bluuebunny/crossref_metadata_2025_split huggingface dataset:
Preventive Effects of Oral Tolerance on Allergic Inflammation and Airway Remodeling in a Murine Model
Authors: Kim Seung Joon , Shin Ji-Hyeon , Kim Seok Chan , Park Chan Kwon , Kim Soo Whan 
Published: February 2013

Background Oral tolerance (OT) is considered as a preventive and therapeutic strategy for treating asthma and allergic rhinitis (AR). We investigated the preventive effects of OT on allergic inflammation and remodeling in the upper and lower airways in a mouse model of allergy. Methods BALB/c mice were divided into four groups: control, allergy, low-dose OT, and high-dose OT. To induce OT, mice were fed ovalbumin (OVA) before sensitization with OVA/Al(OH)3 at a dose of 1 mg for 6 days in low-dose OT group and a single dose of 25 mg in high-dose OT group. After sensitization followed by OVA challenge, nasal symptoms, interleukin (IL)-13, interferon (IFN)-gamma, IL-10, and transforming growth factor (TGF) beta-1 levels in nasal lavage (NAL) and bronchoalveolar lavage (BAL) fluids were measured, and OVA-specific IgE, IgG1, and IgG2a levels were measured in the serum. The airway hyperresponsiveness (AHR) was measured by enhanced pause. The goblet cell hyperplasia and the thickness of lamina propria were observed in the upper and lower airways. Results In the allergy group, the allergic behavior scores, AHR, and OVA-specific IgE, IgG1, and IgG2a levels; inflammatory cells; IFN-gamma levels; and IL-13 levels in NAL/BAL fluids were elevated compared with the control group, low-dose OT group, and high-dose OT group. The allergy group had higher levels of IL-10 and TGF-beta-1 in BAL fluids when compared with the other groups. The goblet cell hyperplasia and the thickness of the lamina propria were attenuated in both OT groups compared with the allergy group. Conclusion OT may effectively prevent AHR, allergic inflammation, and airway remodeling in the upper and lower airways.
Changes of Histamine Receptors and CC Chemokines in Nasal Epithelial Cells and Fibroblasts after Respiratory Syncytial Virus Infection
Authors: Jung Su Young , Shin Seung Youp , Eun Young Gyu , Kim Sung Wan , Cho Joong Saeng 
Published: February 2013

Background Respiratory syncytial virus (RSV) is reported as the most influential factor that triggers hyperreactivity of the airway and causes asthma in infants and children. However, the mechanisms remain to be elucidated. The study evaluated the changes in the levels of four types of histamine receptor (HR) and CC chemokines, such as eotaxin and regulated on activation, normal T cell expressed and presumably secreted (RANTES), in nasal epithelial cells and fibroblasts after RSV infection. Methods Nasal cavity mucosa attained from 20 patients who had undergone inferior turbinoplasty were cleaned by normal saline mixed with gentamicin. Each sample was divided in half. One-half was used for incubation of epithelial cells, and the other half was used for culturing fibroblasts. The levels of HR 1 (H1R), 2 (H2R), 3 (H3R), 4 (H4R), eotaxin, and RANTES were measured by real-time polymerase chain reaction 0, 12, and 36 hours after infection with RSV. Results H1R was significantly increased at 12 and 36 hours compared with 0 hours in both cell types. The level of H2R was significantly increased in epithelial cells from 0 to 36 and 12 to 36 hours and in fibroblasts from 0 to 12 and 0 to 36 hours. There were significant increases of H3R level in fibroblasts from 0 to 12 and 0 to 36 hours, and of H4R in epithelial cells and fibroblasts from 0 to 12 and 0 to 36 hours. Eotaxin and RANTES were also significantly increased in both epithelial cells and fibroblasts from 0 to 12 and 0 to 36 hours. Conclusion RSV infection increases the levels of all four HRs, especially H1R and H2R, as well as the levels of eotaxin and RANTES in nasal epithelial cells and fibroblasts. These findings suggest that RSV infection might cause respiratory tract hyperreactivity by increasing the content of HRs and CC chemokines.
Processing of RecombinantListeria monocytogenesProteins for MHC Class I Presentation Follows a Dedicated, High-Efficiency Pathway
Authors: Wolf Benjamin J. , Princiotta Michael F. 
Published: February 2013

