bluuebunny/crossref_metadata_2025_split huggingface dataset:
Airway re-narrowing following deep inspiration in asthmatic and nonasthmatic subjects
Authors: Salome C.M. , Thorpe C.W. , Diba C. , Brown N.J. , Berend N. , King G.G. 
Published: June 2003

After bronchoconstriction, deep inspiration (DI) causes dilatation followed by airway re-narrowing. Re-narrowing may be faster in asthmatic than nonasthmatic subjects. This study investigated the relationship between re-narrowing and the magnitude of both DI-induced dilatation and the volume-dependence of respiratory system resistance (Rrs) during tidal breathing.In 25 asthmatic and 18 nonasthmatic subjects the forced oscillation technique was used to measureRrsat baseline and after methacholine challenge, during 1 min of tidal breathing, followed by DI to total lung capacity (TLC) and passive return to functional residual capacity (FRC). Dilatation was measured as the decrease inRrsbetween end tidal inspiration and TLC, re-narrowing asRrsat FRC immediately after DI, as per centRrsat end-tidal expiration, and volume dependent tidal fluctuation as the difference between meanRrsat end-expiration and end-inspiration.Asthmatic subjects had greater re-narrowing, less dilatation, and greater tidal fluctuations both at baseline and after challenge. Re-narrowing correlated with baseline tidal fluctuation and inversely with dilatation. Both baseline tidal fluctuation and dilatation were significant independent predictors of re-narrowing.Following deep inspiration-induced dilatation, faster airway re-narrowing in asthmatic than nonasthmatic subjects is associated not only with reduced deep inspiration-induced dilatation but also with some property of the airways that is detectable prior to challenge as an increased volume dependence of resistance.
Increased ventilation with NiIPPV does not necessarily improve exercise capacity in COPD
Authors: Highcock M.P. , Shneerson J.M. , Smith I.E. 
Published: June 2003

Evidence that noninvasive intermittent positive-pressure ventilation (NiIPPV) improves exercise capacity in chronic obstructive pulmonary disease (COPD) is limited. The effectiveness of different ventilators in this setting has not been studied.Three bilevel pressure support ventilators (Bipap S/T 30, Nippy2 and Vpap II ST), appliedviaa mouthpiece, were compared during submaximal treadmill exercise in eight subjects with COPD. Subjects walked to exhaustion with each of the ventilators and while breathing through the mouthpiece alone, in random order. In addition, four unencumbered walks were performed.The unencumbered distance (mean±sd) walked was 259±123 m. With the mouthpiece alone this decreased to 211±96 m and fell further to 145±76 m with NiIPPV. There was no difference between the brands of ventilator. At the break-point of exercise, significant increases were seen in tidal volume and minute ventilation in the ventilator walks compared with the mouthpiece alone.Noninvasive intermittent positive-pressure ventilation increased ventilation but did not improve exercise capacity in the subjects in this study. No significant differences were seen between the ventilators. The effectiveness of this technique and the optimal method of assistance require further clarification.
RNA analysis of B cell lines arrested at defined stages of differentiation allows for an approximation of gene expression patterns during B cell development
Authors: Tsapogas Panagiotis , Breslin Thomas , Bilke Sven , Lagergren Anna , Månsson Robert , Liberg David , Peterson Carsten , Sigvardsson Mikael 
Published: June 2003

Abstract
The development of a mature B lymphocyte from a bone marrow stem cell is a highly ordered process involving stages with defined features and gene expression patterns. To obtain a deeper understanding of the molecular genetics of this process, we have performed RNA expression analysis of a set of mouse B lineage cell lines representing defined stages of B cell development using Affymetrix™ microarrays. The cells were grouped based on their previously defined phenotypic features, and a gene expression pattern for each group of cell lines was established. The data indicated that the cell lines representing a defined stage generally presented a high similarity in overall expression profiles. Numerous genes could be identified as expressed with a restricted pattern using dCHIP-based, quantitative comparisons or presence/absence-based, probabilistic state analysis. These experiments provide a model for gene expression during B cell development, and the correctly identified expression patterns of a number of control genes suggest that a series of cell lines can be useful tools in the elucidation of the molecular genetics of a complex differentiation process.
G protein-coupled receptors in natural killer cells
Authors: Maghazachi Azzam A 
Published: June 2003

