bluuebunny/crossref_metadata_2025 huggingface dataset:
E2A and CBP/p300 Act in Synergy To Promote Chromatin Accessibility of the Immunoglobulin κ Locus
Authors: Sakamoto Shuji , Wakae Kousho , Anzai Yuki , Murai Kiyohito , Tamaki Nobuyuki , Miyazaki Masaki , Miyazaki Kazuko , Romanow William J. , Ikawa Tomokatsu , Kitamura Daisuke , Yanagihara Itaru , Minato Nagahiro , Murre Cornelis , Agata Yasutoshi
Published: April 2012

V(D)J recombination of Ig and TCR genes is strictly regulated in a lineage- and stage-specific manner by the accessibility of target gene chromatin to the recombinases RAG1 and RAG2. It has been shown that enforced expression of the basic helix–loop–helix protein, E2A, together with RAG1/2 in a nonlymphoid cell line BOSC23 can induce V(D)J recombination in endogenous Igκ and TCR loci by increasing chromatin accessibility of target gene segments. In this study, we demonstrate that ectopically expressed E2A proteins in BOSC23 cells have the ability to bind directly to the promoter and recombination signal sequence of Vκ genes and to recruit histone acetyltransferase CBP/p300. Overexpression of CBP/p300 in conjunction with E2A results in enhancement of E2A-induced histone acetylation, germline transcription, and Igκ rearrangement. Conversely, knockdown of endogenous CBP/p300 expression by small interfering RNA leads to a decrease in histone acetylation, germline transcription and Igκ rearrangement. Furthermore, analyses using a mouse pre-B cell line revealed that endogenous E2A proteins also bind to a distinct set of Vκ genes and regulatory regions in the mouse Igκ locus and act to increase histone acetylation by recruiting p300, confirming the similar findings observed with BOSC23 cells. These observations indicate that E2A plays critical roles in inducing Igκ rearrangement by directly binding to and increasing chromatin accessibility at target gene segments.
Two Preferentially Expressed Proteins Protect Vascular Endothelial Cells from an Attack by Peptide-Specific CTL
Authors: Thommen Daniela S. , Schuster Heiko , Keller Mario , Kapoor Sarika , Weinzierl Andreas O. , Chennakesava Cuddapah S. , Wang Xueya , Rohrer Lucia , von Eckardstein Arnold , Stevanovic Stefan , Biedermann Barbara C.
Published: April 2012

Vascular endothelial cells (EC) are an exposed tissue with intimate contact with circulating Ag-specific CTL. Experimental in vitro and clinical data suggested that endothelial cells present a different repertoire of MHC class I-restricted peptides compared with syngeneic leukocytes or epithelial cells. This endothelial-specific peptide repertoire might protect EC from CTL-mediated cell death. The HLA-A*02-restricted peptide profile of human EC and syngeneic B lymphoblastoid cells was biochemically analyzed and compared. For EC selective peptides, source protein expression, peptide binding affinity, and peptide–HLA-A*02 turnover were measured. The significance of abundant peptide presentation for target cell recognition by immunodominant CTL was tested by small interfering RNA treatment of EC to knock down the source proteins. High amounts of two peptides, PTRF56–64 and CD59106–114, were consistently detected in EC. This predominance of two endothelial peptides was explained by cell type-specific source protein expression that compensated for poor HLA-A*02 binding affinity and short half-live of peptide/HLA-A*02 complexes. Knocking down the source proteins containing the abundant endothelial peptide motifs led to a nearly 100-fold increase of surface expression of SMCY311–319, an immunodominant minor histocompatibility Ag, as detected by cytotoxicity assays using SMCY311–319-specific CTL. We conclude that EC express and present preferentially two distinct HLA-A*02-restricted peptides at extraordinary high levels. These abundant self-peptides may protect EC from CTL-mediated lysis by competing for HLA-A*02 binding sites with immunodominant scarcely expressed antigenic peptides.
Strong Impact of CD4+Foxp3+ Regulatory T Cells and Limited Effect of T Cell-Derived IL-10 on Pathogen Clearance during Plasmodium yoelii Infection
Authors: Abel Simone , Lückheide Nadja , Westendorf Astrid M. , Geffers Robert , Roers Axel , Müller Werner , Sparwasser Tim , Matuschewski Kai , Buer Jan , Hansen Wiebke
Published: April 2012

It is well established that CD4+CD25+Foxp3+ regulatory T cells (Tregs) play a crucial role in the course of different infectious diseases. However, contradictory results have been published regarding to malaria infection. In this study, we report that specific ablation of Foxp3+ Tregs in Plasmodium yoelii-infected DEREG-BALB/c mice leads to an increase in T cell activation accompanied by a significant decrease in parasitemia. To better understand how Foxp3+ Tregs orchestrate this phenotype, we used microarrays to analyze CD4+CD25+Foxp3+ Tregs and CD4+CD25−Foxp3− T cells in the course of P. yoelii infection. Using this approach we identified genes specifically upregulated in CD4+CD25+Foxp3+ Tregs in the course of infection, such as G-protein-coupled receptor 83 and Socs2. This analysis also revealed that both CD4+CD25+Foxp3+ Tregs and CD4+CD25−Foxp3− T cells upregulate CTLA-4, granzyme B, and, more strikingly, IL-10 during acute blood infection. Therefore, we aimed to define the function of T cell-derived IL-10 in this context by Cre/loxP-mediated selective conditional inactivation of the IL-10 gene in T cells. Unexpectedly, IL-10 ablation in T cells exerts only a minor effect on parasite clearance, even though CD8+ T cells are more strongly activated, the production of IFN-γ and TNF-α by CD4+CD25- T cells is increased, and the suppressive activity of CD4+CD25+ Tregs is reduced upon infection. In summary, these results suggest that CD4+Foxp3+ Tregs modulate the course of P. yoelii infection in BALB/c mice. Moreover, CD4+ T cell-derived IL-10 affects T effector function and Treg activity, but has only a limited direct effect on parasite clearance in this model.
CRTH2 Is A Critical Regulator of Neutrophil Migration and Resistance to Polymicrobial Sepsis
Authors: Ishii Makoto , Asano Koichiro , Namkoong Ho , Tasaka Sadatomo , Mizoguchi Kosuke , Asami Takahiro , Kamata Hirofumi , Kimizuka Yoshifumi , Fujiwara Hiroshi , Funatsu Yohei , Kagawa Shizuko , Miyata Jun , Ishii Ken , Nakamura Masataka , Hirai Hiroyuki , Nagata Kinya , Kunkel Steven L. , Hasegawa Naoki , Betsuyaku Tomoko
Published: April 2012

