bluuebunny/crossref_metadata_2025_split huggingface dataset:
Particulate adjuvants can induce macrophage survival, DNA synthesis, and a synergistic proliferative response to GM-CSF and CSF-1
Authors: Hamilton John A , Byrne Robert , Whitty Genevieve 
Published: January 2018

Abstract
The mode of action of immunological adjuvants is not yet completely understood. Many are particulate. Certain antigen-presenting (dendritic) cell populations belong to the monocyte/macrophage lineage and, like other members of the lineage, in some tissues appear to be short-lived. We report that many poorly degradable, particulate adjuvants, for example, aluminum hydroxide, oil-in-water emulsions, calcium phosphate, and silica, enhance murine bone marrow-derived macrophage survival; induction of DNA synthesis was even observed. No evidence could be found for a requirement for endogenous granulocyte-macrophage colony-stimulating factor (GM-CSF) or macrophage-CSF (M-CSF or CSF-1). Synergy for the proliferative effects was noted in the presence of added GM-CSF or CSF-1. It is suggested from these in vitro findings that one function of certain particulate adjuvants may be to increase by enhanced survival or even proliferation the number of cells available for subsequent antigen presentation and cytokine production. J. Leukoc. Biol. 67: 226–232; 2000.
Ecto-enzymes: physiology meets pathology
Authors: Goding James W 
Published: January 2018

Abstract
Ecto-enzymes are catalytic membrane proteins with their active sites outside the cell. They include cholinesterase, which inactivates acetylcholine, and angiotensin-converting enzyme, which converts angiotensin I to biologically active angiotensin II, and numerous other peptidases, transpeptidases, nucleotidases, phosphodiesterases, and phosphatases. Many CD antigens of leukocytes are ecto-enzymes; some CD antigens for which no function is currently known are probably ectoenzymes. Expression is highly regulated and correlated with differentiation and activation. Some are highly restricted in distribution; others are ubiquitous. Many are shared between leukocytes and non-hematogenous cells. Biological functions appear to depend on the type and location of the cell in which expression occurs, and include recycling of nutrients, local control of response to cytokines and hormones, bone formation, cell mobility, invasion, and metastasis. Many novel regulatory functions of ecto-enzymes remain to be discovered, and may reveal new mechanisms of local extracellular control of cellular function. J. Leukoc. Biol. 67: 285–311; 2000.
Regulation of phagocytic leukocyte activities by C-reactive protein
Authors: Mortensen Richard F , Zhong Wangjian 
Published: January 2018

Abstract
The classic acute phase reactant C-reactive protein (CRP) is classified as an effector of innate host resistance because it activates the classical complement cascade and is opsonic. The latter action occurs via specific CRP receptors (CRP-R) that have recently been identified as both FcγRI and FcγRII on human phagocytic leukocytes. New findings also suggest an anti-inflammatory role for CRP because it modulates endotoxin shock and inhibits chemotaxis and the respiratory burst of neutrophils. CRP inhibited phorbol myristate acetate-induced superoxide (O) production more efficiently than the fMLP-triggered response. An examination of the inhibition of the protein kinase C (PKC)-dependent assembly of the NADPH oxidase complex revealed that both phosphorylation and translocation of PKC-β2 to the membrane were inhibited by a threshold acute phase dose of ∼50 μg/mL CRP. Translocation to the membrane and serine-phosphorylation of the major cytosolic p47-phox component of the NADPH oxidase complex was inhibited by CRP. CRP also inhibited membrane localization of activated Rac2, the small G protein regulator of the assembly of the oxidase components in activated neutrophils as well as the cytoskeleton during chemotactic movement. CRP-mediated regulation occurs via the CRP-R because an IgM mouse mAb to the human CRP-R mimicked CRP-induced inhibition of O production and chemotaxis. CRP may serve as an antiinflammatory regulator of activities at sites of tissue damage where it selectively accumulates and thus influences neutrophil infiltration and polymorphonuclear neutrophil activities. By contrast, CRP activates cells of the monocyte/macrophage lineage, suggesting differential regulation of these two leukocyte populations at the level of signaling. CRP appears to be a multifunctional protein with the capability of exerting both effector functions for innate host resistance, as well as exerting specific anti-inflammatory effects. J. Leukoc. Biol. 67: 495–500; 2000.
A negative autoregulatory link between Nramp 1 function and expression
Authors: Baker Stephen T , Barton C Howard , Biggs Thelma E 
Published: January 2018