Abstract
Natural killer (NK) cells are capable of killing tumor as well as virally infected cells. How these cells migrate toward the infected sites in the body is not completely understood. Chemokine receptors that belong to the heptahelical family of receptors and characteristically bind heterotrimeric G proteins are present in most NK cells. Recent results showed that resting NK cells highly express constitutive chemokine receptors (CCR4, CCR7, CXCR4, and CX3CR1) with low expression of a limited repertoire of inflammatory chemokine receptors (CCR1 and CXCR3). However, only a subset of these cells expressing the CD56dim and adhesion moleculehigh phenotype is capable of in vivo binding to vascular endothelium. Under pathological conditions where inflammatory cytokines are present, these cells are induced to express inflammatory chemokine receptors. Resting as well as activated NK cells also express receptors for another member of the heptahelical family of receptors that bind phosphorylated or glycosylated lysolipids. These include sphingosine 1-phosphate (S1P)1, S1P4, and S1P5, the receptors for S1P; lysophosphatidic acid (LPA)1, LPA2, and LPA3, the receptors for LPA; and T cell death-associated gene 8, the receptor for psychosine. Similar to chemokines, S1P, LPA, and psychosine induce the chemotaxis of NK cells through heterotrimeric G proteins. However, in contrast to chemokines, which enhance the cytotoxicity of NK cells, lysolipids inhibit this function. We hope that gaining knowledge regarding the distribution of activated NK cells toward the sites of tumor growth or virally infected sites will give an advantage in designing strategies using these cells as tools for the prevention and treatment of immunodeficiencies.
Cell-specific expression of B lymphocyte (APRIL, BLyS)- and Th2 (CD30L/CD153)-promoting tumor necrosis factor superfamily ligands in human placentas
Authors: Phillips Teresa A , Ni Jian , Hunt Joan S 
Published: June 2003

Abstract
Apoptosis-inducing tumor necrosis factor (TNF) ligands and receptors have been reported in human placentas, but the expression patterns of family members lacking this function [a proliferation-inducing ligand (APRIL), B lymphocyte stimulator (BLyS), CD30L/CD153, CD40L/CD154, TNF-related activation-induced cytokine, CD27L/CD70, OX40L, activation-inducible TNF receptor ligand (AITRL)] are incompletely documented or unknown. We therefore investigated expression of these eight ligands and nine of their receptors (B cell maturation antigen, transmembrane activator and calcium-modulator and cyclophilin ligand-interactor, CD30, CD40, receptor activator of nuclear factor-κB, osteoprotegerin, CD27, OX40/CD134, AITR). Analysis by reverse transcriptase-polymerase chain reaction revealed mRNAs encoding only three of the ligands (APRIL, BLyS, CD30L/CD153). Immunoblots demonstrated all three proteins in first-trimester and term placentas, and immunohistochemical experiments showed that expression was cell-specific and gestation-related. Although mRNAs encoding receptors for the three expressed ligands were absent, those encoding receptors for all of the unexpressed ligands were detectable. Collectively, the results are consistent with the postulate that nonapoptosis-inducing, placenta-derived TNF superfamily cytokines contribute to the T helper cell type 2 bias required for successful pregnancy. Patterns of placental expression of receptors suggest bidirectional maternal–fetal cytokine communication.
Composition of MHC class II-enriched lipid microdomains is modified during maturation of primary dendritic cells
Authors: Setterblad Niclas , Roucard Corinne , Bocaccio Claire , Abastado Jean-Pierre , Charron Dominique , Mooney Nuala 
Published: June 2003

