bluuebunny/crossref_metadata_2025_split huggingface dataset:
The β-thromboglobulins and platelet factor 4: blood platelet-derived CXC chemokines with divergent roles in early neutrophil regulation
Authors: Brandt Ernst , Petersen Frank , Ludwig Andreas , Ehlert Jan E , Bock Lothar , Flad Hans-D 
Published: January 2018

Abstract
The recruitment of neutrophil granulocytes to sites of tissue injury is one of the earliest events during host defense. Several chemotactic cytokines belonging to the CXC subfamily of chemokines are thought to be implicated in this kind of response. Especially those CXC chemokines that are stored in blood platelets and become immediately released upon activation are likely to dominate neutrophil-dependent host defense at the onset of inflammation. The major platelet-derived CXC chemokines are the β-thromboglobulins and platelet factor 4 (PF-4), which are both released into the blood at micromolar concentrations. The availability as well as the functional activity of these mediators appear to be subject to tight control by diverse regulatory mechanisms. These include proteolytic processing of chemokine precursors, oligomer formation, and the differential usage of neutrophil-expressed receptors. Herein we review our work on early neutrophil regulation by PF-4, the β-thromboglobulin neutrophil-activating peptide 2 (NAP-2) and its major precursor connective tissue-activating peptide III (CTAP-III). We moreover propose a model to assess the contribution by either of these chemokines to coordinated recruitment and activation of neutrophils in response to acute tissue injury. J. Leukoc. Biol. 67: 471–478; 2000.
Activation of cAMP-dependent protein kinase is necessary for actin rearrangements in human neutrophils during phagocytosis
Authors: Ydrenius Liselotte , Majeed Meytham , Rasmusson Birgitta J , Stendahl Olle , Särndahl Eva 
Published: January 2018

Abstract
We have investigated the role of cAMP and cAMP-dependent protein kinase (cAPK) in neutrophil phagocytosis. Inhibition of cAPK with H-89 reduced complement- and IgG-dependent phagocytosis to 83 and 46%, respectively. Fluorescence intensity measurements of phalloidin-stained actin in neutrophils showed a reduced amount of filamentous actin (F-actin) in pseudopods and around the phagosome in cells treated with H-89 or cAMP-elevating agents (forskolin and rolipram). The amount of phosphotyrosine-containing proteins was also reduced in pseudopods and around the phagosome. Taken together, the data show that cAMP/cAPK regulates F-actin reorganization during receptor-mediated phagocytosis, particularly triggered by IgG-FcR interaction. Our results support the hypothesis that active subcortical reorganization of F-actin is a prerequisite for FcR-mediated phagocytosis, but is less important during CR3-mediated ingestion. J. Leukoc. Biol. 67: 520–528; 2000.
Theophylline induces neutrophil apoptosis through adenosine A2A receptor antagonism
Authors: Yasui Kozo , Agematsu Kazunaga , Shinozaki Koji , Hokibara Sho , Nagumo Haruo , Nakazawa Takayuki , Komiyama Atsushi 
Published: January 2018

Abstract
This study was designed to determine whether theophylline would augment granulocyte apoptosis via a mechanism of adenosine A2A receptor antagonism. A selective adenosine A2 receptor agonist (CGS-21680, 1 μM) exhibited the most efficient potency for decreasing neutrophil apoptosis for 16 h from 63 ± 5 to 19 ± 4% (P &lt; 0.001); it exerted poor and adverse effects on eosinophil survival. A selective protein kinase A inhibitor KT-5720 (10 μM) reversed the capacity of dibu-tyryl cAMP but not CGS-21680 to induce an inhibitory effect on neutrophil apoptosis, suggesting that occupancy of adenosine A2 receptors inhibit neutrophil apoptosis by a cAMP-independent mechanism. Theophylline derivatives show the following pattern of potency for inducing neutrophil apoptosis competing with CGS-21680: 8-phenyltheophylline = 8-p-sulfophenyltheophylline &gt; theophylline ≫ enprofylline. This pattern is consistent with the affinity established for A2A receptors. Theophylline demonstrated an additive effect to that of anti-Fas antibody (CH11, 1 μg/mL) in inducing neutrophil apoptosis, but not to that of adenosine deaminase or KF-17837 (a selective A2 receptor antagonist; 1 μM), suggesting conflicting effects on the receptor antagonism. These findings suggest that theophylline has an immunomodulatory action on neutrophil apoptosis via a mechanism of A2A antagonism. J. Leukoc. Biol. 67:529–535; 2000.
Chymase is a potent chemoattractant for human monocytes and neutrophils
Authors: Tani Kenji , Ogushi Fumitaka , Kido Hiroshi , Kawano Tetsuya , Kunori Yuichi , Kamimura Takashi , Cui Ping , Sone Saburo 
Published: January 2018

