotid arteries (CCA) at a site free of plaques. The genetic association was tested using genotype and haplotype analyses.

Results—

In a multivariate analysis including both polymorphisms and vascular risk factors, carotid plaques were more frequent in ε4 homozygotes (adjusted odds ratio=2.12, 95% CI=1.27 to 3.53) and less frequent in ε2 carriers (adjusted odds ratio=0.79, 95% CI=0.66 to 0.95) compared with ε3 homozygotes. Adjusting for and stratifying on lipid levels did not modify these results. CCA-IMT was higher in carriers of the ε34 genotype (mean CCA-IMT=0.744 mm versus 0.732 mm for the ε33 genotype,
P
=0.002), but the association disappeared after excluding subjects with carotid plaques. No association was found between the -219 polymorphism and either carotid plaques or CCA-IMT, and there was no interaction or cis-effect between -219 and ε.

Conclusions—

This study, conducted on a large population cohort of French elderly, demonstrated that carotid plaques were significantly associated with the apoE ε polymorphism independently of the -219 polymorphism and vascular risk factors, in particular lipid levels.
Language Rehabilitation in Chronic Aphasia and Time Postonset
Authors: Moss Aviva , Nicholas Marjorie
Published: November 2006

Background and Purpose—

This article is a comprehensive review of aphasia treatment studies for the purpose of investigating the relationship between time postonset of aphasia and response to treatment for aphasia in chronic patients at ≥1 year after symptom onset.

Methods—

Studies that demonstrated treatment response (defined as a measurable change in task performance compared with a control task performance) through the use of single-subject design methodologies on measures of verbal output or auditory comprehension were selected. Individual subject data were extracted from the 23 studies that met criteria identifying the subjects as those who received direct continuous therapy for spoken language deficits and whose changes in response to therapy were measurable. Percent of maximum possible change was used as a measurement of outcome.

Results—

Nonparametric correlation statistics (Spearman ρ) and comparisons of group means (Kruskal–Wallis) were used to compare the relationship between time postonset and improvement. Time postonset at which treatment was initiated did not correlate with response to treatment. No significant differences in response to treatment were found between groups of patients according to times postonset.

Conclusions—

Time postonset is not related to response to treatment for aphasia in patients >1 year postonset of aphasia.
Academic Discourses on School–Based Teacher Collaboration: Revisiting the Arguments
Authors: Lavié José Manuel
Published: November 2006

Purpose: After decades arguing the necessity of transforming schools into collaborative workplaces, teacher collaboration has been taken up by various discursive logics offering different viewpoints of the concept. This article reviews some of these discourses and looks at their main arguments, pointing to the contradictions and tensions between them and highlighting the contested and cooptive nature of teacher collaboration.

Proposed Conceptual Argument: This article differentiates provisionally between five discourses on teacher collaboration: Cultural discourses describe teacher collaboration as being embedded in cultural forms that blur the boundaries between personal and professional and stimulate interdependency and collective responsibility. School effectiveness and improvement discourses depict teacher collaboration as a product of cultural management led by the school's principal. School–as–community discourses embed teacher collaboration in a vision of schools as communities, where contractual models of relationships are transcended in pursuit of more inclusive environments. Restructuring discourses elaborate the idea of a “new professional” capable of getting involved in collaborative practices within an ever–learning organization. Finally, critical discourses articulate an approach that integrates democratic practices, community participation, and shared reflection on teaching as a social and political praxis.

Implications: Although valuable lessons can be learned by considering these discourses as providing a complementary grasp, they also advance differing arguments as to the purposes of teacher collaboration, the differentiated way in which it is approached, and the position of conflict in collaborative processes. As value–embedded frameworks, discourses orientate the practice of collaboration toward substantially different projects of school change resulting in conservative or transformative practices.
Acculturation in Mexican Immigrants
Authors: Page Robin L.
Published: November 2006

The concept of acculturation in Mexican immigrants was analyzed using the concept analysis technique developed by Walker and Avant. The related concepts for acculturation are assimilation, separation, and marginalization. The defining attributes identified for acculturation are original cultural identity, exposure to a culture different from one’s own, and changes in the behavioral, affective, and/or cognitive domains of one’s functioning after exposure to a new culture. An antecedent for acculturation is that identification with one’s culture of origin must be well established. Another antecedent is the willingness to modify one’s original cultural identity. Transition is identified as a consequence of acculturation. Acculturation is a complex, multifaceted concept and cannot be adequately captured by measures that use language preference alone. Other factors such as social class, employment, education, and income should also be considered when acculturation is a factor in nursing practice and research.
A Pilot Study of Healing Touch and Progressive Relaxation for Chronic Neuropathic Pain in Persons With Spinal Cord Injury
Authors: Wardell Diane Wind , Rintala Diana H. , Duan Zhigang , Tan Gabriel
Published: November 2006