Although arachidonic acid cascade has been shown to be involved in sepsis, little is known about the role of PGD2 and its newly found receptor, chemoattractant receptor-homologous molecule expressed on Th2 cells (CRTH2), on the septic response. Severe sepsis is associated with the failure of neutrophil migration. To investigate whether CRTH2 influences neutrophil recruitment and the lethality during sepsis, sepsis was induced by cecal ligation and puncture (CLP) surgery in mice. CRTH2 knockout (CRTH2−/−) mice were highly resistant to CLP-induced sepsis, which was associated with lower bacterial load and lower production of TNF-α, IL-6, and CCL3. IL-10, an anti-inflammatory cytokine, was higher in CRTH2−/− mice, blunting CLP-induced lethality in CRTH2−/− mice. Neutrophil accumulation in the peritoneum was more pronounced after CLP in CRTH2−/− mice, which was associated with higher CXCR2 levels in circulating neutrophils. Furthermore, sepsis caused a decrease in the level of acetylation of histone H3, an activation mark, at the CXCR2 promoter in wild-type neutrophils, suggesting that CXCR2 expression levels are epigenetically regulated. Finally, both pharmacological depletion of neutrophils and inhibition of CXCR2 abrogated the survival benefit in CRTH2−/− mice. These results demonstrate that genetic ablation of CRTH2 improved impaired neutrophil migration and survival during severe sepsis, which was mechanistically associated with epigenetic-mediated CXCR2 expression. Thus, CRTH2 is a potential therapeutic target for polymicrobial sepsis.
Incorporation of Transmembrane Hydrophobic Mutations in the TCR Enhance Its Surface Expression and T Cell Functional Avidity
Authors: Haga-Friedman Astar , Horovitz-Fried Miryam , Cohen Cyrille J.
Published: April 2012

TCR-gene transfer represents an effective way to redirect the specificity of T lymphocytes for therapeutic purposes. Recent successful clinical trials have underscored the potential of this approach in which efficient expression of the exogenous TCR has been directly linked to the efficacy of T cell activity. It has been also demonstrated that the TCR exhibits a lack of stability associated with the presence of positively charged residues in its transmembrane (TM) region. In this study, we designed an original approach selectively to improve exogenous TCR stability by increasing the hydrophobic nature of the TCRα TM region. Incorporation of hydrophobic residues at evolutionarily permissive positions resulted in an enhanced surface expression of the TCR chains, leading to an improved cellular avidity and anti-tumor TCR activity. Furthermore, this strategy was successfully applied to different TCRs, enabling the targeting of human tumors from different histologies. We also show that the combination of these hydrophobic mutations with another TCR-enhancing approach further improved TCR expression and function. Overall, these findings provide information regarding TCR TM composition that can be applied for the improvement of TCR-gene transfer-based treatments.
Mycobacterium tuberculosisModulates Macrophage Lipid-Sensing Nuclear Receptors PPARγ and TR4 for Survival
Authors: Mahajan Sahil , Dkhar H. Kitdorlang , Chandra Vemika , Dave Sandeep , Nanduri Ravikanth , Janmeja Ashok Kumar , Agrewala Javed N. , Gupta Pawan
Published: April 2012

Mycobacterium tuberculosis–macrophage interactions are key to pathogenesis and clearance of these bacteria. Although interactions between M. tuberculosis-associated lipids and TLRs, non-TLRs, and opsonic receptors have been investigated, interactions of these lipids and infected macrophage lipid repertoire with lipid-sensing nuclear receptors expressed in macrophages have not been addressed. In this study, we report that M. tuberculosis–macrophage lipids can interact with host peroxisome proliferator-activated receptor γ and testicular receptor 4 to ensure survival of the pathogen by modulating macrophage function. These two lipid-sensing nuclear receptors create a foamy niche within macrophage by modulating oxidized low-density lipoprotein receptor CD36, phagolysosomal maturation block by induction of IL-10, and a blunted innate response by alternative polarization of the macrophages, which leads to survival of M. tuberculosis. These results also suggest possible heterologous ligands for peroxisome proliferator-activated receptor γ and testicular receptor 4 and are suggestive of adaptive or coevolution of the host and pathogen. Relative mRNA expression levels of these receptors in PBMCs derived from clinical samples convincingly implicate them in tuberculosis susceptibility. These observations expose a novel paradigm in the pathogenesis of M. tuberculosis amenable for pharmacological modulation.
Prostaglandin E2 Affects T Cell Responses through Modulation of CD46 Expression
Authors: Kickler Karoline , Maltby Kathryn , Ni Choileain Siobhán , Stephen Jillian , Wright Sheila , Hafler David A. , Jabbour Henry N. , Astier Anne L.
Published: April 2012