Abstract
Chymase is a major chymotrypsin-like serine protease expressed in the secretory granules of mast cells in many mammalian species. In this study, we revealed the chemotactic activity of chymase for human mononuclear cells and neutrophils with a 48-well microchemotaxis chamber technique. Human chymase showed the potent chemotactic activity for monocytes and neutrophils dose-dependently in a concentration range from 0.1 to 10 μg/mL, corresponding to about 4–400 μM. The activity was as potent as that of N-formyl-methionyl-leucyl-phenylalanine. Chymase also stimulated cell migration of lymphocytes and purified T cells, but checkerboard analysis revealed that the effect was chemokinetic rather than chemotactic. Inhibition of chymase activities with chymase inhibitors, such as antileukoprotease and Bowman-Birk soybean trypsin inhibitor, significantly inhibited the chemotactic activity of chymase, suggesting that the proteolytic activity of chymase participates in the chemotactic activity. Our results suggest that mast cell chymase acts as a chemoattractant, and may play a role in the accumulation of inflammatory cells in development of the chronic inflammatory responses of allergic and nonallergic diseases. J. Leukoc. Biol. 67: 585–589; 2000.
Definition of human blood monocytes
Authors: Ziegler-Heitbrock H W L 
Published: January 2018

Abstract
At the Definition of Human Blood Monocytes conference held in Munich, Germany in October 1999, experts met to discuss data on the characterization of monocytes in health and disease. Emphasis was on how to best define these cells, on which subpopulations can be identified, and on how the monocytes can best be distinguished from other cells such as natural killer cells, granulocytes, and dendritic cell precursors. J. Leukoc. Biol. 67: 603–606; 2000.
Insights into the role of γδ T lymphocytes in the immunopathogenic response to thermal injury
Authors: Schwacha Martin G , Ayala Alfred , Chaudry Irshad H 
Published: January 2018

Abstract
Studies have shown that cell-mediated immunity is markedly suppressed after thermal injury. T lymphocyte dysfunction and macrophage hyperactivity have been implicated as causative factors. Previous studies have primarily examined the effects of thermal injury on αβ T lymphocytes; however, the role of γδ T lymphocytes in the immune response after thermal injury is unclear. Therefore, wild-type mice and mice lacking the TCR δ gene (TCR δ−/−) were subjected to a third-degree scald burn and cell-mediated immune responses assessed at 7 days post-injury. TCR δ−/−mice had 75% mortality after burn injury compared with 25% mortality in the wild-type group. Plasma interluekin-6 (IL-6) levels were significantly elevated at 2, 4, and 18 h post-injury, whereas no difference was observed in tumor necrosis factor α (TNF-α) and prostaglandin E2 (PGE2) plasma levels. Plasma levels of these inflammatory mediators were similar in wild-type and TCR δ−/-_ mice post-injury. Splenic macrophage PGE2, IL-6, TNF-α, and IL-10 production was significantly increased in wild-type mice at 7 days post-injury, whereas macrophages from injured TCR δ−/− mice had a significantly attenuated capacity to produce IL-6 and TNF-α. In contrast, the increased release of PGE2 and IL-10 by macrophages post-injury was not reduced in TCR δ−/− mice. These results implicate a dual role for γδ T lymphocytes in the immunopathogenic response to burn injury: (1) they contribute to survival from the insult; and (2) they mediate the induction of a pro-inflammatory macrophage phenotype at 7 days post-injury. Thus, γδ T lymphocytes, in part through the modulation of macrophage activity, appear to contribute to the immune dysfunction after thermal injury. J. Leukoc. Biol. 67: 644–650; 2000.
Scavenger receptor-mediated delivery of muramyl dipeptide activates antitumor efficacy of macrophages by enhanced secretion of tumor-suppressive cytokines
Authors: Srividya S , Roy Rajendra P , Basu Sandip K , Mukhopadhyay Amitabha 
Published: January 2018

