bluuebunny/crossref_metadata_2025 huggingface dataset:
Executive Coaching: A Conceptual Framework From an Integrative Review of Practice and Research
Authors: Joo Baek-Kyoo (Brian)
Published: October 2005

Executive coaching has become increasingly popular despite limited empirical evidence about its impact and wide disagreement about necessary or desired professional qualifications. This article examines the practice of executive coaching, investigating the useful underlying theories by reviewing previous research. It also provides a conceptual framework of executive coaching, integrating the literature on executive coaching and related areas such as mentoring, career success, 360-degree feedback, and training and development. The significance of this article lies in its integration of the extant literature on executive coaching and the development of a conceptual framework of executive coaching and related propositions derived from the literature. The article discusses the implications for future research and for human resource development.
Conceptualizing On-the-Job Learning Styles
Authors: Berings Marjolein G. M. C. , Poell Rob F. , Simons P. Robert-Jan
Published: October 2005

The broad aims of this study are to gain insight into employees'on-the-job learning activities to help them improve their on-the-job learning. The authors define on-the-job learning styles and operationalize the concept to include both mental and overt learning styles and both interpersonal and intrapersonal learning styles. Organizations and employees can benefit from an awareness of employees'on-the-job learning styles, by developing an adaptive flexibility in the use of on-the-job learning strategies.
Behavioral and Neurophysiological Analyses of Dynamic Learning Processes
Authors: Suzuki Wendy A. , Brown Emery N.
Published: October 2005

In this article, the authors address two topics relevant to the study of the brain basis of associative learning. In Part 1, they compare and contrast the patterns and time course of dynamic learning-related neural activity that have been reported in the medial temporal lobe, premotor cortex, prefrontal cortex, and striatum during various associative learning tasks. In Part 2, they examine the statistical methodologies that have been used to analyze both behavioral learning and learning-related neural activity. They describe a state-space model of behavioral learning that provides accurate estimates of dynamic learning processes and a point-process filter algorithm that tracks the dynamic changes in neural activity on a millisecond time scale. Future challenges for these statistical methodologies and their application to the study of the brain basis of associative learning are discussed.
Transformations of Visuospatial Images
Authors: Zacks Jeffrey M. , Michelon Pascale
Published: October 2005

Transformations of visuospatial mental images are important for action, navigation, and reasoning. They depend on representations in multiple spatial reference frames, implemented in the posterior parietal cortex and other brain regions. The multiple systems framework proposes that different transformations can be distinguished in terms of which spatial reference frame is updated. In an object-based transformation, the reference frame of an object moves relative to those of the observer and the environment. In a perspective transformation, the observer's egocentric reference frame moves relative to those of the environment and of salient objects. These two types of spatial reference frame updating rely on distinct neural processing resources in the parietal, occipital, and temporal cortex. They are characterized by different behavioral patterns and unique individual differences. Both object-based transformations and perspective transformations interact with posterior frontal cortical regions subserving the simulation of body movements. These interactions indicate that multiple systems coordinate to support everyday spatial problem solving.
Regulation of ITAM-positive receptors: role of IL-12 and IL-18
Authors: Ortaldo John R. , Winkler-Pickett Robin , Wigginton Jon , Horner Meagan , Bere Earl W. , Mason Anna T. , Bhat Narayan , Cherry James , Sanford Michael , Hodge Deborah L. , Young Howard A.
Published: October 2005

Our previous studies have identified mechanisms by which cytokine production, blocked by Ly49G2 receptor cross-linking, can be overridden. In this study we analyzed the regulation of other ITAM-positive receptor signaling on NK, NKT, and T cells and characterized the biochemical pathways involved in this signaling. Our studies demonstrate that cross-linking of NKG2D and NK1.1 results in a synergistic NK IFN-γ response when combined with IL-12 or IL-18. Examination of NKT- and T-cell responses demonstrated that cross-linking of NKG2D and CD3 resulted in potent synergy when combined with IL-12 and, to a lesser degree, with IL-18. We have now found that both the p38 MAP kinase and the ERK-dependent signal transduction pathways are required for the synergistic response. Further mechanistic examination of the synergy indicated a potent up-regulation of total IFN-γ mRNA in the nuclear and the cytoplasmic compartment, but mRNA half-life was not affected. Fifteen minutes of IL-12 pretreatment was sufficient to result in maximal synergistic activation, indicating that the response of the cells to the IL-12 signal was rapid and immediate. Thus, our data demonstrate that multiple convergent signals maximize the innate immune response by triggering complementary biochemical signaling pathways.
Tumor rejection by the poliovirus receptor family ligands of the DNAM-1 (CD226) receptor
Authors: Tahara-Hanaoka Satoko , Shibuya Kazuko , Kai Hirayasu , Miyamoto Akitomo , Morikawa Yoshihiro , Ohkochi Nobuhiro , Honda Shin-ichiro , Shibuya Akira
Published: October 2005