The ubiquitous protein CD46, a regulator of complement activity, promotes T cell activation and differentiation toward a regulatory Tr1-like phenotype. The CD46-mediated differentiation pathway is defective in several chronic inflammatory diseases, underlying the importance of CD46 in controlling T cell function and the need to understand its regulatory mechanisms. Using an RNA interference-based screening approach in primary T cells, we have identified that two members of the G protein-coupled receptor kinases were involved in regulating CD46 expression at the surface of activated cells. We have investigated the role of PGE2, which binds to the E-prostanoid family of G protein-coupled receptors through four subtypes of receptors called EP 1–4, in the regulation of CD46 expression and function. Conflicting roles of PGE2 in T cell functions have been reported, and the reasons for these apparent discrepancies are not well understood. We show that addition of PGE2 strongly downregulates CD46 expression in activated T cells. Moreover, PGE2 differentially affects T cell activation, cytokine production, and phenotype depending on the activation signals received by the T cells. This was correlated with a distinct pattern of the PGE2 receptors expressed, with EP4 being preferentially induced by CD46 activation. Indeed, addition of an EP4 antagonist could reverse the effects observed on cytokine production after CD46 costimulation. These data demonstrate a novel role of the PGE2–EP4 axis in CD46 functions, which might at least partly explain the diverse roles of PGE2 in T cell functions.
Ceramide Synthase 6 Plays a Critical Role in the Development of Experimental Autoimmune Encephalomyelitis
Authors: Schiffmann Susanne , Ferreiros Nerea , Birod Kerstin , Eberle Max , Schreiber Yannick , Pfeilschifter Waltraud , Ziemann Ulf , Pierre Sandra , Scholich Klaus , Grösch Sabine , Geisslinger Gerd
Published: April 2012

Ceramides are mediators of apoptosis and inflammatory processes. In an animal model of multiple sclerosis (MS), the experimental autoimmune encephalomyelitis (EAE) model, we observed a significant elevation of C16:0-Cer in the lumbar spinal cord of EAE mice. This was caused by a transiently increased expression of ceramide synthase (CerS) 6 in monocytes/macrophages and astroglia. Notably, this corresponds to the clinical finding that C16:0-Cer levels were increased 1.9-fold in cerebrospinal fluid of MS patients. NO and TNF-α secreted by IFN-γ–activated macrophages play an essential role in the development of MS. In murine peritoneal and mouse-derived RAW 264.7 macrophages, IFN-γ–mediated expression of inducible NO synthase (iNOS)/TNF-α and NO/TNF-α release depends on upregulation of CerS6/C16:0-Cer. Downregulation of CerS6 by RNA interference or endogenous upregulation of C16:0-Cer mediated by palmitic acid in RAW 264.7 macrophages led to a significant reduction or increase in NO/TNF-α release, respectively. EAE/IFN-γ knockout mice showed a significant delay in disease onset accompanied by a significantly less pronounced increase in CerS6/C16:0-Cer, iNOS, and TNF-α compared with EAE/wild-type mice. Treatment of EAE mice with l-cycloserine prevented the increase in C16:0-Cer and iNOS/TNF-α expression and caused a remission of the disease. In conclusion, CerS6 plays a critical role in the onset of MS, most likely by regulating NO and TNF-α synthesis. CerS6 may represent a new target for the inhibition of inflammatory processes promoting MS development.
IRF5 Risk Polymorphisms Contribute to Interindividual Variance in Pattern Recognition Receptor-Mediated Cytokine Secretion in Human Monocyte-Derived Cells
Authors: Hedl Matija , Abraham Clara
Published: April 2012

Monocyte-derived cells display highly variable cytokine secretion upon pattern recognition receptor (PRR) stimulation across individuals; such variability likely affects interindividual inflammatory/autoimmune disease susceptibility. To define mechanisms for this heterogeneity, we examined PRR-induced monocyte-derived cell cytokine secretion from a large cohort of healthy individuals. Although cytokine secretion ranged widely among individuals, the magnitude of cytokine induction after individual nucleotide-binding oligomerization domain 2 (Nod2) and TLR2 stimulation (a cohort of 86 individuals) or stimulation of multiple TLRs (a cohort of 77 individuals), either alone or in combination with Nod2, was consistent intraindividually across these stimuli. Nod2 and TLRs signal through IFN regulatory factor 5 (IRF5), and common IRF5 polymorphisms confer risk for autoimmunity. We find that cells from rs2004640 IRF5 risk-associated allele carriers secrete increased cytokines upon individual or synergistic PRR stimulation in a gene dose- and ligand dose-dependent manner in both monocyte-derived dendritic cells and monocyte-derived macrophages. IRF5 expression knockdown in IRF5 risk allele carrier cells significantly decreases PRR-induced cytokines. Moreover, we find that IRF5 knockdown profoundly decreases Nod2-mediated MAPK and NF-κB pathway activation, whereas the PI3K and mammalian target of rapamycin pathways are not impaired. Finally, the IRF5 rs2004640 polymorphism is a major determinant of the variance (r2 = 0.53) in Nod2-induced cytokine secretion by monocyte-derived cells from different individuals. We therefore show a profound contribution of a single gene to the variance in interindividual PRR-induced cytokines. The hyperresponsiveness of IRF5 disease-associated polymorphisms to a wide spectrum of microbial triggers has broad implications on global immunological responses, host defenses against pathogens, and inflammatory/autoimmune disease susceptibility.
TLR9 Provokes Inflammation in Response to Fetal DNA: Mechanism for Fetal Loss in Preterm Birth and Preeclampsia
Authors: Scharfe-Nugent Andrea , Corr Sinéad C. , Carpenter Susan B. , Keogh Louise , Doyle Brendan , Martin Cara , Fitzgerald Katherine A. , Daly Sean , O’Leary John J. , O’Neill Luke A. J.
Published: April 2012