Abstract
We showed that muramyl dipeptide (MDP) conjugated to maleylated bovine serum albumin (MBSA) was internalized by macrophages (M) through scavenger receptor (SCR)-mediated endocytosis, which leads to 50-fold higher cytotoxic activity against non-M tumor cells compared with that elicited by free MDP-treated M. The enhanced cytotoxic effect of MBSA-MDP was found to be a result of higher secretion of interleukin (IL)-1, IL-6, tumor necrosis factor α (TNF-α), and nitric oxide (NO) because the addition of antibodies directed against IL-1, IL-6, or TNF-α in combination with M cultures totally abrogated the tumoricidal activity of MBSA-MDP. It is interesting to note that MBSA-MDP triggers the secretion of IL-12, whereas IL-10, a M suppressor cytokine, could be detected only on free MDP treatment. The cytotoxic activity of MBSA-MDP was inhibited by indomethacin, indicating a regulatory role for prostaglandin E2 (PGE2). Efficient SCR-mediated intracellular delivery of MDP leading to elimination of cancer cells suggests the immunotherapeutic potential of this approach for treatment of neoplasia. J. Leukoc. Biol. 67: 683–690; 2000.
Differential chemokine receptor expression and function in human monocyte subpopulations
Authors: Weber Christian , Belge Kai-Uwe , von Hundelshausen Philipp , Draude Georg , Steppich Birgit , Mack Mathias , Frankenberger Marion , Weber Kim S C , Ziegler-Heitbrock H W Löms 
Published: January 2018

Abstract
The subset of human blood monocytes expressing low levels of CD14 and high levels of CD16 (CD14+CD16+) exhibits features resembling mature tissue macrophages and can be expanded in inflammatory conditions. We analyzed expression of CC chemokine receptors (CCR) in CD14+CD16+ versus CD14++ monocytes, which may be crucial for specific trafficking. Multicolor flow cytometric analysis of whole peripheral blood revealed that, as opposed to CD14++ monocytes, the CD14+CD16+ subset lacked surface expression of monocyte chemotactic protein-1 (MCP-1) receptor CCR2, however, it showed significantly higher surface expression of the macrophage inflammatory protein 1α (MIP-1α)/RANTES receptor CCR5. This was paralleled by differences in mRNA expression in the subsets, as shown by reverse transcriptase-polymerase chain reaction using sorted cells. In comparison to CD14++ monocytes, CD14+CD16+ cells expressed lower CCR2 but higher CCR5 transcript levels, whereas CCR1 levels were equivalent. Flow cytometric analysis of isolated human monocytes recovered after transendothelial chemotaxis assays revealed that the percentage of CD14+CD16+ cells was dramatically reduced in the fraction migrating toward MCP-1 compared with the fraction that did not migrate or the input, showing that polarized CCR2 expression was accompanied by a differential chemotactic responsiveness. Moreover, CD11b surface expression was preferentially up-regulated by MCP-1 in CD14++ cells but by MIP-1α in CD14+CD16+ monocytes, confirming the functional relevance of distinct CCR expression. The characteristics of CD14+CD16+ cells may reflect preactivation by cytokines and determine their predilective localization during specific inflammatory conditions or susceptibility to infection. J. Leukoc. Biol. 67: 699–704; 2000.
Positive regulation of human T cell activation by Gi2 proteins and interleukin-8
Authors: Lippert Eric , Jacques Yannick , Hermouet Sylvie 
Published: January 2018

