bluuebunny/crossref_metadata_2025 huggingface dataset:
A Transparency Gap?
Authors: Heard-Lauréote Karen
Published: March 2007

How much are European citizens entitled to know about the European Union's (EU) Common Agricultural Policy (CAP) governance system in general and the European Commission's Agricultural Advisory Committees (AACs) (Agricultural Advisory Groups since April 2004) in particular, and to what extent can EU institutions, the public, and committee members exercise scrutiny over the AACs? Two themes underlie these questions: access to information and scrutiny. These are intrinsic to the notion of transparency, which the article sets out to explore and comment on. It attempts to define the notion in relation to its essential components and in order to assess whether CAP governance through committees is transparent enough to ensure that citizens are ultimately able to exercise democratic control over it, this article gauges AAC intelligibility. Using original empirical research carried out in Autumn 2003, based on interviews with AAC members derived from socio-economic groups as well as European institutions' internal documentary evidence, the article argues that these structures suffer a substantial transparency deficit.
Defending Philadelphia
Authors: Knowles Scott Gabriel
Published: March 2007

The city of Philadelphia, today, is in the midst of revamping its plans for emergency preparedness. For a city of its size, age, and infrastructural complexity, this presents a number of critical challenges. This article examines the last era in which emergency preparedness—in the form of early cold war civil defense—stood at the forefront of the city’s challenges. This article develops a historical case study of Philadelphia’s civil defense efforts against atomic attack in the 1950s, especially in the earliest planning and implementation stages under retired Major General Norman D. Cota. Civil defense failed in Philadelphia, as it did across the nation, and this article considers in detail the role that Cota’s “command- and-control” methods led to this failure.
Drawing From Freirian Empowerment Methods to Develop and Use Innovative Learning Maps: Increasing Enrollment of Uninsured Children on Detroit's Eastside
Authors: Lopez Ellen D. S. , Lichtenstein Richard , Lewis Alonzo , Banaszak-Holl Jane , Lewis Cheryl , Johnson Penni , Riley Scherry , Baum Nancy M.
Published: March 2007

In 2001, virtually every child on Detroit's eastside was eligible for health coverage, yet approximately 3,000 children remained uninsured. The primary aim of the Eastside Access Partnership (EAP), a community-based participatory research collaboration, was to increase enrollment of uninsured children in state programs. To achieve this aim, one of the approaches that EAP is using is the innovative Learning Map© titled Choosing the Healthy Path, which was developed in collaboration with Root Learning, Inc. Although Learning Maps were originally developed to assist corporations in implementing strategic change, their integration of visualization and interactive dialogue incorporates Freirian principles of empowerment education, making them a viable option for providing meaningful learning opportunities for community residents. This article presents the collaborative process involving the University of Michigan, local community-based organizations, community members, and Root Learning consultants to develop a visual map that enables community residents to understand and overcome the barriers that prevent them from obtaining health insurance for their children.
University Students' Perspectives on a Physical Activity Record-Keeping Log
Authors: Tucker Patricia , Irwin Jennifer D.
Published: March 2007

This qualitative study explored characteristics of a record-keeping log that students would find appealing and be receptive to using. A heterogeneous sample of undergraduate university students aged 18 to 25 years participated. An experienced moderator, using a semistructured interview guide, conducted 13 focus groups (N = 65). All focus groups were audio-recorded and transcribed verbatim. Inductive content analysis was conducted independently by two qualitative researchers. Measures were incorporated throughout the study to ensure data trustworthiness. Four themes illustrated students' suggestions for the log: layout, convenience, maximum distribution, and concerns. In particular, students discussed the use of a computer-based versus a paper-based log, hesitancies in using a log, and the need for: additional health information, multivenue distribution, and low to no cost. Students confirmed that a record-keeping log tailored to their needs and preferences would be attractive and appealing to students.
Community-Based Prevention Marketing
Authors: Bryant Carol A. , McCormack Brown Kelli R. , McDermott Robert J. , Forthofer Melinda S. , Bumpus Elizabeth C. , Calkins Susan A. , Zapata Lauren B.
Published: March 2007

This article describes the application and refinement of community-based prevention marketing (CBPM), an example of community-based participatory research that blends social marketing theories and techniques and community organization principles to guide voluntary health behavior change. The Florida Prevention Research Center has worked with a community coalition in Sarasota County, Florida to define locally important health problems and issues and to develop responsive health-promotion interventions. The CBPM framework has evolved as academic and community-based researchers have gained experience applying it. Community boards can use marketing principles to design evidence-based strategies for addressing local public health concerns. Based on 6 years of experience with the “Believe in All Your Possibilities” program, lessons learned that have led to revision and improvement of the CBPM framework are described.
From Evidence-Based Practice Making to Practice-Based Evidence Making
Authors: McDonald Paul W. , Viehbeck Sarah
Published: March 2007

Models of research translation frequently emphasize independent roles for research producers and intended users. This article describes a novel approach for enhancing exchange between researchers and practitioners. The framework is based on Wenger's notion of Communities of Practice (CoP) where knowledge is regarded as a social enterprise at the center of member interactions. Research-based practices and policies emerge when research producers and users mutually engage one another about specific health promotion problems through negotiation and by creating and sharing technical standards and other resources. CoPs are more than loose networks or task-oriented teams. They aim to create both social and intellectual capital through mutual negotiation, reciprocity, trust, and cohesion. A Consortium of Quitline Operators across North America and a Canadian project to enhance research capacity for tobacco control research serve as examples of how the model has been successfully operationalized.
Competition
Authors: Clay Wayman Jennifer J. , Beall Tom , Thackeray Rosemary , McCormack Brown Kelli R.
Published: March 2007