Abstract
Nramp 1 (natural resistance-associated macrophage protein) controls resistance to infection by intracellular pathogens in mice. Nramp 1 regulates the microenvironment of the invading pathogen by increasing the luminal iron that participates in the Haber-Weiss reaction, producing radicals that attack the pathogen. We have studied the effect of inflammatory stimuli, iron, and sodium nitroprusside on Nramp 1 expression in bone marrow macrophages. Investigations show all three up-regulate Nramp 1 expression with a parallel increase in immunoreactivity to an amino-terminal antibody and Nramp 1 mRNA. Growth rates are reduced in macrophage cell lines expressing Nramp 1. This is through a decrease in iron availability, shown by an increase in IRP2 activity and a reciprocal decrease in conventional protein kinase Cβ-1 expression. We propose that Nramp 1 activity may control its own expression via a negative autoregulatory loop that is important for iron homeostasis and maintenance of low cytoplasmic redox active iron levels in the macrophage. J. Leukoc. Biol. 67: 501–507; 2000.
The critical role of CD40/CD40L in the CD4-dependent generation of CD8+ T cell immunity
Authors: Clarke Sally R McK 
Published: January 2018

Abstract
Control of virus infections and eradication of tumors usually involves the lytic activity of CD8+ cytotoxic T lymphocytes (CTLs). The induction of effective CTL immunity relies on several factors, one of the most important of which is CD4+ T cell help. Numerous studies have demonstrated the dependence of CTL priming on the presence of CD4+ T cells, but until recently little was known of the mechanisms regulating this process. Based on reports that CD4+ and CD8+ T cells must recognize antigen on the same antigen-presenting cell (APC), help was originally thought to be provided through the delivery of short-range, CD4+ T cell-secreted cytokines. However, the results of subsequent studies favor an alternative mechanism, whereby CD4+ T cells modify the APC, converting it into a stimulatory cell for CD8+ T cell priming. It is important that CD40 and its ligand, CD40L, have been implicated in the provision of this help and, in particular, the generation of long-lasting CTL memory. J. Leukoc. Biol. 67: 607–614; 2000.
Induction of cyclooxygenase-2 by human monocytes exposed to group B streptococci
Authors: Maloney Christopher G , Thompson Samuel D , Hill Harry R , Bohnsack John F , McIntyre Thomas M , Zimmerman Guy A 
Published: January 2018

Abstract
Group B streptococcal (GBS) infections are associated with high morbidity and mortality. The molecular pathways mediating the pathophysiological events in GBS infection are not fully delineated. Cyclooxygenases (COX) are the enzymes that convert arachidonate to active eicosanoids. To identify the effects of GBS on eicosanoid metabolism and regulatory mechanisms, we exposed human monocytes to GBS and found that they secreted prostaglandin E2, prostacyclin, and thromboxane A2. Exposure to GBS caused monocytes to express COX-2 mRNA and protein in both a time- and concentration-dependent manner that correlated with eicosanoid production. COX-1 protein was unchanged. Addition of the anti-inflammatory cytokines interleukin (IL)-4 or IL-10 markedly attenuated GBS-induced COX-2 protein accumulation after GBS exposure, as did inhibition of p38 MAPK. Our experiments are the first to show that exposure of monocytes to a gram-positive bacterium (GBS) results in induction of functional COX-2, suggesting that eicosanoids may play important roles in the pathogenesis of GBS infections. J. Leukoc. Biol. 67: 615–621; 2000.
Migration of dendritic cells within 3-D collagen lattices is dependent on tissue origin, state of maturation, and matrix structure and is maintained by proinflammatory cytokines
Authors: Gunzer Matthias , Friedl Peter , Niggemann Bernd , Bröcker Eva-B , Kämpgen Eckhart , Zänker Kurt S 
Published: January 2018