This pilot study assessed the role of Healing Touch (HT), an energy-based therapy, in modulating chronic neuropathic pain and the associated psychological distress from post spinal cord injury. Twelve veterans were assigned to either HT or guided progressive relaxation for six weekly home visits. The instruments selected showed sensitivity, although there was a large variation among the groups. There was a significant difference in the composite of interference on the Brief Pain Inventory ( t = -2.71, p = .035). The mean score of the fatigue subscale of the Profile of Moods decreased ( ns) in the HT group and in the subscale of confusion yet remained stable in the control group. The Diener Satisfaction With Life Scale showed increased well-being in the HT group and no change in the control group. Participants reported various experiences with HT sessions indicating that it may have benefit in the complex response to chronic pain.
Spirituality and Stress Management in Healthy Adults
Authors: Tuck Inez , Alleyne Renee , Thinganjana Wantana
Published: November 2006

The purposes of this longitudinal, descriptive pilot study were to (a) test the acceptability and feasibility of a 6-week spiritual intervention; (b) determine the relationship between spirituality and stress; (c) explore the effects of the intervention on measures of perceived stress, spiritual perspective, and spiritual well-being; and (d) explore the meaning of spirituality. The sample consisted of 27 community-dwelling adults. Six categories emerged from the qualitative data as descriptors of the meaning and significance of spirituality. The survey data indicated that there were significant negative correlations between perceived stress and spiritual well-being at three time intervals, a significant decline in the levels of perceived stress, and a significant increase in spiritual perspective from the pretest to the 6-week follow-up. There were no significant changes in spiritual well-being. The intervention proved effective in reducing stress in this healthy adult sample.
Walking Pilgrimage as Caritas Action in the World
Authors: Watson Jean
Published: November 2006

This essay draws on the personal experiences of a spiritual pilgrimage in northern Spain. Using pilgrimage as metaphor and the experience of walking a portion of the famous Spanish El Camino, (the way), the author raises questions such as: How do we walk through life? How do we get our footing to bring artistry of caring into our lives and work and world? What steps do we take that speak to who we are and our raison d’être? This perspective is grounded in Newman’s health as evolving consciousness, Rogers’s science of unitary being, Quinn’s view of sacred space, and Watson’s caritas (cosmic loving consciousness) as the highest form of consciousness, and the infinite source of healing/wholeness. A walking spiritual pilgrimage serves as metaphoric invitation for nurses and nursing to engage in conscious, creative, artful steps, imprinting self and society with caritas in our lives, our work, and our world.
Issues and Priorities in Non-governmental Organisation Research
Authors: Lewis David
Published: November 2006

This article aims to do three things. First, it briefly sketches out the history of the recent rise to prominence of NGOs as an issue in development studies, linking this with the both the growth of and resistance to neo-liberal policy agendas. Second, it reflects on the strengths and weaknesses of NGO research to date, which although wide-ranging and diverse, has often lacked theoretical rigour, contextual understanding and empirical detail. Third, some ideas are presented for moving forward the NGO research agenda, both at the level of theory building and inter-disciplinarity, and in relation to ways that can improve the relevance of NGO research to practice. Themes included in the paper include the need for trans-disciplinary research, the importance of linking both Northern and Southern contexts of research and practice, and the need to build opportunities for providing more effective relationships between researchers and research ‘users’ in the South Asian context.
The Changing Local Rural Power Structure
Authors: Hossain Abul
Published: November 2006

This article examines the growth of small local NGOs in Bangladesh which have received far less attention than their larger counterparts. It examines the formation of small NGOs, the strategies of survival they use within the local environment, and their relations with the changing local power structure. NGOs have become more embedded in the local power structure since the 1990s, although the local elite still show mixed attitudes towards NGOs programmes. Organisations emerged in separate decades can be identified with older NGOs depending on securing patrons and resources from the centre, while newer NGOs facing a lack of patrons at the centre have developed strategies to access resources locally. NGO politics in the local area is also associated with changes of political regimes at the national level, and the rise of factional NGO politics can be attributed to conflicts between the NGO elite at the national level. Changes in regime have created opportunities for smaller NGO in pursuing patrons and resources. However, the links between NGOs and the elite does not mean that NGOs do not contribute in important ways to development in rural Bangladesh. But it would be wrong to see their necessarily as part of an independent ‘force for good’ in rural areas and more accurate to see them as ‘embedded’ in local power and politics.
Regulatory Challenges and Non-profit Welfarism
Authors: Ravichandran N.
Published: November 2006