In public health social marketing, is there such a thing as “healthy competition,” or is the term an oxymoron? The primary focus of this article is on a type of competition that may not often be considered by public health social marketers—competition from other marketing activities that exist in the marketplace in which your intervention is operating. This could also be termed “promotion” competition. The purpose of this article is to briefly review promotion competition and then review competitive factors that can impact a social marketing initiative's success, examine how to conduct a useful competitive analysis, and offer strategies for maximizing the benefits and minimizing the negative implications of competition on your efforts.
CTLA-4 polymorphisms and clinical outcome after allogeneic stem cell transplantation from HLA-identical sibling donors.
Authors: Pérez-García Arianne , De la Cámara Rafael , Román-Gómez Jose , Jiménez-Velasco Antonio , Encuentra Maite , Nieto Jose B. , de la Rubia Javier , Urbano-Ispizúa Alvaro , Brunet Salut , Iriondo Arturo , González Marcos , Serrano David , Espigado Ildefonso , Solano Carlos , Ribera Josep M. , Pujal Josep M. , Hoyos Montserrat , Gallardo David ,   the GVHD/Immunotherapy Committee of the Spanish Group of Hematopoietic Stem Cell Transplantation
Published: March 2007

CTLA-4 is an inhibitory molecule that down-regulates T-cell activation. Although polymorphisms at CTLA-4 have been correlated with autoimmune diseases their association with clinical outcome after allogeneic hematopoietic stem cell transplantation (allo-HSCT) has yet to be explored. A total of 5 CTLA-4 single-nucleotide polymorphisms were genotyped on 536 HLA-identical sibling donors of allo-HSC transplants. Genotypes were tested for an association with patients' posttransplantation outcomes. The effect of the polymorphisms on cytotoxic T-lymphocyte antigen 4 (CTLA-4) mRNA and protein production were determined in 60 healthy control participants. We observed a reduction in the mRNA expression of the soluble CTLA-4 isoform in the presence of a G allele at CT60 and +49. Patients receiving stem cells from a donor with at least 1 G allele in position CT60 had worse overall survival (56.2% vs 69.8% at 5 years; P = .001; hazard ratio [HR], 3.80; 95% confidence interval [CI], 1.75-8.22), due to a higher risk of relapse (P = .049; HR, 1.71; 95% CI, 1.00-2.93). Acute graft-versus-host disease (aGVHD) was more frequent in patients receiving CT60 AA stem cells (P = .033; HR, 1.54; 95% CI, 1.03-2.29). This is the first study to report an association between polymorphisms at CTLA-4 and clinical outcome after allo-HSCT. The CT60 genotype influences relapse and aGVHD, probably due to its action on CTLA-4 alternative splicing.
Strain-dependent resistance to allergen-induced lung pathophysiology in mice correlates with rate of apoptosis of lung-derived eosinophils
Authors: Tumes Damon J , Cormie James , Calvert Michael G , Stewart Kalev , Nassenstein Christina , Braun Armin , Foster Paul S , Dent Lindsay A
Published: March 2007

Although exposed to similar allergic and environmental stimuli, not all humans develop asthma. Similarly, mouse strains vary in the degree of pathophysiology seen following induction of experimental asthma. Three mouse strains (CBA/Ca, BALB/c, and C57BL/6) were used to determine if the extent and duration of inflammation influenced the degree of lung tissue damage in an OVA-induced allergic asthma model. Airways obstruction, leukocyte infiltration, edema, eosinophil accumulation, and degranulation were less severe in wild-type (wt) CBA/Ca mice than wt BALB/c and C57BL/6 mice. F1 hybrids of CBA/Ca mice crossed with BALB/c or C57BL/6 mice had bronchoalveolar lavage leukocyte (BAL) and cell-free protein profiles similar to those of the respective disease-susceptible parental strain. IL-5 transgene expression on each of the three genetic backgrounds accentuated the difference between CBA/Ca and the other two strains. Importantly, even when overexpressing IL-5, CBA/Ca mice did not develop substantial airways obstruction. Eosinophils recovered from the airways of allergic wt and IL-5 transgenic (Tg) CBA/Ca mice entered apoptosis at a faster rate than eosinophils from the other parental strains and F1 hybrids. In contrast, eosinophils harvested from the peritoneal cavities of untreated CBA/Ca IL-5 Tg mice had a relatively low rate of apoptosis in vitro. The CBA/Ca mouse strain is therefore relatively resistant to experimental asthma, and this may be a consequence of a propensity for apoptosis of eosinophils recruited into the allergic lung. Restricting survival of a key effector cell may thus limit pathogenesis in this experimental model and in humans.
Reactive Structural Dynamics of Synaptic Mitochondria in Ischemic Delayed Neuronal Death
Authors: BERTONI‐FREDDARI CARLO , FATTORETTI PATRIZIA , CASOLI TIZIANA , DI STEFANO GIUSEPPINA , SOLAZZI MORENO , PERNA ELISA , DE ANGELIS CLARA
Published: March 2007

Abstract:  The effect of transient global ischemia on the ultrastructural features of synaptic mitochondria at the distal dendrites of CA1 hippocampal neurons was investigated in 3‐month‐old rats. Sham surgery was performed on age‐matched controls. The number of mitochondria/μm3 of neurophils (Nv: numeric density), the mitochondrial average size (average volume: V), and longer diameter (Fmax) as well as the overall fraction of neurophils occupied by mitochondria (volume density: Vv) were measured by computer‐assisted morphometry. In ischemic rats, a 10% nonsignificant decrease of Nv was found, V increased nonsignificantly by 11%, and Fmax increased nonsignificantly by 5% versus controls. As a final outcome of these balanced changes, Vv remained unchanged between the two experimental groups investigated. In ischemic animals, the percentage distribution of V showed that the population of CA1 synaptic mitochondria was composed by an increased fraction of oversized organelles, while the Fmax distribution revealed that this enlargement was due to an increased percentage of elongated organelles. Thus, the observed increase in size should not be considered as a swelling phenomenon; on the contrary, it may represent a physiological and well‐documented step in mitochondrial biogenesis. The above parameters are currently supposed to provide information on the adaptive structural reorganization of mitochondrial morphology under different environmental stimulations. Conceivably, these findings document a positive reactive response to ischemia of the mitochondrial structural dynamics at CA1 synaptic terminals and suggest consideration of these organelles as reliable targets in the development of neuroprotective therapeutic interventions to treat vascular brain diseases, for example, stroke.
Membrane Fluidity Changes Are Associated with Benzo[a]Pyrene‐Induced Apoptosis in F258 Cells
Authors: GORRIA MORGANE , TEKPLI XAVIER , SERGENT ODILE , HUC LAURENCE , GABORIAU FRANÇOIS , RISSEL MARY , CHEVANNE MARTINE , DIMANCHE‐BOITREL MARIE‐THÉRÈSE , LAGADIC‐GOSSMANN DOMINIQUE
Published: March 2007

