bluuebunny/crossref_metadata_2025_split huggingface dataset:
Oral Care Interventions and Oropharyngeal Colonization in Children Receiving Mechanical Ventilation
Authors: Pedreira Mavilde L.G. , Kusahara Denise M. , de Carvalho Werther Brunow , Núñez Silvia Cristina , Peterlini Maria Angélica S. 
Published: June 2009

Background Recent progress in identification of oral microorganisms has shown that the oropharynx can be a site of origin for dissemination of pathogenic organisms to distant body sites, such as the lungs.Objective To compare the oropharyngeal microbiological profile, duration of mechanical ventilation, and length of stay in the intensive care unit of children receiving mechanical ventilation who had pharmacological or nonpharmacological oral care.Methods A randomized and controlled study was performed in a pediatric intensive unit in São Paulo, Brazil. A total of 56 children were randomly assigned to an experimental group (n=27, 48%) that received oral care with use of 0.12% chlorhexidine digluconate or a control group (n=29, 52%) that received oral care without an antiseptic. Oropharyngeal secretions were collected and cultured on days 0, 2, and 4, and at discharge.Results The 2 groups had similar demographic characteristics, preexisting underlying diseases, and pharmacological, nutritional, and ventilatory support. Gram-negative bacteria were the predominant pathogens: Acinetobacter baumannii, Pseudomonas aeruginosa, Klebsiella pneumoniae, and Enter-obacter species. The 2 groups did not differ significantly in the colonization of normal (P= .72) or pathogenic (P= .62) flora, in the duration of mechanical ventilation (P= .67), or in length of stay in the intensive care (P= .22).Conclusion Use of chlorhexidine combined with nonpharmacological oral care did not decrease the colonization profile, duration of mechanical ventilation, or length of stay in critically ill children receiving mechanical ventilation.
Living With Depressive Symptoms: Patients With Heart Failure
Authors: Dekker Rebecca L. , Peden Ann R. , Lennie Terry A. , Schooler Mary P. , Moser Debra K. 
Published: June 2009

Background Patients with heart failure often experience depressive symptoms that affect health-related quality of life, morbidity, and mortality. Researchers have not described the experience of patients with heart failure living with depressive symptoms. Understanding this experience will help in developing interventions to decrease depressive symptoms.Objective To describe the experience of patients with heart failure living with depressive symptoms.Methods This study was conducted by using a qualitative descriptive design. The sample consisted of 10 outpatients (50% female, mean age 63 [SD, 13] years, 70% New York Heart Association class III or IV) with heart failure who were able to describe depressive symptoms. Data were collected via taped, individual, 30- to 60-minute interviews. ATLAS ti (version 5) was used for content analysis.Results Participants described emotional and somatic symptoms of depression. Negative thinking was present in all participants and reinforced their depressed mood. The participants experienced multiple stressors that worsened depressive symptoms. The overarching strategy for managing depressive symptoms was “taking my mind off of it.” Patients managed depressive symptoms by engaging in activities such as exercise and reading, and by using positive thinking, spirituality, and social support.Conclusions Patients with heart failure experience symptoms of depression that are similar to those experienced by the general population. Clinicians should assess patients with heart failure for stressors that worsen depressive symptoms. Strategies that researchers and clinicians can use to reduce depressive symptoms in patients with heart failure include engaging patients in activities, positive thinking, and spirituality. Helping patients find enhanced social support may also be important.
TLR2 Is a Negative Regulator of Th17 Cells and Tissue Pathology in a Pulmonary Model of Fungal Infection
Authors: Loures Flávio V. , Pina Adriana , Felonato Maíra , Calich Vera L. G. 
Published: June 2009