Preterm birth, the major cause of neonatal mortality in developed countries, is associated with intrauterine infections and inflammation, although the exact mechanisms underlying this event are unclear. In this study, we show that circulating fetal DNA, which is elevated in pregnancies complicated by preterm labor or preeclampsia, triggers an inflammatory reaction that results in spontaneous preterm birth. Fetal DNA activates NF-κB, shown by IκBα degradation in human PBMCs resulting in production of proinflammatory IL-6. We show that fetal resorption and preterm birth are rapidly induced in mice after i.p. injection of CpG or fetal DNA (300 μg/dam) on gestational day 10–14. In contrast, TLR9−/− mice were protected from these effects. Furthermore, this effect was blocked by oral administration of the TLR9 inhibitor chloroquine. Our data therefore provide a novel mechanism for preterm birth and preeclampsia, highlighting TLR9 as a potential therapeutic target for these common disorders of pregnancy.
CD13 Regulates Dendritic Cell Cross-Presentation and T Cell Responses by Inhibiting Receptor-Mediated Antigen Uptake
Authors: Ghosh Mallika , McAuliffe Beata , Subramani Jaganathan , Basu Sreyashi , Shapiro Linda H.
Published: April 2012

Dendritic cell (DC) Ag cross-presentation is generally associated with immune responses to tumors and viral Ags, and enhancement of this process is a focus of tumor vaccine design. In this study, we found that the myeloid cell surface peptidase CD13 is highly and specifically expressed on the subset of DCs responsible for cross-presentation, the CD8+ murine splenic DCs. In vivo studies indicated that lack of CD13 significantly enhanced T cell responses to soluble OVA Ag, although development, maturation, and Ag processing and presentation of DCs are normal in CD13KO mice. In vitro studies showed that CD13 regulates receptor-mediated, dynamin-dependent endocytosis of Ags such as OVA and transferrin but not fluid-phase or phagocytic Ag uptake. CD13 and Ag are cointernalized in DCs, but CD13 did not coimmunoprecipitate with Ag receptors, suggesting that CD13 does not control internalization of specific receptors but regulates endocytosis at a more universal level. Mechanistically, we found that phosphorylation of the endocytic regulators p38MAPK and Akt was dysregulated in CD13KO DCs, and blocking of these kinases perturbed CD13-dependent endocytic uptake. Therefore, CD13 is a novel endocytic regulator that may be exploited to enhance Ag uptake and T cell activation to improve the efficacy of tumor-targeted vaccines.
MicroRNA-494 Is Required for the Accumulation and Functions of Tumor-Expanded Myeloid-Derived Suppressor Cells via Targeting of PTEN
Authors: Liu Yang , Lai Lihua , Chen Qingyun , Song Yinjing , Xu Sheng , Ma Feng , Wang Xiaojian , Wang Jianli , Yu Hai , Cao Xuetao , Wang Qingqing
Published: April 2012

Myeloid-derived suppressor cells (MDSCs) potently suppress the anti-tumor immune responses and also orchestrate the tumor microenvironment that favors tumor angiogenesis and metastasis. The molecular networks regulating the accumulation and functions of tumor-expanded MDSCs are largely unknown. In this study, we identified microRNA-494 (miR-494), whose expression was dramatically induced by tumor-derived factors, as an essential player in regulating the accumulation and activity of MDSCs by targeting of phosphatase and tensin homolog (PTEN) and activation of the Akt pathway. TGF-β1 was found to be the main tumor-derived factor responsible for the upregulation of miR-494 in MDSCs. Expression of miR-494 not only enhanced CXCR4-mediated MDSC chemotaxis but also altered the intrinsic apoptotic/survival signal by targeting of PTEN, thus contributing to the accumulation of MDSCs in tumor tissues. Consequently, downregulation of PTEN resulted in increased activity of the Akt pathway and the subsequent upregulation of MMPs for facilitation of tumor cell invasion and metastasis. Knockdown of miR-494 significantly reversed the activity of MDSCs and inhibited the tumor growth and metastasis of 4T1 murine breast cancer in vivo. Collectively, our findings reveal that TGF-β1–induced miR-494 expression in MDSCs plays a critical role in the molecular events governing the accumulation and functions of tumor-expanded MDSCs and might be identified as a potential target in cancer therapy.
Cutting Edge: In the Absence of Regulatory T Cells, a Unique Th Cell Population Expands and Leads to a Loss of B Cell Anergy
Authors: Leonardo Steven M. , De Santis Jessica L. , Malherbe Laurent P. , Gauld Stephen B.
Published: April 2012

The absence of regulatory T cells (Tregs) results in significant immune dysregulation that includes autoimmunity. The mechanism(s) by which Tregs suppress autoimmunity remains unclear. We have shown that B cell anergy, a major mechanism of B cell tolerance, is broken in the absence of Tregs. In this study, we identify a unique subpopulation of CD4+ Th cells that are highly supportive of Ab production and promote loss of B cell anergy. Notably, this novel T cell subset was shown to express the germinal center Ag GL7 and message for the B cell survival factor BAFF, yet failed to express markers of the follicular Th cell lineage. We propose that the absence of Tregs results in the expansion of a unique nonfollicular Th subset of helper CD4+ T cells that plays a pathogenic role in autoantibody production.
Severe Impairment of Leukocyte Recruitment in ppGalNAcT-1–Deficient Mice
Authors: Block Helena , Ley Klaus , Zarbock Alexander
Published: April 2012