Abstract:  Polycyclic aromatic hydrocarbons (PAHs) such as benzo[a]yrene (B[a]P) constitute a widely distributed class of environmental pollutants, responsible for highly toxic effects. Elucidating the intracellular mechanisms of this cytotoxicity thus remains a major challenge. Besides the activation of the p53 apoptotic pathway, we have previously found in F258 hepatic cells that the B[a]P (50 nM)‐induced apoptosis was also dependent upon the transmembrane transporter NHE1, whose activation might result from membrane alterations in our model. We here demonstrate that: (1) B[a]P induces a membrane fluidization surprisingly linked to NHE1 activation; (2) membrane stabilization by exogenous cholesterol protects cells from B[a]P‐induced apoptosis, via an effect on late acidification and iron uptake.
Metal‐Containing Proteins in the Apoptosis and Redox Processes in the Rat Prostate and Human Prostate Cells
Authors: GRBAVAC I. , WOLF C. , WENDA N. , ALBER D. , KÜHBACHER M. , BEHNE D. , KYRIAKOPOULOS A.
Published: March 2007

Abstract:  Several trace elements, such as Se, Cu, Mn, and Zn are bound to proteins (metallo‐ and metalloidproteins) in the prostate gland. Currently, it is known that some of those elements play a role in the apoptosis of different cells and redox processes. For the detection of such proteins, analytical and biochemical procedures were combined. SEC and ICP‐MS were used to detect some trace elements, which are bound to proteins in the prostate cytosol and/or in the human prostate cell lines. Several antibodies against specific proteins were tested. By means of some of these antibodies several trace element–containing proteins, such as selenoproteins and Cu‐ and Cu‐Zn‐proteins, could be identified in the prostate. In addition, the localization of such metal‐ and metalloid‐containing proteins in the micro organelles and cytosol of the prostate indicates specific functions of these proteins because, as it is known, such metal‐ and metalloid proteins play a role in the apoptosis and especially in the redox processes.
Apoptotic Cell Signaling in Lymphocytes from HIV+ Patients during Successful Therapy
Authors: GRELLI SANDRO , BALESTRIERI EMANUELA , MATTEUCCI CLAUDIA , MINUTOLO ANTONELLA , D'ETTORRE GABRIELLA , LAURIA FILIPPO , MONTELLA FRANCESCO , VULLO VINCENZO , VELLA STEFANO , FAVALLI CARTESIO , MASTINO ANTONIO , MACCHI BEATRICE
Published: March 2007

Abstract:  The impact of antiretroviral therapy (ART) on immune‐reconstitution and its relationship with the complex scenario of multiple cell signaling associated with apoptosis in HIV infection has not yet been fully elucidated. Here we report the results of the analysis of the expression of 13 genes involved in the apoptotic pathway, simultaneously detected by RNA‐protection assay in peripheral blood mononuclear cells (PBMCs) of 12 HIV‐1‐infected responder patients before and during successful ART. In particular, we calculated the correlations among apoptosis and viral load (VL) levels versus the quantitative expression of genes associated with death receptors or to Bcl‐2 pathways. Nonparametric bivariate Spearman's analysis of significant correlations showed that apoptosis was directly correlated with mRNA levels for caspase‐8, FasL, and TRAIL. Conversely, apoptosis levels were inversely correlated with mRNA levels for Bcl‐xl, Bcl‐2, and Mcl‐1, respectively. In addition, while VL was directly correlated with the expression of caspase 8, it was inversely correlated with mRNA levels for Bcl‐2 and Mcl‐1. These results, although worthy of further investigation, show that variations of apoptosis levels in PBMCs of HIV‐1+ patients during ART are strictly related to the modulation of a complex network of signaling involving both death and survival of lymphocytes.
Ceramide Modulation of Antigen‐ Triggered Ca2+ Signals and Cell Fate
Authors: KISS ENDRE , SÁRMAY GABRIELLA , MATKÓ JÁNOS
Published: March 2007

Abstract:  Ceramide is a widely accepted mediator of T cell apoptosis and is released upon receiving various death or stress signals. Recently we have shown that the fate of T cells, life or death, depends strictly on the strength and duration of the ceramide‐generating stimulus. Subapoptotic ceramide signals were shown to negatively regulate the antigen‐specific activation signaling in T cells. Here we show that these subapoptotic ceramide signals also inhibit the antigen‐triggered Ca2+ signals in B lymphocytes or the FcɛRI‐mediated response of mast cells to antigen, but in a differential manner. Burkitt B lymphoma cells, frequently used models of mature B cells, and marginal zone B cells were largely resistant to the inhibitory action of ceramide. The response to cell death–inducing (strong/long duration) ceramide stimuli, resulting in massive apoptosis in T cells, was also differential among the various immunocytes in terms of both the death mechanism and the sensitivity. Our data suggest that ceramide's effects on life and death signaling in immunocytes are cell type‐/stage‐specific.
Cytotoxicity of TRAIL/Anticancer Drug Combinations in Human Normal Cells
Authors: MEURETTE OLIVIER , FONTAINE ANNE , REBILLARD AMELIE , LE MOIGNE GWENAELLE , LAMY THIERRY , LAGADIC‐GOSSMANN DOMINIQUE , DIMANCHE‐BOITREL MARIE‐THERESE
Published: March 2007

