bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Nursing Clinical Decision Support System and Potential Predictors of Head-of-Bed Position for Patients Receiving Mechanical Ventilation
Authors: Lyerla Frank , LeRouge Cynthia , Cooke Dorothy A. , Turpin Debra , Wilson Lisa 
Published: January 2010

Background Patients receiving mechanical ventilation are at high risk for pneumonia due to aspiration. Published guidelines recommend elevating the head of the bed 30° to 45°, if not contraindicated, to reduce risk, but this intervention is underused.Objectives To facilitate incorporating evidence-based practice by improving positioning of patients receiving mechanical ventilation and to identify patient and nurse characteristics that predict use of the guideline.Methods A modified interrupted time-series design was used. Data were collected on 43 patients and 33 nurses 3 separate times in a 12-bed intensive care unit at a medium-sized hospital. A total of 105 observations were recorded for analysis each time.Results Mean elevations of the head of the bed increased significantly from phase 1 (27.7°) to phase 2 (31.7°) and from phase 1 to phase 3 (31.1°). Elevations were higher for tube-fed patients than for patients not given enteral tube feedings. Elevations were higher for patients with a pulmonary-related diagnosis and lower for patients with a gastrointestinal diagnosis than for patients with other diagnoses. Elevations were lower for patients with a body mass index between 25.0 and 29.9 (overweight) than for patients with other body mass index values. Nurse characteristics were not significant predictors of elevation.Conclusion A nursing clinical decision support system integrated into a patient’s electronic flow sheet can increase nurses’ adherence to guidelines. Pulmonary and gastrointestinal diagnoses, body mass index, and tube feeding are predictors of elevation of the head of the bed.
Essential Roles of IL-6 Trans-Signaling in Colonic Epithelial Cells, Induced by the IL-6/Soluble–IL-6 Receptor Derived from Lamina Propria Macrophages, on the Development of Colitis-Associated Premalignant Cancer in a Murine Model
Authors: Matsumoto Satoshi , Hara Taeko , Mitsuyama Keiichi , Yamamoto Mayuko , Tsuruta Osamu , Sata Michio , Scheller Jürgen , Rose-John Stefan , Kado Sho-ichi , Takada Toshihiko 
Published: December 2009

Abstract
Activation of the IL-6/Stat3 via IL-6 trans-signaling plays an important role in the pathogenesis of inflammatory bowel disease. Colitis-associated cancer (CAC) is a large bowel cancer and occurs with long-standing inflammatory bowel disease. The role of the IL-6/Stat3 in the development of CAC has not been fully understood. We investigate whether IL-6 trans-signaling contributes to the development of CAC using a mouse colitis-associated premalignant cancer (CApC) model. Chronic colitis (CC) was induced in BALB/c mice using dextran sodium sulfate. CApC was induced by dextran sodium sulfate treatment to CC-affected mice. IL-6 expression was determined by quantitative RT-PCR and immunofluorescence staining in colon. Phospho-Stat3 expression was examined by Western blotting and immunofluorescence analysis. The expression of IL-6 receptors (i.e., the IL-6R α-chain and gp130) and tumor necrosis factor-α converting enzyme in the colon was examined by laser-capture microdissection and immunofluorescence staining. Soluble IL-6Rα (sIL-6Rα) was examined by Western blotting of epithelial cell-depleted colonic tissues. We also investigated whether a soluble gp130-Fc fusion protein could prevent CApC. IL-6 expression was increased in the colon of CC- and CApC-affected mice and was restricted to lamina propria-macrophages. The expression of IL-6Rα and tumor necrosis factor-α converting enzyme was increased in the lamina propria CD11b-macrophages of CC-affected mice. sIL-6Rα expression was also increased in these tissues. Reduced levels of IL-6Rα generation were observed in the colonic epithelial cells of CC- and CApC-affected mice and were associated with the increased expression of gp130 and phospho-Stat3. Treatment with soluble gp130Fc significantly reduced the CApC. IL-6 trans-signaling in epithelial cells induced by macrophage-derived IL-6/sIL-6Rα plays a crucial role in the development of CAC.
IL-10 Induction by Bordetella parapertussis Limits a Protective IFN-γ Response
Authors: Wolfe Daniel N. , Karanikas Alexia T. , Hester Sara E. , Kennett Mary J. , Harvill Eric T. 
Published: December 2009

