bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Major Role for Bim in Regulatory T Cell Homeostasis
Authors: Chougnet Claire A. , Tripathi Pulak , Lages Celine S. , Raynor Jana , Sholl Allyson , Fink Pamela , Plas David R. , Hildeman David A. 
Published: November 2010

AbstractWe have previously shown that regulatory T cells (Treg) accumulate dramatically in aged animals and negatively impact the ability to control persistent infection. However, the mechanisms underlying the age-dependent accrual of Treg remain unclear. In this study, we show that Treg accumulation with age is progressive and likely not the result of increased thymic output, increased peripheral proliferation, or from enhanced peripheral conversion. Instead, we found that Treg from aged mice are more resistant to apoptosis than Treg from young mice. Although Treg from aged mice had increased expression of functional IL-7Rα, we found that IL-7R signaling was not required for maintenance of Treg in vivo. Notably, aged Treg exhibit decreased expression of the proapoptotic molecule Bim compared with Treg from young mice. Furthermore, in the absence of Bim, Treg accumulate rapidly, accounting for &gt;25% of the CD4+ T cell compartment by 6 mo of age. Additionally, accumulation of Treg in Bim-deficient mice occurred after the cells left the transitional recent thymic emigrant compartment. Mechanistically, we show that IL-2 drives preferential proliferation and accumulation of Bimlo Treg. Collectively, our data suggest that chronic stimulation by IL-2 leads to preferential expansion of Treg having low expression of Bim, which favors their survival and accumulation in aged hosts.
Mast Cell-Derived IL-10 Suppresses Germinal Center Formation by Affecting T Follicular Helper Cell Function
Authors: Chacón-Salinas Rommel , Limón-Flores Alberto Y. , Chávez-Blanco Alma D. , Gonzalez-Estrada Alexei , Ullrich Stephen E. 
Published: November 2010

AbstractThe most prevalent cancer diagnosed in the world is sunlight-induced skin cancer. In addition to being a complete carcinogen, UV radiation, the causative agent of skin cancer, induces immune suppression. Because UV-induced immune suppression is a well-recognized risk factor for skin cancer induction, it is crucial to understand the mechanisms underlying UV-induced immune suppression. Mast cells, which have recently emerged as immune regulatory cells, are particularly important in UV-induced immune suppression. UV exposure does not induce immune suppression in mast cell-deficient mice. We report that UV irradiation blocks germinal center (GC) formation, Ab secretion, and T follicular helper (Tfh) cell function, in part by altering the expression of transcription factors BCL-6 and BLIMP-1. No suppression of GC formation, Tfh cell IL-21 expression, or Ab secretion was observed in UV-irradiated mast cell-deficient (KitW-sh/W-sh) mice. When mast cell-deficient mice were reconstituted with wild type mast cells, immune suppression was restored. Reconstituting the mast cell-deficient mice with bone marrow-derived mast cells from IL-10–deficient mice failed to restore the ability of UV radiation to suppress GC formation. Our findings demonstrate a function for mast cells, suppression of Tfh cell production, GC formation, and Ab production in vivo.
Evolutional Conservation of Molecular Structure and Antiviral Function of a Viral RNA Receptor, LGP2, in Japanese Flounder, Paralichthys olivaceus
Authors: Ohtani Maki , Hikima Jun-ichi , Kondo Hidehiro , Hirono Ikuo , Jung Tae-Sung , Aoki Takashi 
Published: November 2010

Abstract
LGP2 is an important intracellular receptor that recognizes viral RNAs in innate immunity. To understand the mechanism of viral RNA recognition, we cloned an LGP2 cDNA and gene in Japanese flounder (Paralichthys olivaceus). Viral hemorrhagic septicemia virus-induced expressions of LGP2 mRNA were evaluated in vivo and in vitro by quantitative real-time PCR (Q-PCR) using primers based on the clone sequences. The expression of LGP2 mRNA in the kidney dramatically increased at 3 d postinfection. The expression of LGP2 mRNA also increased in the head kidney leukocytes stimulated with artificial dsRNA (polyinosin-polycytidylic acid) in vitro. To evaluate the antiviral activity of the flounder LGP2, three expression constructs containing pcDNA4-LGP2 (full-length), pcDNA4-LGP2ΔRD (regulatory domain deleted), and pcDNA4-Empty (as a negative control) were transfected into the hirame (flounder) natural embryo (hirame natural embryo) cell line. Forty-eight hours after transfection, the transfected cells were infected with ssRNA viruses, viral hemorrhagic septicemia virus, or hirame rhabdovirus. The cytopathic effects of the viruses were delayed by the overexpression of Japanese flounder LGP2. The Q-PCR demonstrated that mRNA expression levels of type I IFN and IFN-inducible genes (Mx and ISG15) in the hirame natural embryo cells overexpressing LGP2 were increased by polyinosin-polycytidylic acid and viral infections. These results suggest that Japanese flounder LGP2 plays an important role in the recognition of both viral ssRNA and dsRNA to induce the antiviral activity by the production of IFN-stimulated proteins.
Neutrophils Activate Alveolar Macrophages by Producing Caspase-6–Mediated Cleavage of IL-1 Receptor-Associated Kinase-M
Authors: Kobayashi Hiroshi , Nolan Anna , Naveed Bushra , Hoshino Yoshihiko , Segal Leopoldo N. , Fujita Yoko , Rom William N. , Weiden Michael D. 
Published: November 2010