The debate over non-profit organisations and then proper role in the liberalisation era continues, periodically grabbing public attention for sustainability, tax exemption, etc. However, as the non-profit sector grows in size and commercial activities, it is becoming indistinguishable from the private sector? The competition between non-profit sectors and private is made even more complex by the fact that the former are moving into activities that have previously been the domain of profit firms; and private firms are expanding into traditionally non-profit areas. To what extent this occurs is important for public policy, since the justification for subsidies, receiving donations and tax exemptions to non-profit sectors hinges on their differentiation from private firms. This is not only questioning the social welfarism philosophy, but also the one of the regulatory challenges that stand in front of us. Attention to NPOs growing commercial activity is necessary because it highlights both the difference between what society expects from them and private firms, and the similarity in the financial constraints that they face. Nevertheless this article aims to understand the available revenue factors that affect NPOs and their activities. In addition, this article also suggests regulations that affect the use of accounting procedures that minimise or eliminate taxable profit, and rules that affect commercial alliances with, or conversions into, private firms.
“It’s not Fair!”: Assessing the Dynamics and Resourcing of Teamwork
Authors: Willcoxson Lesley E.
Published: November 2006

Team-based assessments are commonly used in management education, yet questions remain about how to adequately differentiate individuals’ levels of input into team processes and project content when grading a team-based assessment. Following an overview of relevant research, this article describes an innovative self- and peer-assessment strategy that may be used initially to develop team dynamics, team management skills, and project planning and resourcing skills, and subsequently to accurately assess individuals’ contributions to team dynamics, team management, and project planning and resourcing.
What can Learning Science Contribute to our Understanding of the Effectiveness of Problem-Based Learning Groups?
Authors: Innes Robert B.
Published: November 2006

Recent education reforms informed by learning science support the effectiveness of collaborative learning strategies such as problem-based learning groups. However, the efficacy of these methods depends on the authenticity of the problem context and the quality of the dialog established. Communication within groups must be dialogic, and students must address problems using relevant concepts and deep principles. Although dialogic communication is rare and difficult to facilitate, if it is achieved, students will construct useful knowledge that can be applied beyond the classroom.
Virtual Team Learning: An Introductory Study Team Exercise
Authors: Clark Delwyn N. , Gibb Jenny L.
Published: November 2006

This article outlines the design, implementation, and evaluation of an innovative virtual team exercise. Cognitive, affective, and action-learning outcomes highlight the relevance of this grounded experiential exercise for management education and practice. Details are provided to enable the exercise to be adopted in a wide range of programs. Prior online experience, motivation, resistance to online environment, and trade-offs were found affect an overall positive experience reported by students.
RNAi-mediated silencing of TEL/AML1 reveals a heat-shock protein– and survivin-dependent mechanism for survival
Authors: Diakos Christofer , Krapf Gerd , Gerner Christopher , Inthal Andrea , Lemberger Christof , Ban Jozef , Dohnal Alexander M. , Panzer-Grümayer E. Renate
Published: November 2006

The TEL/AML1 fusion gene results from the most frequent t(12;21)(p13;q22) translocation in childhood acute lymphoblastic leukemia (ALL). Its contribution to transformation is largely unknown, in particular with respect to survival and apoptosis. We therefore silenced TEL/AML1 expression in leukemic REH cells by RNA inhibition, which eventually led to programmed cell death. Microarray and 2D gel electrophoresis data demonstrated a differential regulation of heat-shock proteins (HSPs), among them HSP90, as well as of its client, survivin. Consistent with these findings, ectopic expression of TEL/AML1 in Ba/F3 cells increased protein levels of HSP90 and survivin and conferred resistance to apoptotic stimuli. Our data suggest that TEL/AML1 not only contributes to leukemogenesis by affecting an antiapoptotic network but also seems to be indispensable for maintaining the malignant phenotype. The functional relationship between TEL/AML1, HSP90, and survivin provides the rational for targeted therapy, be it the fusion gene or the latter 2 proteins.
Gfi1b:green fluorescent protein knock-in mice reveal a dynamic expression pattern of Gfi1b during hematopoiesis that is largely complementary to Gfi1
Authors: Vassen Lothar , Okayama Taro , Möröy Tarik
Published: November 2006

