bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cross-Talk between Programmed Death-1 and Suppressor of Cytokine Signaling-1 in Inhibition of IL-12 Production by Monocytes/Macrophages in Hepatitis C Virus Infection
Authors: Zhang Ying , Ma Cheng J. , Ni Lei , Zhang Chun L. , Wu Xiao Y. , Kumaraguru Uday , Li Chuan F. , Moorman Jonathan P. , Yao Zhi Q. 
Published: January 2011

Abstract
Hepatitis C virus (HCV) dysregulates innate immune responses and induces persistent viral infection. We previously demonstrated that HCV core protein impairs IL-12 expression by monocytes/macrophages (M/MΦs) through interaction with a complement receptor gC1qR. Because HCV core-mediated lymphocyte dysregulation occurs through the negative immunomodulators programmed death-1 (PD-1) and suppressor of cytokine signaling-1 (SOCS-1), the aim of this study was to examine their role in HCV core-mediated IL-12 suppression in M/MΦs. We analyzed TLR-stimulated, primary CD14+ M/MΦs from chronically HCV-infected and healthy subjects or the THP-1 cell line for PD-1, SOCS-1, and IL-12 expression following HCV core treatment. M/MΦs from HCV-infected subjects at baseline exhibited comparatively increased PD-1 expression that significantly correlated with the degree of IL-12 inhibition. M/MΦs isolated from healthy and HCV-infected individuals and treated with HCV core protein displayed increased PD-1 and SOCS-1 expression and decreased IL-12 expression, an effect that was also observed in cells treated with gC1qR’s ligand, C1q. Blocking gC1qR rescued HCV core-induced PD-1 upregulation and IL-12 suppression, whereas blocking PD-1 signaling enhanced IL-12 production and decreased the expression of SOCS-1 induced by HCV core. Conversely, silencing SOCS-1 expression using small interfering RNAs increased IL-12 expression and inhibited PD-1 upregulation. PD-1 and SOCS-1 were found to associate by coimmunoprecipitation studies, and blocking PD-1 or silencing SOCS-1 in M/MΦ led to activation of STAT-1 during TLR-stimulated IL-12 production. These data suggested that HCV core/gC1qR engagement on M/MΦs triggers the expression of PD-1 and SOCS-1, which can associate to deliver negative signaling to TLR-mediated pathways controlling expression of IL-12, a key cytokine linking innate and adaptive immunity.
Septic Shock Is Associated with Receptor for Advanced Glycation End Products Ligation of LPS
Authors: Yamamoto Yasuhiko , Harashima Ai , Saito Hidehito , Tsuneyama Koichi , Munesue Seiichi , Motoyoshi So , Han Dong , Watanabe Takuo , Asano Masahide , Takasawa Shin , Okamoto Hiroshi , Shimura Satoshi , Karasawa Tadahiro , Yonekura Hideto , Yamamoto Hiroshi 
Published: January 2011

Abstract
Septic shock is a severe systemic response to bacterial infection. Receptor for advanced glycation end products (RAGE) plays a role in immune reactions to recognize specific molecular patterns as pathogen recognition receptors. However, the interaction between LPS, the bioactive component of bacterial cell walls, and RAGE is unclear. In this study, we found direct LPS binding to RAGE by a surface plasmon resonance assay, a plate competition assay, and flow cytometry. LPS increased TNF-α secretion from peritoneal macrophages and an NF-κB promoter-driven luciferase activity through RAGE. Blood neutrophils and monocytes expressed RAGE, and TLR2 was counterregulated in RAGE−/− mice. After LPS injection, RAGE+/+ mice showed a higher mortality, higher serum levels of IL-6, TNF-α, high mobility group box 1, and endothelin-1, and severe lung and liver pathologies compared with RAGE−/− mice without significant differences in plasma LPS level. Administration of soluble RAGE significantly reduced the LPS-induced cytokine release and tissue damage and improved the LPS-induced lethality even in RAGE−/− as well as RAGE+/+ mice. The results thus suggest that RAGE can associate with LPS and that RAGE system can regulate inflammatory responses. Soluble RAGE would be a therapeutic tool for LPS-induced septic shock.
2B4 Engagement Mediates Rapid LFA-1 and Actin-Dependent NK Cell Adhesion to Tumor Cells as Measured by Single Cell Force Spectroscopy
Authors: Hoffmann Sabrina C. , Cohnen André , Ludwig Thomas , Watzl Carsten 
Published: January 2011