The poliovirus receptor CD155 and its family member CD112 (nectin-2) are the ligands for the activating cell-surface receptor DNAM-1 on CD8+ T cells and natural killer (NK) cells. Here, we demonstrate that, whereas the RMA tumor grew in syngeneic mice, DNAM-1 ligand-transduced RMA was rejected, in which CD8+ T cells and NK cells played an essential role. Importantly, CD8+ memory cytotoxic T cells to parental RMA were generated in these mice. We found that DNAM-1 was also expressed on CD8α+, rather than CD8α-, dendritic cells (DCs). Cross-linking DNAM-1 induced maturation of CD8α+ DCs. Antigen presentation by these stimulated DCs drove Th1 cells. Moreover, the rejection of DNAM-1 ligand-transduced RMA was canceled in CD4+ T-cell–depleted and major histocompatibility complex class II–deficient mice. Taken together, these results suggest that DNAM-1 ligands stimulate innate immunity by CD8α+ DCs as well as NK cells, which efficiently prime cell-mediated tumor-specific immunity.
VEGFR-1 (FLT-1) activation modulates acute lymphoblastic leukemia localization and survival within the bone marrow, determining the onset of extramedullary disease
Authors: Fragoso Rita , Pereira Teresa , Wu Yan , Zhu Zhenping , Cabeçadas José , Dias Sérgio
Published: October 2005

The presence of persistent circulating leukemia cells, or engrafted into extramedullary tissues, is a bad prognostic factor for patients with acute leukemia. However, little is known about the mechanisms that regulate the exit of leukemia cells from the bone marrow (BM) microenvironment. We reveal that vascular endothelial growth factor receptor 1 (FLT-1) modulates acute leukemia distribution within the BM, along VEGF and PlGF gradients, regulating leukemia survival and exit into the peripheral circulation. FLT-1 activation on acute lymphoblastic leukemia (ALL) cells results in cell migration and proliferation in vitro, whereas in vivo FLT-1-overexpressing cells accumulate in the BM epiphysis of nonobese diabetic-severe combined immunodeficient (NOD-SCID) recipients and are detected in circulation 2 weeks after inoculation. In turn, FLT-1 neutralization affects leukemia localization (now in the BM diaphysis), increases leukemia apoptosis, and impedes the exit of ALL cells, prolonging the survival of inoculated mice. We demonstrate further that FLT-1-induced cell migration involves actin polymerization and lipid raft formation. Taken together, we show that FLT-1 regulates the BM localization of ALL cells, determining their survival and exit into the circulation and ultimately the survival of inoculated recipients. FLT-1 targeting on subsets of acute leukemias may delay the onset of extramedullary disease, which may be advantageous in combinatorial therapeutic settings.
Iron metabolism in the hemoglobin-deficit mouse: correlation of diferric transferrin with hepcidin expression
Authors: Wilkins Sarah J. , Frazer David M. , Millard Kirstin N. , McLaren Gordon D. , Anderson Gregory J.
Published: October 2005

The iron requirements of the erythroid compartment modulate the expression of hepcidin in the liver, which in turn alters intestinal iron absorption and iron release from the reticuloendothelial system. We have taken advantage of an inherited anemia of the mouse (hemoglobin deficit, or hbd) to gain insights into the factors regulating hepcidin expression. hbd mice showed a significant anemia but, surprisingly, their iron absorption was not increased as it was in wild-type animals made anemic to a similar degree by dietary iron depletion. In wild-type mice hepatic hepcidin levels were decreased but in hbd animals a significant and unexpected increase was observed. The level of absorption was appropriate for the expression of hepcidin in each case, but in hbd mice did not reflect the degree of anemia. However, this apparent inappropriate regulation of hepcidin correlated with increased transferrin saturation and levels of diferric transferrin in the plasma, which in turn resulted from the reduced capacity of hbd animals to effectively use transferrin-bound iron. These data strengthen the proposal that diferric transferrin is a key indicator of body iron requirements.
Primitive human hematopoietic cells give rise to differentially specified daughter cells upon their initial cell division
Authors: Giebel Bernd , Zhang Tao , Beckmann Julia , Spanholtz Jan , Wernet Peter , Ho Anthony D. , Punzel Michael
Published: October 2005

It is often predicted that stem cells divide asymmetrically, creating a daughter cell that maintains the stem-cell capacity, and 1 daughter cell committed to differentiation. While asymmetric stem-cell divisions have been proven to occur in model organisms (eg, in Drosophila), it remains illusive whether primitive hematopoietic cells in mammals actually can divide asymmetrically. In our experiments we have challenged this question and analyzed the developmental capacity of separated offspring of primitive human hematopoietic cells at a single-cell level. We show for the first time that the vast majority of the most primitive, in vitro–detectable human hematopoietic cells give rise to daughter cells adopting different cell fates; 1 inheriting the developmental capacity of the mother cell, and 1 becoming more specified. In contrast, approximately half of the committed progenitor cells studied gave rise to daughter cells, both of which adopted the cell fate of their mother. Although our data are compatible with the model of asymmetric cell division, other mechanisms of cell fate specification are discussed. In addition, we describe a novel human hematopoietic progenitor cell that has the capacity to form natural killer (NK) cells as well as macrophages, but not cells of other myeloid lineages.
Influence of hypoxia on the domiciliation of Mesenchymal Stem Cells after infusion into rats: possibilities of targeting pulmonary artery remodeling via cells therapies?
Authors: Rochefort Y Gaël , Vaudin Pascal , Bonnet Nicolas , Pages Jean-Christophe , Domenech Jorge , Charbord Pierre , Eder Véronique
Published: October 2005

Background

Bone marrow (BM) cells are promising tools for vascular therapies. Here, we focused on the possibility of targeting the hypoxia-induced pulmonary artery hypertension remodeling with systemic delivery of BM-derived mesenchymal stem cells (MSCs) into non-irradiated rats.