Abstract
We investigated whether pertussis toxin (PT)-sensitive heterotrimeric Gi proteins (Gi1, Gi2, Gi3) are involved in the regulation of TCR-induced activation of human T cells. First, Gi proteins were inactivated by PT: pretreatment with PT of purified blood T lymphocytes before CD3 cross-linking inhibited cell proliferation (-71.1 ± 22.0%, P &lt; 0.001), production of interleukin-2 (IL-2; -47.3 ± 12.6%, P = 0.008), and expression of CD25 (-24.6 ± 11.7%, P &lt; 0.001) and CD69 (-25.7 ± 9.0%, P &lt; 0.001). Then, to identify which of the three Gi was involved, Gi1, Gi2, and Gi3 proteins were specifically inactivated by stably transfecting dominant-negative mutated forms of their α subunit in Jurkat cells. After activation, IL-2 production and CD69 expression were inhibited only in cells expressing inactive Gi2. We then studied the effects of interleukin-8 (IL-8), a CXC-chemokine with receptors coupled to Gi2 and produced in an autocrine fashion by activated T cells. Although its effects varied among donors, exogenous IL-8 stimulated proliferation and CD25 expression (up to, respectively, 200 and 77%) of PB T lymphocytes in response to CD3 activation, in a PT-sensitive manner. IL-8 also stimulated IL-2 production (by up to 42%) and CD69 expression, although weakly (+27%). Anti-human IL-8 antibody inhibited proliferation (-43%) and CD25 up-regulation (-45%) of activated T lymphocytes. In summary, several major responses of human T lymphocytes to TCR-mediated activation are regulated by Gi2 proteins, which for this function can be activated by IL-8 in an autocrine manner.
Toll receptors: an expanding role in our understanding of human disease
Authors: Schuster James M , Nelson Peter S 
Published: January 2018

Abstract
Toll receptor proteins in Drosophila are involved in establishing the dorsal-ventral axis in embryogenesis as well as participating in the innate immune response to invading pathogens. The basic mediators of this response show striking similarities in plants, insects, and vertebrates. The cytoplasmic signaling cascade is exemplified by the human interleukin-1 receptor complex (IL-1R), resulting in transcriptional activation of effector proteins through nuclear factor-κB (NF-κB). Six mammalian/human Toll-like receptors (TLR) have been described to date. The TLRs share the IL-1R cytoplasmic signaling cascade but are distinguished by their extracellular leucine-rich repeat (LRR) structure. The LRR superfamily comprises a diverse group of proteins, including a cohort involved in transmembrane signaling. Two of the human TLRs (TLR2, TLR4) have been shown to be involved in the innate response to bacterial pathogens and appear to provide a link between the innate and adaptive immune response. A better understanding of this response may provide improved therapeutic modalities in the treatment of bacterial and fungal sepsis, which continues to be a significant source of morbidity and mortality worldwide. In addition, similar to Drosophila, Toll receptors and related proteins in the LRR superfamily may also be involved in human development, as well as in noninfectious human disease. J. Leukoc. Biol. 67: 767–773; 2000.
Oral feeding of an immunodominant MHC donor-derived synthetic class I peptide prolongs graft survival of heterotopic cardiac allografts in a high-responder rat strain combination
Authors: Zavazava Nicholas , Fändrich Fred , Zhu Xiaofeng , Freese Anja , Behrens Dirk , Yoo-Ott Kyoung-Ae 
Published: January 2018

Abstract
The efficacy of two synthetic major histocompatibility complex (MHC)-derived DA (RT1.Aa) 25-mer peptides (residues 56–80 and 96–120) to modulate alloreactivity was tested in Lewis (RT1.A1) responder animals. The DA peptide 56–80, but not peptide 96–120, induced delayedtype hypersensitivity (DTH). DTH was significantly reduced by oral feeding of peptide 56–80, P = 0.004. In addition, oral feeding of this peptide in combination with a short course of cyclosporin A (CsA) prolonged graft survival of 60% of heterotope transplanted DA cardiac allografts in Lewis recipient rats. Long-term survivors developed low levels of allo-antibodies against donor tissue as compared to rejecting animals and increased levels of interleukin-4 (IL-4) within the allograft. Similarly, IL-4-secreting splenocytes were identified by flow cytometry in these animals, indicating a Th2-type cytokine pattern. However, graft survival was particularly limited to cardiac allografts because donor-type skin grafts were acutely rejected in tolerant animals. It is interesting that residue alignment of peptide 56–80 to the motif of the RT1.A1 molecule showed a preferred class I motif within this sequence, suggesting indirect presentation of this peptide to recipient T cells. Thus, peptide 56–80 appears to represent a dominant epitope that can be exploited for establishing tolerance in this transplantation strain combination. J. Leukoc. Biol. 67: 793–800; 2000.
Characterization of activated lymphocyte-tumor cell adhesion
Authors: Neeson Paul J , Thurlow Peter J , Jamieson Gary P 
Published: January 2018