Abstract:  TRAIL (TNF‐α‐Related Apoptosis‐Inducing Ligand) is a promising anticancer agent. In fact, it induces apoptosis in cancer cells and not in most normal cells. Nevertheless, certain cancer cells are resistant to TRAIL‐induced apoptosis and this could limit TRAIL's efficiency in cancer therapy. To overcome TRAIL resistance, a combination of TRAIL with chemotherapy could be used in cancer treatment. However, sensitivity of human normal cells to such combinations is not well known. We showed in this study that TRAIL/cisplatin, in contrast to TRAIL/5‐fluorouracil, was toxic toward human primary hepatocytes and resting lymphocytes. Furthermore, both combinations are toxic toward PHA‐IL2‐activated lymphocytes. In contrast, freshly isolated neutrophils are resistant to TRAIL in combination or not with anticancer drugs.
Human Recombinant Vasostatin‐1 May Interfere with Cell–Extracellular Matrix Interactions
Authors: DI FELICE VALENTINA , CAPPELLO FRANCESCO , MONTALBANO ANTONELLA , ARDIZZONE NELLA , CAMPANELLA CLAUDIA , DE LUCA ANGELA , AMELIO DANIELA , TOTA BRUNO , CORTI ANGELO , ZUMMO GIOVANNI
Published: March 2007

Abstract:  Vasostatin‐1 (VS‐1), the N‐terminal fragment derived from the cleavage of chromogranin A (CgA), has been shown to exert several biological activities on several tissues and organs. Recently, it has been reported that human recombinant VS‐1 (STA‐CGA1‐78) may alter myocardial contractility in eel, frog, and rat hearts. In this article we have explored if STA‐CGA1‐78 can induce intracellular cascades interacting both with adhesion molecules and/or extracellular matrix (ECM), components, that is, involvement of the heat shock protein 90 (HSP90) and the endothelial NOS (eNOS), known to be implicated in signal transduction mechanisms affecting myocardial contractility. We used 3D cultured adult rat cardiomyocytes cultivated over fibronectin or fibroblasts or embedded in matrigel or collagen type I. Aurion‐conjugated VS‐1 (Au‐STA‐CGA1‐78) has been used to identify possible sites of interaction of this molecule with the cell membrane. We found that in our 3D culture, cell–ECM interactions played a crucial role in the cellular localization of HSP90 as well as in the expression of eNOS. VS‐1 appeared to modulate cell–ECM interactions, thereby remarkably leading to a different cellular localization of HSP90. Moreover, Au‐STA‐CGA1‐78 was never detected inside the cell nor overlapping the plasma membrane, but nearby the outer side of the cardiomyocyte plasmalemma, at a particular distance, typical of integrins. On the whole, these data suggest that VS‐1 does not have a classic receptor on the membrane but that integrins may represent a nonconventional VS‐1 receptor modulating eNOS signaling pathway.
Grb2‐Associated Binder 1 (Gab1) Adaptor/Scaffolding Protein Regulates Erk Signal in Human B Cells
Authors: ANGYAL ADRIENN , MEDGYESI DAVID , SARMAY GABRIELLA
Published: March 2007

Abstract:  RNA silencing experiments showed that knocking down Gab1 adaptor protein in BL41 human Burkitt lymphoma cells significantly reduced B cell receptor (BCR)–induced Erk phosphorylation, indicating that Gab1 plays a pivotal role in regulating Erk activity in B cells.
CXC Receptor and Chemokine Expression in Human Meningioma
Authors: BARBIERI FEDERICA , BAJETTO ADRIANA , PORCILE CAROLA , PATTAROZZI ALESSANDRA , MASSA ALESSANDRO , LUNARDI GIANLUIGI , ZONA GIANLUIGI , DORCARATTO ALESSANDRA , RAVETTI JEAN LOUIS , SPAZIANTE RENATO , SCHETTINI GENNARO , FLORIO TULLIO
Published: March 2007

Abstract:  Recent evidence indicates that cancer cells express chemokine (CK) receptors and that their signaling is crucial for tumor proliferation, migration, and angiogenesis. The profiles of expression of CXC CK receptors (CXCR1‐5) and their main ligands (growth‐related oncogene, GRO1‐2‐3/CXCL1‐2‐3; interleukin 8, IL‐8/CXCL8; monokine‐induced γ‐interferon MIG/CXCL9; γ‐interferon‐inducible‐protein‐10, IP‐10/CXCL10; stromal cell‐derived factor‐1, SDF1/CXCL12; B‐cell activating CK‐1, BCA‐1/CXCL13) were analyzed by reverse transcription polymerase chain reaction (RT‐PCR) in surgical samples of human meningiomas. All the five receptors displayed high percentages of positive cases: 92% CXCR1, 89% CXCR2, 83% CXCR3, 78% CXCR4, and 94% CXCR5. Conversely, their ligands showed a lower pattern of expression: 40% IL‐8, 42% GRO1‐3, 42% IP‐10, 28% MIG, 53% SDF1, and 3% BCA‐1. SDF1/CXCR4 interaction plays a pivotal role in cancer proliferation. Thus, the signaling mechanisms activated by the exclusive binding between SDF1 and CXCR4 was investigated in 12 primary cultures from meningioma tissues. CXCR4 was functionally coupled as demonstrated by the significant increase of DNA synthesis in meningioma cells in response to SDF1, measured by [3H]‐thymidine uptake. In three primary cultures, the SDF1‐dependent mitogenic activity was associated with a marked phosphorylation of extracellular signal‐regulated kinase (ERK1/2) as evaluated by Western blots. PD98059 (a MEK inhibitor) significantly reduced ERK1/2 activation, thus linking the SDF1/CXCR4 pathway to meningioma cell proliferation via ERK1/2 signal transduction. We demonstrate, for the first time in human meningiomas, the simultaneous expression of CXCR1‐5 and their CKs and the mitogenic activity of SDF1/CXCR4, suggesting a pivotal role of these receptor–ligand pairs in meningeal tumors.
Upregulation of VEGF by 15‐Deoxy‐Δ12,14‐Prostaglandin J2 via Heme Oxygenase‐1 and ERK1/2 Signaling in MCF‐7 Cells
Authors: KIM EUN‐HEE , NA HYE‐KYUNG , SURH YOUNG‐JOON
Published: March 2007