AbstractCD8+ T lymphocytes recognize short peptides of ∼8–10 aa bound to MHC class I molecules (pMHC) on the surface of APCs. These peptides can be generated from either endogenous proteins synthesized by the biosynthetic machinery of the presenting cell or from exogenously sourced proteins. Because much of the research characterizing the MHC class I processing pathway has focused on endogenously synthesized proteins, it is not known whether differences exist in the processing pathway followed by endogenously synthesized versus exogenously sourced proteins. To highlight potential differences in the processing of endogenous versus exogenous proteins, we developed a model system to measure the efficiency of pMHC generation from nearly identical recombinant proteins expressed from vaccinia virus and Listeria monocytogenes. In these experiments, we uncovered a striking difference in the way recombinant Listeria Ags are processed and presented when compared with endogenously synthesized viral proteins. Specifically, we find that pMHC production from secreted Listeria proteins occurs at the same rate, independent of the cellular half-life of the protein from which it is derived, whereas the rate of pMHC production from endogenously synthesized viral proteins is absolutely dependent on its protein half-life. Accordingly, our data demonstrate the existence of a distinct and highly efficient MHC class I presentation pathway used for the processing of at least some exogenously synthesized proteins.
IL-21 Enhances Phagocytosis in Mononuclear Phagocyte Cells: Identification of Spleen Tyrosine Kinase as a Novel Molecular Target of IL-21
Authors: Vallières Francis , Girard Denis 
Published: February 2013

Abstract
The biological significance of the IL-21/IL-21R system in human monocytes/macrophages is not well documented, and the expression of IL-21R is unclear and has been disputed. In this study, we showed for the first time, to our knowledge, that human monocyte–like THP-1 cells expressed the two IL-21R components, CD132 (γc) and IL-21Rα, on their cell surface, as assessed by flow cytometry. Moreover, IL-21 was found to enhance FcR-mediated phagocytosis, but not endocytosis. The ability of IL-21 to enhance phagocytosis was not associated with an increased expression of both IL-21R components at the cell surface, and IL-21 did not act in synergy with IL-15. IL-21 activated spleen tyrosine kinase (Syk), as evidenced by its ability to increase Syk phosphorylation. Using a pharmacological approach to inhibit Syk activity, and an antisense technique to downregulate Syk protein expression, we demonstrated the importance of Syk in IL-21–induced phagocytosis. In addition, both CD132 and IL-21Rα were expressed on the cell surface of naive monocytes, as well as in GM-CSF–monocyte-derived macrophages. Moreover, IL-21 also induced phagocytosis in these cells. We conclude that IL-21 possesses important biological effects in mononuclear phagocyte cells and that Syk is a novel molecular target of IL-21 that was previously unknown. Therefore, future development of therapeutic strategies targeting the IL-21/IL-21R system should consider that monocyte and macrophage cell physiology may be affected by this system.
A Novel IRAK1–IKKε Signaling Axis Limits the Activation of TAK1–IKKβ Downstream of TLR3
Authors: Bruni Daniela , Sebastia Jordi , Dunne Susan , Schröder Martina , Butler Marion P. 
Published: February 2013