Methods

Six-week-old Wistar rats were exposed to 3-week chronic hypoxia leading to pulmonary artery wall remodeling. Domiciliation of adhesive BM-derived CD45- CD73+ CD90+ MSCs was first studied after a single intravenous infusion of Indium-111-labeled MSCs followed by whole body scintigraphies and autoradiographies of different harvested organs. In a second set of experiments, enhanced-GFP labeling allowed to observe distribution at later times using sequential infusions during the 3-week hypoxia exposure.

Results

A 30% pulmonary retention was observed by scintigraphies and no differences were observed in the global repartition between hypoxic and control groups. Intrapulmonary radioactivity repartition was homogenous in both groups, as shown by autoradiographies. BM-derived GFP-labeled MSCs were observed with a global repartition in liver, in spleen, in lung parenchyma and rarely in the adventitial layer of remodeled vessels. Furthermore this global repartition was not modified by hypoxia. Interestingly, these cells displayed in vivo bone marrow homing, proving a preservation of their viability and function. Bone marrow homing of GFP-labeled MSCs was increased in the hypoxic group.

Conclusion

Adhesive BM-derived CD45- CD73+ CD90+ MSCs are not integrated in the pulmonary arteries remodeled media after repeated intravenous infusions in contrast to previously described in systemic vascular remodeling or with endothelial progenitor cells infusions.
HDACs and the senescent phenotype of WI-38 cells
Authors: Place Robert F , Noonan Emily J , Giardina Charles
Published: October 2005

Background

Normal cells possess a limited proliferative life span after which they enter a state of irreversible growth arrest. This process, known as replicative senescence, is accompanied by changes in gene expression that give rise to a variety of senescence-associated phenotypes. It has been suggested that these gene expression changes result in part from alterations in the histone acetylation machinery. Here we examine the influence of HDAC inhibitors on the expression of senescent markers in pre- and post-senescent WI-38 cells.

Results

Pre- and post-senescent WI-38 cells were treated with the HDAC inhibitors butyrate or trichostatin A (TSA). Following HDAC inhibitor treatment, pre-senescent cells increased p21WAF1 and β-galactosidase expression, assumed a flattened senescence-associated morphology, and maintained a lower level of proteasome activity. These alterations also occurred during normal replicative senescence of WI-38 cells, but were not accentuated further by HDAC inhibitors. We also found that HDAC1 levels decline during normal replicative senescence.

Conclusion

Our findings indicate that HDACs impact numerous phenotypic changes associated with cellular senescence. Reduced HDAC1 expression levels in senescent cells may be an important event in mediating the transition to a senescent phenotype.
Pneumomediastinum as initial presentation of paralytic rabies: A case report
Authors: Kietdumrongwong Pongtorn , Hemachudha Thiravat
Published: October 2005

Background

Rabies is readily diagnosed when it presents as the classic furious form. Paralytic and atypical forms can pose significant problems in diagnosis. Catastrophic incidents included 7 organ transplant recipients who died of rabies recently in United States and Germany. Although rabies remains top in the lists of differential diagnosis of encephalitis in rabies endemic area, its complication may divert physicians from making a relevant management. We encountered an unusual case of paralytic rabies who presented with spontaneous pneumomediastinum.

Case Presentation

A young male presented with fever and dysphagia. There was a history of fluctuating consciousness and aerophobia but they were absent or could not be demonstrated at the time of admission. He exhibited subcutaneous chest wall emphysema and was found to have pneumomediastinum which resulted in surgical intervention. He developed paralysis followed by seizures during postoperative period. Diagnosis was confirmed by demonstration of rabies RNA in saliva during the preterminal phase and by the autopsy. Over 200 hospital staff subsequently received rabies postexposure prophylaxis.

Conclusion

Spontaneous pneumomediastinum can be a rare complication of rabies. It may lead clinicians to perform inappropriate treatment, particularly when phobic spasms are not present and agitation is not prominent. High level of awareness of rabies in any patient with confusion albeit subtle or with any obscure neurological presentations such as difficulty swallowing with no identifiable causes must be borne in mind.
Barriers to successful care for chronic kidney disease
Authors: Lenz Oliver , Mekala Durga P , Patel Daniel V , Fornoni Alessia , Metz David , Roth David
Published: October 2005

Background

The National Kidney Foundation has formulated clinical practice guidelines for patients with chronic kidney disease (K/DOQI). However, little is know about how many patients actually achieve these goals in a dedicated clinic for chronic kidney disease.

Methods

We performed a cross-sectional analysis of 198 patients with an estimated glomerular filtration rate of less than 30 ml/min/1.73 m2 and determined whether K/DOQI goals were met for calcium, phosphate, calcium-phosphate product, parathyroid hormone, albumin, bicarbonate, hemoglobin, lipids, and blood pressure.

Results

We found that only a small number of patients achieved K/DOQI targets. Recent referral to the nephrologist, failure to attend scheduled clinic appointments, African American ethnicity, diabetes, and advanced renal failure were significant predictors of low achievement of K/DOQI goals.

Conclusion

We conclude that raising awareness of chronic kidney disease and K/DOQI goals among primary care providers, early referral to a nephrologist, the exploration of socioeconomic barriers and cultural differences, and both patient and physician education are critical to improve CKD care in patients with Stage 4 and 5 CKD.
Chance mechanisms affecting the burden of metastases
Authors: Kendal Wayne S
Published: October 2005

Background

The burden of cancer metastases within an individual is commonly used to clinically characterize a tumor's biological behavior. Assessments like these implicitly assume that spurious effects can be discounted. Here the influence of chance on the burden of metastasis is studied to determine whether or not this assumption is valid.