Abstract
To study the role of TLR2 in a experimental model of chronic pulmonary infection, TLR2-deficient and wild-type mice were intratracheally infected with Paracoccidioides brasiliensis, a primary fungal pathogen. Compared with control, TLR2−/− mice developed a less severe pulmonary infection and decreased NO synthesis. Equivalent results were detected with in vitro-infected macrophages. Unexpectedly, despite the differences in fungal loads both mouse strains showed equivalent survival times and severe pulmonary inflammatory reactions. Studies on lung-infiltrating leukocytes of TLR2−/− mice demonstrated an increased presence of polymorphonuclear neutrophils that control fungal loads but were associated with diminished numbers of activated CD4+ and CD8+ T lymphocytes. TLR2 deficiency leads to minor differences in the levels of pulmonary type 1 and type 2 cytokines, but results in increased production of KC, a CXC chemokine involved in neutrophils chemotaxis, as well as TGF-β, IL-6, IL-23, and IL-17 skewing T cell immunity to a Th17 pattern. In addition, the preferential Th17 immunity of TLR2−/− mice was associated with impaired expansion of regulatory CD4+CD25+FoxP3+ T cells. This is the first study to show that TLR2 activation controls innate and adaptive immunity to P. brasiliensis infection. TLR2 deficiency results in increased Th17 immunity associated with diminished expansion of regulatory T cells and increased lung pathology due to unrestrained inflammatory reactions.
Significance of N-Terminal Proteolysis of CCL14a to Activity on the Chemokine Receptors CCR1 and CCR5 and the Human Cytomegalovirus-Encoded Chemokine Receptor US28
Authors: Richter Rudolf , Casarosa Paola , Ständker Ludger , Münch Jan , Springael Jean-Yves , Nijmeijer Saskia , Forssmann Wolf-Georg , Vischer Henry F. , Vakili Jalal , Detheux Michel , Parmentier Marc , Leurs Rob , Smit Martine J. 
Published: June 2009

Abstract
The CC chemokine CCL14a is constitutively expressed in a large variety of tissues and its inactive proform CCL14a(1–74) circulates in high concentrations in plasma. CCL14a(1–74) is converted into CCL14a(9–74) by the proteases urokinase-type plasminogen activator and plasmin and is a highly active agonist for the chemokine receptors CCR1 and CCR5. In this study, a new CCL14a analog, CCL14a(12–74), was isolated from blood filtrate. To elucidate the functional role of the N terminus, a panel of N-terminally truncated CCL14a analogs were tested on the receptors CCR1 to CCR5 and on the human cytomegalovirus (HCMV)-encoded chemokine receptor US28. The rank order of binding affinity to these receptors and of the activation of CCR1 and CCR5-mediated intracellular Ca2+ concentration mobilization is CCL14a(6–74)&lt;(7–74)&lt;(8–74)≪(9–74) = (10–74)≫(11–74)≫(12–74). The almost identical affinities of CCL14a(7–74), CCL14a(9–74), and CCL14a(10–74) for the US28 receptor and the inhibition of US28-mediated HIV infection of 293T cells by all of the N-terminally truncated CCL14a analogs support the promiscuous nature of the viral chemokine receptor US28. In high concentrations, CCL14a(12–74) did reveal antagonistic activity on intracellular Ca2+ concentration mobilization in CCR1- and CCR5-transfected cells, which suggests that truncation of Tyr11 might be of significance for an efficient inactivation of CCL14a. A putative inactivation pathway of CCL14a(9–74) to CCL14a(12–74) may involve the dipeptidase CD26/dipeptidyl peptidase IV (DPPIV), which generates CCL14a(11–74), and the metalloprotease aminopeptidase N (CD13), which displays the capacity to generate CCL14a(12–74) from CCL14a(11–74). Our results suggest that the activity of CCL14a might be regulated by stringent proteolytic activation and inactivation steps.
Expression of a Modified Form of CD4 Results in the Release of an Anti-HIV Factor Derived from the Env Sequence
Authors: Zaldívar Irene , Muñoz-Fernández María Ángeles , Alarcón Balbino , San José Ester 
Published: June 2009

AbstractWe have studied the inhibitory effect of a CD4 chimera (CD4ε15) on HIV replication. This chimera is retained in the endoplasmic reticulum and traps the HIV envelope precursor gp160, preventing its maturation. Retroviral expression of the chimera strongly inhibited HIV replication even when it is expressed by only a minority of the T cell population. This protective effect on bystander nontransduced cells is mediated by a soluble factor that we identified as a fragment of HIV gp120 envelope protein and accordingly, we named this factor Env-derived antiviral factor (EDAF). Biochemical and immunoreactivity data show that EDAF is comprised of the gp120 C3-C5 regions and indeed, a recombinant protein bearing this sequence reproduces the anti-HIV properties of EDAF. Surprisingly, three tryptic peptides derived from EDAF are homologous but not identical with the corresponding sequences of the HIV isolate used to generate EDAF. We propose that EDAF results from an alternative intracellular processing of the Env protein provoked by its association to CD4ε15 and the selection of the best fitted Env protein sequences contained within the HIV isolate. The presence of EDAF improves the therapeutic potential of the CD4ε15 gene and it opens new possibilities for antiviral treatment and vaccine development.
Identification of a Novel IL-1 Cytokine Family Member in Teleost Fish
Authors: Wang Tiehui , Bird Steve , Koussounadis Antonis , Holland Jason W. , Carrington Allison , Zou Jun , Secombes Christopher J. 
Published: June 2009