Abstract
Bordetella parapertussis causes the prolonged coughing illness known as pertussis or whooping cough, persisting for weeks within the respiratory tracts of infected hosts but inducing a very poor T cell response relative to that induced by Bordetella pertussis, the more common cause of pertussis. In this study, we examine the contributions of cytokines involved in the clearance of B. parapertussis and immunomodulation that delays effective clearance. The slow elimination of this pathogen from the respiratory tracts of mice coincides with the gradual accumulation of CD4+ T cells in the lungs and B. parapertussis-responsive IFN-γ–producing cells in the spleen. IFN-γ–deficient mice were defective in the accumulation of leukocytes in lungs and in clearance of B. parapertussis from the lungs. In vitro B. parapertussis-stimulated macrophages produced IL-10, which inhibited the generation of the IFN-γ response that is required for protection in vivo. As compared with wild-type mice, IL-10–deficient mice produced significantly higher levels of IFN-γ, had higher numbers of leukocytes accumulated in the lungs, and cleared B. parapertussis more rapidly. Together, these data indicate that B. parapertussis induces the production of IL-10, which facilitates its persistence within infected hosts by limiting a protective IFN-γ response.
Critical Protective Role for MCP-1 in Pneumonic Burkholderia mallei Infection
Authors: Goodyear Andrew , Jones Abby , Troyer Ryan , Bielefeldt-Ohmann Helle , Dow Steven 
Published: December 2009

Abstract
Burkholderia mallei is a Gram-negative bacterial pathogen of domestic equidae and humans that can cause severe, rapidly life-threatening pneumonic infections. Little is known regarding the role of chemokines and early cellular immune responses in protective immunity to pulmonary infection with B. mallei. Although the role of MCP-1 in Gram-positive bacterial infections has been previously investigated, the role of MCP-1 in immunity to acute pneumonia caused by Gram-negative bacteria, such as B. mallei, has not been assessed. In a mouse model of pneumonic B. mallei infection, we found that both MCP-1−/− mice and CCR2−/− mice were extremely susceptible to pulmonary infection with B. mallei, compared with wild-type (WT) C57Bl/6 mice. Bacterial burden and organ lesions were significantly increased in CCR2−/− mice, compared with WT animals, following B. mallei challenge. Monocyte and dendritic cell recruitment into the lungs of CCR2−/− mice was significantly reduced in comparison with that in WT mice following B. mallei infection, whereas neutrophil recruitment was actually increased. Depletion of monocytes and macrophages prior to infection also greatly raised the susceptibility of WT mice to infection. Production of IL-12 and IFN-γ in the lungs after B. mallei infection was significantly impaired in both MCP-1−/− and CCR2−/− mice, whereas treatment of CCR2−/− mice with rIFN-γ restored protection against lethal challenge with B. mallei. Thus, we conclude that MCP-1 plays a key role in regulating cellular immunity and IFN-γ production following pneumonic infection with B. mallei and therefore may also figure importantly in other Gram-negative pneumonias.
TCRβ Feedback Signals Inhibit the Coupling of Recombinationally Accessible Vβ14 Segments with DJβ Complexes
Authors: Yang-Iott Katherine S. , Carpenter Andrea C. , Rowh Marta A. W. , Steinel Natalie , Brady Brenna L. , Hochedlinger Konrad , Jaenisch Rudolf , Bassing Craig H. 
Published: December 2009

Abstract
Ag receptor allelic exclusion is thought to occur through monoallelic initiation and subsequent feedback inhibition of recombinational accessibility. However, our previous analysis of mice containing a V(D)J recombination reporter inserted into Vβ14 (Vβ14Rep) indicated that Vβ14 chromatin accessibility is biallelic. To determine whether Vβ14 recombinational accessibility is subject to feedback inhibition, we analyzed TCRβ rearrangements in Vβ14Rep mice containing a preassembled in-frame transgenic Vβ8.2Dβ1Jβ1.1 or an endogenous Vβ14Dβ1Jβ1.4 rearrangement on the homologous chromosome. Expression of either preassembled VβDJβC β-chain accelerated thymocyte development because of enhanced cellular selection, demonstrating that the rate-limiting step in early αβ T cell development is the assembly of an in-frame VβDJβ rearrangement. Expression of these preassembled VβDJβ rearrangements inhibited endogenous Vβ14-to-DJβ rearrangements as expected. However, in contrast to results predicted by the accepted model of TCRβ feedback inhibition, we found that expression of these preassembled TCR β-chains did not downregulate recombinational accessibility of Vβ14 chromatin. Our findings suggest that TCRβ-mediated feedback inhibition of Vβ14 rearrangements depends on inherent properties of Vβ14, Dβ, and Jβ recombination signal sequences.
Promoting Immune Responses by LIGHT in the Face of Abundant Regulatory T Cell Inhibition
Authors: Wang Yugang , Zhu Mingzhao , Yu Ping , Fu Yang-Xin 
Published: December 2009