Abstract
The function of dendritic cells (DC) depends on active migration through three-dimensional (3-D) extracellular matrices. We have analyzed the migration of murine DC from different tissue origins within 3-D collagen lattices through the use of time-lapse videomicroscopy and single-cell tracking. Directly after incorporation, 50–90% of DC from the spleen (spDC) and Langerhans cells freshly isolated from the epidermis (fLC) displayed active motility in these matrices. Whereas mature spDC showed multilateral pseudopod dynamics as well as fast and heterogeneous migration, immature fLC displayed a spherical shape with faint membrane processes and very homogenous, slow migration characteristics. In the absence of external stimuli, migration of both, spDC and fLC, vanished after &gt;36 h due to cell death. Maintaining fLC viability by external granulocyte-macrophage colony-stimulating factor or tumor necrosis factor a prolonged migration up to 5 days. During this period fLC transformed into mature cells with large dendrites, thereby developing a heterogeneous migration pattern more similar to spDC. In randomly polymerized collagen matrices cell paths were without preferential orientation. In contrast, in artificially aligned lattices directional paths in accordance with the forced fiber orientation were observed. Thus, migration is an inherent property of DC, largely influenced by tissue origin, degree of maturity, and the 3-D structure of the environment. J. Leukoc. Biol. 67: 622–629; 2000.
Calcitonin-gene related peptide (CGRP) inhibits interleukin-7-induced pre-B cell colony formation
Authors: Fernandez Stefan , Knopf Melissa A , McGillis Joseph P 
Published: January 2018

Abstract
Calcitonin gene-related peptide (CGRP) is a sensory neuropeptide with inflammatory and immunoregulatory activities. Its role in B lymphocyte development was investigated using a pre-B cell colony-forming assay. Physiological concentrations of CGRP inhibited pre-B cell responses to interleukin-7 (IL-7). Inhibition was specific in that it was blocked by the CGRP antagonist CGRP8-37. Adrenomedulin, substance P, and calcitonin had no effect on B cell precursor responses. Similar responses were observed with B220+/IgM− B cell precursors. Inhibition of IL-7 responses in B220+/IgM− cells suggests that CGRP has a direct effect on B cell precursors. Studies with cultured bone marrow-adherent cells found that CGRP also has an indirect effect on IL-7 responses. Cultured bone marrow-adherent cells were treated with CGRP for 24 h, and anti-CGRP was added to the supernatants to neutralize CGRP. Concentrations of CGRP as low as 0.01 nM induced a factor that inhibited colony formation. In contrast, CGRP did not induce an inhibitory factor in cultured bone marrow macrophages, suggesting that CGRP induces an inhibitory factor in some adherent cell other than macrophages. The results show that CGRP has both direct and indirect effects on developing B cells and support a role for CGRP as an inhibitor of early B cell development. J. Leukoc. Biol. 67: 669–676; 2000.
Abnormal down-regulation of PKC is responsible for giant granule formation in fibroblasts from CHS (beige) mice—a thiol proteinase inhibitor, E-64-d, prevents giant granule formation in beige fibroblasts
Authors: Tanabe Fuminori , Cui Shao-Hui , Ito Masahiko 
Published: January 2018

Abstract
We have previously reported that the abnormally rapid down-regulation of protein kinase C (PKC) activity is responsible for the cellular dysfunction in natural killer (NK) cells and polymorphonuclear leukocytes (PMNs) from Chediak-Higashi syndrome (beige) mice. In this report, we examined whether the down-regulation of PKC is associated with giant granule formation in fibroblasts from beige mice. In cultured beige fibroblasts, the membrane-bound PKC activity declined significantly after phorbol ester stimulation. We found that E-64-d, which is a thiol proteinase inhibitor and protects PKC from calpain-mediated proteolysis, reversed the declined PKC activity and prevented giant granule formation in beige fibroblasts. Moreover, E-64-d corrected the reduced lysosomal elastase and cathepsin G activity in beige fibroblasts. In contrast, specific PKC inhibitors, chelerythrin and calphostin C, promoted giant granule formation in normal fibroblasts. We also demonstrate that ceramide production is enhanced in beige fibroblasts and is involved in the rapid down-regulation of PKC. These results suggest that the accelerated breakdown of PKC observed in beige fibroblasts is caused by enhanced ceramide production and is also responsible for giant granule formation. J. Leukoc. Biol. 67: 749–755; 2000.
Inhibition of TNF-α processing and TACE-mediated ectodomain shedding by ethanol
Authors: Zhang Zili , Cork John , Ye Peng , Lei Dinghua , Schwarzenberger Paul O , Summer Warren R , Shellito Judd E , Nelson Steve , Kolls Jay K 
Published: January 2018