Methods

Monte Carlo simulations were performed to estimate tumor burdens sustained by individuals with cancer, based upon empirically derived and validated models for the number and size distributions of metastases. Factors related to the intrinsic metastatic potential of tumors and their host microenvironments were kept constant, to more clearly demonstrate the contribution from chance.

Results

Under otherwise identical conditions, both the simulated numbers and the sizes of metastases were highly variable. Comparable individuals could sustain anywhere from no metastases to scores of metastases, and the sizes of the metastases ranged from microscopic to macroscopic. Despite the marked variability in the number and sizes of the metastases, their respective growth times were rather more narrowly distributed. In such situations multiple occult metastases could develop into fully overt lesions within a comparatively short time period.

Conclusion

Chance can have a major effect on the burden of metastases. Random variability can be so great as to make individual assessments of tumor biology unreliable, yet constrained enough to lead to the apparently simultaneous appearance of multiple overt metastases.
Age as a determinant of nutritional status: A cross sectional study
Authors: Forster Sarah , Gariballa Salah
Published: October 2005

Background

Undenutrition is known to be prevalent and largely unrecognised in older patients; however, aberrations in indicators of nutritional status may simply reflect effects of age and/or functional disability.

Objective

The aim of this study was to measure the effect, if any of age on nutritional status in older patients.

Design

445 randomly selected hospitalised patients consented to nutritional status assessment derived from anthropometric, haematological, and biochemical data within 72 hours of admission. Nutritional status was compared between those age < 75 years and those aged 75 years or more. Using multiple regression models, we measured the association between age and nutritional assessment variables after adjusting for disability, chronic illness, medications, smoking and tissue inflammation.

Results

Body weight, body mass index, mid-upper arm circumference, haemoglobin, serum albumin and plasma ascorbic acid were all significantly lower in people aged ≥ 75 years compared with those < 75 years of age. Although riboflavin (vitamin B2), 25OH VitD3, red-cell folate and vitamin B12 concentrations were lower in those aged ≥ 75 years, differences were not statistically significant. After adjusting for disability and co-morbidity in a multivariate analysis, age alone had a significant and independent effect on important anthropometric and biochemical nutritional assessment variables.

Conclusion

Increasing age is independently associated with poor nutritional status. This may partly explain the poor clinical outcome in older patients.
Dietary inulin intake and age can significantly affect intestinal absorption of calcium and magnesium in rats: a stable isotope approach
Authors: Coudray Charles , Rambeau Mathieu , Feillet-Coudray Christine , Tressol Jean Claude , Demigne Christian , Gueux Elyett , Mazur Andrzej , Rayssiguier Yves
Published: October 2005

Background

previous studies have shown that non-digestible inulin-type fructan intake can increase intestinal mineral absorption in both humans and animals. However, this stimulatory effect on intestinal absorption may depend on experimental conditions such as duration of fermentable fiber intake, mineral diet levels and animals' physiological status, in particular their age.

Objectives

the aim of this study was to determine the effect of inulin intake on Ca and Mg absorption in rats at different age stages.

Methods

eighty male Wistar rats of four different ages (2, 5, 10 and 20 months) were randomized into either a control group or a group receiving 3.75% inulin in their diet for 4 days and then 7.5% inulin for three weeks. The animals were fed fresh food and water ad libitum for the duration of the experiment. Intestinal absorption of Ca and Mg was determined by fecal monitoring using stable isotopic tracers. Ca and Mg status was also assessed.

Results

absorption of Ca and Mg was significantly lower in the aged rats (10 and 20 mo) than in the young and adult rat groups. As expected, inulin intake increased Ca and Mg absorption in all four rat groups. However, inulin had a numerically greater effect on Ca absorption in aged rats than in younger rats whereas its effect on Mg absorption remained similar across all four rat age groups.

Conclusion

the extent of the stimulatory effect of inulin on absorption of Ca may differ according to animal ages. Further studies are required to explore this effect over longer inulin intake periods, and to confirm these results in humans.
Reliability of old and new ventricular fibrillation detection algorithms for automated external defibrillators
Authors: Amann Anton , Tratnig Robert , Unterkofler Karl
Published: October 2005

Background

A pivotal component in automated external defibrillators (AEDs) is the detection of ventricular fibrillation by means of appropriate detection algorithms. In scientific literature there exists a wide variety of methods and ideas for handling this task. These algorithms should have a high detection quality, be easily implementable, and work in real time in an AED. Testing of these algorithms should be done by using a large amount of annotated data under equal conditions.

Methods

For our investigation we simulated a continuous analysis by selecting the data in steps of one second without any preselection. We used the complete BIH-MIT arrhythmia database, the CU database, and the files 7001 – 8210 of the AHA database. All algorithms were tested under equal conditions.

Results

For 5 well-known standard and 5 new ventricular fibrillation detection algorithms we calculated the sensitivity, specificity, and the area under their receiver operating characteristic. In addition, two QRS detection algorithms were included. These results are based on approximately 330 000 decisions (per algorithm).

Conclusion

Our values for sensitivity and specificity differ from earlier investigations since we used no preselection. The best algorithm is a new one, presented here for the first time.
Severe allergic reactions to guinea pig
Authors: Zacharisen Michael C , Levy Michael B , Shaw Jeffrey L , Kurup Viswanath P
Published: October 2005

Background

Allergic sensitization and reactions to guinea pig (Cavia porcellus) have been well documented in laboratory animal handlers, primarily manifesting as rhinitis, conjunctivitis, and asthma. Severe allergic reactions, however, are rare.

