bluuebunny/crossref_metadata_2025_split huggingface dataset:
Aggressive Blood Pressure Control Increases Coronary Heart Disease Risk Among Diabetic Patients
Authors: Zhao Wenhui , Katzmarzyk Peter T. , Horswell Ronald , Wang Yujie , Li Wei , Johnson Jolene , Heymsfield Steven B. , Cefalu William T. , Ryan Donna H. , Hu Gang 
Published: May 2013

OBJECTIVE
Blood pressure control can reduce the risk of coronary heart disease (CHD) among diabetic patients; however, it is not known whether the lowest risk of CHD is among diabetic patients with the lowest blood pressure level.

RESEARCH DESIGN AND METHODS
We performed a prospective cohort study (2000–2009) on diabetic patients including 17,536 African Americans and 12,618 whites. Cox proportional hazards regression models were used to estimate the association of blood pressure with CHD risk.

RESULTS
During a mean follow-up of 6.0 years, 7,260 CHD incident cases were identified. The multivariable-adjusted hazard ratios of CHD associated with different levels of systolic/diastolic blood pressure at baseline (&lt;110/65, 110–119/65–69, 120–129/70–80, and 130–139/80–90 mmHg [reference group]; 140–159/90–100; and ≥160/100 mmHg) were 1.73, 1.16, 1.04, 1.00, 1.06, and 1.11 (P trend &lt;0.001), respectively, for African American diabetic patients, and 1.60, 1.27, 1.08, 1.00, 0.95, and 0.99 (P trend&lt;0.001) for white diabetic patients, respectively. A U-shaped association of isolated systolic and diastolic blood pressure at baseline as well as blood pressure during follow-up with CHD risk was observed among both African American and white diabetic patients (all Ptrend &lt;0.001). The U-shaped association was present in the younger age-group (30–49 years), and this U-shaped association changed to an inverse association in the older age-group (≥60 years).

CONCLUSIONS
Our study suggests that there is a U-shaped or inverse association between blood pressure and the risk of CHD, and aggressive blood pressure control (blood pressure &lt;120/70 mmHg) is associated with an increased risk of CHD among both African American and white patients with diabetes.
Apports de la recherche familiale dans les troubles du comportement alimentaire de l'enfant et de l'adolescent : acquis, défis et nouvelles perspectives
Authors: Cook-Darzens Solange 
Published: May 2013

Cet article cherche à démontrer l’intérêt d’une pratique familiale basée sur les faits ( evidence-based ) dans le champ des troubles du comportement alimentaire (TCA) de l’enfant et de l’adolescent, en proposant dans un premier temps une synthèse critique de la littérature empirique : 1) sur le fonctionnement des familles d’enfants et d’adolescents souffrant de TCA, et 2) sur l’efficacité des thérapies familiales dans le traitement de ces troubles. Les nouvelles lignes directrices ainsi que les lacunes et biais qui en émergent seront soulignés et discutés, et un modèle de pratique clinique, basée sur la recherche scientifique, l’expertise du clinicien et les préférences et motivations du patient ou de la famille sera proposé en fin d’article. Les liens ainsi tissés entre théorie, recherche et pratique clinique, décrivent une démarche dont la pertinence dépasse largement le simple champ des TCA.
Couples homosexuels et familles homoparentales
Authors: D’Amore Salvatore , Miscioscia Marina , Scali Thérèse , Haxhe Stéphanie , Bullens Quentin 
Published: May 2013