P-selectin glycoprotein ligand-1 plays an important role in leukocyte recruitment. Its binding affinity to selectins is modulated by posttranslational modifications. The polypeptide N-acetylgalactosamine transferase-1 (ppGalNAcT-1) initiates core-type protein O-glycosylation. To address whether the glycosylation of P-selectin glycoprotein ligand-1 by ppGalNAcT-1 is important for leukocyte recruitment in vivo, we investigated leukocyte recruitment in untreated and TNF-α–treated cremaster muscles comparing ppGalNAcT-1–deficient mice (Galnt1−/−) and wild-type mice. In untreated and TNF-α–treated Galnt1−/− mice, leukocyte rolling, adhesion, and transmigration were significantly reduced, with markedly increased rolling velocity compared with control mice. L-selectin–dependent leukocyte rolling was completely abolished in Galnt1−/− mice compared with wild-type mice. Thioglycollate-induced peritonitis experiments with chimeric mice revealed that hematopoietic ppGalNAcT-1 is important for leukocyte recruitment. These data show that the loss of ppGalNAcT-1 led to reduced leukocyte rolling and recruitment and increased rolling velocity, suggesting a predominant role for ppGalNAcT-1 in attaching functionally relevant O-linked glycans to selectin ligands.
A narrative hermeneutical adventure: Seafarers and their complex relationship with their families
Authors: Viljoen Chris J. , Müller Julian C.
Published: May 2012

This research project is an attempt to develop a rich understanding about the relationship between seafarers and their families by means of a conversational construction between a number of co-researchers. In order to do this, the question that is explored is: How can there be a better understanding of the lives, the circumstances and the problems that seafarers are experiencing in the relationship with their families? The answer put forward in this research is that this can be accomplished through a narrative approach guided by the ABDCE formula which applies the metaphor of story writing to research. The research was motivated by pastoral and missionary concerns. The epistemologies that informed this research were social constructionism, the narrative approach and postfoundationalism with its emphasis on the interdisciplinary approach. In this article the main character for this research was a seafarer called John1 from Nigeria who was brought into conversation with a number of other co- researchers. The understanding that was developed found that the career choice of seafarers creates problems in their relationship with their family because they become in a sense strangers and outsiders to their loved ones. On the other hand seafarers are empowered, many times through their faith, to handle the challenges of their career, in addition to which this profession offers opportunities that would otherwise not have been possible. The relationship between a seafarer and his or her family was described as a complex one and thin, superficial and stereotypical conclusions were hopefully in the process deconstructed.
Novel Cardiac-Specific Biomarkers and the Cardiovascular Continuum
Authors: Vassiliadis Efstathios , Barascuk Natasha , Didangelos Athanasios , Karsdal Morten A
Published: May 2012

The concept of the cardiovascular continuum, introduced during the early 1990s, created a holistic view of the chain of events connecting cardiovascular-related risk factors with the progressive development of pathological-related tissue remodelling and ultimately, heart failure and death. Understanding of the tissue-specific changes, and new technologies developed over the last 25–30 years, enabled tissue remodelling events to be monitored in vivo and cardiovascular disease to be diagnosed more reliably than before. The tangible product of this evolution was the introduction of a number of biochemical markers such as troponin I and T, which are now commonly used in clinics to measure myocardial damage. However, biomarkers that can detect specific earlier stages of the cardiovascular continuum have yet to be generated and utilised. The majority of the existing markers are useful only in the end stages of the disease where few successful intervention options exist. Since a large number of patients experience a transient underlying developing pathology long before the signs or symptoms of cardiovascular disease become apparent, the requirement for new markers that can describe the early tissue-specific, matrix remodelling process which ultimately leads to disease is evident. This review highlights the importance of relating cardiac biochemical markers with specific time points along the cardiovascular continuum, especially during the early transient phase of pathology progression where none of the existing markers aid diagnosis.
La investigación en Comunicación. Análisis bibliométrico de las revistas de mayor impacto del ISI
Authors: Castillo Esparcia Antonio , Rubio Moraga Ángel , Almansa Martínez Ana
Published: April 2012

Mediante el presente artículo se pretenden analizar algunos de los problemas metodológicos más comunes que se presentan a la hora de evaluar las revistas científicas de comunicación y para ello se han tomado como referencia las 10 publicaciones indexadas en el Social Sciences Citation Index con mayor impacto. Mediante el análisis de contenido se estudiará la procedencia y vinculación académico-investigadora de los autores que aparecen reflejados en estas publicaciones, así como las temáticas de los artículos, los géneros y las metodologías utilizadas. Con todo ello se pretenden dos objetivos principales: por un lado analizar el papel de la evaluación de las publicaciones científicas en el ámbito de la comunicación en los procesos de valoración de la investigación lo que nos permitirá poner de manifiesto las dificultades de aplicación de los métodos bibliométricos de repercusión aplicados por la base de datos de Thomson Scientific y, por otro lado, establecer un marco de desarrollo de las publicaciones científicas españolas en el ámbito de la comunicación que cumplen algunos de los requisitos indicados pero que, bien porque su factor de impacto es aún bajo, o bien porque carecen de difusión internacional aún no han sido registradas en el Social Sciences Citation Index. Está investigación ha contado con financiación del Instituto de Investigación en Relaciones Públicas de la Universidad de Málaga.
Nacionalismo e ideología en la prensa vasca a través de la guerra de Malvinas
Authors: Canga Larequi Jesús
Published: April 2012