Methods

We report two patients with severe allergic reactions following non-occupational exposure to guinea pigs. The first patient, an 11-year-old female, developed ocular, nasal, skin and laryngeal edema symptoms immediately after handling a guinea pig. The second patient, a 24-year-old female, developed symptoms of isolated laryngeal edema after cleaning a guinea pig cage. Percutaneous skin testing, RAST, ELISA and ELISA inhibition testing with guinea pig extract were performed.

Results

Both patients had IgE-mediated allergy to guinea pig confirmed by ELISA and either RAST or skin testing. ELISA inhibition studies confirmed the specificity of the IgE reactivity to guinea pig.

Conclusion

Severe IgE-mediated reactions can occur following non-occupational guinea pig exposure. Physicians should be aware of this possibility.
Dual role of TRBP in HIV replication and RNA interference: viral diversion of a cellular pathway or evasion from antiviral immunity?
Authors: Gatignol Anne , Lainé Sébastien , Clerzius Guerline
Published: October 2005

Increasing evidence indicates that RNA interference (RNAi) may be used to provide antiviral immunity in mammalian cells. Human micro (mi)RNAs can inhibit the replication of a primate virus, whereas a virally-encoded miRNA from HIV inhibits its own replication. Indirect proof comes from RNAi suppressors encoded by mammalian viruses. Influenza NS1 and Vaccinia E3L proteins can inhibit RNAi in plants, insects and worms. HIV-1 Tat protein and Adenovirus VA RNAs act as RNAi suppressors in mammalian cells. Surprisingly, many RNAi suppressors are also inhibitors of the interferon (IFN)-induced protein kinase R (PKR) but the potential overlap between the RNAi and the IFN pathways remains to be determined. The link between RNAi as an immune response and the IFN pathway may be formed by a cellular protein, TRBP, which has a dual role in HIV replication and RNAi. TRBP has been isolated as an HIV-1 TAR RNA binding protein that increases HIV expression and replication by inhibiting PKR and by increasing translation of structured RNAs. A recent report published in the Journal of Virology shows that the poor replication of HIV in astrocytes is mainly due to a heightened PKR response that can be overcome by supplying TRBP exogenously. In two recent papers published in Nature and EMBO Reports, TRBP is now shown to interact with Dicer and to be required for RNAi mediated by small interfering (si) and micro (mi)RNAs. The apparent discrepancy between TRBP requirement in RNAi and in HIV replication opens the hypotheses that RNAi may be beneficial for HIV-1 replication or that HIV-1 may evade the RNAi restriction by diverting TRBP from Dicer and use it for its own benefit.
Surfactant application during extracorporeal membrane oxygenation improves lung volume and pulmonary mechanics in children with respiratory failure
Authors: Hermon Michael , Burda Gudrun , Male Christoph , Boigner Harald , Ponhold Walter , Khoss August , Strohmaier Wolfgang , Trittenwein Gerhard
Published: October 2005

Introduction

This study was performed to determine whether surfactant application during extracorporeal membrane oxygenation (ECMO) improves lung volume, pulmonary mechanics, and chest radiographic findings in children with respiratory failure or after cardiac surgery.

Methods

This was a retrospective chart review study in a pediatric intensive care unit (PICU). Seven patients received surfactant before weaning from ECMO was started (group S). They were compared to six patients treated with ECMO who did not receive surfactant (group C). These control patients were matched based on age, weight, and underlying diagnosis. Demographic data, ventilator settings, tidal volume, compliance of respiratory system (calculated from tidal volume/(peak inspiratory pressure – positive end-expiratory pressure), and ECMO flow were extracted. Chest radiographs were scored by two blinded and independent radiologists. Changes over time were compared between groups by repeated-measures analysis of variance (time*group interaction). Values are given as percentages of baseline values.

Results

The groups did not differ with regard to demographic data, duration of ECMO, ventilator settings, PICU and hospital days. After application of surfactant, mean tidal volume almost doubled in group S (from 100% before to 186.2%; p = 0.0053). No change was found in group C (100% versus 98.7%). Mean compliance increased significantly (p = 0.0067) in group S (from 100% to 176.1%) compared to group C (100% versus 97.6%). Radiographic scores tended to decrease in group S within 48 h following surfactant application. ECMO flow tended to decrease in group S within 10 h following surfactant application but not in group C. Mortality was not affected by treatment.

Conclusion

Surfactant application may be of benefit in children with respiratory failure treated with ECMO, but these findings need confirmation from prospective studies.
Cytokine-regulated expression and inhibitory function of FcγRIIB1 and -B2 receptors in human dendritic cells
Authors: Guriec Nathalie , Daniel Catherine , Le Ster Karine , Hardy Elisabeth , Berthou Christian
Published: October 2005