Les couples et les familles avec partenaires et parents LGBT (lesbiens, gays, bisexuels, transgenres) sont souvent passés sous silence dans l’approche systémique. Ce silence trouve ses racines dans l’hétérocentrisme qui a influencé la définition de couple, de famille et de relations familiales ainsi que de leur « normalité » vs « pathologie ». Qu’on soit chercheur ou clinicien, il est intéressant de prendre en considération l’impact de l’homophobie, de l’hétérosexisme, de l’hétéronormativité dans la vie quotidienne de ces couples, de ces familles et de leurs enfants. En particulier dans la consultation clinique, il semble important d’en évaluer leur degré de stress, d’ambiguïté relationnelle, d’homonégativité intériorisée ainsi que de support social. Nous réfléchirons aussi sur les atouts et les limites des modèles majeurs de thérapie de couple et de famille dans le travail thérapeutique ainsi que sur la nécessité d’envisager des pistes dans la formation du futur thérapeute sur les questions LGBT. Formation qui pourrait être basée sur le modèle de la diversité comme modèle inclusif des différences familiales et relationnelles contemporaines.
L'« Intervention systémique brève » : un manuel thérapeutique
Authors: Carneiro Claudio , Vaudan Christel , Duc Marwood Alessandra , Darwiche Joëlle , Despland Jean-Nicolas , de Roten Yves 
Published: May 2013

Evaluer l’efficacité d’une thérapie ne devrait pas se limiter à en étudier l’impact sur différentes dimensions pertinentes. En effet, la recherche en psychothérapie insiste sur l’importance de développer des manuels thérapeutiques, afin de décrire ce que les thérapeutes font et donc comprendre ce qui est efficace, ainsi que des protocoles d’adhérence à ces manuels, afin de pouvoir évaluer si les intervenants font effectivement ce qu’ils prétendent faire. Cet article présente le manuel thérapeutique de l’Intervention systémique brève (ISB), un modèle d’intervention en six séances, utilisé dans une consultation pour couples et familles au Département de psychiatrie du CHUV à Lausanne. Ce modèle fait l’objet d’une recherche visant à évaluer son efficacité à court et moyen termes, au moyen de questionnaires remplis par les patients, évaluant différents niveaux : 1) les symptômes individuels, 2) la satisfaction conjugale, 3) la qualité des relations parentales, 4) la qualité des relations coparentales et 5) les relations familiales. L’ISB est un modèle intégratif des principales écoles de thérapie familiale systémique. Pour élaborer le manuel de l’ISB, nous nous sommes basés sur certains principes généraux communs aux différentes approches systémiques. La difficulté d’élaborer un tel manuel thérapeutique intégratif systémique sera discutée.
De deux à trois... Transition à la parentalité et alliances familiales dans les familles lesboparentales
Authors: Miscioscia Marina , D’Amore Salvatore , Delvoye Marie 
Published: May 2013

Le présent travail s’intéresse au moment particulier du cycle de vie familial dénommé « transition à la parentalité ». Les études ayant approfondi ce moment délicat ont souligné la nécessité d’adopter une perspective multifactorielle et procédurale pour une meilleure compréhension du système en voie de développement. Deux principaux facteurs d’étude ont été déterminés : a) le développement des compétences interactives de la famille, la capacité du couple à organiser des modèles interactifs triadiques pendant la grossesse et de les réorganiser successivement dans la relation avec l’enfant ; b) les caractéristiques propres à l’enfant, par exemple le tempérament, sont des facteurs pouvant influencer le développement des compétences interactives précoces ainsi que le style de parenting . Ces aspects ont été amplement étudiés au sein des familles hétéroparentales, mais très peu au sein des familles homoparentales. La plupart des recherches se sont intéressées à une comparaison du développement de l’enfant dans ces deux types de familles, et ce sur différentes dimensions telles que la qualité des relations parent-enfant, le développement cognitif, le développement psycho-social et l’identité de genre. Nous proposons ici de présenter la situation d’une famille, issue de la recherche longitudinale que nous effectuons actuellement au sein du Service de clinique systémique et psychopathologie relationnelle de l’Université de Liège. Notre exposé présentera deux étapes de la passation du Lausanne Trilogue Play (LTP) : prénatale au 7 e mois de grossesse et postnatale au 3 e mois de vie de l’enfant. Nous observerons l’intérêt de cette procédure du LTP prénatal en tant qu’instrument prédictif des capacités parentales à agir leurs compétences interactives à la naissance de l’enfant, vérifiées par la procédure du LTP postnatal.
Enhancement of CCL15 Expression and Monocyte Adhesion to Endothelial Cells (ECs) after Hypoxia/Reoxygenation and Induction of ICAM-1 Expression by CCL15 via the JAK2/STAT3 Pathway in ECs
Authors: Park Keun Hyung , Lee Tae Hoon , Kim Chan Woo , Kim Jiyoung 
Published: May 2013