Abstract:  The vascular endothelial growth factor (VEGF) induces angiogenesis in ischemic or inflamed tissues during tumor growth. 15‐Deoxy‐Δ12,14‐prostaglandin J2 (15d‐PGJ2), an endogenous ligand of peroxisome proliferator‐activated receptor (PPAR) γ, has been reported to upregulate VEGF synthesis through the induction of heme oxygenase (HO)‐1. In this work, we found that treatment of human breast cancer (MCF‐7) cells with 15d‐PGJ2 led to time‐dependent increases in the expression of HO‐1. The PPAR γ antagonist GW9662 and N‐acetylcysteine failed to block induction of HO‐1 by 15d‐PGJ2. Elevated expression or activity of HO‐1 has been reported to stimulate proliferation and to accelerate angiogenesis in several tumor cells. The induction of HO‐1 expression preceded the upregulation of VEGF in MCF‐7 cells stimulated with 15d‐PGJ2. In another experiment, 15d‐PGJ2 induced phosphorylation of extracellular signal‐regulated kinase (ERK1/2) in 12 h. Treatment of MCF‐7 cells with U0126 or transient transfection with dominant negative ERK (DN‐ERK) abrogated 15d‐PGJ2‐induced VEGF expression. To determine whether the induction of HO‐1 is responsible for ERK1/2 activation, the HO‐1 inhibitor, zinc protoporphyrin (ZnPP) was used. The phosphorylation of ERK1/2 by 15d‐PGJ2 was abolished by ZnPP. These results suggest that 15d‐PGJ2 upregulates VEGF expression via induction of HO‐1 and ERK‐1 and ‐2 phosphorylation, which may contribute to increased angiogenesis of the tumor cells.
Insulin Primes Human Neutrophils for CCL3‐Induced Migration
Authors: MONTECUCCO FABRIZIO , BIANCHI GIORDANO , BERTOLOTTO MARIA , VIVIANI GIORGIO , DALLEGRI FRANCO , OTTONELLO LUCIANO
Published: March 2007

Abstract: The present article shows that a short‐term exposure of purified human neutrophils to recombinant insulin conferred on these cells both the ability to migrate and the capacity to mobilize [Ca2+]i in response to CCL3, a chemokineper seineffective with native neutrophils. Furthermore, the effects of recombinant insulin were reproduced by short‐term incubation with sera from adult patients with metabolic syndrome, known to be characterized by a hyperinsulinemic state. A strict linear correlation (P< 0.01) between sera insulin levels and sera's ability to induce neutrophil locomotion was indeed found. Our data also suggest that (i) insulin primed neutrophils for migration to CCL3 via the selective activation of JNK 1/2, as shown by the use of inhibitors and kinase activation assay; (ii) the activation of Src kinases was necessary but not sufficient for CCL3‐induced locomotory activity; (iii) PI3K‐Akt, ERK 1/2, and p38 MAPK were not involved in insulin‐induced migratory competence. In summary, we provided evidence that the exposition of neutrophils to insulin, as it occurs in hyperinsulinemic conditions, confers the competence of the cells to migrate in response to CCL3, known to be generated near atherosclerotic plaques. As neutrophils have been recently suggested to be involved in breaking unstable atherosclerotic plaques, the present findings contribute to the understanding of the pathophysiology of plaque instability. Finally, biochemical analysis herein carried out raises the hypothesis of JNK 1/2 as an attractive therapeutic target.
Amyloid Precursor Protein Modulates ERK‐1 and ‐2 Signaling
Authors: VENEZIA VALENTINA , NIZZARI MARIO , REPETTO EMANUELA , VIOLANI ELISABETTA , CORSARO ALESSANDRO , THELLUNG STEFANO , VILLA VALENTINA , CARLO PIA , SCHETTINI GENNARO , FLORIO TULLIO , RUSSO CLAUDIO
Published: March 2007

Abstract:  The amyloid precursor protein (APP) is a transmembrane protein with a short cytoplasmic tail whose physiological function is unclear, although it is well documented that the proteolytic processing of APP could influence the development of Alzheimer's disease (AD) through the formation of membrane‐bound C‐terminal fragments (CTFs) and of β‐amyloid peptides (Aβ). We have recently shown that tyrosine‐phosphorylated APP and CTFs may interact with Grb2 and ShcA adaptor proteins and that this coupling occurs at a higher extent in AD subjects only. To study the interaction between APP or CTFs and ShcA/Grb2 and to investigate their molecular target we have used as experimental model two different cell lines: H4 human neuroglioma cells and APP/APLP null mouse embryonic fibroblast cells (MEFs). Here we show that in H4 cells APP interacts with Grb2; conversely in APP/APLP‐null MEF cells this interaction is possible only after the reintroduction of human APP by transfection. We have also shown that in MEF cells the transfection of a plasmid encoding for human APP wild‐type enhances the phosphorylation of ERK‐1 and ‐2 as revealed by Western blotting and immunofluorescence experiments. Finally, also in H4 cells the overexpression of APP upregulates the levels of phospho‐ERK‐1 and ‐2. In summary our data suggest that APP may influence phospho‐ERK‐1 and ‐2 signaling through its binding with Grb2 and ShcA adaptors. The meaning of this event is not clear, but APP interaction with these adaptors could be relevant to regulate mitogenic pathway.
Effects of Hypoxia on Glucose, Insulin, Glucagon, and Modulation by Corticotropin-Releasing Factor Receptor Type 1 in the Rat
Authors: Chen Xue-Qun , Dong Jing , Niu Chen-Ying , Fan Jun-Ming , Du Ji-Zeng
Published: March 2007