Dendritic cells (DC) capture immune complexes (IC) via Fc receptors for immunoglobulin G FcγRII and elicit antigen presentation and protective antitumoral immune response in mice. Two protocols are commonly used to differentiate human monocyte-derived DC in vitro. They associate granulocyte macrophage-colony stimulating factor (CM-CSF) with interleukin (IL)-4 or IL-13. In this study, we first assessed the ability of the two types of DCto initiate an immune response against an IC-linked antigen. We evidenced that IL-4 and IL-13 DC display comparable lymphocyte stimulatory capacity and similar lifetimes. We next characterized FcγRIIs expressed by pure populations of circulating myeloid DC (BDCA1+DC), IL-4, and IL-13 DC. We highlighted the expression of FcγRIIA, -B1, and -B2 by pure populations of BDCA1 myeloid DCs and IL-4 and IL-13 DC. Moreover, IL-4 and IL-13 DC displayed greater FcγRIIB expression than monocytes but a comparable FcγRIIA. We next investigated the FcγRIIB mechanism of action. We evidenced that deleting FcγRIIB increased the ability of IC-pulsed DC to stimulate autologous lymphocytes. FcγRIIB acted by lowering IC uptake, surface expression of costimulation molecules, and cytokine release. Finally, the balance between activating FcγRIIA/inhibitory FcγRIIB (B1+B2) could be modulated in vitro by inflammation mediators. By lowering FcγRIIB expression without significantly affecting FcγRIIA, prostaglandin E2 (PGE-2) appeared to be a major regulator of this balance. IL-1β and tumor necrosis factor α were also found to potentiate PGE-2 action. Altogether, our results evidence an inhibitory role for FcγRIIB in human DC and provide an easy way to possibly improve in vitro the induction of immune response against IC-linked antigen.
Activation of human eosinophils via P2 receptors: novel findings and future perspectives
Authors: Ferrari Davide , la Sala Andrea , Panther Elisabeth , Norgauer Johannes , Di Virgilio Francesco , Idzko Marco
Published: October 2005

A growing body of information indicates that release of intracellular nucleotides represents an important way to modulate several cell pathways in physiological or pathological conditions. Nucleotides released as a consequence of cell damage, cell stress, bacterial infection, or other noxious stimuli signal at a class of plasma membrane receptors—P2 receptors—activating diverse intracellular pathways in many tissues and organs. For example, nucleotides secreted in the airway system control chloride/liquid secretion, goblet cell degranulation, and ciliary beat frequency. Several studies indicate that nucleotides play a role in airway diseases through their action on multiple cell types, including mast cells, dendritic cells, neurons, and eosinophils. Recent work by us and other groups led to the identification and characterization of P2 receptors expressed by human eosinophils. In this review, we will summarize recent developments in this field and put forward a hypothesis about the role of P2 receptors in pathophysiological conditions where eosinophils are major players.
Different Molecular Mechanisms Underlie Ethanol-Induced Bone Loss in Cycling and Pregnant Rats
Authors: Shankar Kartik , Hidestrand Mats , Haley Rani , Skinner Robert A. , Hogue William , Jo Chan-Hee , Simpson Pippa , Lumpkin Charles K. , Aronson James , Badger Thomas M. , Ronis Martin J. J.
Published: October 2005

Chronic ethanol (EtOH) consumption can result in osteopenia. In the current study, we examined the modulation of EtOH-induced bone loss during pregnancy. Nonpregnant and pregnant dams were intragastrically infused either control or EtOH-containing diets throughout gestation (gestation d 5 through 20 or an equivalent period of 15 d) by total enteral nutrition. The effects of EtOH (8.5 to 14 g/kg/d) on tibial bone mineral density (BMD), mineral content (BMC), and bone mineral area were assessed at gestation d 20 via peripheral quantitative computerized tomography. EtOH caused a dose-dependent decrease in BMD and BMC without affecting bone mineral area. Trabecular BMD and BMC were significantly lower in EtOH-treated, nonpregnant dams, compared with pregnant cohorts at the same infused dose of EtOH and urinary ethanol concentrations. Static histomorphometric analysis of tibiae from pregnant rats after EtOH treatment showed decreased osteoblast and osteoid surface, indicating inhibited bone formation, whereas EtOH-treated cycling rats showed higher osteoclast and eroded surface, indicative of increased bone resorption. Circulating osteocalcin and 1,25-dihydroxyvitamin D3 were lower in both EtOH-fed nonpregnant and pregnant rats. Gene expression of osteoclast markers, 70 kDa v-ATPase, and tartrate-resistant acid phosphatase were increased selectively in nonpregnant EtOH-treated rats but not pregnant rats. Moreover, only nonpregnant EtOH-fed rats showed induction in bone marrow receptor activator of nuclear factor-κB ligand mRNA and decreased circulating 17β-estradiol levels. Our data suggest that EtOH-induced bone loss in pregnant rats is mainly due to inhibited bone formation, whereas in nonpregnant rats, the data are consistent with increased osteoclast activation and bone resorption concomitant with decreased estradiol levels.
Both Estrogen Receptor-α and -β Are Required for Sexual Differentiation of the Anteroventral Periventricular Area in Mice
Authors: Bodo Cristian , Kudwa Andrea E. , Rissman Emilie F.
Published: October 2005