Abstract
Alveolar macrophages (AMs) are exposed to respirable microbial particles. Similar to phagocytes in the gastrointestinal tract, AMs can suppress inflammation after exposure to nonpathogenic organisms. IL-1R–associated kinase-M (IRAK-M) is one inhibitor of innate immunity, normally suppressing pulmonary inflammation. During pneumonia, polymorphonuclear neutrophils (PMNs) are recruited by chemotactic factors released by AMs to produce an intense inflammation. We report that intact IRAK-M is strongly expressed in resting human AMs but is cleaved in patients with pneumonia via PMN-mediated induction of caspase-6 (CASP-6) activity. PMN contact is necessary and PMN membranes are sufficient for CASP-6 induction in macrophages. PMNs fail to induce TNF-α fully in macrophages expressing CASP-6 cleavage-resistant IRAK-M. Without CASP-6 expression, PMN stimulation fails to cleave IRAK-M, degrade IκBα, or induce TNF-α. CASP-6−/− mice subjected to cecal ligation and puncture have impaired TNF-α production in the lung and decreased mortality. LPS did not induce or require CASP-6 activity demonstrating that TLR2/4 signaling is independent from the CASP-6 regulated pathway. These data define a central role for CASP-6 in PMN-driven macrophage activation and identify IRAK-M as an important target for CASP-6. PMNs de-repress AMs via CASP-6–mediated IRAK-M cleavage. This regulatory system will blunt lung inflammation unless PMNs infiltrate the alveolar spaces.
Leishmania Inhibitor of Serine Peptidase 2 Prevents TLR4 Activation by Neutrophil Elastase Promoting Parasite Survival in Murine Macrophages
Authors: Faria Marilia S. , Reis Flavia C. G. , Azevedo-Pereira Ricardo L. , Morrison Lesley S. , Mottram Jeremy C. , Lima Ana Paula C. A. 
Published: November 2010

Abstract
Leishmania major is a protozoan parasite that causes skin ulcerations in cutaneous leishmaniasis. In the mammalian host, the parasite resides in professional phagocytes and has evolved to avoid killing by macrophages. We identified L. major genes encoding inhibitors of serine peptidases (ISPs), which are orthologs of bacterial ecotins, and found that ISP2 inhibits trypsin-fold S1A family peptidases. In this study, we show that L. major mutants deficient in ISP2 and ISP3 (Δisp2/3) trigger higher phagocytosis by macrophages through a combined action of the complement type 3 receptor, TLR4, and unregulated activity of neutrophil elastase (NE), leading to parasite killing. Whereas all three components are required to mediate enhanced parasite uptake, only TLR4 and NE are necessary to promote parasite killing postinfection. We found that the production of superoxide by macrophages in the absence of ISP2 is the main mechanism controlling the intracellular infection. Furthermore, we show that NE modulates macrophage infection in vivo, and that the lack of ISP leads to reduced parasite burdens at later stages of the infection. Our findings support the hypothesis that ISPs function to prevent the activation of TLR4 by NE during the Leishmania–macrophage interaction to promote parasite survival and growth.
Nonconventional CD8+ T Cell Responses to Listeria Infection in Mice Lacking MHC Class Ia and H2-M3
Authors: Cho Hoonsik , Choi Hak-Jong , Xu Honglin , Felio Kyrie , Wang Chyung-Ru 
Published: November 2010