Gfi1b and Gfi1 are 37- and 55-kDa transcriptional repressors that share common features such as a 20-amino acid (aa) N-terminal SNAG domain, a nonconserved intermediary domain, and 6 highly conserved C-terminal zinc fingers. Both gene loci are under autoregulatory and cross-regulatory feedback control. We have generated a reporter mouse strain by inserting the cDNA for green fluorescent protein (GFP) into the Gfi1b gene locus which allowed us to follow Gfi1b expression during hematopoiesis and lymphopoiesis by measuring green fluorescence. We found highly dynamic expression patterns of Gfi1b in erythroid cells, megakaryocytes, and their progenitor cells (MEPS) where Gfi1 is not detected. Vice versa, Gfi1b could not be found in granulocytes, activated macrophages, or their granulomonocytic precursors (GMPs) or in mature naive or activated lymphocytes where Gfi1 is expressed, suggesting a complementary regulation of both loci during hematopoiesis. However, Gfi1b was found to be up-regulated in early stages of B-cell and in a subset of early T-cell development, where Gfi1 is also present, suggesting that cross-regulation of both loci exists but is cell-type specific.
In vivo dynamics of regulatory T-cell trafficking and survival predict effective strategies to control graft-versus-host disease following allogeneic transplantation
Authors: Nguyen Vu H. , Zeiser Robert , daSilva Daniel L. , Chang Daisy S. , Beilhack Andreas , Contag Christopher H. , Negrin Robert S.
Published: November 2006

CD4+CD25+ regulatory T cells (Tregs) suppress immune responses to alloantigens. The in vivo circulation and tissue localization of Tregs during an adaptive immune response remain unclear. We noninvasively tracked luciferase-expressing Tregs over time in an allogeneic bone marrow transplant model and demonstrated colocalization with effector T cells and initial expansion in secondary lymphoid organs before migration into inflamed tissues. Inflammation induced by irradiation and the allogeneic setting provided crucial stimuli for early Treg expansion and migration, leading to parallel reduction of effector T-cell proliferation in lymphoid organs and peripheral tissues. Treg transplants conferred long-term protection from systemic inflammatory challenge consistent with Treg in vivo survival. Suppression occurred during multiple phases of inflammation, but is optimal in the initial phase, providing protection from graft-versus-host disease while maintaining the graft-versus-tumor effect even at physiologic doses of Tregs due to their in vivo expansion, hence overcoming a major barrier to potential clinical applications of Tregs given their rarity.
Infiltrating neutrophils induce allospecific CTL in response to immunization with apoptotic cells via MCP-1 production
Authors: Shiratsuchi Yoshiko , Iyoda Takuya , Tanimoto Naoko , Kegai Daisuke , Nagata Kisaburo , Kobayashi Yoshiro
Published: November 2006

Our previous studies demonstrated that i.p. injection of late apoptotic P388 cells caused phagocytosis by macrophages and transient infiltration of neutrophils into the peritoneal cavity. As neutrophils are known to function as effectors as well as regulators in the immune response, we examined the roles of infiltrating neutrophils in alloantigen-specific CTL induction after immunization with late apoptotic P388 cells. The CTL induction and infiltration of CD8+ T cells into the peritoneal cavity were inhibited by depletion of neutrophils by anti-Gr-1 mAb or inhibition of neutrophil infiltration by anti-MIP-2 antibody, suggesting that neutrophils are involved in CD8+ T cell infiltration into the peritoneal cavity. It is known that MIP-1α, MIP-1β, and MCP-1 are capable of attracting CD8+ T cells and that they are produced by neutrophils. These chemokines were detected in the peritoneal cavity, and among them, MCP-1 production was reduced remarkably by suppression of neutrophil infiltration. Moreover, infiltration of CD8+ T cells into the peritoneal cavity as well as CTL activity was clearly reduced by administering anti-MCP-1 antibody i.p. Furthermore, the CTL induction and infiltration of CD8+ T cells in neutrophil-depleted mice were restored significantly by administering recombinant murine MCP-1 into the peritoneal cavity. These results indicate that MCP-1 appears to link infiltration of neutrophils with CTL induction.
Estradiol Stimulates Progesterone Synthesis in Hypothalamic Astrocyte Cultures
Authors: Micevych Paul E. , Chaban Victor , Ogi Julie , Dewing Phoebe , Lu John K. H. , Sinchak Kevin
Published: November 2006