Abstract
Dendritic cells (DCs) are the most potent antigen presenting cells. Major histocompatibility complex (MHC) class II molecule expression changes with maturation; immature DCs concentrate MHC class II molecules intracellularly, whereas maturation increases surface expression of MHC class II and costimulatory molecules to optimize antigen presentation. Signal transduction via MHC class II molecules localized in lipid microdomains has been described in B lymphocytes and in the THP-1 monocyte cell line. We have characterized MHC class II molecules throughout human DC maturation with particular attention to their localization in lipid-rich microdomains. Only immature DCs expressed empty MHC class II molecules, and maturation increased the level of peptide-bound heterodimers. Ligand binding to surface human leukocyte antigen (HLA)-DR induced rapid internalization in immature DCs. The proportion of cell-surface detergent-insoluble glycosphingolipid-enriched microdomain-clustered HLA-DR was higher in immature DCs despite the higher surface expression of HLA-DR in mature DCs. Constituents of HLA-DR containing microdomains included the src kinase Lyn and the cytoskeletal protein tubulin in immature DCs. Maturation modified the composition of the HLA-DR-containing microdomains to include protein kinase C (PKC)-δ, Lyn, and the cytoskeletal protein actin, accompanied by the loss of tubulin. Signaling via HLA-DR redistributed HLA-DR and -DM and PKC-δ as well as enriching the actin content of mature DC microdomains. The increased expression of HLA-DR as a result of DC maturation was therefore accompanied by modification of the spatial organization of HLA-DR. Such regulation could contribute to the distinct responses induced by ligand binding to MHC class II molecules in immature versus mature DCs.
PU.1 regulates glutathione peroxidase expression in neutrophils
Authors: Throm Stacy L , Klemsz Michael J 
Published: June 2003

Abstract
Based on knockout models, the transcription factor PU.1 has been shown to be important for the maturation of neutrophils. As the list of genes PU.1 directly regulates in neutrophils is still quite limited, defining PU.1 target genes for this lineage will provide valuable insight into how this factor regulates neutrophil development and terminal function. Using the combined techniques of representational difference analysis and a cDNA library screen, we identified four genes that were differentially expressed in the PU.1-expressing 503PU myeloid cell line but not the PU.1 null parent cell line 503. Two of these genes, glutathione peroxidase (GPx) and serine leukoprotease inhibitor, are involved in protecting neutrophils from the products they make to destroy pathogens and were analyzed further to determine if PU.1 directly regulates their expression. These studies showed that PU.1 directly regulated the expression of only the GPx gene through binding sites in the promoter and a 3′ regulatory region. Thus, PU.1 not only regulates the expression of molecules involved in the production of reactive oxygen species but also a gene that protects the neutrophils from these same destructive enzymes.
Proteinase-3 directly activates MMP-2 and degrades gelatin and Matrigel; differential inhibition by (−)epigallocatechin-3-gallate
Authors: Pezzato Elga , Donà Massimo , Sartor Luigi , Dell’Aica Isabella , Benelli Roberto , Albini Adriana , Garbisa Spiridione 
Published: June 2003

Abstract
Proteinase-3 (PR-3), a serine-proteinase mainly expressed by polymorphonuclear leukocytes (PMNs), can degrade a variety of extracellular matrix proteins and may contribute to a number of inflammation-triggered diseases. Here, we show that in addition to Matrigel™ components, PR-3 is also able to degrade denatured collagen and directly activate secreted but not membrane-bound pro-MMP-2, a matrix metallo-proteinase instrumental to cellular invasion. In contrast, following addition of purified PR-3 or PMNs to HT1080 tumor cells, dose-dependent inhibition of in vitro Matrigel™ invasion is registered. (−)Epigallocatechin-3-gallate (EGCG), the main flavanol in green tea and known to inhibit inflammation and tumor invasion, exerts dose-dependent inhibition of degradation of gelatin (IC50&lt;20 μM) and casein, which is directly triggered by PR-3. The presence of EGCG does not modify the colocalization of MMP-2 and exogenous PR-3 at the cell surface and does not restrain secreted pro-MMP-2 and pro-MMP-9 activation or degradation of a specific, synthetic peptide by PR-3. These results add new activities to the list of those exerted by PR-3 and indicate a differential inhibition as a result of EGCG.
Generation and functional characterization of a clonal murine periportal Kupffer cell line from H-2K
b –tsA58 mice
Authors: Dory Daniel , Echchannaoui Hakim , Letiembre Maryse , Ferracin Fabrizia , Pieters Jean , Adachi Yoshiyuki , Akashi Sachiko , Zimmerli Werner , Landmann Regine 
Published: June 2003