Este artículo es fruto de la investigación llevada a cabo tras la catalogación y el análisis de la información subjetiva (editoriales y artículos de opinión) que publicaron los cinco diarios vascos de referencia en la Comunidad Autónoma Vasca durante los 68 días que duró la guerra anglo-argentina. El estudio se desarrolla sobre un conjunto de 309 ejemplares de diarios, publicados entre el 3 de abril y el 22 de junio de 1982, con un total de 799 páginas analizadas.
Molecular Characterization of Diarrheagenic Escherichia coli from Libya
Authors: Ali Mostafa Mohamed M. , Mohamed Zienat Kamel , Klena John D. , Ahmed Salwa Fouad , Moussa Tarek A. A. , Ghenghesh Khalifa Sifaw
Published: May 2012

Diarrheagenic Escherichia coli (DEC) are important enteric pathogens that cause a wide variety of gastrointestinal diseases, particularly in children. Escherichia coli isolates cultured from 243 diarrheal stool samples obtained from Libyan children and 50 water samples were screened by polymerase chain reaction (PCR) for genes characteristic of enteroaggregative E. coli (EAEC), enteropathogenic E. coli (EPEC), enterotoxigenic E. coli (ETEC), enterohemorrhagic E. coli (EHEC), and enteroinvasive E. coli (EIEC). The DEC were detected in 21 (8.6%) children with diarrhea; 10 (4.1%) cases were identified as EAEC, 3 (1.2%) as EPEC, and 8 (3.3%) were ETEC; EHEC, and EIEC were not detected. All DEC were grouped phylogenetically by PCR with the majority (> 70%) identified as phylogenetic groups A and B1. The EAEC isolates were also tested for eight genes associated with virulence using PCR. Multi-virulence (≥ 3 virulence factors) was found in 50% of EAEC isolates. Isolated EAEC possessed different virulence traits and belonged to different phylogenetic groups indicating their heterogeneity.
Medicolegal Issues in Obstetric and Gynecologic Ultrasound
Authors: Chervenak Frank A , Chervenak Judith L
Published: May 2012

Professional liability risks exist in the practice of ultrasound. In this article, basic aspects of medical negligence are reviewed. The guidelines published by ACOG and AIUM are presented and discussed relating to the importance of instrumentation and safety, documentation, and indications for first, second and third trimester ultrasound examinations as well at the content of these examinations. Litigation related to ultrasound is presented and the controversial nonmedical use of ultrasonography is discussed.

How to cite this article

Chervenak FA, Chervenak JL. Medicolegal Issues in Obstetric and Gynecologic Ultrasound. Donald School J Ultrasound Obstet Gynecol 2012;6(1):9-13.
Effect of Maternal Fever on Fetal Behavior Assessed by KANET Test
Authors: Honemeyer Ulrich , Talic Amira
Published: May 2012

Objective of the study was to assess the possible effect of maternal fever without clinical chorioamnionitis on fetal behavior. In a period of 18 months, in a prospective longitudinal cohort study, Kurjak antenatal neurological test (KANET) was applied to assess fetal behavior in both normal pregnancies and pregnancies complicated by maternal fever. According to the primary localization of the infection, maternal fever group was divided into four groups: Respiratory tract infection, urinary tract infection, malaria and gastrointestinal tract infection. According to KANET test, fetuses with scores >14 were considered normal, 6 to 13 borderline and abnormal, if KANET scores were <5. Differences between groups were examined by Mann-Whitney U-test, differences between subgroups by Steel test. KANET scores differed statistically significant between two main groups. The largest proportion of abnormal KANET scores was found in pregnancies complicated by malaria, while the largest proportion of borderline scores showed fetuses from pregnancies complicated by urinary tract infection. There was no statistical significant difference in KANET scores between the control group and fetuses from pregnancies complicated by respiratory tract infection. KANET test has been shown to be a reliable means to distinguish normal and abnormal fetal behavior. Postnatal follow-up should confirm the data from prenatal assessment of fetal behavior.

How to cite this article

Talic A, Kurjak A, Honemeyer U. Effect of Maternal Fever on Fetal Behavior Assessed by KANET Test. Donald School J Ultrasound Obstet Gynecol 2012;6(2):160-165.
Role of Ultrasound in the Assessment of Postmenopausal Bleeding
Authors: Appleton Kallie
Published: May 2012

Uterine bleeding is a symptom seen by gynecologists in approximately 70% of their visits with women of peri and postmenopausal age. A common symptom, postmenopausal bleeding sometimes can be indicative of malignant pathology. While traditional diagnosis took place via endometrial biopsy, diagnosis is trending toward the use of ultrasound. Benefits of ultrasound include its noninvasive nature, decreased cost, and increased accuracy in diagnosis of postmenopausal bleeding. We present a case-based approach to the usage of various ultrasonography techniques including 2D and color Doppler ultrasound, saline infusion sonography (SIS), 3D and 3D power Doppler ultrasound, as complements to traditional diagnosis of endometrial biopsy. In each of the cases, ultrasonography reveals the diagnosis of postmenopausal pathologies, including atrophic endometrium, endometrial polyps, endometrial hyperplasia, and the malignant pathology, such as endometrial carcinoma, uterine leiomyosarcoma and cervical carcinoma. By the end of our case-based discussion, learners are encouraged to test their knowledge in self-assessment quiz.

How to cite this article

Appleton K, Plavsic SK. Role of Ultrasound in the Assessment of Postmenopausal Bleeding. Donald School J Ultrasound Obstet Gynecol 2012;6(2):197-206.
Juvenile Scleredema of Buschke
Authors: Rani J Dhanuja , Patil Suneel G , Murthy ST Srinivas , Koshy Ajit V , Nagpal Deepak , Gupta Sheeba
Published: May 2012

Aim

To recognize a line of treatment for scleredema of Buschke in an adolescent.