Abstract
CD8+ T cells restricted to MHC class Ib molecules other than H2-M3 have been shown to recognize bacterial Ags. However, the contribution of these T cells to immune responses against bacterial infection is not well defined. To investigate the immune potential of MHC class Ib-restricted CD8+ T cells, we have generated mice that lack both MHC class Ia and H2-M3 molecules (Kb−/−D b−/−M3−/−). The CD8+ T cells present in Kb−/−D b−/−M3−/− mice display an activated surface phenotype and are able to secrete IFN-γ rapidly upon anti-CD3 and anti-CD28 stimulation. Although the CD8+ T cell population is reduced in Kb−/−D b−/−M3−/− mice compared with that in Kb−/−D b−/− mice, this population retains the capacity to expand significantly in response to primary infection with the bacteria Listeria monocytogenes. However, Kb−/−D b−/−M3−/− CD8+ T cells do not expand upon secondary infection, similar to what has been observed for H2-M3–restricted T cells. CD8+ T cells isolated from Listeria-infected Kb−/−D b−/−M3−/− mice exhibit cytotoxicity and secrete proinflammatory cytokines in response to Listeria-infected APCs. These T cells are protective against primary Listeria infection, as Listeria-infected Kb−/−D b−/−M3−/− mice exhibit reduced bacterial burden compared with that of infected β2-microglobulin–deficient mice that lack MHC class Ib-restricted CD8+ T cells altogether. In addition, adoptive transfer of Listeria-experienced Kb−/−D b−/−M3−/− splenocytes protects recipient mice against subsequent Listeria infection in a CD8+ T cell-dependent manner. These data demonstrate that other MHC class Ib-restricted CD8+ T cells, in addition to H2-M3–restricted T cells, contribute to antilisterial immunity and may contribute to immune responses against other intracellular bacteria.
Netrin-1 Signaling Dampens Inflammatory Peritonitis
Authors: Mirakaj Valbona , Gatidou Dimitra , Pötzsch Claudia , König Klemens , Rosenberger Peter 
Published: November 2010

Abstract
Previous studies implicated the anti-inflammatory potential of the adenosine 2B receptor (A2BAR). A2BAR activation is achieved through adenosine, but this is limited by its very short t1/2. To further define alternative adenosine signaling, we examined the role of netrin-1 during acute inflammatory peritonitis. In this article, we report that animals with endogenous repression of netrin-1 (Ntn1+/−) demonstrated increased cell count, increased peritoneal cytokine concentration, and pronounced histological changes compared with controls in a model of zymosan A peritonitis. Exogenous netrin-1 significantly decreased i.p. inflammatory changes. This effect was not present in animals with deletion of A2BAR (A2BAR−/−). A2BAR−/− animals demonstrated no change in cell count, i.p. cytokine concentration, or histology in response to netrin-1 injection. These data strengthen the role of netrin-1 as an immunomodulatory protein exerting its function in dependence of the A2BAR and further define alternative adenosine receptor signaling.
Graft-versus-Host Disease Is Independent of Innate Signaling Pathways Triggered by Pathogens in Host Hematopoietic Cells
Authors: Li Hongmei , Matte-Martone Catherine , Tan Hung Sheng , Venkatesan Srividhya , McNiff Jennifer , Demetris Anthony J. , Jain Dhanpat , Lakkis Fadi , Rothstein David , Shlomchik Warren D. 
Published: November 2010

Abstract
Graft-versus-host disease (GVHD) is initiated by APCs that prime alloreactive donor T cells. In antipathogen responses, Ag-bearing APCs receive signals through pattern-recognition receptors, including TLRs, which induce the expression of costimulatory molecules and production of inflammatory cytokines, which in turn mold the adaptive T cell response. However, in allogeneic hematopoietic stem cell transplantation (alloSCT), there is no specific pathogen, alloantigen is ubiquitous, and signals that induce APC maturation are undefined. To investigate APC activation in GVHD, we used recipient mice with hematopoietic cells genetically deficient in pathways critical for APC maturation in models in which host APCs are absolutely required. Strikingly, CD8-mediated and CD4-mediated GVHD were similar whether host APCs were wild-type or deficient in MyD88, TRIF, or MyD88 and TRIF, which excludes essential roles for TLRs and IL-1β, the key product of inflammasome activation. Th1 differentiation was if anything augmented when APCs were MyD88/TRIF−/−, and T cell production of IFN-γ did not require host IL-12. GVHD was also intact when APCs lacked the type I IFNR, which amplifies APC activation pathways that induce type I IFNs. Thus in GVHD, alloreactive T cells can be activated when pathways critical for antipathogen T cell responses are impaired.
A reflection on critical management studies
Authors: Akella Devi 
Published: November 2010