The brain synthesizes steroids de novo, especially progesterone. Recently estradiol has been shown to stimulate progesterone synthesis in the hypothalamus and enriched astrocyte cultures derived from neonatal cortex. Estradiol-induced hypothalamic progesterone has been implicated in the control of the LH surge. The present studies were undertaken to determine whether hypothalamic astrocytes derived from female neonatal or female postpubertal rats increased production of progesterone in response to an estradiol challenge. Estradiol induced progesterone synthesis in postpubertal astrocytes but not neonatal astrocytes. This estradiol action was blocked by the estrogen receptor antagonist ICI 182,780. Previously we had demonstrated that estradiol stimulates a rapid increase in free cytosolic Ca2+ ([Ca2+]i) spikes in neonatal cortical astrocytes acting through a membrane estrogen receptor. We now report that estradiol also rapidly increased [Ca2+]i spikes in hypothalamic astrocytes. The membrane-impermeable estradiol-BSA construct also induced [Ca2+]i spikes. Both estradiol-BSA and estradiol were blocked by ICI 182,780. Depleting intracellular Ca2+ stores prevented the estradiol-induced increased [Ca2+]i spikes, whereas removing extracellular Ca2+ did not prevent estradiol-induced [Ca2+]i spikes. Together these results indicate that estradiol acts through a membrane-associated receptor to release intracellular stores of Ca2+. Thapsigargin, used to mimicked the intracellular release of Ca2+ by estradiol, increased progesterone synthesis, suggesting that estradiol-induced progesterone synthesis involves increases in [Ca2+]i. Estradiol treatment did not change levels of steroid acute regulatory protein, P450 side chain cleavage, 3β-hydroxysteroid dehydrogenase, and sterol carrier protein-2 mRNAs as measured by quantitative RT-PCR, suggesting that in vitro, estradiol regulation of progesterone synthesis in astrocytes does not depend on transcription of new steroidogenic proteins. The present results are consistent with our hypothesis that estrogen-positive feedback regulating the LH surge involves stimulating local progesterone synthesis by hypothalamic astrocytes.
Pharmacological Characterization of a Novel Nonpeptide Antagonist of the Human Gonadotropin-Releasing Hormone Receptor, NBI-42902
Authors: Struthers R. Scott , Xie Qui , Sullivan Susan K. , Reinhart Greg J. , Kohout Trudy A. , Zhu Yun-Fei , Chen Chen , Liu Xin-Jun , Ling Nicholas , Yang Weidong , Maki Richard A. , Bonneville Anne K. , Chen Ta-Kung , Bozigian Haig P.
Published: November 2006

Suppression of the hypothalamic-pituitary-gonadal axis by peptides that act at the GnRH receptor has found widespread use in clinical practice for the management of sex-steroid-dependent diseases (such as prostate cancer and endometriosis) and reproductive disorders. Efforts to develop orally available GnRH receptor antagonists have led to the discovery of a novel, potent nonpeptide antagonist, NBI-42902, that suppresses serum LH concentrations in postmenopausal women after oral administration. Here we report the in vitro and in vivo pharmacological characterization of this compound. NBI-42902 is a potent inhibitor of peptide radioligand binding to the human GnRH receptor (Ki = 0.56 nm). Tritiated NBI-42902 binds with high affinity (Kd = 0.19 nm) to a single class of binding sites and can be displaced by a range of peptide and nonpeptide GnRH receptor ligands. In vitro experiments demonstrate that NBI-42902 is a potent functional, competitive antagonist of GnRH stimulated IP accumulation, Ca2+ flux, and ERK1/2 activation. It did not stimulate histamine release from rat peritoneal mast cells. Finally, it is effective in lowering serum LH in castrated male macaques after oral administration. Overall, these data provide a benchmark of pharmacological characteristics required for a nonpeptide GnRH antagonist to effectively suppress gonadotropins in humans and suggest that NBI-42902 may have clinical utility as an oral agent for suppression of the hypothalamic-pituitary-gonadal axis.
Normal Food Intake and Body Weight in Mice Lacking the G Protein-Coupled Receptor GPR39
Authors: Tremblay Frédéric , Perreault Mylène , Klaman Lori D. , Tobin James F. , Smith Erica , Gimeno Ruth E.
Published: November 2006

It has been recently proposed that obestatin, a peptide encoded by the ghrelin gene, reduces food intake by activating the orphan G protein-coupled receptor GPR39. To gain further insights into the role of GPR39 in body weight homeostasis, we characterized the phenotype of mice with targeted disruption of the GPR39 gene. Body weight, adiposity, and food intake were found to be similar between GPR39+/+ and GPR39−/− mice. Furthermore, fasting glucose and insulin levels were similar between both genotypes. Injection of obestatin peptide (1 μmol/kg, ip) obtained from multiple sources did not consistently inhibit food intake in wild-type mice after an overnight fast, and no difference in food intake was observed between wild-type and GPR39 knockout mice after injection of the peptide. Finally, ectopic expression of GPR39 in HEK293T cells revealed a constitutive activation of the receptor that was unaffected by stimulation with obestatin. Our phenotypic characterization suggests that GPR39 is not a major modulator of food intake in mice, although a more subtle role cannot be excluded. The role of GPR39 in normal physiology requires further study and should be conducted independently of the function of obestatin.
The Orphan Receptor Tyrosine Kinase Ror2 Promotes Osteoblast Differentiation and Enhances ex Vivo Bone Formation
Authors: Liu Yan , Bhat Ramesh A. , Seestaller-Wehr Laura M. , Fukayama Shoichi , Mangine Annamarie , Moran Robert A. , Komm Barry S. , Bodine Peter V. N. , Billiard Julia
Published: November 2006