AbstractCCL15, a member of the CC chemokine family, is a potent chemoattractant for leukocytes and endothelial cells (ECs). Given that chemokines play key roles in vascular inflammation, we investigated the effects of hypoxia/reoxygenation (H/R) on expression of human CCL15 and a role of CCL15 in upregulating ICAM-1 in ECs. We found that exposure of ECs to H/R increased expression of CCL15 and ICAM-1, which resulted in an increase in monocyte adhesivity to the ECs. Further studies revealed that knockdown of CCL15 or CCR1 attenuated expression of ICAM-1 in ECs after H/R, suggesting that expression of ICAM-1 is upregulated by CCL15. Stimulation of ECs with CCL15 significantly increased expression of ICAM-1 predominantly via the CCR1 receptor. We observed that phosphorylation of JAK2 and STAT3 was stimulated by CCL15 treatment of ECs. Results from reporter and chromatin immunoprecipitation assays revealed that CCL15 activates transcription from the IFN-γ activation site promoter and stimulates binding of STAT3 to the ICAM-1 promoter. Our data also showed that CCL15 increased cell adhesion of human monocytes to ECs under static and shear-stress conditions. Pretreatment of these cells with inhibitors for JAK, PI3K, and AKT prevented the CCL15-induced expression of ICAM-1 and monocyte adhesion to ECs, suggesting the involvement of those signaling molecules in ICAM-1 gene activation by CCL15. The results suggest that CCR1 and its ligands may be a potential target for treating inflammatory diseases involving upregulation of cell adhesion molecules.
IL-7 Produced by Thymic Epithelial Cells Plays a Major Role in the Development of Thymocytes and TCRγδ+ Intraepithelial Lymphocytes
Authors: Shitara Soichiro , Hara Takahiro , Liang Bingfei , Wagatsuma Keisuke , Zuklys Saulius , Holländer Georg A. , Nakase Hiroshi , Chiba Tsutomu , Tani-ichi Shizue , Ikuta Koichi 
Published: May 2013

Abstract
IL-7 is a cytokine essential for T cell development and survival. However, the local function of IL-7 produced by thymic epithelial cells (TECs) is poorly understood. To address this question, we generated IL-7–floxed mice and crossed them with FoxN1 promoter–driven Cre (FoxN1-Cre) mice to establish knockout mice conditionally deficient for the expression of IL-7 by TECs. We found that αβ and γδ T cells were significantly reduced in the thymus of IL-7f/f FoxN1-Cre mice. Proportion of mature single-positive thymocytes was increased. In lymph nodes and the spleen, the numbers of T cells were partially restored in IL-7f/f FoxN1-Cre mice. In addition, γδ T cells were absent from the fetal thymus and epidermis of IL-7f/f FoxN1-Cre mice. Furthermore, TCRγδ+ intraepithelial lymphocytes (IELs) were significantly decreased in the small intestines of IL-7f/f FoxN1-Cre mice. To evaluate the function of IL-7 produced in the intestine, we crossed the IL-7f/f mice with villin promoter–driven Cre (Vil-Cre) mice to obtain the mice deficient in IL-7 production from intestinal epithelial cells. We observed that αβ and γδ IELs of IL-7f/f Vil-Cre mice were comparable to control mice. Collectively, our results suggest that TEC-derived IL-7 plays a major role in proliferation, survival, and maturation of thymocytes and is indispensable for γδ T cell development. This study also demonstrates that IL-7 produced in the thymus is essential for the development of γδ IELs and indicates the thymic origin of γδ IELs.
SOCS3 Regulates BAFF in Human Enterocytes under Ribosomal Stress
Authors: Do Kee Hun , Choi Hye Jin , Kim Juil , Park Seong-Hwan , Kim Ki-Hyung , Moon Yuseok 
Published: May 2013