Abstract
A novel IL-1 family member (nIL-1F) has been discovered in fish, adding a further member to this cytokine family. The unique gene organization of nIL-1F, together with its location in the genome and low homology to known family members, suggests that this molecule is not homologous to known IL-1F. Nevertheless, it contains a predicted C-terminal β-trefoil structure, an IL-1F signature region within the final exon, a potential IL-1 converting enzyme cut site, and its expression level is clearly increased following infection, or stimulation of macrophages with LPS or IL-1β. A thrombin cut site is also present and may have functional relevance. The C-terminal recombinant protein antagonized the effects of rainbow trout rIL-1β on inflammatory gene expression in a trout macrophage cell line, suggesting it is an IL-1β antagonist. Modeling studies confirmed that nIL-1F has the potential to bind to the trout IL-1RI receptor protein, and may be a novel IL-1 receptor antagonist.
Propionic Acid Secreted from Propionibacteria Induces NKG2D Ligand Expression on Human-Activated T Lymphocytes and Cancer Cells
Authors: Andresen Lars , Hansen Karen Aagaard , Jensen Helle , Pedersen Stine Falsig , Stougaard Peter , Hansen Helle Rüsz , Jurlander Jesper , Skov Søren 
Published: June 2009

Abstract
We found that propionic acid secreted from propionibacteria induces expression of the NKG2D ligands MICA/B on activated T lymphocytes and different cancer cells, without affecting MICA/B expression on resting peripheral blood cells. Growth supernatant from propionibacteria or propionate alone could directly stimulate functional MICA/B surface expression and MICA promoter activity by a mechanism dependent on intracellular calcium. Deletion and point mutations further demonstrated that a GC-box motif around −110 from the MICA transcription start site is essential for propionate-mediated MICA promoter activity. Other short-chain fatty acids such as lactate, acetate, and butyrate could also induce MICA/B expression. We observed a striking difference in the molecular signaling pathways that regulate MICA/B. A functional glycolytic pathway was essential for MICA/B expression after exposure to propionate and CMV. In contrast, compounds with histone deacetylase-inhibitory activity such as butyrate and FR901228 stimulated MICA/B expression through a pathway that was not affected by inhibition of glycolysis, clearly suggesting that MICA/B is regulated through different molecular mechanisms. We propose that propionate, produced either by bacteria or during cellular metabolism, has significant immunoregulatory function and may be cancer prophylactic.
IL-33 Enhances Lipopolysaccharide-Induced Inflammatory Cytokine Production from Mouse Macrophages by Regulating Lipopolysaccharide Receptor Complex
Authors: Espinassous Quentin , Garcia-de-Paco Elvira , Garcia-Verdugo Ignacio , Synguelakis Monique , von Aulock Sonja , Sallenave Jean-Michel , McKenzie Andrew N. J. , Kanellopoulos Jean 
Published: June 2009

Abstract
Bacterial LPS triggers monocytes and macrophages to produce several inflammatory cytokines and mediators. However, once exposed to LPS, they become hyporesponsive to a subsequent endotoxin challenge. This phenomenon is defined as LPS desensitization or tolerance. Previous studies have identified some components of the biochemical pathways involved in negative modulation of LPS responses. In particular, it has been shown that the IL-1R-related protein ST2 could be implicated in LPS tolerance. The natural ligand of ST2 was recently identified as IL-33, a new member of the IL-1 family. In this study, we investigated whether IL-33 triggering of ST2 was able to induce LPS desensitization of mouse macrophages. We found that IL-33 actually enhances the LPS response of macrophages and does not induce LPS desensitization. We demonstrate that this IL-33 enhancing effect of LPS response is mediated by the ST2 receptor because it is not found in ST2 knockout mice. The biochemical consequences of IL-33 pretreatment of mouse macrophages were investigated. Our results show that IL-33 increases the expression of the LPS receptor components MD2 (myeloid differentiation protein 2) and TLR-4, the soluble form of CD14 and the MyD88 adaptor molecule. In addition, IL-33 pretreatment of macrophages enhances the cytokine response to TLR-2 but not to TLR-3 ligands. Thus, IL-33 treatment preferentially affects the MyD88-dependent pathway activated by the TLR.
SUMO Conjugation Contributes to Immune Deviation in Nonobese Diabetic Mice by Suppressing c-Maf Transactivation of IL-4
Authors: Leavenworth Jianmei W. , Ma Xiaojing , Mo Yin-yuan , Pauza Mary E. 
Published: June 2009