To determine the influence of continuous hypoxia on body weight, food intake, hepatic glycogen, circulatory glucose, insulin, glucagon, leptin, and corticosterone, and the involvement of the corticotropin-releasing factor receptor type 1 (CRFR1) in modulation of these hormones, rats were exposed to a simulated altitude of 5 km (∼10.8% O2) in a hypobaric chamber for 1, 2, 5, 10, and 15 d. Potential involvement of CRFR1 was assessed through five daily sc injections of a CRFR1 antagonist (CP-154,526) prior to hypoxia. Results showed that the levels of body weight, food intake, blood glucose, and plasma insulin were significantly reduced; the content of hepatic glycogen initially and transiently declined, whereas the early plasma glucagon and leptin remarkably increased; plasma corticosterone was markedly increased throughout the hypoxic exposure of 1–15 d. Compared with hypoxia alone, CRFR1 antagonist pretreatment in the hypoxic groups prevented the rise in corticosterone, whereas the levels of body weight and food intake were unchanged. At the same time, the reduction in blood glucose was greater and the pancreatic glucose was increased, plasma insulin reverted toward control, and plasma glucagon decreased. In summary, prolonged hypoxia reduced body weight, food intake, blood glucose, and plasma insulin but transiently enhanced plasma glucagon and leptin. In conclusion, CRFR1 is potentially involved in the plasma insulin reduction and transient glucagon increase in hypoxic rats.
The Ultraviolet Filter Benzophenone 2 Interferes with the Thyroid Hormone Axis in Rats and Is a Potent in Vitro Inhibitor of Human Recombinant Thyroid Peroxidase
Authors: Schmutzler Cornelia , Bacinski Anja , Gotthardt Inka , Huhne Katrin , Ambrugger Petra , Klammer Holger , Schlecht Christiane , Hoang-Vu Cuong , Grüters Annette , Wuttke Wolfgang , Jarry Hubertus , Köhrle Josef
Published: March 2007

Endocrine disrupting chemicals (EDCs), either plant constituents or contaminants deriving from industrial products, may interfere with the thyroid hormone (TH) axis. Here, we examined whether selected EDCs inhibit the key reactions of TH biosynthesis catalyzed by thyroid peroxidase (TPO). We used a novel in vitro assay based on human recombinant TPO (hrTPO) stably transfected into the human follicular thyroid carcinoma cell line FTC-238. F21388 (synthetic flavonoid), bisphenol A (building block for polycarbonates), and the UV filter benzophenone 2 (BP2) inhibited hrTPO. BP2 is contained in numerous cosmetics of daily use and may be in regular contact with human skin. Half-maximal inhibition in the guaiacol assay occurred at 450 nmol/liter BP2, a concentration 20- and 200-fold lower than those required in case of the TPO-inhibiting antithyroid drugs methimazole and propylthiouracil, respectively. BP2 at 300 nmol/liter combined with the TPO substrate H2O2 (10 μmol/liter) inactivated hrTPO; this was, however, prevented by micromolar amounts of iodide. BP2 did not inhibit iodide uptake into FRTL-5 cells. In BP2-treated rats (333 and 1000 mg/kg body weight), serum total T4 was significantly decreased and serum thyrotropin was significantly increased. TPO activities in the thyroids of treated animals were unchanged, a finding also described for methimazole and propylthiouracil. Thus, EDCs, most potently BP2, may disturb TH homeostasis by inhibiting or inactivating TPO, effects that are even more pronounced in the absence of iodide. This new challenge for endocrine regulation must be considered in the context of a still prevailing iodide deficiency in many parts of the world.
Activation of the Novel Estrogen Receptor G Protein-Coupled Receptor 30 (GPR30) at the Plasma Membrane
Authors: Filardo E. , Quinn J. , Pang Y. , Graeber C. , Shaw S. , Dong J. , Thomas P.
Published: March 2007

G protein-coupled receptor 30 (GPR30), a seven-transmembrane receptor (7TMR), is associated with rapid estrogen-dependent, G protein signaling and specific estrogen binding. At present, the subcellular site of GPR30 action is unclear. Previous studies using antibodies and fluorochrome-labeled estradiol (E2) have failed to detect GPR30 on the cell surface, suggesting that GPR30 may function uniquely among 7TMRs as an intracellular receptor. Here, we show that detectable expression of GPR30 on the surface of transfected HEK-293 cells can be selected by fluorescence-activated cell sorting. Expression of GPR30 on the cell surface was confirmed by confocal microscopy using the lectin concanavalin A as a plasma membrane marker. Stimulation of GPR30-expressing HEK-293 cells with 17β-E2 caused sequestration of GPR30 from the cell surface and resulted in its codistribution with clathrin and mobilization of intracellular calcium stores. Evidence that GPR30 signals from the cell surface was obtained from experiments demonstrating that the cell-impermeable E2-protein conjugates E2-BSA and E2-horseradish peroxidase promote GPR30-dependent elevation of intracellular cAMP concentrations. Subcellular fractionation studies further support the plasma membrane as a site of GPR30 action with specific [3H]17β-E2 binding and G protein activation associated with plasma membrane but not microsomal, or other fractions, prepared from HEK-293 or SKBR3 breast cancer cells. These results suggest that GPR30, like other 7TMRs, functions as a plasma membrane receptor.
The Brain Natriuretic Peptide (BNP) Precursor Is the Major Immunoreactive Form of BNP in Patients with Heart Failure
Authors: Seferian Karina R , Tamm Natalia N , Semenov Alexander G , Mukharyamova Kadriya S , Tolstaya Anastasya A , Koshkina Ekaterina V , Kara Andrei N , Krasnoselsky Mihail I , Apple Fred S , Esakova Tatiana V , Filatov Vladimir L , Katrukha Alexey G
Published: March 2007

Background: Peptides derived from brain natriuretic peptide (BNP) precursor (proBNP), BNP, and the N-terminal fragment of proBNP (NT-proBNP) are used as biomarkers of heart failure. It remains unclear which forms of these peptides circulate in blood and which forms are measured by assays for these natriuretic peptides.

Methods: To design assays for immunodetection of proBNP, NT-proBNP, and BNP, we used a panel of BNP- and NT-proBNP–specific monoclonal antibodies (MAbs). All MAbs were tested in 2-site combinations in time-resolved fluoroimmunoassays with recombinant or synthetic antigens and plasma from heart failure (HF) patients. ProBNP and related molecules were assayed in HF plasma samples and plasma extracts by means of gel filtration fast protein liquid chromatography (FPLC) before and after protein fractionation on Sep-Pak C18 cartridges.