Abstract
Alcohol (EtOH) is a well-documented immunosuppressant. Acute EtOH-induced immunosuppression is partially due to suppression of tumor necrosis factor α (TNF-α) secretion. We investigated the mechanism of acute EtOH-induced TNF-α suppression in two monocytic cell lines, Mono Mac 6 and DRM. EtOH inhibited TNF-α secretion in a dose-dependent manner. However, TNF-α transcription was not affected by EtOH. Enzyme-linked immunosorbent assay and confocal microscopy showed that EtOH treatment increased cell-associated TNF-α. Ectodomain shedding of TNF-α from the cell surface is mediated by TNF-α converting enzyme (TACE). In contrast with TNF-α, EtOH did not inhibit interleukin-8 (IL-8) secretion, which does not require shedding. Furthermore, TNF p75 receptor shedding, a biomarker for TACE activity, was inhibited by EtOH in both cell lines. EtOH also inhibited TNF p75 receptor shedding in TACE-reconstituted fibroblasts, suggesting that EtOH inhibits the shedding process. These data show that acute EtOH exposure can posttranscriptionally suppress TNF-α production, resulting in specific defects in immune defense. J. Leukoc. Biol. 67: 856–862; 2000.
Serum-induced monocyte differentiation and monocyte chemotaxis are regulated by the p38 MAP kinase signal transduction pathway
Authors: Ayala Julia M , Goyal Shefali , Liverton Nigel J , Claremon Dave A , O'Keefe Stephen J , Hanlon William A 
Published: January 2018

Abstract
Regulation by the p38 mitogen-activated protein (MAP) kinase signaling pathway of monocytic inflammatory functions was evaluated using L-790,070, a potent and selective inhibitor of p38 MAP kinase. Three major functions of monocytes were investigated: differentiation, chemotaxis, and phagocytosis. L-790,070 inhibited serum-induced monocyte differentiation with an IC50 of 0.5 nM. Monocyte chemotaxis induced by RANTES, macrophage inflammatory protein-1α (MIP-1α), monocyte chemotactic protein-1 (MCP-1), and fMLP were all sensitive to L-790,070. When titrated, L-790,070 inhibited MCP-1-induced chemotaxis in a concentration-dependent manner with an IC50 of 0.3 nM. However, the ability of serum-derived macrophages to phagocytose apoptotic neutrophils was unaffected by L-790,070. The concentration with which L-790,070 inhibited both differentiation and chemotaxis was similar to that necessary to inhibit p38 MAP kinase activation of MAPKAP kinase (0.3 nM) in response to stimulation by lipopolysaccharide. Therefore, the data in this report suggest that the mechanism by which L-790,070 blocked monocyte differentiation and prevented chemotaxis was by inhibiting p38 MAP kinase activity. J. Leukoc. Biol. 67: 869–875; 2000.
iTRAQ‐Based Proteomic Analysis Exploring the Influence of Hypoxia on the Proteome of Dental Pulp Stem Cells under 3D Culture
Authors: Dou Lei , Yan Qifang , Liang Panpan , Zhou Pengfei , Zhang Yan , Ji Ping 
Published: January 2018

AbstractHypoxic preconditioning is commonly applied to enhance mesenchymal stem cells (MSCs) therapeutic effect before transplantation. Elucidating the effect of hypoxic preconditioning would be beneficial for improved application. However, the influence of hypoxia on dental tissue derived MSCs cultured in 3D was unknown. Thus, the present study is to investigate gene expression and proteome of dental pulp stem cells (DPSCs) after hypoxic preconditioning. DPSCs were isolated, cultured in a 3D system under the normoxic and hypoxic conditions. The gene expression was examined with reverse transcription polymerase chain reaction, and the proteome was analyzed using iTRAQ‐based mass spectrometry. The expressions of HIF‐1α, VEGFA, KDR at mRNA level was upregulated while BMP‐2 was downregulated. Two thousand one hundred and fifteen proteins were identified and 57 proteins exhibited significant differences after hypoxic preconditioning (30 up‐regulated, 27 down‐regulated). Bioinformatic analysis revealed the majority of up‐regulated proteins are involved in cellular process, angiogenesis, protein binding and transport, regulation of response to stimulus, metabolic processes, and immune response. Increased IL‐6 and decreased TGF‐1β protein expression under hypoxic condition were verified by ELISA. Hypoxic preconditioning partly affected the gene and protein expression in DPSCs under 3D culture and may enhance the efficacy of MSCs transplantation.
Reductive Alkaline Release of N‐Glycans Generates a Variety of Unexpected, Useful Products
Authors: Figl Rudolf , Altmann Friedrich 
Published: January 2018