Abstract
Murine Kupffer cells (KCs) are heterogeneous and survive only for a short time in vitro. Here, a clonal, murine KC line was generated from transgenic mice, expressing the thermolabile mutant tsA58 of the Simian virus 40 large T antigen under the control of the H-2Kb promoter. Thirty-three degrees Celsius and 37°C but not 39°C have been permissive for growth of the clone; it required conditioned media from hepatocytes and endothelial cells for proliferation. In contrast to primary cells, the cells of the clone were uniform, survived detachment, and could therefore be analyzed by cytofluorimetry. The clone, as primary KCs, constitutively expressed nonspecific esterase, peroxidase, MOMA-2, BM8, scavenger receptor A, CD14, and Toll-like receptor 4 (TLR4); the antigen-presenting molecules CD40, CD80, and CD1d; and endocytosed dextran–fluorescein isothiocyanate. It lacked complement, Fc receptors, F4/80 marker, and the phagosomal coat protein tryptophan aspartate-containing coat protein (TACO). The clone exhibited CD14- and TLR4/MD2-independent, plasma-dependent lipopolysaccharide (LPS) binding, Escherichia coli and Streptococcus pneumoniae phagocytosis, and LPS- and interferon-γ-induced NO production but no tumor necrosis factor α, interleukin (IL)-6, or IL-10 release. The large size, surface-marker expression, and capacity to clear gram-negative and -positive bacteria indicate that the clone was derived from the periportal, large KC subpopulation. The clone allows molecular studies of anti-infective and immune functions of KCs.
Expression of and functional responses to protease-activated receptors on human eosinophils
Authors: Bolton Sarah J , McNulty Clare A , Thomas Rebecca J , Hewitt Colin R A , Wardlaw Andrew J 
Published: June 2003

Abstract
Eosinophil recruitment to airway tissue is a key feature of asthma, and release of a wide variety of toxic mediators from eosinophils leads to the tissue damage that is a hallmark of asthma pathology. Factors that control the release of these toxic mediators are targets for potential therapeutic intervention. Protease-activated receptors (PARs) are a novel class of receptors that are activated by cleavage of the N terminus of the receptor by proteases such as thrombin or trypsin-like enzymes. To date, PAR1–4 have been identified, and there are several studies that have demonstrated the expression of PARs in airway tissue, particularly the respiratory epithelium. We have investigated whether eosinophils express PARs and if activation of these receptors will then trigger a functional response. Using a combination of reverse transcriptase-polymerase chain reaction, Western blotting, and flow cytometry analysis, we have demonstrated that eosinophils express PAR1 and PAR2. FACS analysis showed that PAR1 could be clearly detected on the surface of the cells, whereas PAR2 appeared to be primarily intracellular. Trypsin and the PAR2 agonist peptide were seen in trigger shape change, release of cysteinyl leukotrienes, and most obviously, generation of reactive oxygen species. In contrast, thrombin had no effect on eosinophil function. The PAR1 agonist peptide did have a minor effect on eosinophil function, but this was most likely down to its ability to activate PAR1 and PAR2. These results demonstrate that PAR2 is the major PAR receptor that is capable of modulating eosinophil function.
Disparate functions of immature and mature human myeloid dendritic cells: implications for dendritic cell-based vaccines
Authors: Tschoep Katharina , Manning Thomas C , Harlin Helena , George Christopher , Johnson Melissa , Gajewski Thomas F 
Published: June 2003

Abstract
Although antigen-loaded dendritic cells (DC) are being investigated as antitumor vaccines, which DC differentiation state is most effective is not clear. Three DC functions that may be critical for immunization potential are expression of CD80/86, cytokine production following CD40 engagement, and migration to chemokine receptor 7-binding chemokines. We therefore examined highly purified human monocyte-derived immature and mature DC for these properties from normal donors and cancer patients. Although high expression of CD80/86 and migration to 6Ckine + macrophage-inflammatory protein-3β were properties of mature DC, cytokine production following CD40 ligation was superior by immature DC. Loss of cytokine secretion occurred with multiple maturation conditions, was not apparently reversible, and was also seen with lipopolysaccharide stimulation in correlation with down-regulated Toll-like receptor expression. Our results suggest that the functions thought to contribute to optimal T cell priming are not coexpressed by the same DC population and that immature and mature DC likely possess distinct CD40-mediated signaling events.
The critical role of ocular-infiltrating macrophages in the development of choroidal neovascularization
Authors: Tsutsumi Chikako , Sonoda Koh-Hei , Egashira Kensuke , Qiao Hong , Hisatomi Toshio , Nakao Shintaro , Ishibashi Minako , Charo Israel F , Sakamoto Taiji , Murata Toshinori , Ishibashi Tatsuro 
Published: June 2003