AbstractAdhesion to tumor target cells is essential for initiation and execution of cellular cytotoxicity. In this study, we use single cell force spectroscopy to determine the exact biophysical values of the interaction forces between NK cells and tumor cells. We show that engagement of the activating NK cell receptor 2B4 can rapidly mediate an increase in the force necessary to separate NK cells from tumor cells, starting from 1 nN and increasing to 3 nN after only 120 s tumor cell contact. This early adhesion was mediated by the integrin LFA-1 and dependent on the actin cytoskeleton. The ability of NK cells to rapidly adhere to tumor target cells is consistent with their function in innate immune responses. Our data further suggest that a killing decision is already made within 120– 300 s of tumor cell contact, supporting the essential function of cell adhesion during the early phase of cellular cytotoxicity.
Host APCs Augment In Vivo Expansion of Donor Natural Regulatory T Cells via B7H1/B7.1 in Allogeneic Recipients
Authors: Yi Tangsheng , Li Xiaofan , Yao Sheng , Wang Lin , Chen Yuhong , Zhao Dongchang , Johnston Heather F. , Young James S. , Liu Hongjun , Todorov Ivan , Forman Stephen J. , Chen Lieping , Zeng Defu 
Published: January 2011

AbstractFoxp3+ regulatory T (Treg) cells include thymic-derived natural Treg and conventional T-derived adaptive Treg cells. Both are proposed to play important roles in downregulating inflammatory immune responses. However, the mechanisms of Treg expansion in inflammatory environments remain unclear. In this study, we report that, in an autoimmune-like graft-versus-host disease model of DBA/2 (H-2d) donor to BALB/c (H-2d) recipients, donor Treg cells in the recipients predominantly originated from expansion of natural Treg cells and few originated from adaptive Treg cells. In vivo neutralization of IFN-γ resulted in a marked reduction of donor natural Treg expansion and exacerbation of graft-versus-host disease, which was associated with downregulation of host APC expression of B7H1. Furthermore, host APC expression of B7H1 was shown to augment donor Treg survival and expansion. Finally, donor Treg interactions with host APCs via B7.1/B7H1 but not PD-1/B7H1 were demonstrated to be critical in augmenting donor Treg survival and expansion. These studies have revealed a new immune regulation loop consisting of T cell-derived IFN-γ, B7H1 expression by APCs, and B7.1 expression by Treg cells.
Dysregulation of TIM-3–Galectin-9 Pathway in the Cystic Fibrosis Airways
Authors: Vega-Carrascal Isabel , Reeves Emer P. , Niki Toshiro , Arikawa Tomohiro , McNally Paul , O’Neill Shane J. , Hirashima Mitsuomi , McElvaney Noel G. 
Published: January 2011

Abstract
The T-cell Ig and mucin domain-containing molecules (TIMs) have emerged as promising therapeutic targets to correct abnormal immune function in several autoimmune and chronic inflammatory conditions. It has been reported that proinflammatory cytokine dysregulation and neutrophil-dominated inflammation are the main causes of morbidity in cystic fibrosis (CF). However, the role of TIM receptors in CF has not been investigated. In this study, we demonstrated that TIM-3 is constitutively overexpressed in the human CF airway, suggesting a link between CF transmembrane conductance regulator (CFTR) function and TIM-3 expression. Blockade of CFTR function with the CFTR inhibitor-172 induced an upregulation of TIM-3 and its ligand galectin-9 in normal bronchial epithelial cells. We also established that TIM-3 serves as a functional receptor in bronchial epithelial cells, and physiologically relevant concentrations of galectin-9 induced TIM-3 phosphorylation, resulting in increased IL-8 production. In addition, we have demonstrated that both TIM-3 and galectin-9 undergo rapid proteolytic degradation in the CF lung, primarily because of neutrophil elastase and proteinase-3 activity. Our results suggest a novel intrinsic defect that may contribute to the neutrophil-dominated immune response in the CF airways.
IFN-α Directly Promotes Programmed Cell Death-1 Transcription and Limits the Duration of T Cell-Mediated Immunity
Authors: Terawaki Seigo , Chikuma Shunsuke , Shibayama Shiro , Hayashi Tamon , Yoshida Takao , Okazaki Taku , Honjo Tasuku 
Published: January 2011