Results: The limits of detection for BNP, proBNP, and NT-proBNP assays were 0.4, 3, and 10 ng/L, respectively. Gel filtration-FPLC studies revealed 1 peak of NT-proBNP (∼25 kDa), 1 peak of proBNP (∼37 kDa), and 2 peaks of BNP immunoreactivity, a major peak (∼37 kDa) for proBNP, and a minor peak (∼4 kDa) for BNP. In patient plasma, the molar concentration of NT-proBNP was almost 10 times that of proBNP. The mean proBNP:BNP ratio in patient plasma was 6.3, ranging from 1.8 to 10.8.

Conclusions: ProBNP is the major BNP-immunoreactive form in human blood. The proBNP:BNP ratio in plasma samples is dependent on the methods used for sample handling and for the measurement of the peptides.
Simultaneous Quantification of Ghrelin and Desacyl-Ghrelin by Liquid Chromatography–Tandem Mass Spectrometry in Plasma, Serum, and Cell Supernatants
Authors: Rauh Manfred , Gröschl Michael , Rascher Wolfgang
Published: March 2007

Background: A sensitive method specific for ghrelins is needed for investigations of this gastrointestinal peptide. Our aim was to develop and validate a quantitative mass spectrometry (MS) method to measure ghrelin and desacyl-ghrelin simultaneously.

Methods: After deproteinization by precipitation, we performed reversed-phase separation with a rapid 2-column online extraction design coupled to a quadrupole mass spectrometer for electrospray ionization MS detection. Chromatography was performed on a C18 monolithic column, with ammonium acetate buffer/methanol as the mobile phase and a chromatographic run time of 6 min/sample. The 4-fold–charged ions were used for multiple reaction monitoring experiments.

Results: The method was linear with injections of 0.01–10 ng. Limits of detection and quantification were 0.02 and 0.07 μg/L for ghrelin, respectively, and 0.03 and 0.35 μg/L for desacyl-ghrelin. Intra- and interday imprecision (CVs) were 9%–4% and 12%–6% at concentrations of 0.33–5.93 μg/L for ghrelin, respectively, and 16%–6% and 15%–8% at concentrations of 1.12–10.02 μg/L for desacyl-ghrelin. The mean (SD) recoveries in plasma of added ghrelin and desacyl-ghrelin were 95.8% (12%) and 101% (1.2%), respectively. Using kinetic modeling, we determined the mean (SD) periods of half-change (t1/2) of ghrelin to be 156 (16) min in EDTA plasma and 49 (1) min in Li-heparin plasma. Bland–Altman analysis showed that the median differences between EIA and liquid chromatography–tandem mass spectrometry (MS/MS) for desacyl-ghrelin were −40% for plasma/serum samples and 85% for cell supernatants and for ghrelin were 6% for enriched plasma samples and 44% for cell supernatants.

Conclusion: Our HPLC-MS/MS procedure has excellent selectivity and sufficient limit of quantification to allow the monitoring of concentration–time profiles in biological matrices.
Multiple Biomarker Use for Detection of Adverse Events in Patients Presenting with Symptoms Suggestive of Acute Coronary Syndrome
Authors: Apple Fred S , Pearce Lesly A , Chung Adrine , Ler Ranka , Murakami MaryAnn M
Published: March 2007

Background: We investigated multiple biomarkers of various pathophysiologic pathways to determine their relationships with adverse outcomes in patients presenting with symptoms of acute coronary syndrome.

Methods: We obtained plasma specimens from 457 patients on admission and measured 7 biomarkers: myeloperoxidase (MPO), soluble CD40 ligand (CD40L), placental growth factor (PlGF), metalloproteinase-9 (MMP-9), high-sensitivity C-reactive protein (hsCRP), cardiac troponin I (cTnI), and N-terminal pro-B-type natriuretic peptide (NT-proBNP). We used the Modification of Diet in Renal Disease formula to calculate the estimated glomerular filtration rate (eGFR). Endpoints were cardiac events (myocardial infarction, percutaneous coronary intervention, coronary artery bypass graft, cardiac death) and all-cause mortality. We estimated cumulative event rates over a 4-month period with the Kaplan–Meier method and relative risk (RR) with the Cox proportional hazards model.

Results: Patients with increased PlGF, NT-proBNP, hsCRP, or cTnI or decreased eGFR had 11% to 20% higher all-cause mortality rates than patients with concentrations within reference intervals: 20.4% (eGFR), 16.0% (PlGF), 15.8% (hsCRP), 12.7% (NT-proBNP), and 11.3% (cTnI; all P ≤0.03). No differences in mortality rates were observed between those with increased vs normal concentrations of MPO, CD40L, or MMP-9. Decreased eGFR (RR 3.4, P = 0.004) and increased NT-proBNP (RR 7.9, P = 0.04) were independently predictive of mortality, and PlGF (RR 2.0, P = 0.08) approached significance. Patients with increased NT-proBNP (12.3%) or cTnI (33.8%) had higher cardiac event rates (each P <0.02), with increased MPO (11.1%) showing a trend (P = 0.09). Patients in whom both cTnI and MPO were increased had a cardiac event rate of 43%.

Conclusion: Multiple biomarkers that are likely indicative of different underlying pathophysiologic mechanisms are independently predictive of increased risk for adverse events in patients with acute coronary syndrome.
Multiplex Genotyping of Cytochrome P450 Single-Nucleotide Polymorphisms by Use of MALDI-TOF Mass Spectrometry
Authors: Misra Ashish , Hong Jun-Yan , Kim Sobin
Published: March 2007

Background: Polymorphisms in cytochrome P450 (CYP450) genes contribute to interindividual differences in the metabolism of xenobiotic chemicals, including the vast majority of drugs, and may lead to toxicity and adverse drug reactions. Studies on these polymorphisms in research and diagnostic settings typically involve large-scale genotyping and hence require high-throughput assays.