Background

Scleredema of Buschke is an uncommon disorder characterized by induration of the skin, which includes a non pitting hardening of the skin around the neck, shoulders, and trunk sometimes the face. Three variants are recognized. The histopathologic features of scleredema are characterized by thickened collagen bundles within the reticular dermis that are separated by mucin containing fenestrations. No consistent treatment modality is currently followed.

Case report

The present case report describes scleredema of Buschke in a 10-year-old female child reported with stiffness of facial skin and difficulty in opening the mouth. The patient was treated with antibiotics and vitamin supplements and there was drastic improvement with decrease in skin stiffness and increase in mouth opening. The stiffness of facial muscles decreased and mouth opening increased.

Conclusion

Multiple treatment modalities for scleredema have been used. In the present case, high-dose antibiotic therapy was used with good prognosis.

Clinical significance

High-dose antibiotic therapy can be used for treatment of dermatologic disorders with reasonably good prognosis.

How to cite this article

Rani JD, Patil SG, Murthy STS, Koshy AV, Nagpal D, Gupta S. Juvenile Scleredema of Buschke. J Contemp Dent Pract 2012;13(1):111-114.
Management of Dens Invaginatus Type III with Large Periradicular Lesion
Authors: de Souza Falcão Luciana , de Freitas Priscila Sousa , de Oliveira Marreiro Raquel , Garrido Ângela Delfina Bittencourt
Published: May 2012

Aim

This study describes a clinical case of type III dens invaginatus with an extensive periradicular lesion treated successfully.

Background

Dens invaginatus is a maldevelopment of the dental germ which occurs as a result of the invagination of the enamel organ. These cases may present difficulties with respect to its diagnosis and treatment because of canal morphology. The success of endodontic therapy requires a knowledge of dental anatomy and its anomalies.

Case report

A 17-year-old female patient is reported presenting right maxillary lateral incisor (tooth no. 7) classified as type III dens invaginatus with necrotic pulp and presence of an extensive radiolucid lesion. Endodontic treatment was recommended for tooth. However, intracanal exudate was present, suggesting a resistant infection. Enucleation of the lesion was performed as a complementary approach. The root canal obturation was carried out by the gutta-percha thermoplastification technique with root canal sealer, followed by restoration of the tooth. Healing of the lesion with hard tissue formation was confirmed at follow-up.

Conclusion

A combination of endodontic and surgical treatments were fundamental to the maintenance of the tooth. The treatment was considered successful.

Clinical significance

Root canal therapy of dens invaginatus should be based on a thorough clinical and radiographic evaluation. The knowledge of classification and anatomical variations of teeth with dens invaginatus are of great importance for correct treatment.

How to cite this article

de Souza Falcão L, de Freitas PS, de Oliveira Marreiro R, Garrido ÂDB. Management of Dens Invaginatus Type III with Large Periradicular Lesion. J Contemp Dent Pract 2012;13(1):119-124.
Fracture Strength of Three All-Ceramic Systems: Top-Ceram compared with IPS-Empress and In-Ceram
Authors: Quran Firas Al , Haj-Ali Reem
Published: May 2012

Purpose

The purpose of this study was to investigate the fracture loads and mode of failure of all-ceramic crowns fabricated using Top-Ceram and compare it with all-ceramic crowns fabricated from well-established systems: IPS-Empress II, In-Ceram.

Materials and methods

Thirty all-ceramic crowns were fabricated; 10 IPS-Empress II, 10 In-Ceram alumina and 10 Top-Ceram. Instron testing machine was used to measure the loads required to introduce fracture of each crown.

Results

Mean fracture load for In-Ceram alumina [941.8 (± 221.66) N] was significantly (p < 0.05) higher than those of Top-Ceram and IPS-Empress II. There was no statistically significant difference between Top-Ceram and IPS-Empress II mean fracture loads; 696.20 (+222.20) and 534 (+110.84) N respectively. Core fracture pattern was highest seen in Top- Ceram specimens.

How to cite this article

Quran AF, Haj-Ali R. Fracture Strength of Three All-Ceramic Systems: Top-Ceram Compared with IPSEmpress and In-Ceram. J Contemp Dent Pract 2012;13(2): 210-215.
Evaluating the influences of biomass burning during 2006 BASE-ASIA: a regional chemical transport modeling
Authors: Fu J. S. , Hsu N. C. , Gao Y. , Huang K. , Li C. , Lin N.-H. , Tsay S.-C.
Published: May 2012