Abstract
Programmed cell death-1 (PD-1) is an inhibitory coreceptor for T lymphocytes that provides feedback inhibition of T cell activation. Although PD-1’s expression on T cells is known to be activation dependent, the factors that determine the timing, intensity, and duration of PD-1 expression in immune reactions are not fully understood. To address this question, we performed a fine mapping analysis of a conserved 5′-flanking region of the PD-1 gene and identified a putative IFN stimulation response element, which was responsible for PD-1 transcription in the 2B4.11 T cell line. Consistent with this finding, activation by IFN-α enhanced both the induction and maintenance of PD-1 expression on TCR-engaged primary mouse T cells through an association IFN-responsive factor 9 (IRF9) to the IFN stimulation response element. Furthermore, PD-1 expression on Ag-specific CD8+ T cells was augmented by IFN-α in vivo. We propose that strong innate inflammatory responses promote primary T cell activation and their differentiation into effector cells, but also cause an attenuated T cell response in sustained immune reactions, at least partially through type I IFN-mediated PD-1 transcription. Based on this idea, we demonstrate that IFN-α administration in combination with PD-1 blockade in tumor-bearing mice effectively augments the antitumor immunity, and we propose this as a novel and rational approach for cancer immunotherapy.
Identification of Semaphorin 4B as a Negative Regulator of Basophil-Mediated Immune Responses
Authors: Nakagawa Yukinobu , Takamatsu Hyota , Okuno Tatsusada , Kang Sujin , Nojima Satoshi , Kimura Tetsuya , Kataoka Tatsuki R. , Ikawa Masahito , Toyofuku Toshihiko , Katayama Ichiro , Kumanogoh Atsushi 
Published: January 2011

Abstract
Basophils are strong mediators of Th2 responses during helminthic infections. Recently, basophils were shown to function as APCs and promote both Th2 skewing and humoral memory responses. However, the mechanisms that regulate basophils are still unclear. In this article, we show that a class IV semaphorin, Sema4B, negatively regulates basophil functions through T cell–basophil contacts. In a screen to identify semaphorins that function in the immune system, we determined that Sema4B is expressed in T and B cells. Interestingly, Sema4B−/− mice had considerably increased serum IgE levels despite normal lymphocyte and dendritic cell functions. Recombinant Sema4B significantly inhibited IL-4 and IL-6 production from basophils in response to various stimuli, including IL-3, papain, and FcεRI cross-linking. In addition, T cell-derived Sema4B, which accumulated at contact sites between basophils and CD4+ T cells, suppressed basophil-mediated Th2 skewing, suggesting that Sema4B regulates basophil responses through cognate cell–cell contacts. Furthermore, Sema4B−/− mice had enhanced basophil-mediated memory IgE production, which was abolished by treating with an anti-FcεRIα Ab. Collectively, these results indicate that Sema4B negatively regulates basophil-mediated Th2 and humoral memory responses.
Aluminum-Based Barrier Development for Nuclear Fusion Applications
Authors: Konys J. , Krauss W. , Holstein N. 
Published: January 2011