Abstract
IRAK1 is involved in the regulation of type I IFN production downstream of TLR3. Previous work indicated that IRAK1 negatively regulates TRIF-mediated activation of IRF3 and IRF7. We report that IRAK1 limits the activation of the TLR3–NF-κB pathway. Following TLR3 stimulation, IRAK1-deficient macrophages produced increased levels of IL-6 and IFN-β compared with wild type macrophages. Pharmacological inhibition of TAK1 reduced this increase in IFN-β, together with the heightened activation of IRF3 and p65 found in TLR3-ligand stimulated IRAK1-deficient macrophages. Recently, IKKε and TANK-binding kinase 1 (TBK1) were reported to limit activation of the NF-κB pathway downstream of IL-1R, TNFR1, and TLRs. We show that TBK1 has a positive role in the TLR3–NF-κB pathway, because we detected reduced levels of IL-6 and reduced activation of p65 in TBK1-deficient macrophages. In contrast, we show that IKKε limits the activation of the TLR3–NF-κB pathway. Furthermore, we show that IRAK1 is required for the activation of IKKε downstream of TLR3. We report impaired activation of ERK1/2 in IRAK1– and IKKε-deficient macrophages, a novel finding for both kinases. Importantly, this work provides novel mechanistic insight into the regulation of the TLR3-signaling pathway, providing strong evidence that an IRAK1-IKKε–signaling axis acts to limit the production of both type I IFNs and proinflammatory cytokines by regulating TAK1 activity.
Human Chorionic Gonadotropin as a Central Regulator of Pregnancy Immune Tolerance
Authors: Schumacher Anne , Heinze Kristina , Witte Jeanette , Poloski Eileen , Linzke Nadja , Woidacki Katja , Zenclussen Ana C. 
Published: February 2013

Abstract
Normal pregnancy is characterized by an early expansion of regulatory T cells (Tregs), which is known to contribute to fetal tolerance. However, mechanisms and factors behind Treg expansion are not yet defined. Recently, we proposed that the pregnancy hormone human chorionic gonadotropin (hCG) efficiently attracts human Tregs to trophoblasts, favoring their accumulation locally. In this study, we hypothesized that hCG not only acts as a chemoattractant of Tregs but also plays a central role in pregnancy-induced immune tolerance. Virgin, normal pregnant, and abortion-prone female mice were treated either with 10 IU/ml hCG or PBS at days 0, 2, 4, and 6 of pregnancy. The hCG effect on Treg frequency and cytokine secretion was determined in Foxp3gfp females. hCG impact on Treg suppressive capacity was studied in vitro. In vivo, we investigated whether hCG enhances Treg suppressive capacity indirectly by modulating dendritic cell maturation in an established mouse model of disturbed fetal tolerance. Application of hCG increased Treg frequency in vivo and their suppressive activity in vitro. In females having spontaneous abortions, hCG provoked not only an augmentation of Treg numbers, but also normalized fetal abortion rates. hCG-generated Tregs were fully functional and could confer tolerance when adoptively transferred. hCG also retained dendritic cells in a tolerogenic state that is likely to contribute to both Treg expansion and prevention of abortion. Our results position hCG in a novel, so far unknown role as modulator of immune tolerance during pregnancy.
IL-10 Inhibits Mature Fibrotic Granuloma Formation during Mycobacterium tuberculosis Infection
Authors: Cyktor Joshua C. , Carruthers Bridget , Kominsky Rachel A. , Beamer Gillian L. , Stromberg Paul , Turner Joanne 
Published: February 2013

Abstract
Protective immunity and latent Mycobacterium tuberculosis infection in humans are associated with the formation of mature protective granulomas within the lung. Unfortunately, understanding the importance of such structures has been hindered by the lack of small-animal models that can develop mature granulomas. In this article, we describe for the first time, to our knowledge, the formation of mature, fibrotic M. tuberculosis–containing pulmonary granulomas in a mouse model of IL-10 deficiency (CBA/J IL-10−/−). Long-term control of M. tuberculosis infection in the absence of IL-10 was also associated with an early and enhanced capacity for Ag presentation and a significant increase in the generation of multifunctional T cells. Although IL-10 deficiency is known to enhance Th1 immune responses in general, we demonstrate in this study using transient anti–IL-10R treatment that it is the presence of IL-10 in vivo during the first month of M. tuberculosis infection that plays a definitive role in the inhibition of optimum protective immunity that can establish the environment for mature granuloma formation. Although the importance of IL-10 during M. tuberculosis infection has been debated, our data demonstrate that in CBA/J mice, IL-10 plays a significant early inhibitory role in preventing the development of protective immunity associated with containment of M. tuberculosis infection.
The Structural Wedge Domain of the Receptor-like Tyrosine Phosphatase CD45 Enforces B Cell Tolerance by Regulating Substrate Specificity
Authors: Zikherman Julie , Parameswaran Ramya , Hermiston Michelle , Weiss Arthur 
Published: February 2013