Abstract
Although the activation of B cells in the gastrointestinal tract is of great importance in the context of immunity to pathogens and mucosal inflammatory diseases, little is known about the mechanisms responsible for the local activation of B cells in the subepithelial area of the intestine. Epithelium-derived BAFF is the major modulator of B cell development and Ig class switching. The present study was performed to address the molecular mechanism of BAFF expression in gut epithelial cells in the presence of proinflammatory stimuli. Inflammation-induced BAFF expression in mucosal epithelial cells might be responsible for diverse mucosa-associated diseases linked to intestinal inflammation and autoimmunity. Although BAFF was marginally expressed in unstimulated epithelial cells, BAFF mRNA was significantly upregulated by proinflammatory IFN-γ. Furthermore, IFN-γ triggered JAK/STAT1 signals via the cytokine receptor, which contributed to epithelial BAFF upregulation. In terms of signaling intervention, ribosomal insult attenuated IFN-γ–activated JAK/STAT signal transduction and subsequent BAFF induction in gut epithelial cells. Ribosomal insults led to the superinduction of SOCS3 by enhancing its mRNA stability via HuR RNA-binding protein. Upregulated SOCS3 then contributed to the blocking of the JAK/STAT-linked signal, which mediated BAFF suppression by ribosomal stress. All of these findings show that ribosomal stress–induced SOCS3 plays a novel regulatory role in epithelial BAFF production, suggesting that epithelial ribosomal dysfunction in association with SOCS3 may be a promising therapeutic point in BAFF-associated human mucosal diseases.
Helicobacter pylori Infection Inhibits Phagocyte Clearance of Apoptotic Gastric Epithelial Cells
Authors: Bimczok Diane , Smythies Lesley E. , Waites Ken B. , Grams Jayleen M. , Stahl Richard D. , Mannon Peter J. , Peter Shajan , Wilcox C. Mel , Harris Paul R. , Das Soumita , Ernst Peter B. , Smith Phillip D. 
Published: May 2013

Abstract
Increased apoptotic death of gastric epithelial cells is a hallmark of Helicobacter pylori infection, and altered epithelial cell turnover is an important contributor to gastric carcinogenesis. To address the fate of apoptotic gastric epithelial cells and their role in H. pylori mucosal disease, we investigated phagocyte clearance of apoptotic gastric epithelial cells in H. pylori infection. Human gastric mononuclear phagocytes were analyzed for their ability to take up apoptotic epithelial cells (AECs) in vivo using immunofluorescence analysis. We then used primary human gastric epithelial cells induced to undergo apoptosis by exposure to live H. pylori to study apoptotic cell uptake by autologous monocyte-derived macrophages. We show that HLA-DR+ mononuclear phagocytes in human gastric mucosa contain cytokeratin-positive and TUNEL-positive AEC material, indicating that gastric phagocytes are involved in AEC clearance. We further show that H. pylori both increased apoptosis in primary gastric epithelial cells and decreased phagocytosis of the AECs by autologous monocyte-derived macrophages. Reduced macrophage clearance of apoptotic cells was mediated in part by H. pylori–induced macrophage TNF-α, which was expressed at higher levels in H. pylori–infected, compared with uninfected, gastric mucosa. Importantly, we show that H. pylori–infected gastric mucosa contained significantly higher numbers of AECs and higher levels of nonphagocytosed TUNEL-positive apoptotic material, consistent with a defect in apoptotic cell clearance. Thus, as shown in other autoimmune and chronic inflammatory diseases, insufficient phagocyte clearance may contribute to the chronic and self-perpetuating inflammation in human H. pylori infection.
CD40 Mediates Downregulation of CD32B on Specific Memory B Cell Populations in Rheumatoid Arthritis
Authors: Zhang Xiaoyu , Burch Erin , Cai Ling , So Edward , Hubbard Fleesie , Matteson Eric L. , Strome Scott E. 
Published: May 2013