Abstract
In the helium-cooled lead-lithium (HCLL) design concept for blanket structures of a future fusion power plant, the eutectic Pb-15.7Li alloy is used as a liquid tritium breeder and is in direct contact with the structural material, e.g., ferritic-martensitic steels. Compatibility tests showed that a high corrosion attack appears and that the dissolved steel elements like Fe and Cr form precipitates, with a high risk of system blockages. Therefore, coatings as corrosion barriers are required for a reliable plant operation. Because of safety reasons, a distinct permeation reduction of the tritium, produced in the Pb-Li alloy by nuclear reactions, into the environment has to be limited, too. Previous developments already showed that Al-based coatings can perform very well as anti-corrosion and tritium permeation (T-permeation) reduction barriers in a PbLi environment. However, industrially relevant coating technologies for fusion application are still missing and/or cannot fulfil low activation criteria. Electrochemical deposition processes are highly flexible and used widely for the production of functional coatings, e.g., for corrosion protection. Nevertheless, because of its unique electrochemistry, Al cannot be deposited from water-based systems. Therefore, the development of two different Al coating processes from nonaqueous systems was initiated and proofed by the successful generation of protective and reproducible scales after heat treatment.
NURSING DIAGNOSIS UNDER STUART’S THEORY THE POINT OF VIEW: CLINICALS CASES REPORT
Authors: Cavalcanti Ana Márcia Tenório de Souza , Araújo Ednaldo Cavalcante de , Santos Cândida Maria Rodrigues dos , Sette Gabriela Cunha Schechtman , Monteiro Ana Maria de Carvalho 
Published: January 2011

RESUMOForam selecionados três estudos de casos clínicos com o objetivo de identificar diagnósticos de enfermagem sob a ótica da Teoria de Stuart na área de Enfermagem em Saúde Mental, após 20 casos estudados por meio de visitas domiciliares realizadas à clientela da Equipe de Ação Avançada do Distrito Sanitário III vinculado a um Centro de Atenção Psicossocial do Recife. Como resultado da investigação foi possível identificar alguns diagnósticos de Enfermagem apresentados pela clientela: processos do pensamento alterados, desesperança e isolamento social; por outro lado, também foi possível planejar intervenções de Enfermagem em Saúde Mental, e por meio da Sistematização da Assistência, constatar resultados benéficos ao usuário e sua família. Descritores: Visita; Domicílio; Enfermagem; Saúde mental; Teoria. ABSTRACTThree clinicals cases report were selected with the objective of identifying nursing diagnoses under Stuart’s Theory the point of view in Mental Health Nursing, after 20 home visits were done by the Advanced Action Team in a period of two months at Recife. With the domiciliary visits investigation, it was possible to identify the most often nursing diagnostics: modified thinking process, hopelessness and social isolation. It was possible to plan specific nursing interventions in mental health and, with the assistance’s systematization, evidence the benefic results to the patient and his family.Descriptors: Visit; Home; Nursing; Mental health; Theory. RESUMENFueron seleccionados tres casos clínicos con el objetivo de identificar los diagnósticos de enfermería bajo el punto de vista de la Teoría de Stuart en Enfermería en Salud Mental, después de 20 casos estudiados por medio de visitas domiciliarias realizadas por el Equipo de Acción Avanzada del Distrito Sanitario III, vinculado a un Centro de Atención Psicosocial de Recife. Como resultado de la investigación fue posible identificar algunos diagnósticos presentados por los clientes: procesos del pensamiento alterados, desesperanza y aislamiento social; por otro lado, fue posible planificar la asistencia específica de Enfermería en Salud Mental y, por medio de la Sistematización de la Asistencia constatar los resultados benéficos para el paciente y su familia.Descriptores: Visita; Domicilio; Enfermería; Salud mental; Teoría.
GREAT-GRANDFATHERS PERCEPTION OF ROLE PLAYED
Authors: Dias Cristina Maria de Souza Brito , Pinto Virgínia Cavalcanti 
Published: January 2011