Abstract
CD4+ regulatory T cell (Treg) populations are believed to play very important roles in the suppression of immune responses. Overriding Treg inhibition is necessary for initiating primary immune reaction upon inflammatory Ag stimulation. LIGHT, TNF superfamily member 14, has been shown to be a costimulatory molecule for effector T cells. Overexpression of lymphotoxin-related inducible ligand that competes for glycoprotein D binding to herpesvirus entry mediator on T cells (LIGHT) on T cells induces strong T cell-mediated experimental intestinal inflammation. How this process is initiated by LIGHT in suppressive intestinal environments remains incompletely understood. In this study, we assessed the effect of LIGHT on Tregs. Our results indicate that LIGHT can support the expansion and function of Tregs. However, when LIGHT was highly expressed, these abundant Tregs failed to suppress the development of T cell-mediated experimental colitis and antitumor immunity. We showed that this might be, in part, due to an ability of LIGHT to promote effector T cell proliferation and differentiation even in a Treg-abundant environment. Our data collectively suggest that LIGHT might be a critical cytokine involved in the development of autoimmune inflammatory diseases and that LIGHT-targeted immunotherapy might be useful in the treatment of these diseases.
Inhibitory Role of Sphingosine 1-Phosphate Receptor 2 in Macrophage Recruitment during Inflammation
Authors: Michaud Jason , Im Dong-Soon , Hla Timothy 
Published: December 2009

AbstractMacrophage recruitment to sites of inflammation is an essential step in host defense. However, the mechanisms preventing excessive accumulation of macrophages remain relatively unknown. The lysophospholipid sphingosine 1-phosphate (S1P) promotes T and B cell egress from lymphoid organs by acting on S1P receptor 1 (S1P1R). More recently, S1P5R was shown to regulate NK cell mobilization during inflammation, raising the possibility that S1P regulates the trafficking of other leukocyte lineages. In this study, we show that S1P2R inhibits macrophage migration in vitro and that S1P2R-deficient mice have enhanced macrophage recruitment during thioglycollate peritonitis. We identify the signaling mechanisms used by S1P2R in macrophages, involving the second messenger cAMP and inhibition of Akt phosphorylation. In addition, we show that the phosphoinositide phosphatase and tensin homolog deleted on chromosome 10, which has been suggested to mediate S1P2R effects in other cell types, does not mediate S1P2R inhibition in macrophages. Our results suggest that S1P serves as a negative regulator of macrophage recruitment by inhibiting migration in these cells and identify an additional facet to the regulation of leukocyte trafficking by S1P.
Regulation of FcεRI Expression during Murine Basophil Maturation: The Interplay between IgE, Cell Division, and FcεRI Synthetic Rate
Authors: Zaidi Asifa K. , MacGlashan Donald W. 
Published: December 2009

Abstract
Expression of FcεRI on basophils and mast cells is modulated by IgE Ab. Previous studies have noted in vivo receptor expression dynamics that are discordant with expectations derived from in vitro studies. The current study presents a formal hypothesis to explain the discordant observations and tests two assumptions that underlie a proposed model of receptor dynamics. After first showing that a murine model of receptor expression on basophils recapitulates observations made using human basophils, the effect of changes in IgE on basophil egress rates was examined. In the proposed model, egress rates from bone marrow (BM) were assumed to be unaffected by changes in IgE concentration. Egress was tested by examining the labeling of BM and peripheral blood (BL) basophils at various times after injection of BrdU with and without injection with IgE. The IgE Ab did not alter the appearance of BrdU label in peripheral BL basophils. In addition, BM and BL basophils were responsive to the elevations in IgE, with receptor expression increasing on BM basophils before BL basophils. It was also noted that BL basophils expressed ∼50% of the receptor density of BM basophils. There was a 3-fold greater synthetic rate of FcεRI on BM basophils that readily explained the difference. These results provide support for the proposed hypothesis of rapid changes in receptor expression being controlled by cell replacement. The studies also support a model whereby receptor expression is limited by cell division and that basophils, once mature, slow their rate of receptor synthesis.
Autoimmune Disease in Lyn-Deficient Mice Is Dependent on an Inflammatory Environment Established by IL-6
Authors: Tsantikos Evelyn , Oracki Sarah A. , Quilici Cathy , Anderson Gary P. , Tarlinton David M. , Hibbs Margaret L. 
Published: December 2009