Ror2 is a receptor tyrosine kinase, the expression of which increases during differentiation of pluripotent stem cells to osteoblasts and then declines as cells progress to osteocytes. To test whether Ror2 plays a role in osteoblastogenesis, we investigated the effects of Ror2 overexpression and down-regulation on osteoblastic lineage commitment and differentiation. Expression of Ror2 in pluripotent human mesenchymal stem cells (hMSCs) by adenoviral infection caused formation of mineralized extracellular matrix, which is the ultimate phenotype of an osteogenic tissue. Concomitantly, Ror2 over-expression inhibited adipogenic differentiation of hMSCs as monitored by lipid formation. Ror2 shifted hMSC fate toward osteoblastogenesis by inducing osteogenic transcription factor osterix and suppressing adipogenic transcription factors CCAAT/enhancer-binding protein α and peroxisome proliferator activated receptor γ. Infection with Ror2 virus also strongly promoted matrix mineralization in committed osteoblast-like MC3T3-E1 cells. Expression of Ror2 in a human preosteocytic cell line by stable transfection also promoted further differentiation, as judged by inhibited alkaline phosphatase activity, potentiated osteocalcin secretion, and increased cellular apoptosis. In contrast, down-regulation of Ror2 expression by short hairpin RNA essentially abrogated dexamethasone-induced mineralization of hMSCs. Furthermore, down-regulation of Ror2 expression in fully differentiated SaOS-2 osteosarcoma cells inhibited alkaline phosphatase activity. We conclude that Ror2 initiates commitment of MSCs to osteoblastic lineage and promotes differentiation at early and late stages of osteoblastogenesis. Finally, using a mouse calvariae ex vivo organ culture model, we demonstrate that these effects of Ror2 result in increased bone formation, suggesting that it may also activate mature osteoblasts.
Análise da demanda de casos de hanseníase aos serviços de saúde através do uso de técnicas de análise espacial
Authors: Lapa Tiago Maria , Albuquerque Maria de Fátima P. Militão de , Carvalho Marilia Sá , Silveira Júnior José Constantino
Published: November 2006

O desafio para redução da prevalência da Hanseníase, endemia de grande importância no cenário brasileiro, tem se fundamentado na descentralização para os serviços de atenção básica. Descreveu-se inicialmente a estruturação e a oferta dos serviços para o atendimento de casos de hanseníase. Em seguida analisou-se a evolução dos indicadores epidemiológicos e operacionais, tomando como referência os períodos pré e pós a municipalização. Por fim, a análise espacial permitiu identificar a distribuição territorial da ocorrência da endemia e analisar o padrão de áreas geográficas construídas segundo o atendimento pelas unidades de saúde e sua evolução. A partir da localização geográfica dos centróides dos setores censitários de residência, e usando técnica de alisamento espacial, com base na estimativa de Kernel, foram construídas áreas de domínio de atendimentos de cada unidade. Após a municipalização, observa-se aumento da detecção e tratamento pelo município, reduzindo a evasão a outros municípios, mudanças no comportamento da demanda, com aumento da clientela referida no uso dos serviços, e alterações importantes nos indicadores epidemiológicos e operacionais.
Propriedades psicométricas do Instrumento Abreviado de Avaliação de Qualidade de Vida da Organização Mundial da Saúde no Estudo Pró-Saúde
Authors: Moreno Arlinda B. , Faerstein Eduardo , Werneck Guilherme L. , Lopes Claudia S. , Chor Dóra
Published: November 2006

Neste artigo, relatam-se propriedades psicométricas do Instrumento Abreviado de Avaliação de Qualidade de Vida da Organização Mundial da Saúde (WHOQOL-Bref), composto por 24 questões distribuídas em quatro domínios (físico, psicológico, relações sociais e meio ambiente) e duas questões globais sobre qualidade de vida e saúde global, quando aplicado no Estudo Pró-Saúde (estudo de coorte de trabalhadores de uma universidade no Estado do Rio de Janeiro, Brasil), em seu estudo piloto e entre os 3.574 participantes da fase 2 (2001) do estudo. Foi estimada a confiabilidade teste-reteste dos escores, com coeficiente de correlação intraclasse variando entre 0,76 e 0,91 nos diversos domínios. Níveis de consistência interna, avaliados pelo coeficiente alfa de Cronbach, variaram entre 0,69 e 0,79. Na análise de fatores, pelo método de fatores principais iterados e rotação varimax, não foi replicada exatamente a estrutura do instrumento original, verificada em seus testes de campo; uma das possíveis razões para as discrepâncias observadas refere-se à natureza da população de estudo, em idade laboral ativa e relativamente saudável.
Estudo epidemiológico de base populacional sobre uso de medicamentos entre idosos na Região Metropolitana de Belo Horizonte, Minas Gerais, Brasil
Authors: Loyola Filho Antônio I. de , Uchoa Elizabeth , Lima-Costa Maria Fernanda
Published: November 2006