Sexual dimorphisms in the hypothalamus are mediated in several cases by local aromatization of androgens to estrogens during the perinatal period. In this series of experiments, the contributions of the two estrogen receptors (ERs), ERα and ERβ, to the differentiation of the sexually dimorphic subpopulation of dopaminergic neurons in the anteroventral periventricular area (AVPV) was examined. In the first experiment, numbers of tyrosine hydroxylase (TH) immunoreactive (-ir) AVPV neurons in ERβ knockout and wild-type (WT) mice of both sexes were measured. In the second experiment, the average number of TH-ir neurons in the medial portion of the AVPV in ERα knockout, ERβ knockout, double-ER knockout, and WT mice of both sexes was calculated. In both experiments TH-ir cell numbers were sexually dimorphic as expected, with female individuals of all genotypes exhibiting more TH-ir neurons than WT males. Interestingly the average number of TH-ir neurons in all knockout males was significantly higher than in WT male littermates. In fact, TH-ir cell numbers in all knockout males were equivalent to females. In a final experiment, C57BL/6J female mice were treated during the first 3 postnatal days with either estradiol, or a specific agonist for one of the two ERs. Additional male and female pups received vehicle injections. Treatments with estradiol or either ER-specific agonist significantly reduced the number of TH-ir AVPV neurons in female brains. Our data demonstrate that both ERα and ERβ are involved in the sexual differentiation of the AVPV in mice.
The G Protein-Coupled Receptor GPR30 Mediates the Proliferative Effects Induced by 17β-Estradiol and Hydroxytamoxifen in Endometrial Cancer Cells
Authors: Vivacqua Adele , Bonofiglio Daniela , Recchia Anna Grazia , Musti Anna Maria , Picard Didier , Andò Sebastiano , Maggiolini Marcello
Published: October 2005

The growth of both normal and transformed epithelial cells of the female reproductive system is stimulated by estrogens, mainly through the activation of estrogen receptor α (ERα), which is a ligand-regulated transcription factor. The selective ER modulator tamoxifen (TAM) has been widely used as an ER antagonist in breast tumor; however, long-term treatment is associated with an increased risk of endometrial cancer. To provide new insights into the potential mechanisms involved in the agonistic activity exerted by TAM in the uterus, we evaluated the potential of 4-hydroxytamoxifen (OHT), the active metabolite of TAM, to transactivate wild-type ERα and its splice variant expressed in Ishikawa and HEC1A endometrial tumor cells, respectively. OHT was able to antagonize only the activation of ERα by 17β-estradiol (E2) in Ishikawa cells, whereas it up-regulated c-fos expression in a rapid manner similar to E2 and independently of ERα in both cell lines. This stimulation occurred through the G protein-coupled receptor named GPR30 and required Src-related and epidermal growth factor receptor tyrosine kinase activities, along with the activation of both ERK1/2 and phosphatidylinositol 3-kinase/AKT pathways. Most importantly, OHT, like E2, stimulated the proliferation of Ishikawa as well as HEC1A cells. Transfecting a GPR30 antisense expression vector in both endometrial cancer cell lines, OHT was no longer able to induce growth effects, whereas the proliferative response to E2 was completely abrogated only in HEC1A cells. Furthermore, in the presence of the inhibitors of MAPK and phosphatidylinositol 3-kinase pathways, PD 98059 and wortmannin, respectively, E2 and OHT did not elicit growth stimulation. Our data demonstrate a new mode of action of E2 and OHT in endometrial cancer cells, contributing to a better understanding of the molecular mechanisms involved in their uterine agonistic activity.
Retinoic acid regulates the expression of dorsoventral topographic guidance molecules in the chick retina
Authors: Sen Jonaki , Harpavat Sanjiv , Peters Maureen A. , Cepko Constance L.
Published: October 2005

Asymmetric expression of several genes in the early eye anlagen is required for the dorsoventral (DV) and anteroposterior (AP) patterning of the retina. Some of these early patterning genes play a role in determining the graded expression of molecules that are needed to form the retinotectal map. The polarized expression of retinoic acid synthesizing and degrading enzymes along the DV axis in the retina leads to several zones of varied retinoic acid (RA)activity. This is suggestive of RA playing a role in DV patterning of the retina. A dominant-negative form of the retinoic acid receptor α(DNhRARα) was expressed in the chick retina to block RA activity. RA signaling was found to play a role in regulating the expression of EphB2,EphB3 and ephrin B2, three molecules whose graded expression in the retina along the DV axis is important for establishing the correct retinotectal map. Blocking RA signaling by misexpression of a RA degrading enzyme, Cyp26A1 recapitulated some but not all the effects of DNhRARα. It also was found that Vax, a ventrally expressed transcription factor that regulates the expression of the EphB and ephrin B molecules, functions upstream of, or in parallel to, RA. Expression of DNhRARα led to increased levels of RA-synthesizing enzymes and loss of RA-degrading enzymes. Activation of such compensatory mechanisms when RA activity is blocked suggests that RA homeostasis is very strictly regulated in the retina.
Set1- and Clb5-deficiencies disclose the differential regulation of centromere and telomere dynamics inSaccharomyces cerevisiaemeiosis
Authors: Trelles-Sticken Edgar , Bonfils Sandrine , Sollier Julie , Géli Vincent , Scherthan Harry , de La Roche Saint-André Christophe
Published: October 2005

The entry into meiosis is characterized by a lengthy premeiotic S phase and a reorganization of the nuclear architecture. Analysis of centromere and telomere dynamics in wild-type Saccharomyces cerevisiae meiosis suggests that resolution of vegetative centromere and telomere clusters are independent events differently connected to premeiotic S phase. Absence of the B-type cyclin Clb5 or the Set1 histone methyltransferase leads to a delay of premeiotic S phase by separate mechanisms. In clb5Δ cells, centromere cluster resolution appears normal, whereas dissolution of the vegetative telomere clusters is impaired and meiosis-specific clustering of telomeres, i.e. bouquet formation, is grossly delayed. In set1Δ cells, centromere and telomere redistribution are both impaired and bouquet nuclei are absent, despite proper location of the meiosis-specific telomere protein Ndj1. Thus, centromere and telomere redistribution at the onset of prophase I is differentially regulated, with centromere dispersion occurring independently of premeiotic S phase. The normal kinetics of dissolution of the vegetative telomere clusters in a set1Δ mec1-1 mutant suggests the presence of a checkpoint that limits the dispersion of telomeres in absence of Set1.
Nuclear levels and patterns of histone H3 modification and HP1 proteins after inhibition of histone deacetylases
Authors: Bártová Eva , Pacherník Jiří , Harničarová Andrea , Kovařík Aleš , Kovaříková Martina , Hofmanová Jirina , Skalníková Magdalena , Kozubek Michal , Kozubek Stanislav
Published: October 2005