Abstract
Lyn-deficient mice develop Ab-mediated autoimmune disease resembling systemic lupus erythematosus where hyperactive B cells are major contributors to pathology. In this study, we show that an inflammatory environment is established in Lyn−/− mice that perturbs several immune cell compartments and drives autoimmune disease. Lyn−/− leukocytes, notably B cells, are able to produce IL-6, which facilitates hyperactivation of B and T cells, enhanced myelopoiesis, splenomegaly, and, ultimately, generation of pathogenic autoreactive Abs. Lyn−/− dendritic cells show increased maturation, but this phenotype is independent of autoimmunity as it is reiterated in B cell-deficient Lyn−/− mice. Genetic deletion of IL-6 on a Lyn-deficient background does not alter B cell development, plasma cell accumulation, or dendritic cell hypermaturation, suggesting that these characteristics are intrinsic to the loss of Lyn. However, hyperactivation of B and T cell compartments, extramedullary hematopoiesis, expansion of the myeloid lineage and autoimmune disease are all ameliorated in Lyn−/−IL-6−/− mice. Importantly, our studies show that although Lyn−/− B cells may be autoreactive, it is the IL-6–dependent inflammatory environment they engender that dictates their disease-causing potential. These findings improve our understanding of the mode of action of anti–IL-6 and B cell-directed therapies in autoimmune and inflammatory disease treatment.
SHP-1 Deficient Mast Cells Are Hyperresponsive to Stimulation and Critical in Initiating Allergic Inflammation in the Lung
Authors: Zhang Li , Oh Sun Young , Wu Xinxing , Oh Min Hee , Wu Fan , Schroeder John T. , Takemoto Clifford M. , Zheng Tao , Zhu Zhou 
Published: December 2009

Abstract
Phosphatase Src homology region 2 domain-containing phosphatase 1 (SHP-1)-deficient mice display an allergic asthma phenotype that is largely IL-13 and STAT6 dependent. The cell types responsible for the Th2 phenotype have not been identified. We hypothesized that SHP-1 deficiency leads to mast cell dysregulation and increased production and release of mediators and Th2 cytokines, leading to the allergic asthma phenotype. We examined SHP-1 regulation of mast cell differentiation, survival, and functional responses to stimulation using bone marrow-derived mast cells from viable motheaten (mev) mice. We assessed pulmonary phenotypical changes in mev mice on the mast cell-deficient KitW-Sh genetic background. The results showed that SHP-1 deficiency led to increased differentiation and survival, but reduced proliferation, of mast cells. SHP-1–deficient mast cells produced and released increased amounts of mediators and Th2 cytokines IL-4 and -13 spontaneously and in response to H2O2, LPS, and FcεI cross-linking, involving c-Kit–dependent and –independent processes. The FcεRI signaling led to binding of SHP-1 to linker for activation of T cells 2 and enhanced linker for activation of T cells 2 phosphorylation in mev bone marrow-derived mast cells. Furthermore, the number of mast cells in the lung tissue of mev mice was increased and mast cell production and release of Th2 cytokines were distinctly increased upon FcεRI stimulation. When backcrossed to the KitW-Sh background, mev mice had markedly reduced pulmonary inflammation and Th2 cytokine production. These findings demonstrate that SHP-1 is a critical regulator of mast cell development and function and that SHP-1–deficient mast cells are able to produce increased Th2 cytokines and initiate allergic inflammatory responses in the lung.
A Recombinant Bispecific Single-Chain Fragment Variable Specific for HLA Class II and FcαRI (CD89) Recruits Polymorphonuclear Neutrophils for Efficient Lysis of Malignant B Lymphoid Cells
Authors: Guettinger Yvonne , Barbin Karin , Peipp Matthias , Bruenke Joerg , Dechant Michael , Horner Heike , Thierschmidt Doreen , Valerius Thomas , Repp Roland , Fey Georg H. , Stockmeyer Bernhard 
Published: December 2009