Este estudo teve por objetivo investigar o consumo de medicamentos e fatores associados (sócio-demográficos, condições de saúde e uso de serviços de saúde) em uma amostra representativa de 1.598 pessoas com 60+ anos de idade, residentes na Região Metropolitana de Belo Horizonte, Minas Gerais, Brasil. A variável dependente foi o número de medicamentos consumido nas duas semanas precedentes. A prevalência do uso de medicamentos foi de 72,1% e a média de medicamentos consumidos igual a 2,18, predominando aqueles com ação sobre o sistema cardiovascular. O consumo de qualquer número de medicamentos apresentou associação independente com sexo feminino, idade (80+ anos), ter visitado um médico e apresentar alguma condição crônica. O consumo de maior número de medicamentos (5+) apresentou associações significativas com escolaridade (8+ anos, OR = 2,28) e pior auto-avaliação da saúde (razoável, OR = 5,45; ruim/muito ruim, OR = 5,35). Os resultados deste trabalho mostram que o tipo de medicamento consumido e os fatores associados a esse consumo foram muito semelhantes ao observado em outras populações, sugerindo que existe uma certa uniformidade no consumo e nos seus determinantes, entre populações diferentes.
Prevalência de transtornos mentais comuns em professores da rede municipal de Belo Horizonte, Minas Gerais, Brasil
Authors: Gasparini Sandra Maria , Barreto Sandhi Maria , Assunção Ada Ávila
Published: November 2006

Estudos realizados em todo o mundo evidenciam que os educadores correm o risco de sofrer esgotamento físico ou mental, em face das dificuldades materiais e psicológicas associadas ao exercício da atividade docente. Objetivou-se estimar a prevalência de transtornos mentais em professores da rede municipal de ensino de Belo Horizonte, Minas Gerais, Brasil, e investigar a associação com as características do trabalho docente. Empregou-se um estudo do tipo corte transversal em professores do ensino fundamental da Regional Nordeste, utilizando-se um questionário auto-aplicado, com seis blocos de questões. O General Health Questionnaire (GHQ) na versão "12" foi o instrumento de rastreamento de transtornos mentais não-psicóticos na população estudada. Participaram do estudo, 751 dos 792 professores do ensino fundamental de vinte e seis escolas municipais da regional citada (94,8%). Os transtornos mentais foram significativamente associados à experiência com a violência e piores condições ambientais, ambiente físico e conforto no trabalho, e organizacionais, margem de autonomia, de criatividade e tempo no preparo das aulas. Os resultados apontam para uma situação grave relativamente à saúde da população pesquisada e fornecem elementos consistentes para a proposição de medidas com vistas à melhoria das condições de trabalho docente.
Produção de melão sob duas densidades de plantio, em diferentes tipos e espaçamentos de gotejadores
Authors: Dias Nildo da Silva , Medeiros José Francismar de , Sathler Nilson de Sousa
Published: November 2006

Com o objetivo de se avaliar o efeito de diferentes tipos e espaçamentos de gotejadores usados no cultivo de melão sob duas densidades de plantio, desenvolveu-se um experimento na Fazenda São João, Município de Mossoró, RN, durante o período de setembro a novembro de 1998. O delineamento experimental utilizado foi o de blocos casualizados completos, em parcelas subdivididas, com três repetições. Nas parcelas experimentais foram instaladas as diferentes linhas de gotejadores (Katif 2,3 L h-1 a 0,40 e 0,60 m; Katif 3,75 L h-1 a 0,60 e 0,80 m; Hydrodrip II 2,3 L h-1 a 0,30 e 0,50 m; Netafim ST-125 1,65 L h-1 a 0,50 m; Chapin 15 Mil 1,12 L h-1 a 0,30 m e Queen gil 1,42 L h-1 a 0,30 m) e, nas subparcelas, as populações de 15.000 e 20.000 plantas ha-1. Os resultados mostraram que o uso de gotejadores de menor espaçamento ou maior vazão com a maior densidade de plantio, proporcionou maior porcentagem do stand de plantas de melão. Maiores rendimentos de melão foram obtidos quando se utilizaram as linhas de gotejadores Queen gil 1,42 L h-1 a 0,30 m e Hydrodrip II 2,3 L h-1 a 0,30 m, embora diferindo estatisticamente apenas da Chapin 15 Mil 1,12 L h-1 a 0,30 m.
Deficiência hídrica e uso granulados em lavoura cafeeira irrigada por gotejamento
Authors: Fernandes André Luís Teixeira , Santinato Roberto , Lessi Ricardo , Yamada Antonio , Silva Vantuir A.
Published: November 2006