Abstract
Altered B cell function is important in the pathogenesis of rheumatoid arthritis (RA). In this report, we show that patients with active RA have an increased frequency of CD32B low/neg cells in the CD27+IgD− memory B cell subset and that these changes are associated with phenotypic and functional B cell activation. Studies using PBMCs from healthy donors revealed that downregulation of CD32B on B cells is mediated by CD40–CD40L interactions and is potentiated by IL-4 and inhibited by both IL-10 and IL-21. These findings appear physiologically relevant because CD4 T cell expression of CD40L correlated with the frequency of CD32B low/neg cells in the CD27+IgD− memory B subset in patients with RA. Our data support a model in which high levels of CD40L, present on circulating T cells in patients with RA, causes B cell activation and CD32B downregulation, resulting in secondary protection of memory B cells from CD32B-mediated cell death.
Galectin-1–Mediated Suppression of Pseudomonas aeruginosa–Induced Corneal Immunopathology
Authors: Suryawanshi Amol , Cao Zhiyi , Thitiprasert Thananya , Zaidi Tanveer S. , Panjwani Noorjahan 
Published: May 2013

Abstract
Corneal infection with Pseudomonas aeruginosa leads to a severe immunoinflammatory lesion, often causing vision impairment and blindness. Although past studies have indicated a critical role for CD4+ T cells, particularly Th1 cells, in corneal immunopathology, the relative contribution of recently discovered Th17 and regulatory T cells is undefined. In this study, we demonstrate that after corneal P. aeruginosa infection, both Th1 and Th17 cells infiltrate the cornea with increased representation of Th17 cells. In addition to Th1 and Th17 cells, regulatory T cells also migrate into the cornea during early as well as late stages of corneal pathology. Moreover, using galectin-1 (Gal-1), an immunomodulatory carbohydrate-binding molecule, we investigated whether shifting the balance among various CD4+ T cell subsets can modulate P. aeruginosa–induced corneal immunopathology. We demonstrate in this study that local recombinant Gal-1 (rGal-1) treatment by subconjunctival injections significantly diminishes P. aeruginosa–mediated corneal inflammation through multiple mechanisms. Specifically, in our study, rGal-1 treatment significantly diminished corneal infiltration of total CD45+ T cells, neutrophils, and CD4+ T cells. Furthermore, rGal-1 treatment significantly reduced proinflammatory Th17 cell response in the cornea as well as local draining lymph nodes. Also, rGal-1 therapy promoted anti-inflammatory Th2 and IL-10 response in secondary lymphoid organs. Collectively, our results indicate that corneal P. aeruginosa infection induces a strong Th17-mediated corneal pathology, and treatment with endogenously derived protein such as Gal-1 may be of therapeutic value for the management of bacterial keratitis, a prevalent cause of vision loss and blindness in humans worldwide.
Antigen-Specific Effector CD4 T Lymphocytes School Lamina Propria Dendritic Cells To Transfer Innate Tolerance
Authors: Cascio Jason A. , Haymaker Cara L. , Divekar Rohit D. , Zaghouani Sarah , Khairallah Marie-Therese , Wan Xiaoxiao , Rowland Linda M. , Dhakal Mermagya , Chen Weirong , Zaghouani Habib 
Published: May 2013