Abstract
It is not clear why the development of protective Th2 cells is poor in type 1 diabetes (T1D). c-Maf transactivates the IL-4 gene promoting Th2 cell development; therefore, abnormalities in c-Maf may contribute to reduced IL-4 production by CD4 cells from nonobese diabetic (NOD) mice. In this study we demonstrate that despite normal expression, c-Maf binds poorly to the IL-4 promoter (IL-4p) in NOD CD4 cells. Immunoblotting demonstrates that c-Maf can be modified at lysine 33 by SUMO-1 (small ubiquitin-like modifier 1). Sumoylation is facilitated by direct interaction with the E2-conjugating enzyme Ubc9 and increases following T cell stimulation. In transfected cells, sumoylation decreases c-Maf transactivation of IL-4p-driven luciferase reporter activity, reduces c-Maf binding to the IL-4p in chromatin immunoprecipitation assays, and enhances c-Maf localization into promyelocytic leukemia nuclear bodies. Sumoylation of c-Maf is increased in NOD CD4 cells as compared with CD4 cells from diabetes-resistant B10.D2 mice, suggesting that increased c-Maf sumoylation contributes to immune deviation in T1D by reducing c-Maf access to and transactivation of the IL-4 gene.
The Polarity Protein Par1b/EMK/MARK2 Regulates T Cell Receptor-Induced Microtubule-Organizing Center Polarization
Authors: Lin Joseph , Hou Kirk K. , Piwnica-Worms Helen , Shaw Andrey S. 
Published: June 2009

Abstract
Engagement of a T cell to an APC induces the formation of an immunological synapse as well as reorientation of the microtubule-organizing center (MTOC) toward the APC. How signals emanating from the TCR induce MTOC polarization is not known. One group of proteins known to play a critical role in asymmetric cell division and cell polarization is the partitioning defective (Par) family of proteins. In this study we found that Par1b, a member of the Par family of proteins, was inducibly phosphorylated following TCR stimulation. This phosphorylation resulted in 14-3-3 protein binding and caused the relocalization of Par1b from the membrane into the cytoplasm. Because a dominant-negative form of Par1b blocked TCR-induced MTOC polarization, our data suggest that Par1b functions in the establishment of T cell polarity following engagement to an APC.
Progesterone Inhibits Activation-Induced Deaminase by Binding to the Promoter
Authors: Pauklin Siim , Petersen-Mahrt Svend K. 
Published: June 2009

Abstract
Regulation of activation-induced deaminase (AID), an essential factor in Ig diversification, can alter not only somatic hypermutation and class switch recombination (CSR), but may also influence oncogenesis. AID deaminates cytosine to uracil in the Ig locus, thereby initiating Ig diversification. Unregulated AID can induce oncogenic DNA alterations in Ig and non-Ig loci, leading to mutations, recombination, and translocations. In this study, we demonstrate that AID mRNA production in activated mouse splenic B cells can be reduced by treatment with the sex hormone progesterone. This down-regulation is independent of translation or splicing and is predominantly achieved by inhibiting transcription. During cell treatment we could detect progesterone receptor bound to the AID promoter in proximity to NF-κB binding. Importantly, the progesterone-induced repression was also extended to the protein level of AID and its activity on somatic hypermutation and class switch recombination.
Annexin-1 Regulates Macrophage IL-6 and TNF via Glucocorticoid-Induced Leucine Zipper
Authors: Yang Yuan H. , Aeberli Daniel , Dacumos April , Xue Jin R. , Morand Eric F. 
Published: June 2009