Com o objetivo de se estudar o desenvolvimento vegetativo e produtivo de uma lavoura de café nas condições de Planaltina de Goiás, GO, instalou-se um experimento numa lavoura de café Mundo Novo, recepada, onde foram comparados diferentes períodos de déficit hídrico (DH) e aplicação de variados produtos granulados no solo. Com avaliações de produção para os anos de 1995, 1996 e 1997, observou-se que, sob irrigação total e sem déficit hídrico, a cultura apresentou a maior produtividade, com acréscimos de até 100% quando comparada com o tratamento sem irrigação. Quanto aos granulados, independentemente do tratamento de irrigação, verificou-se melhor desempenho da associação triadimenol + dissulfoton, com aumentos de produtividade de 20 a 25%.
Eficiência da cloração da água de irrigação no tratamento de gotejadores com entupimento de causa biológica
Authors: Resende Ronaldo Souza , Coelho Rubens Duarte , Piedade Sônia Maria de Stéfano
Published: November 2006

Com o propósito de se avaliar a eficiência de diferentes dosagens de cloro na desobstrução por tratamento de choque de gotejadores, conduziu-se um experimento no Laboratório de Irrigação do Departamento de Engenharia Rural da Escola Superior de Agricultura "Luiz de Queiroz"- ESALQ/USP, no qual foram utilizados os seguintes tipos de gotejador Netafim: Streamline 100, Ram 17L, Dripline 2000, Tiran 17 e Typhoon 20, e avaliadas as dosagens de cloro de 150, 300, 450 e 600 mg L-1. A água utilizada no ensaio foi proveniente de fonte hídrica superficial, aproveitada para irrigação. Para os tratamentos de recuperação dos emissores, utilizou-se o hipoclorito de sódio comercial (12%) como fonte de cloro, aplicado continuamente por 60 min, e logo após, deixou-se o produto interagir por 12 h na mangueira, sem fluxo na rede. Para todos os emissores, exceto o Streamline, a aplicação de cloro resultou em aumento da vazão média. Para o modelo Dripline, o tratamento com cloro reduziu a uniformidade de emissão e a eficiência da cloração aumentou após a segunda aplicação, para o modelo Tiran.
Efeito do tamanho de séries históricas na demanda de irrigação do perímetro irrigado do Gorutuba, MG
Authors: Carvalho Daniel Fonseca de , Marques Débora Candeias , Ferreira Expedito José , Oliveira Luiz Fernando Coutinho de
Published: November 2006

Este trabalho foi desenvolvido com o objetivo de se estudar a influência do número de anos da série histórica de dados climáticos no volume de água para irrigação, no perímetro irrigado do Gorutuba. Utilizando-se um aplicativo desenvolvido em ambiente Windows 95, em linguagem DELPHI, foram estudadas três situações de séries históricas e, para cada uma, o volume de água estimado foi comparado com o volume derivado no perímetro para o ano de 1996, em que os resultados mostraram que: utilizando-se a série histórica de 1984-1994, os volumes de água estimados foram, em média, 16,2% por mês, inferiores àqueles estimados, empregando-os com a série 1984-1998, e de 53,8% por mês, inferiores aos volumes estimados utilizando-se os dados climáticos de 1996, e que o número de anos da série histórica de dados climáticos pode influenciar decisivamente na estimativa do volume de água para irrigação.
Modelamento da perda de qualidade de sementes de soja, em função das condições iniciais e da atmosfera no armazenamento
Authors: Afonso Júnior Paulo César , Corrêa Paulo César , Queiroz Daniel Marçal de
Published: November 2006

Com o objetivo de se predizer o potencial germinativo de sementes de soja durante o armazenamento, foi conduzido um experimento com sementes da variedade Santa Rosa, com umidade inicial 0,333 (base seca), que passaram por um processo de secagem a temperatura de 30 °C e 40 % de umidade relativa, até atingirem os teores de umidade de 0,111, 0,176 e 0,250 base seca. As sementes foram acondicionadas em sacos de papel e mantidas em diferentes temperaturas de armazenagem (5, 10, 20 e 30 °C) e sua viabilidade foi avaliada depois da secagem e a cada 10 dias, durante 60 dias, empregando-se o teste-padrão de germinação. De maneira geral, para a maioria dos testes a temperatura e o teor de umidade afetaram a germinação das sementes de soja, durante o período de armazenamento, porém para as temperaturas de armazenagem de 5 e 10 °C, as sementes mantiveram a viabilidade em níveis satisfatórios, independente do teor de umidade do produto. Os resultados experimentais de germinação foram avaliados ajustando-se os modelos matemáticos: exponencial e probabilístico. Os resultados obtidos neste trabalho permitiram concluir-se que a temperatura e o teor de umidade das sementes afetam a germinação das sementes de soja, durante o período de armazenamento, e que o modelo exponencial foi o que melhor se ajustou aos dados experimentais.