AbstractRelease of O‐glycans by reductive β‐elimination has become routine in many glyco‐analytical laboratories and concomitant release of N‐glycans has repeatedly been observed. Revisiting this somewhat forgotten mode of N‐glycan release revealed that all kinds of N‐glycans including oligomannosidic and complex‐type N‐glycans from plants with 3‐linked fucose and from mammals with or without 6‐linked fucose and with sialic acid could be recovered. However, the mass spectra of the obtained products revealed very surprising facts. Even after 16 h incubation in 1 M sodium borohydride, a large part of the glycans occurred in reducing form. Moreover, about one third emerged in the form of the stable amino‐functionalized 1‐amino‐1‐deoxy‐glycitol. When avoiding acidic conditions, considerable amounts of glycosylamine were observed. In addition, a compound with a reduced asparagine and de‐N‐acetylation products, in particular of sialylated glycans, was seen. The relative yields of the products reducing glycosylamine, reducing N‐glycan, 1‐amino‐1‐deoxy‐glycitol or glycitol could be controlled by the release conditions, foremost by temperature and borohydride concentration. Thus, chemical release of N‐glycans constitutes a cost‐saving alternative to enzymatic hydrolysis for the preparation of precursors for the production of reference compounds for various formats of N‐glycan analysis. Moreover, it allows to obtain a stable amino‐functionalized glycan derivative, which can be employed to construct glycan arrays or affinity matrices.
Nebulized hypertonic saline in infants hospitalized with moderately severe bronchiolitis due to RSV infection: A multicenter randomized controlled trial
Authors: Morikawa Yoshihiko , Miura Masaru , Furuhata Megumi Y. , Morino Saeko , Omori Tae , Otsuka Masahiro , Chiga Michiko , Obonai Toshimasa , Hataya Hiroshi , Kaneko Tetsuji , Ishikura Kenji , Honda Masataka , Hasegawa Yukihiro ,   on behalf of the Tokyo Pediatric Clinical Research Network
Published: January 2018

AbstractIntroductionThe efficacy of nebulized hypertonic saline (HS) therapy for shortening hospital length of stay (LOS) or improving bronchiolitic symptoms remains controversial. Most studies enrolled small numbers of subjects and did not consider the role of respiratory syncytial virus (RSV), the most common cause of acute bronchiolitis. Our aim was to evaluate the efficacy and safety of nebulized HS therapy for acute bronchiolitis due to RSV in moderately ill hospitalized infants.Materials and MethodsThis was an open‐label, multicenter, randomized controlled trial comparing a nebulized HS treatment group with a normal saline (NS) group. The subjects, 128 infants with bronchiolitis due to RSV, were admitted to five hospitals in Tokyo, Japan. Three‐percent HS or NS was administered via bronchodilator four times daily post‐admission. The primary outcome was LOS, defined as the time until the patients fulfilled the discharge criteria, namely, absence of fever, no need for supplemental oxygen, and adequate feeding. Survival analysis was conducted in accordance with the intention‐to‐treat principle.ResultsThe baseline characteristics were similar between the two groups. There was no significant overall difference in LOS between the groups (4.81 ± 2.14 days in HS vs 4.61 ± 2.18 days in NS; P = 0.60). Survival analysis by log‐rank test also showed no significance (P = 0.62). Multivariate adjustment did not significantly alter the results. The treatment was well‐tolerated, with no adverse effects attributable to the use of HS.ConclusionsNebulized HS therapy did not significantly reduce LOS among infants with bronchiolitis due to RSV.
A new reliability analysis method for repairable systems with closed‐loop feedback links
Authors: Yi Xiao‐Jian , Shi Jian , Dhillon B.S. , Hou Peng , Dong Hai‐Ping 
Published: January 2018

AbstractA new reliability analysis method for repairable systems with closed‐loop feedback link (CLFL) is proposed based on GO methodology. A method for creating new function GO operators is used to describe the CLFL. Next, methods for deducing the formulae of the new GO function are proposed. In addition, a 2‐level GO model is proposed for the GO operation of repairable systems with CLFL. And then, quantitative and qualitative analysis methods for repairable systems with CLFL based on the GO method are proposed, and a process for analyzing repairable systems with CLFL based on the new GO method is formulated. Finally, we used this new GO method to analyze the reliability of an electro‐hydraulic servo speed control system and a power‐shift steering transmission control system for a heavy vehicle. To verify the feasibility, advantages, and reasonability of the new GO method, we compared our results with those obtained by fault tree analysis, Monte Carlo Simulation, and an existing GO method using serial and parallel structures to represent the CLFL. All in all, the proposed method overcomes the limitations of the existing methods as well as increasing its applicability. And it provides a new approach for reliability analysis of repairable systems with CLFL.