AbstractCritical Management Studies (CMS) is interested in examining and challenging the legitimacy of traditional management theories, values and assumptions. CMS believes by reflecting and questioning existing management practices, it is possible to generate better norms, policies, ideas and management values. The essence of CMS is to deconstruct the various management techniques and functions, to expose any forms of discrimination and exploitation taking place in contemporary organisations and emancipate employees from their pain, suffering and frustration.This paper seeks to make a contribution in the area of CMS, by examining the overall effectiveness of CMS in fulfilling its objectives. It seeks to address the effectiveness of CMS in achieving its goals in organisations, with the support of an empirical study conducted at a professional accounting firm.
Block or traditional? An analysis of student choice of teaching format
Authors: Burton Suzan , Nesbit Paul L 
Published: November 2010

AbstractBlock (or intensive) teaching is used by many management schools, but the factors that drive students to choose (or avoid) block subjects are not well understood. This paper reviews the research findings on intensive teaching and analyses the factors which predict student choice between different teaching formats, based on an analysis of qualitative and quantitative survey data. If studying one subject at a time, a majority of students appear to prefer a less intensive format. However the results show that three factors influence students' likelihood to choose the block format: their experience with the format, their perception of their ability in a particular subject and their concurrent subject load. There are also subject specific differences in student preferences. Implications for block scheduling and for actions to address perceived disadvantages of the block method are addressed.
Working and caring for a child with chronic illness: Barriers in achieving work-family balance
Authors: George Ajesh , Vickers Margaret H , Wilkes Lesley , Barton Belinda 
Published: November 2010

AbstractThis paper shares some findings from the initial, qualitative stage of a larger, national study currently being undertaken in Australia, exploring the experiences of parents who are working full-time and caring for a child with chronic illness. The findings highlight the limited support that most parents receive in their workplace, especially from employers. In-depth interviews revealed the negative and unsupportive attitude that employers had towards these parents. The provision of flexible work arrangements and leave entitlements, which were critical supports for these parents, were rarely offered by employers. Respondents reported high levels of frustration and difficulty balancing their dual roles.
Vascular Access Using the Superficial Femoral Vein
Authors: Scollay John M. , Skipworth Richard J.E. , Severn Alison , Nagy John , Howd Alison , Griffiths Gareth D. 
Published: November 2010

Purpose The superficial femoral vein (SFV) provides an alternative autologous conduit for fistula formation in patients who might otherwise require a prosthetic graft for hemodialysis (HD) access. The purpose of this study was to assess the results of this technique. Methods Patients who underwent formation of a SFV fistula were identified from a prospectively maintained database. Casenotes were reviewed for details of the operation, complications, subsequent interventions, and to determine whether the fistula was used for vascular access. Results Fifteen patients (seven males, eight females; median age 53, range 28–72 yrs) were identified. Patients had a median of four (range 2–9) previous fistulae. In three patients, the mobilized SFV was transferred to the upper limb while 12 patients had lower limb fistulae. Twelve patients (80%) used their SFV fistula for HD. Eleven patients developed a wound complication (infection, dehiscence, hematoma or bleeding), with four patients returning to theater for formal exploration and three requiring application of a vacuum dressing. Two patients developed post-operative lower limb ischemia. Two patients died during a median follow-up time of 7 (range 1–27) months. Conclusion In selected patients who have exhausted conventional routes for vascular access the SFV fistula can be used for the maintenance of HD. There is, however, significant associated morbidity and repeated intervention is often required.
VenaTrac™ Device for Over-the-Wire Placement of Chronic Dialysis Catheters
Authors: Mojibian Hamid R. , Oneal Patrice , Eliseo Donna , Tal Michael G. 
Published: November 2010

Purpose The VenaTrac™ is designed for exchange and primary placement of chronic tunneled hemodialysis catheters over a wire. It occludes both lumens of the catheter for the purpose of reducing the risk of air embolism and blood loss. The purpose of this paper is to report our experience with the use of this device. Methods A retrospective review of chronic hemodialysis dialysis catheters exchanges over a 30-month period was performed. Two hundred and ninety-seven over-the-wire catheter exchanges and 47 primary placements using the VenaTrac™ device were reviewed. In addition, 430 over-the-wire catheter exchanges without the use of the VenaTrac™ were reviewed. Results No insertional complications or air embolism occurred when using the VenaTrac™. Symptomatic air embolism was documented in 5 out of 430 catheter exchanges performed without the use of VenaTrac™ (1.2%). Conclusions VenaTrac™ over-the-wire insertion device demonstrated safe and reliable use with no incidence of air embolism.
Malnutrition, Infection and Arteriovenous Fistula Failure: Is There a Link?
Authors: Gagliardi Gian Manlio , Rossi Stefania , Condino Francesca , Mancuso Domenico , Greco Francesca , Tenuta Robert , Savino Olga , Bonofiglio Renzo , Domma Filippo , Latorre Giovanni 
Published: November 2010