Abstract
CD45 is a receptor-like tyrosine phosphatase that positively regulates BCR signaling by dephosphorylating the inhibitory tyrosine of the Src family kinases. We showed previously that a single point mutation, E613R, introduced into the cytoplasmic membrane–proximal “wedge” domain of CD45 is sufficient to drive a lupus-like autoimmune disease on a susceptible genetic background. To clarify the molecular mechanism of this disease, we took advantage of a unique allelic series of mice in which the expression of CD45 is varied across a broad range. Although both E613R B cells and those with supraphysiologic CD45 expression exhibited hyperresponsive BCR signaling, they did so by opposite regulation of the Src family kinase Lyn. We demonstrated that the E613R allele of CD45 does not function as a hyper- or hypomorphic allele but rather alters the substrate specificity of CD45 for Lyn. Despite similarly enhancing BCR signaling, only B cells with supraphysiologic CD45 expression became anergic, whereas only mice harboring the E613R mutation developed frank autoimmunity on a susceptible genetic background. We showed that selective impairment of a Lyn-dependent negative-regulatory circuit in E613R B cells drove autoimmunity in E613R mice. This demonstrates that relaxing negative regulation of BCR signaling, rather than enhancing positive regulation, is critical for driving autoimmunity in this system.
In Situ Measurement of Vapor Uptake in the Rodent Upper Respiratory Tract
Authors: Morris John B. , Cichocki Joseph A. , Smith Gregory J. 
Published: February 2013

AbstractThe response of respiratory tract tissue target sites to inhaled vapors depends on the amount of inhaled vapor that is delivered to those sites. Direct measurement of vapor absorption within a specific airway of the living animal requires that the airway be isolated, which currently can only be performed on the upper airways. Towards this end, the upper respiratory tract (all airways anterior to the larynx) is surgically isolated in the anesthetized rat by tracheostomy and insertion of two endotracheal tubes, one leading anteriorly and the other posteriorly. The surgically manipulated animal is then placed in a nose‐only inhalation chamber and test‐vapor‐laden air is drawn through the isolated upper airways under defined air flow conditions via the anterior endotracheal tube. The animal spontaneously respires clean air into the lungs during this procedure via the posterior endotracheal tube. The concentration of test vapor in air entering and the air exiting the upper airways is measured by gas chromatography, and the difference in concentrations provides a measure of vapor absorption in that site. A rich database is available on upper respiratory tract vapor absorption as measured by this methodology, to which newly obtained data can be compared. These data have been instrumental not only in understanding the regional airway toxicity of inspired vapors, but also for developing mathematical models to describe inhaled vapor dosimetry. Curr. Protoc. Toxicol. 55:24.1.1‐24.1.10. © 2013 by John Wiley & Sons, Inc.
In Vitro Enrichment of Tumor‐Initiating Cells from Human Established Cell Lines
Authors: Benayoun Liat , Shaked Yuval 
Published: February 2013

AbstractThis unit describes protocols for culturing and subsequently enriching cancer stem cells (CSCs), also referred to as tumor‐initiating cells (TICs), from human established cell lines. TICs are thought to display the major cell population in the tumor with the proliferative capacity to seed tumors, implying that theyare critical in initiating and driving tumorigenesis. The protocols show the methods for enriching and subsequently characterizing TIC populations from a series of human tumors including glioblastoma, breast, and pancreatic tumors. Protocols evaluating the morphology, phenotypic, and functional properties of TICs are described. Long‐term cultures grown either as monolayers (“TIC‐low”) or as non‐adherent tumor spheres (“TIC‐high”) are generated. As a result, cells from the TIC‐high culture exhibit increased expression of stem cell surface markers, such as CD133, CD44, and CD24, high aldehyde dehydrogenase (ALDH) activity, and elevated expression levels of p21, in comparison to cells from the TIC‐low culture. Studying TICs by using such protocols is cost effective and is considered as a suitable and simple way for studying them. Curr. Protoc. Stem Cell Biol. 24:3.7.1‐3.7.15. © 2013 by John Wiley & Sons, Inc.
First experiences with the GORE® Septal Occluder in children and adults with atrial septal defects
Authors: Nyboe Camilla , Hjortdal Vibeke E. , Nielsen‐Kudsk Jens Erik 
Published: February 2013