Abstract
Annexin-1 (ANXA1) is a mediator of the anti-inflammatory actions of endogenous and exogenous glucocorticoids (GC). The mechanism of ANXA1 effects on cytokine production in macrophages is unknown and is here investigated in vivo and in vitro. In response to LPS administration, ANXA1−/− mice exhibited significantly increased serum IL-6 and TNF compared with wild-type (WT) controls. Similarly, LPS-induced IL-6 and TNF were significantly greater in ANXA1−/− than in WT peritoneal macrophages in vitro. In addition, deficiency of ANXA1 was associated with impairment of the inhibitory effects of dexamethasone (DEX) on LPS-induced IL-6 and TNF in macrophages. Increased LPS-induced cytokine expression in the absence of ANXA1 was accompanied by significantly increased LPS-induced activation of ERK and JNK MAPK and was abrogated by inhibition of either of these pathways. No differences in GC effects on MAPK or MAPK phosphatase 1 were observed in ANXA1−/− cells. In contrast, GC-induced expression of the regulatory protein GILZ was significantly reduced in ANXA1−/− cells by silencing of ANXA1 in WT cells and in macrophages of ANXA1−/− mice in vivo. GC-induced GILZ expression and GC inhibition of NF-κB activation were restored by expression of ANXA1 in ANXA1−/− cells, and GILZ overexpression in ANXA1−/− macrophages reduced ERK MAPK phosphorylation and restored sensitivity of cytokine expression and NF-κB activation to GC. These data confirm ANXA1 as a key inhibitor of macrophage cytokine expression and identify GILZ as a previously unrecognized mechanism of the anti-inflammatory effects of ANXA1.
A Subcytotoxic Dose of Subtilase Cytotoxin Prevents Lipopolysaccharide-Induced Inflammatory Responses, Depending on its Capacity to Induce the Unfolded Protein Response
Authors: Harama Daisuke , Koyama Kensuke , Mukai Mai , Shimokawa Naomi , Miyata Masanori , Nakamura Yuki , Ohnuma Yuko , Ogawa Hideoki , Matsuoka Shuji , Paton Adrienne W. , Paton James C. , Kitamura Masanori , Nakao Atsuhito 
Published: June 2009

Abstract
Subtilase cytotoxin (SubAB) is the prototype of a newly identified family of AB5 cytotoxins produced by Shiga toxigenic Escherichia coli. SubAB specifically cleaves the essential endoplasmic reticulum (ER) chaperone BiP (GRP78), resulting in the activation of ER stress-induced unfolded protein response (UPR). We have recently shown that the UPR following ER stress can suppress cellular responses to inflammatory stimuli during the later phase, in association with inhibition of NF-κB activation. These findings prompted us to hypothesize that SubAB, as a selective UPR inducer, might have beneficial effects on inflammation-associated pathology via a UPR-dependent inhibition of NF-κB activation. The pretreatment of a mouse macrophage cell line, RAW264.7, with a subcytotoxic dose of SubAB-triggered UPR and inhibited LPS-induced MCP-1 and TNF-α production associated with inhibition of NF-κB activation. SubAA272B, a SubAB active site mutant that cannot induce UPR, did not show such effects. In addition, pretreatment with a sublethal dose of SubAB, but not SubAA272B, protected the mice from LPS-induced endotoxic lethality associated with reduced serum MCP-1 and TNF-α levels and also prevented the development of experimental arthritis induced by LPS in mice. Collectively, although SubAB has been identified originally as a toxin associated with the pathogenesis of hemolytic uremic syndrome, the unique ability of SubAB to selectively induce the UPR may have the potential to prevent LPS-associated inflammatory pathology under subcytotoxic conditions.
IL-17 and IFN-γ Mediate the Elicitation of Contact Hypersensitivity Responses by Different Mechanisms and Both Are Required for Optimal Responses
Authors: He Donggou , Wu Lizhi , Kim Hee Kyung , Li Hui , Elmets Craig A. , Xu Hui 
Published: June 2009

Abstract
Hapten-induced contact hypersensitivity (CHS) in the skin is a delayed type cellular immune response that can be mediated by CD8+ T cells that produce IFN-γ or IL-17. However, mechanisms for these cytokines in the elicitation of CHS remain to be fully elucidated. In this study, we show that adoptive transfer of CHS with hapten-primed wild-type (WT) CD8+ T cells is reduced in IFN-γR−/− or IL-17R−/− mice compared with WT controls. The infiltration of granulocytes and macrophages in the hapten challenged skin of IL-17R−/− recipients is significantly reduced whereas it is less affected in IFN-γR−/− recipients although CD8+ T cell infiltration is inhibited in both recipients. In contrast, the activity of reactive oxidative species is significantly inhibited in IFN-γR−/− but is less affected in IL-17R−/− recipients. Further analysis reveals that the expression of chemokines and cytokines is differentially regulated in the hapten-challenged skin of IFN-γR−/− or IL-17R−/− recipients compared with WT controls. Interestingly, injection of rIL-17 in the skin induces inflammation with a high level of leukocyte infiltration whereas injection of IFN-γ induces inflammation with a high level of reactive oxidative species. Moreover, neutralization of IL-17 in IFN-γR−/− or IFN-γ in IL-17R−/− mice further suppresses the adoptive transfer of CHS by hapten-primed WT CD8+ T cells. The study demonstrates that IFN-γ and IL-17 mediate the elicitation of CHS by different mechanisms and that both cytokines are required for optimal responses. This outcome improves understanding of pathogenesis and provides new insights into therapeutic strategies for CHS.