Introduction The histology of neointimal hyperplasia, the primary cause of arteriovenous fistula (AVF) stenosis, resembles the histology of atherosclerosis. We evaluated classic atherogenic risk factors such as hypertension, smoking, diabetes, cholesterol, and evaluated the role of expanded risk factors such as: cytomegalovirus (CMV), Helicobacter pylori (H. pylori), Chlamydia pneumoniae (C. pneumoniae), infection, and malnutrition, as possible causes of AVF failure in hemodialysis (HD) patients. Methods AVF of 91 HD patients were monitored by on-line blood flow measurement (Qac); levels of albumin, fibrinogen, C-reactive protein and plasma cholesterol were recorded. Nutrition was evaluated via the Malnutrition Inflammation Score and the normalized protein intake (nPCR). Seropositivity to CMV, C. pneumoniae and H. Pylori were assessed. Results Twenty-one patients had at least one episode of vascular access thrombosis; 17 patients had stenotic lesions. Analysis of survival tables revealed that patients who had high IgG CMV antibody levels had a higher probability of AVF failure than patients with lower CMV antibody levels. The difference in the empirical survival functions was statistically significant when we stratified by CMV antibody levels, unlike H. pylori or C. pneumoniae. In a logistic regression model, CMV, increased cholesterol, and decreases in nPCR and Qac significantly increased the risk of AVF failure. Conclusion Our study suggests that CMV infection, total plasma cholesterol, decreased Qac, and nPCR are important risk factors of AVF failure in HD patients.
Explanation of Totally Implantable Venous Access Ports of the Forearm: Reasons for Removal and Observed Complications
Authors: Goltz Jan P. , Kickuth Ralph , Scholl Anne , Machann Wolfram , Ritter Christian O. , Hahn Dietbert , Wittenberg Günther 
Published: November 2010

Purpose To evaluate indications for, and complications during, explantation of interventionally placed totally implantable venous access ports (TIVAPs) of the forearm. Background Many studies analyze the explantation procedure of pectorally placed TIVAPs. The literature on TIVAPs in the forearm is limited, and the explantation procedure of these devices in the forearm has not been sufficiently evaluated yet. Methods We retrospectively reviewed the archives of our institute between May 2006 and May 2009 and identified 850 TIVAPs that had been implanted in the forearm. Of these TIVAPs, 145/850 (80 in women, 65 in men; mean age 52 years, range 15–82 years) were explanted during this period either by interventionists (n=109) or by general surgeons (n=36). Results Mean catheter survival was 322 days. Reasons for explantation were end of therapy (63.4%), infection (29.0%), thrombosis (3.4%), occlusion (1.4%), or dislocation (1.4%) of the TIVAP. Primary technical success rate was 97.2% for the surgical as well as for the interventional procedure. The overall success rate was 100%. The reasons for retrieval failure by interventionists (3/108) as well as by surgeons (1/36) were post-thrombotic adhesions of the port catheter to the blood vessel wall. Conclusions Removal of TIVAPs of the forearm shows a high technical success rate and a low complication rate. End of therapy is the most common indication for explantation. There is a low risk of interventional removal failure with a resulting need for open surgery to remove the device.
Central Venous Catheters in Neonates: From Simple Monolumen to Port Catheter
Authors: Caruselli Marco , Carboni Laura , Franco Federica , Torino Giovanni , Camilletti Gianfranco , Piattellini Gianmarco , Giretti Roberto , Pagni Raffaella 
Published: November 2010

The use of Central Venous Catheters (CVCs) represents an important step in the management of the surgical, onco-hematology and critically ill patients. CVCs in neonates, like in adult patients, are mainly used to infuse hyperosmolar solutions, to take blood samples and for hemodynamic monitoring. The need for CVCs is higher in neonates than in adults. Poor peripheral access and the high demand for IV access and blood samples are already valuable indications for a CVC.