Abstract. To evaluate the impact of biomass burning from Southeast Asia to East Asia, this study conducted numerical simulations during NASA's 2006 Biomass-burning Aerosols in South-East Asia: Smoke Impact Assessment (BASE-ASIA). Two typical episode periods (27–28 March and 13–14 April) were examined. Two emission inventories, FLAMBE and GFED, were used in the simulations. The influences during two episodes in the source region (Southeast Asia) contributed to the surface CO, O3 and PM2.5 concentrations as high as 400 ppbv, 20 ppbv and 80 μg m−3, respectively. The perturbations with and without biomass burning of the above three species during the intense episodes were in the range of 10 to 60%, 10 to 20% and 30 to 70%, respectively. The impact due to long-range transport could spread over the southeastern parts of East Asia and could reach about 160 to 360 ppbv, 8 to 18 ppbv and 8 to 64 μg m−3 on CO, O3 and PM2.5, respectively; the percentage impact could reach 20 to 50% on CO, 10 to 30% on O3, and as high as 70% on PM2.5. In March, the impact of biomass burning mainly concentrated in Southeast Asia and southern China, while in April the impact becomes slightly broader and even could go up to the Yangtze River Delta region. Two cross-sections at 15° N and 20° N were used to compare the vertical flux of biomass burning. In the source region (Southeast Asia), CO, O3 and PM2.5 concentrations had a strong upward transport from surface to high altitudes. The eastward transport becomes strong from 2 to 8 km in the free troposphere. The subsidence process during the long-range transport contributed 60 to 70%, 20 to 50%, and 80% on CO, O3 and PM2.5, respectively to surface in the downwind area. The study reveals the significant impact of Southeastern Asia biomass burning on the air quality in both local and downwind areas, particularly during biomass burning episodes. This modeling study might provide constraints of lower limit. An additional study is underway for an active biomass burning year to obtain an upper limit and climate effects.
Spatial variation of aerosol optical properties around the high-alpine site Jungfraujoch (3580 m a.s.l.)
Authors: Zieger P. , Kienast-Sjögren E. , Starace M. , von Bismarck J. , Bukowiecki N. , Baltensperger U. , Wienhold F. G. , Peter T. , Ruhtz T. , Collaud Coen M. , Vuilleumier L. , Maier O. , Emili E. , Popp C. , Weingartner E.
Published: May 2012

Abstract. This paper presents results of the extensive field campaign CLACE 2010 (Cloud and Aerosol Characterization Experiment) performed in summer 2010 at the Jungfraujoch (JFJ) and the Kleine Scheidegg (KLS) in the Swiss Alps. The main goal of this campaign was to investigate the vertical variability of aerosol optical properties around the JFJ and to show the consistency of the different employed measurement techniques considering explicitly the effects of relative humidity (RH) on the aerosol light scattering. Various aerosol optical and microphysical parameters were recorded using in-situ and remote sensing techniques. In-situ measurements of aerosol size distribution, light scattering, light absorption and scattering enhancement due to water uptake were performed at the JFJ at 3580 m (a.s.l.). A unique set-up allowed remote sensing measurements of aerosol columnar and vertical properties from the KLS located about 1500 m below and within the line of sight to the JFJ (horizontal distance of approx. 4.5 km). In addition, two satellite retrievals from the Spinning Enhanced Visible and Infrared Imager (SEVIRI) and the Moderate Resolution Imaging Spectroradiometer (MODIS) as well as back trajectory analyses were added to the comparison to account for a wider geographical context. All in-situ and remote sensing measurements were in clear correspondence. The ambient extinction coefficient measured in-situ at the JFJ agreed well with the KLS-based LIDAR (Light Detection and Ranging) retrieval at the altitude-level of the JFJ under plausible assumptions on the LIDAR ratio. However, we can show that the quality of this comparison is affected by orographic effects due to the exposed location of the JFJ on a saddle between two mountains and next to a large glacier. The local RH around the JFJ was often higher than in the optical path of the LIDAR measurement, especially when the wind originated from the south via the glacier, leading to orographic clouds which remained lower than the LIDAR beam. Furthermore, the dominance of long-range transported Saharan dust was observed in all measurements for several days, however only for a shorter time period in the in-situ measurements due to the vertical structure of the dust plume. The optical properties of the aerosol column retrieved from SEVIRI and MODIS showed the same magnitude and a similar temporal evolution as the measurements at the KLS and the JFJ. Remaining differences are attributed to the complex terrain and simplifications in the aerosol retrieval scheme in general.
Long-term volatility measurements of submicron atmospheric aerosol in Hyytiälä, Finland
Authors: Häkkinen S. A. K. , Äijälä M. , Lehtipalo K. , Junninen H. , Backman J. , Virkkula A. , Nieminen T. , Vestenius M. , Hakola H. , Ehn M. , Worsnop D. R. , Kulmala M. , Petäjä T. , Riipinen I.
Published: May 2012

Abstract. The volatility of atmospheric 20–500 nm aerosol particles was investigated at a boreal forest site in Hyytiälä, Finland. Measurements were performed continuously between January 2008 and May 2010. The ambient aerosol sample was heated step-wise to six temperatures ranging from 80 °C to 280 °C and the total mass concentration of aerosol particles was determined from the measured particle number size distributions before and after heating assuming particle density of 1.6 g cm−3. On average 19% of the total aerosol mass stayed in the condensed phase even after heating to 280 °C. The observed non-volatile residual at 280 °C had a seasonal pattern; during winter the aerosol mass fraction remaining after heating was the highest and during summer the lowest. Black carbon concentrations correlated positively with the non-volatile fraction of the aerosol, but could not explain the presence of the non-volatile material completely: most of the time a notable fraction of the non-volatile residual was something else than black carbon. Using additional information on ambient meteorological conditions and trajectories, and results from an Aerodyne aerosol mass spectrometer (AMS), the chemical composition of the non-volatile residual and its seasonal behavior was further examined. During winter and spring months the non-volatile mass fraction had a marked positive linear correlation with pollutant trace gases, such as CO, SO2 and NOx. This suggests an anthropogenic influence on the non-volatile fraction of the aerosol in winter and spring. The anthropogenic effect on the formation of the low-volatility material was furthermore supported by observed correlation between the non-volatile residual and the mass fractions of poly-aromatic hydrocarbons (PAHs) sampled simultaneously at the site. During the fall the aerosol particles had relatively more non-volatile material in them when the aerosol mass fractions of organic nitrate and organics in the AMS data were high, and when the measurement site was influenced by clean air masses passing over the forest. Thus, the existence of very low volatile organic nitrates in the aerosol phase can be speculated.