ObjectivesIn this study, we report the first experiences with the GORE® Septal Occluder in transcatheter treatment of patients with atrial septal defects (ASD).MethodsTwenty‐two patients with secundum ASD were selected for GORE® Septal Occluder device closure. Mean age was 25.8 ± 4.6 years (range 4–60), 10 were children below the age of 15. Closure was guided by transeosophageal or intracardiac echocardiography and transthoracic echocardiography was used at follow‐up (median time 3 months). All defects were balloon sized and device size was chosen according to an occluder/defect size ratio ≥2.ResultsThe mean ASD size was 11.4 ± 0.5 mm (range 6–15). All GORE® Septal Occluder sizes (15, 20, 25 and 30 mm) were used. Six patients had additional defects. The aortic rim was deficient in twelve patients and four patients had a septal aneurysm. Symptoms were seen in 17 patients and 19 had dilated right ventricles. Implantation was successful in all patients with no complications. Delivery was easy and intuitive by the new delivery system. None of the patients had residual shunts at follow‐up. Mean procedure time was 38 ± 5 min (range 20–120). All patients had resolution or improvement in symptoms. There were no new onset arrhythmias or AV valve regurgitation and right ventricular dimensions were normalized.ConclusionsThe GORE® Septal Occluder is an efficient device for closing ASDs up to 15 mm. It is feasible for defects with different anatomy including a deficient aortic rim, septal aneurysm and multiple fenestrations and due to its compliance and conformability it has a presumed low risk of erosion. © 2013 Wiley Periodicals, Inc.
ChemInform Abstract: The Fluoride Route to Lindqvist Clusters: Synthesis and Crystal Structure of Layered Hexatantalate Na8Ta6O19·26H2O.
Authors: Britvin Sergey N. , Siidra Oleg I. , Lotnyk Andriy , Kienle Lorenz , Krivovichev Sergey V. , Depmeier Wulf 
Published: February 2013

AbstractThe title compound is synthesized by reacting H2TaF7 with 7M aq.
ChemInform Abstract: Remarkable Activation of an Alkyne [2 + 2 + 2]‐Cycloaddition Catalyst, 2‐Iminomethylpyridine (dipimp)/CoCl2·6H2O/Zn, by a Phthalate Additive.
Authors: Sugiyama Yu‐ki , Kariwa Takuma , Sakurada Tetsuya , Okamoto Sentaro 
Published: February 2013

AbstractThe procedure provides highly substituted benzene derivatives.
ChemInform Abstract: Regioselective Synthesis of Substituted Naphthalenes and Phenanthrenes by FeCl3‐Promoted Annulation of Aryl and Naphthyl Acetaldehydes with Alkynes.
Authors: Bu Xiuli , Hong Longcheng , Liu Ruiting , Hong Jianquan , Zhang Zhengxing , Zhou Xigeng 
Published: February 2013

AbstractThe present new procedure for the regioselective synthesis of substituted naphthalenes and phenanthrenes is only applicable to internal alkynes.
ChemInform Abstract: Visible‐Light‐Driven Oxidation of 1,3‐Dicarbonyl Compounds via Catalytic Disproportionation of TEMPO by Photoredox Catalysis.
Authors: Koike Takashi , Yasu Yusuke , Akita Munetaka 
Published: February 2013