Methods: We used the previously developed solid-phase capture–single-base extension (SPC-SBE) approach for concurrent analysis of 40 single-nucleotide polymorphisms (SNPs) of CYP2C9 and 50 SNPs of CYP2A13, both genes belonging to the CYP450 family. Desired SNP-containing regions for each gene were amplified in a single-step multiplex PCR. We designed a library of primers to anneal immediately upstream of the selected SNPs and extended it with biotinylated terminators using PCR products as templates. Biotinylated extension products were isolated by affinity purification and analyzed with MALDI-TOF mass spectrometry to determine SNP genotypes.

Results: We analyzed 11 samples for CYP2C9 and 14 samples for CYP2A13 with unambiguous detection of SNPs in all samples. Many samples showed a high occurrence of heterozygotes for both genes, with as many as 10 of 50 SNPs appearing as heterozygotes in 1 sample genotyped for CYP2A13.

Conclusions: The SPC-SBE method provides an efficient means for genotyping SNPs from the CYP450 family. This approach is suitable for automation and can be extended to other genotyping applications.
Diagnostic Accuracy of Blood Lactate-to-Pyruvate Molar Ratio in the Differential Diagnosis of Congenital Lactic Acidosis
Authors: Debray François-Guillaume , Mitchell Grant A , Allard Pierre , Robinson Brian H , Hanley James A , Lambert Marie
Published: March 2007

Background: Although the blood lactate-to-pyruvate (L:P) molar ratio is used to distinguish between pyruvate dehydrogenase deficiency (PDH-D) and other causes of congenital lactic acidosis (CLA), its diagnostic accuracy for differentiating between these 2 types of CLA has not been evaluated formally.

Methods: We conducted a retrospective study of all patients followed for mitochondrial diseases between 1985 and 2005 in a tertiary care pediatric hospital.

Results: At the recommended cut point of ∼25, individual median L:P ratio demonstrated low sensitivity and specificity (77% and 91%, respectively) for differentiating between patients with enzymatically proven PDH-D (n = 11) and those with mitochondrial disease but normal pyruvate dehydrogenase (PDH) activity (non-PDH; n = 35). We observed a strong positive association between L:P ratio and blood lactate in non-PDH CLA, whereas this association was weak in PDH-D CLA. Consequently, patient classification based on median L:P ratio showed improved diagnostic accuracy at higher lactate concentrations: for lactate <2.5 mmol/L the area under the ROC curve was not statistically different from 0.5 (P = 0.3), whereas it was statistically different for lactate >2.5 mmol/L. In the 2.5 to 5.0 mmol/L lactate category, the sensitivity and specificity at an optimal cut point of 18.4 were 93% (95% CI, 77%–99%) and 71% (95% CI, 20%–96%), respectively; for lactate >5.0 mmol/L, with an optimal cut point of 25.8, sensitivity and specificity were 96% (95% CI, 77%–99%) and 100% (95% CI, 59%–100%), respectively.

Conclusion: Usefulness of the L:P ratio for differentiating non-PDH and PDH-D types of CLA increases at higher lactate concentrations.
Parenting and Cultures of Risk: A Comparative Analysis of Infidelity, Aggression, and Witchcraft
Authors: QUINLAN ROBERT J. , QUINLAN MARSHA B.
Published: March 2007

Parenting behavior may respond flexibly to environmental risk to help prepare children for the environment they can expect to face as adults. In hazardous environments where child outcomes are unpredictable, unresponsive parenting could be adaptive. Child development associated with parenting practices, in turn, may influence cultural patterns related to insecurity and aggression (which we call the “risk‐response model”). We test these propositions in a cross‐cultural analysis. The Standard Cross‐Cultural Sample (SCCS) includes indicators of parental responsiveness: father–infant sleeping proximity, father involvement, parental response to infant crying, and breastfeeding duration (age at weaning). Unresponsive parenting was associated with cultural models including greater acceptance of extramarital sex, aggression, theft, and witchcraft. Socialization practices in later childhood were not better predictors of the outcomes than was earlier parenting. We conclude that some cultural adaptations appear rooted in parenting practices that affect child development.
Book Reviews
Authors: GEERTZ HILDRED
Published: March 2007

Sacred Painting in Bali: Tradition in Transition. Thomas L. Cooper. Bangkok: Orchid Press, 2005. 184 pp.
Book Reviews
Authors: BROWN CLIFFORD T.
Published: March 2007

The Chattahoochee Chiefdoms. John H. Blitz and Karl G. Lorenz. Tuscaloosa: University of Alabama Press, 2006. 328 pp.
Book Reviews
Authors: HAENN NORA
Published: March 2007

Polluted Promises: Environmental Racism and the Search for Justice in. Southern Town. Melissa Checker. New York: New York University Press, 2005. 273 pp.
Book Reviews
Authors: WALSH CASEY
Published: March 2007

Gender, Water, and Development. Anne Coles and Tina Wallace, eds. New York: Berg, 2005. 240 pp.
Book Reviews
Authors: ASHER KIRAN
Published: March 2007

Democracy in Latin America, 1760–1900. Carlos A. Forment. Chicago: University of Chicago Press, 2003. 454 pp.
Book Reviews
Authors: ANGROSINO MICHAEL
Published: March 2007

Caribbean Rum:. Social and Economic History. Frederick H. Smith. Gainesville: University Press of Florida, 2005. 339 pp.
Book Reviews
Authors: BENSON JANET
Published: March 2007

Migration and Economy: Global and Local Dynamics. Lillian Trager, ed. Lanham, MD: AltaMira Press, 2005. 332 pp.
Book Reviews
Authors: FRASER GRACE MORTH
Published: March 2007

Home Cooking in the Global Village: Caribbean Food from Buccaneers to Ecotourists. Richard Wilk. New York: Berg, 2006. 236 pp.
Book Reviews
Authors: ENGLISH‐LUECK J. A.
Published: March 2007

Janitors, Street Vendors, and Activists: The Lives of Mexican Immigrants in Silicon Valley. Christian Zlolniski. Berkeley: University of California Press, 2006. 249 pp.