Abstract
Bispecific Abs offer new perspectives for cancer immunotherapy. In this study, we describe a recombinant bispecific single-chain fragment variable (bsscFv) directed against FcαRI (CD89) on polymorphonuclear neutrophils (PMNs) or monocytes/macrophages and HLA class II on lymphoma target cells. FcαRI and HLA class II-directed single-chain fragment variable (scFv) fragments were isolated from phage display libraries, established from the hybridomas A77 and F3.3, respectively. The two scFv molecules were connected with a 20 aa flexible linker sequence. After expression in SF21 insect cells and chromatographic purification, the bispecific molecule showed specific binding to both Ags at KD values of 148 ± 42 nM and 113 ± 25 nM for the anti-FcαRI and anti-HLA class II scFv components in the bsscFv, respectively. In Ab-dependent cytotoxicity assays with PMNs as effectors and a series of lymphoma-derived cell lines (ARH-77, RAJI, REH, NALM-6, RS4;11), the bsscFv was significantly more cytotoxic than the parental murine IgG1 and its chimeric IgG1 derivative. When targeting primary tumor cell isolates from six patients with B cell malignancies, the killing capacity of the (FcαRI × HLA class II) bsscFv compared favorably to conventional HLA class II mAb. Importantly, the cell lines NALM-6 and RS411, as well as two primary tumor cell isolates, were exclusively lysed by the bsscFv. To our knowledge, this is the first report of an FcαRI-directed bsscFv effectively recruiting PMNs for redirected cytotoxicity against human B cell malignancies. Our data show that an (FcαRI × HLA class II) bsscFv is an interesting candidate for further engineering of small, modular immunopharmaceuticals.
A Single TCRα-Chain with Dominant Peptide Recognition in the Allorestricted HER2/neu-Specific T Cell Repertoire
Authors: Liang Xiaoling , Weigand Luise U. , Schuster Ingrid G. , Eppinger Elfriede , van der Griendt Judith C. , Schub Andrea , Leisegang Matthias , Sommermeyer Daniel , Anderl Florian , Han Yanyan , Ellwart Joachim , Moosmann Andreas , Busch Dirk H. , Uckert Wolfgang , Peschel Christian , Krackhardt Angela M. 
Published: December 2009

Abstract
T cells can recognize tumor cells specifically by their TCR and the transfer of TCR-engineered T cells is a promising novel tool in anticancer therapies. We isolated and characterized four allorestricted TCRs with specificity for the HER2/neu-derived peptide 369 (HER2369) demonstrating high peptide specificity. PBMCs transduced with especially one TCR, HER2-1, mediated specific tumor reactivity after TCR optimization suggesting that this TCR represents a potential candidate for targeting HER2 by TCR-transduced effector cells. Another TCR showed high-peptide specificity without tumor reactivity. However, the TCRα-chain of this TCR specifically recognized HER2369 not only in combination with the original β-chain but also with four other β-chains of the same variable family deriving from TCRs with diverse specificities. Pairing with one β-chain derived from another HER2369-specific TCR potentiated the chimeric TCRs in regard to functional avidity, CD8 independency, and tumor reactivity. Although the frequency of such TCR single chains with dominant peptide recognition is currently unknown, they may represent interesting tools for TCR optimization resulting in enhanced functionality when paired to novel partner chains. However, undirected mispairing with novel partner chains may also result in enhanced cross-reactivity and self-reactivity. These results may have an important impact on the further design of strategies for adoptive transfer using TCR-transduced T cells.
Cutting Edge: Nucleotide-Binding Oligomerization Domain 1-Dependent Responses Account for Murine Resistance against Trypanosoma cruzi Infection
Authors: Silva Grace K. , Gutierrez Fredy R. S. , Guedes Paulo M. M. , Horta Catarina V. , Cunha Larissa D. , Mineo Tiago W. P. , Santiago-Silva Juliana , Kobayashi Koichi S. , Flavell Richard A. , Silva João S. , Zamboni Dario S. 
Published: December 2009

Abstract
An effective innate immune recognition of the intracellular protozoan parasite Trypanosoma cruzi is critical for host resistance against Chagas disease, a severe and chronic illness that affects millions of people in Latin America. In this study, we evaluated the participation of nucleotide-binding oligomerization domain (Nod)-like receptor proteins in host response to T. cruzi infection and found that Nod1-dependent, but not Nod2-dependent, responses are required for host resistance against infection. Bone marrow-derived macrophages from Nod1−/− mice showed an impaired induction of NF-κB–dependent products in response to infection and failed to restrict T. cruzi infection in presence of IFN-γ. Despite normal cytokine production in the sera, Nod1−/− mice were highly susceptible to T. cruzi infection, in a similar manner to MyD88−/− and NO synthase 2−/− mice. These studies indicate that Nod1-dependent responses account for host resistance against T. cruzi infection by mechanisms independent of cytokine production.