The effects of the histone deacetylase inhibitors (HDACi) trichostatin A (TSA) and sodium butyrate (NaBt) were studied in A549, HT29 and FHC human cell lines. Global histone hyperacetylation, leading to decondensation of interphase chromatin, was characterized by an increase in H3(K9) and H3(K4) dimethylation and H3(K9) acetylation. The levels of all isoforms of heterochromatin protein, HP1, were reduced after HDAC inhibition. The observed changes in the protein levels were accompanied by changes in their interphase patterns. In control cells, H3(K9) acetylation and H3(K4) dimethylation were substantially reduced to a thin layer at the nuclear periphery, whereas TSA and NaBt caused the peripheral regions to become intensely acetylated at H3(K9) and dimethylated at H3(K4). The dispersed pattern of H3(K9) dimethylation was stable even at the nuclear periphery of HDACi-treated cells. After TSA and NaBt treatment, the HP1 proteins were repositioned more internally in the nucleus, being closely associated with interchromatin compartments, while centromeric heterochromatin was relocated closer to the nuclear periphery. These findings strongly suggest dissociation of HP1 proteins from peripherally located centromeres in a hyperacetylated and H3(K4) dimethylated environment. We conclude that inhibition of histone deacetylases caused dynamic reorganization of chromatin in parallel with changes in its epigenetic modifications.
Differential contributions of connexin37 and connexin43 to oogenesis revealed in chimeric reaggregated mouse ovaries
Authors: Gittens Joanne E. I. , Kidder Gerald M.
Published: October 2005

The gap junction proteins connexin37 and connexin43 are required for ovarian folliculogenesis in the mouse. To define their respective roles in oogenesis, chimeric ovaries containing either null mutant oocytes and wild-type granulosa cells or the reverse combination were grafted to the renal capsules of immunodeficient female mice. After three weeks, the oocytes were tested for meiotic competence and fertilizability in vitro. Ovaries composed of connexin43-deficient oocytes and wild-type granulosa cells produced antral follicles enclosing oocytes that could develop to at least the two-cell stage, demonstrating that oocytes need not express connexin43 to reach maturity. Conversely, both follicle development and oocyte maturation were impaired in ovaries containing either wild-type oocytes and connexin43-deficient granulosa cells or connexin37-deficient oocytes and wild-type granulosa cells. Thus absence of connexin43 from granulosa cells or connexin37 from oocytes is sufficient to compromise both oocyte and follicle development. Wild-type oocytes paired with connexin37-deficient granulosa cells generated antral follicles containing oocytes that developed to at least the two-cell stage. Therefore, connexin37 absence from granulosa cells need not impair fertility in mice. Dye transfer experiments revealed persistent oocyte-granulosa cell coupling in those follicles, indicating functional compensation by another connexin. The results indicate that mouse oocytes do not need to express connexin43 in order to develop into meiotically competent, fertilizable gametes, but must express connexin37 for communication with granulosa cells, a requirement for oogenesis.
Assigning functions to distinct regions of the N-terminus of the prion protein that are involved in its copper-stimulated, clathrin-dependent endocytosis
Authors: Taylor David R. , Watt Nicole T. , Perera W. Sumudhu S. , Hooper Nigel M.
Published: October 2005

The cellular prion protein (PrPC) is essential for the pathogenesis and transmission of prion diseases. Although PrPC is known to be located in detergent-insoluble lipid rafts at the surface of neuronal cells, the mechanism of its internalisation is unclear, with both raft/caveolae-based and clathrin-mediated processes being proposed. We have investigated the mechanism of copper-induced internalisation of PrPC in neuronal cells by immunofluorescence microscopy, surface biotinylation assays and buoyant sucrose density gradient centrifugation in the presence of Triton X-100. Clathrin-mediated endocytosis was selectively blocked with tyrphostin A23, which disrupts the interaction between tyrosine motifs in the cytosolic domains of integral membrane proteins and the adaptor complex AP2, and a dominant-negative mutant of the adaptor protein AP180. Both these agents inhibited the copper-induced endocytosis of PrPC. Copper caused PrPC to move laterally out of detergent-insoluble lipid rafts into detergent-soluble regions of the plasma membrane. Using mutants of PrPC that lack either the octapeptide repeats or the N-terminal polybasic region, and a construct with a transmembrane anchor, we show that copper binding to the octapeptide repeats promotes dissociation of PrPC from lipid rafts, whereas the N-terminal polybasic region mediates its interaction with a transmembrane adaptor protein that engages the clathrin endocytic machinery. Our results provide an experimental basis for reconciling the apparently contradictory observations that the prion protein undergoes clathrin-dependent endocytosis despite being localised in lipid rafts. In addition, we have been able to assign distinct functions in the endocytic process to separate regions of the protein.