AbstractVisible light irradiation of a mixture of 1,3‐dicarbonyls and TEMPO in the presence of a photoredox catalyst affords two types of oxidized products.
ChemInform Abstract: Iron‐Catalyzed Alkyl—Alkyl Suzuki—Miyaura Coupling.
Authors: Hatakeyama Takuji , Hashimoto Toru , Kathriarachchi Kalum K. A. D. S. , Zenmyo Takeshi , Seike Hirofumi , Nakamura Masaharu 
Published: February 2013

AbstractMagnesium tetraalkylborates prepared from olefins, BH3·Me2S, and iPrMgCl under optimized conditions are coupled with various primary and secondary alkyl bromides to give the corresponding long‐chain alkanes including fatty acid derivatives.
ChemInform Abstract: Direct Amidation of Carboxylic Acids Catalyzed by ortho‐Iodo Arylboronic Acids: Catalyst Optimization, Scope, and Preliminary Mechanistic Study Supporting a Peculiar Halogen Acceleration Effect.
Authors: Gernigon Nicolas , Al‐Zoubi Read M. , Hall Dennis G. 
Published: February 2013

AbstractThe ortho‐iodo arylboronic acid shown in the scheme efficiently promotes the direct amidation of carboxylic acids, which allows convenient formation of a wide range of carboxylic amides.
ChemInform Abstract: Enantioselective Copper‐Catalyzed 1,4‐Addition of Dialkylzincs to Enones Using a Novel N,N,P‐Cu(II) Complex.
Authors: Ebisu Yasuhiro , Kawamura Kenjiro , Hayashi Masahiko 
Published: February 2013

AbstractThe applied chiral ligand is prepared in a five‐step synthesis.
ChemInform Abstract: Rhodium‐Catalyzed [2 + 2] Cycloaddition of Ynamides with Nitroalkenes.
Authors: Smith Donna L. , Chidipudi Suresh Reddy , Goundry William R. , Lam Hon Wai 
Published: February 2013

AbstractYnamides bearing an aliphatic substituent generate only an inseparable mixture of diastereomers.
ChemInform Abstract: Direct Transformation of Secondary Amides into Secondary Amines: Triflic Anhydride Activated Reductive Alkylation.
Authors: Xiao Kai‐Jiong , Wang Ai‐E , Huang Pei‐Qiang 
Published: February 2013

AbstractA one‐pot method for the direct transformation of secondary amides to secondary amines with different substituent patterns is developed.
ChemInform Abstract: Enantioselective Synthesis of Tertiary α‐Hydroxyketones from Unfunctionalized Ketones: Palladium‐Catalyzed Asymmetric Allylic Alkylation of Enolates.
Authors: Trost Barry M. , Koller Raffael , Schaeffner Benjamin 
Published: February 2013

AbstractHighly functionalized tertiary α‐hydroxyketones are obtained in high yield with excellent enantioselectivity.
ChemInform Abstract: Synthesis of Substituted Phenanthrene by Iron(III)‐Catalyzed Intramolecular Alkyne—Carbonyl Metathesis.
Authors: Bera Krishnendu , Sarkar Soumen , Jalal Swapnadeep , Jana Umasish 
Published: February 2013

AbstractA new and efficient method to prepare various substituted phenanthrenes is described.
ChemInform Abstract: Organocatalytic Asymmetric Synthesis of 3‐Chlorooxindoles Bearing Adjacent Quaternary—Tertiary Centers.
Authors: Noole Artur , Jaerving Ivar , Werner Franz , Lopp Margus , Milkov Andrei , Kanger Toenis 
Published: February 2013

AbstractAliphatic nitroolefins fail to react [cf.(VIa)].
ChemInform Abstract: Lewis Acid‐Catalyzed Friedel—Crafts Alkylations of 3‐Hydroxy‐2‐oxindole: An Efficient Approach to the Core Structure of Azonazine.
Authors: Ghosh Santanu , Kinthada Lakshmana K. , Bhunia Subhajit , Bisai Alakesh 
Published: February 2013

AbstractA Lewis acid‐catalyzed Friedel—Crafts reaction of electron‐rich aromatics with oxindoles (I) is developed.