Abstract
Choroidal neovascularization (CNV) is directly related to visual loss in some eye diseases, such as age-related macular degeneration. Although several human histological studies have suggested the participation of macrophages in CNV formation, the precise mechanisms are still not fully understood. In this study, we elucidated the role of ocular-infiltrating macrophages in experimental CNV using CCR2 knockout (KO) mice, wild-type mice, and C57BL/6 (B6) mice. CCR2 is the receptor of monocyte chemoattractant protein-1, and the number of infiltrating macrophage and the area of CNV were significantly reduced in CCR2 KO mice. Enriched ocular-infiltrating macrophages from B6 mice actually showed angiogenic ability in a dorsal air sac assay. Moreover, their expression of class II, CD40, B7-1 and B7-2 molecules, and the mRNA for potential angiogenic factors, such as vascular endothelial growth factor, basic fibroblast growth factor, and tumor necrosis factor α, was also observed. Collectively, we conclude that ocular-infiltrating macrophages play an important role in CNV generation.
Activation by prion peptide PrP106–126 induces a NF-κB-driven proinflammatory response in human monocyte-derived dendritic cells
Authors: Bacot Silvia M , Lenz Petra , Frazier-Jessen Michelle R , Feldman Gerald M 
Published: June 2003

Abstract
Specific prion peptides have been shown to mimic the pathologic isoform of the prion protein (PrP) and to induce a neurotoxic effect in vitro and in vivo. As monocytic cells are thought to play a role in the transmission and pathogenesis of prion disease, the use of these peptides in regulating monocytic cell function is under intense investigation. In the current study, we characterize the ability of prion peptide PrP106–126 to activate specific signaling pathways in human monocyte-derived dendritic cells (DCs). Electrophoretic mobility shift assays establish the activation of transcription factor nuclear factor-κB within 15 min of exposure, with as little as 25 μM peptide. This signaling cascade results in the up-regulation of inflammatory cytokines interleukin (IL)-1β, IL-6, and tumor necrosis factor α (TNF-α) at the mRNA and protein levels. Phenotypic activation of DCs exposed to PrP106–126 is partly a result of an autocrine TNF-α response and results in an increased ability of these cells to induce lymphocyte proliferation. The effects of PrP106–126 on DCs were elicited through a receptor complex distinct from that used by human monocytes, demonstrating the ability of this peptide to interact with a multiplicity of receptors on various cell types. Together, these data suggest an involvement of DCs in prion disease pathogenesis.
CEACAM1 is a potent regulator of B cell receptor complex-induced activation
Authors: Greicius Gediminas , Severinson Eva , Beauchemin Nicole , Öbrink Björn , Singer Bernhard B 
Published: June 2003

Abstract
Carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1, CD66a) is a member of the immunoglobulin (Ig) superfamily, previously characterized as an adhesion and signaling molecule in epithelial, endothelial, and hematopoietic cells. Here, we show that the CEACAM1 isoform expression pattern is different in nonactivated and activated primary mouse B lymphocytes and that CEACAM1 influences B cell receptor complex-mediated activation. A CEACAM1-specific monoclonal antibody strongly triggered proliferation of mouse B cells when combined with surface IgM cross-linking. However, anti-CEACAM1 was not mitogenic when added alone. The proliferation was more pronounced and lasted longer as compared with other activators of B cells, such as anti-IgM in the presence of interleukin-4 or lipopolysaccharide. A similar, costimulatory effect was exerted by CEACAM1-expressing fibroblasts, indicating that homophilic CEACAM1–CEACAM1 cell-mediated binding is the physiological stimulus for CEACAM1-triggered B cell signaling. The anti-CEACAM1/anti-IgM-activated cells aggregated in a lymphocyte function-associated antigen-1-dependent manner. Furthermore, cells that were activated by anti-CEACAM1/anti-IgM secreted Ig but did not go through Ig class-switching. Anti-CEACAM1 induced phosphorylation of c-Jun N-terminal kinase (stress-activated protein kinase) but did not activate the extracellular signal-regulated kinase or p38 mitogen-activated protein kinases.