RESUMOEsta pesquisa teve como objetivo geral investigar como bisavôs percebem seu papel no seio da família e se relacionam com os bisnetos. Participaram 21 bisavôs, com média de idade de 77 anos, que foram entrevistados em suas residências. Foram objetos de estudo: significado e sentimentos experimentados no papel; ajuda prestada à família; dificuldades sentidas no relacionamento com os bisnetos; avaliação do relacionamento com a família; atividades desenvolvidas e freqüência do contato com os bisnetos; percepção das mudanças ao longo do tempo e significado de família. Pode-se constatar que o papel foi percebido de forma bastante positiva. Houve, por parte de alguns, dificuldades que podem ser atribuídas aos conflitos com os familiares, à distância geográfica e à difícil situação econômica. Descritores: Bisavós; Quarta-geração; Interação familiar. ABSTRACTThe aim at this research was to investigate the perceptions and feelings in great-grandfathers about the role play of them as great-grandfathers and the relationship with their great-grandchildren. The interviewers were 21 great-grandfathers with age average 77 years. They were interviewed in their own residences. It were subject of this research: feelings and meaning about their role play one; supporting given to the family; difficulties regards to the relationship with the great-grandchildren; how they see the relationships with the family; activities realized with the great-grandchildren; frequency of contact with them; perception about the changes over time and family’ meaning. The conclusion was that the role was seen as positive. They related difficulties regards to relationships familiar, geographic distance and poor economic situation by some of them.Descriptors: Great-grandfathers; Fourth-generation; Family interaction. RESUMENLo objetivo de esta investigación fue explorar las opiniones y las sensaciones en los bisabuelos, sobre el papel que desempeñan y la relación con sus bisnietos. Participaron 21 bisabuelos, con 77 años como promedio de edad; fueron entrevistados en sus propias residencias. Los objetivos principales fueron: sensaciones y significado sobre su papel; ayuda a la familia; la relación con los bisnietos; cómo ven las relaciones con la familia; actividades desarrolladas y frecuencia de contactos con los bisnietos; percepción de los cambios observados y significado de la familia. Se pudo constatar que el papel fue percibido de forma bastante positiva. Por parte de algunos hubo dificultades que pueden ser atribuidas a los conflictos con familiares, distancia geográfica y la situación económica de algunos de ellos.Descriptores: Bisabuelos; Cuarta generación; Interacción de la familia.
IMPORTANCE OF THE FAMILIAR THERAPY AS TOOL AUXILIARY IN THE SUCCESSORY PROCESS OF FAMILIAR COMPANIES
Authors: Bastos Luís Othon , Lima Iana Bezerra 
Published: January 2011

RESUMONeste estudo de revisão de literatura foi apresentada a importância da terapia familiar como ferramenta auxiliar no processo sucessório de empresas familiares, visando a redução dos conflitos interpessoais entre os membros da família e agregados, condição mister para a paz do clã e a perenidade da empresa mantenedora da família. Foi realizado um levantamento do acervo referente ao tema estudado e para tanto foram consultados livros, artigos científicos, anais de congressos e revistas especializadas que tratam do assunto. A análise apresentada tem como fonte de dados um total de 24 estudos. A escolha pautou-se na priorização dos textos que forneciam elementos satisfatórios para a compreensão da temática abordada. Por fim, ficou evidente a contribuição da terapia de família no sentido de unir esforços na redução dos conflitos de poder inerentes ao processo de sucessão das empresas familiares.Descritores: Empresa familiar; Sucessão; Terapia familiar; Mediação. ABSTRACTIn this study of review literature was presented the familiar therapy’s importance as tool auxiliary in the successory process of familiar companies, aiming at reduction of interpersonal conflicts between the family members and aggregates, condition necessary for the peace of the clan and the existence of the family company. A survey of the subject studied had been carried out in scientific books, articles, congress annals and journal specialized. It was presented the analysis of 24 studies. The criteria for choosing the texts that supplied this study, has elements satisfactory in the understanding of the thematic boarded. Finally, it was evident that the family therapy contributes in the power conflicts reduction inherent to the process of succession of the familiar companies. Descriptors: Familiar company; Succession; Familiar therapy; Mediation. RESUMENEste estudio de revisión de literatura exploró la importancia de la terapia familiar como herramienta auxiliar en el proceso sucesorio de compañías familiares, teniendo como objetivo la reducción de conflictos interpersonales entre los miembros de la familia y los allegados, la condición necesaria para la paz del clan y la existencia de la compañía de la familia. Fue realizado un relevamiento del acervo del tema estudiado, se consultaron libros, artículos, anales científicos de congresos y revistas especializadas. El análisis presentado está basado en 24 estudios. Los criterios para elegir los textos fueron que proporcionaran elementos satisfactorios para la comprensión de la temática investigada. Finalmente, quedó evidente que la terapia de la familia contribuye en la reducción de los conflictos de poder inherente al proceso de la sucesión de las compañías familiares.Descriptores: Compañía familiar; Sucesión; Terapia familiar; Mediación.