AbstractDendritic cells (DCs) have been shown to play a major role in oral tolerance, and this function has been associated with their ability to produce anti-inflammatory cytokines and to induce suppressive regulatory T cells. In this study, we demonstrate that upon oral administration of Ag, lamina propia (LP) DCs engage specific T cells and acquire a novel mechanism by which they transfer tolerance against diverse T cell specificities. Indeed, when Ig-myelin oligodendrocyte glycoprotein (MOG) carrying the MOG35–55 epitope was orally administered into either T cell–sufficient or –deficient mice, only the T cell–sufficient hosts yielded CD8α+ and CD8α− LP DCs that were able to transfer tolerance to a variety of MHC class II–restricted effector T cells. Surprisingly, these LP DCs upregulated programmed cell death ligand 1 during the initial interaction with MOG-specific T cells and used this inhibitory molecule to suppress activation of T cells regardless of Ag specificity. Furthermore, oral Ig-MOG was able to overcome experimental autoimmune encephalomyelitis induced with CNS homogenate, indicating that the DCs are able to modulate disease involving diverse T cell specificities. This previously unrecognized attribute potentiates DCs against autoimmunity.
IL-1α Signaling Initiates the Inflammatory Response to Virulent Legionella pneumophila In Vivo
Authors: Barry Kevin C. , Fontana Mary F. , Portman Jonathan L. , Dugan Aisling S. , Vance Russell E. 
Published: May 2013

Abstract
Legionella pneumophila is an intracellular bacterial pathogen that is the cause of a severe pneumonia in humans called Legionnaires’ disease. A key feature of L. pneumophila pathogenesis is the rapid influx of neutrophils into the lungs, which occurs in response to signaling via the IL-1R. Two distinct cytokines, IL-1α and IL-1β, can stimulate the type I IL-1R. IL-1β is produced upon activation of cytosolic sensors called inflammasomes that detect L. pneumophila in vitro and in vivo. Surprisingly, we find no essential role for IL-1β in neutrophil recruitment to the lungs in response to L. pneumophila. Instead, we show that IL-1α is a critical initiator of neutrophil recruitment to the lungs of L. pneumophila–infected mice. We find that neutrophil recruitment in response to virulent L. pneumophila requires the production of IL-1α specifically by hematopoietic cells. In contrast to IL-1β, the innate signaling pathways that lead to the production of IL-1α in response to L. pneumophila remain poorly defined. In particular, although we confirm a role for inflammasomes for initiation of IL-1β signaling in vivo, we find no essential role for inflammasomes in production of IL-1α. Instead, we propose that a novel host pathway, perhaps involving inhibition of host protein synthesis, is responsible for IL-1α production in response to virulent L. pneumophila. Our results establish IL-1α as a critical initiator of the inflammatory response to L. pneumophila in vivo and point to an important role for IL-1α in providing an alternative to inflammasome-mediated immune responses in vivo.
Recent Thymic Emigrants and Mature Naive T Cells Exhibit Differential DNA Methylation at Key Cytokine Loci
Authors: Berkley Amy M. , Hendricks Deborah W. , Simmons Kalynn B. , Fink Pamela J. 
Published: May 2013

Abstract
Recent thymic emigrants (RTEs) are the youngest T cells in the lymphoid periphery and exhibit phenotypic and functional characteristics distinct from those of their more mature counterparts in the naive peripheral T cell pool. We show in this study that the Il2 and Il4 promoter regions of naive CD4+ RTEs are characterized by site-specific hypermethylation compared with those of both mature naive (MN) T cells and the thymocyte precursors of RTEs. Thus, RTEs do not merely occupy a midpoint between the thymus and the mature T cell pool, but represent a distinct transitional T cell population. Furthermore, RTEs and MN T cells exhibit distinct CpG DNA methylation patterns both before and after activation. Compared with MN T cells, RTEs express higher levels of several enzymes that modify DNA methylation, and inhibiting methylation during culture allows RTEs to reach MN T cell levels of cytokine production. Collectively, these data suggest that the functional differences that distinguish RTEs from MN T cells are influenced by epigenetic mechanisms and provide clues to a mechanistic basis for postthymic maturation.