Abstract
This study demonstrates the variable expression of ICAM-1 and leukocyte function antigen-3 (LFA-3) on four tumor cell lines (COLO526, K562, Daudi, and HT-29). In addition, phorbol ester (PMA) activation of lymphocytes modulated LFA-1 from a uniform to a clustered surface distribution; whereas after treatment with high levels of Mg2+ ions, the unique epitope for high-affinity LFA-1 was identified using clone Mab24. Using a flow cytometric adhesion assay it was demonstrated that PMA-activated lymphocytes formed conjugates with COLO526 and Daudi, and that these conjugates were inhibited by anti-CD2 with varying inhibition by LFA-1 clones MHM24 and 25.3.1. When lymphocytes were induced to express the high-affinity form of LFA-1, conjugates were identified with COLO526, K562, and Daudi and these conjugates were sensitive to the presence of both CD2 and LFA-1 antibodies. Further studies using confocal microscopy confirmed significant adhesion between peripheral blood lymphocytes pre-treated with either PMA or high levels of Mg2+ and the adherent cell line COLO526. In conclusion, this unique study has demonstrated for the first time the important role of the active form of LFA-1 on the lymphocyte cell surface for conjugate formation with an ICAM-1-expressing tumor cell; also, two pathways of cell signaling were identified for conjugate formation to occur. J. Leukoc. Biol. 67: 847–855; 2000.
Computational Tools for the Identification and Interpretation of Sequence Motifs in Immunopeptidomes
Authors: Alvarez Bruno , Barra Carolina , Nielsen Morten , Andreatta Massimo 
Published: January 2018

AbstractRecent advances in proteomics and mass‐spectrometry have widely expanded the detectable peptide repertoire presented by major histocompatibility complex (MHC) molecules on the cell surface, collectively known as the immunopeptidome. Finely characterizing the immunopeptidome brings about important basic insights into the mechanisms of antigen presentation, but can also reveal promising targets for vaccine development and cancer immunotherapy. This report describes a number of practical and efficient approaches to analyze immunopeptidomics data, discussing the identification of meaningful sequence motifs in various scenarios and considering current limitations. Guidelines are provided for the filtering of false hits and contaminants, and to address the problem of motif deconvolution in cell lines expressing multiple MHC alleles, both for the MHC class I and class II systems. Finally, it is demonstrated how machine learning can be readily employed by non‐expert users to generate accurate prediction models directly from mass‐spectrometry eluted ligand data sets.
Discussion of “The power of monitoring: how to make the most of a contaminated multivariate sample”
Authors: Perrotta Domenico , Torti Francesca 
Published: January 2018

AbstractWe contribute to the discussion of an article where Andrea Cerioli, Marco Riani, Anthony Atkinson and Aldo Corbellini review the advantages of analyzing multivariate data by monitoring how the estimated model parameters change as the estimation parameters vary. The focus is on robust methods and their sensitivity to the nominal efficiency and breakdown point. In congratulating with the authors for the clear and stimulating exposition, we contribute to its discussion with an overview of what we experienced in applying the monitoring in our application domain.
Facilitating adherence to endocrine therapy in breast cancer: stability and predictive power of treatment expectations in a 2-year prospective study
Authors: Pan Yiqi , Heisig Sarah R. , von Blanckenburg Pia , Albert Ute-Susann , Hadji Peyman , Rief Winfried , Nestoriuc Yvonne 
Published: January 2018

Abstract
Purpose
To identify modifiable factors predictive of long-term adherence to adjuvant endocrine therapy (AET).

Methods
As part of a 2-year cohort study in primary care (n = 116), we investigated whether initial treatment expectations predict adherence at 24 months after controlling for demographic, medical, and psychosocial variables. Treatment expectations were measured as necessity–concern beliefs, expected side-effect severity, and expected coping with side effects. Their stability over time and differences of trajectories between the adherent and nonadherent group were examined.

Results
Nonadherence at 24 months was 14.7% (n = 17). Side-effect severity at 3 months [OR 0.25, 95% CI (0.08, 0.81), p = 0.02] and necessity–concern beliefs [OR 2.03, 95% CI (1.11, 3.72), p = 0.02] were the sole predictors of adherence. Necessity–concern beliefs remained stable over 2 years, whereas expected side-effect severity (p = 0.01, η
p
2
= 0.07) and expected coping with side effects became less optimistic over time (p < 0.001, η
p
2
= 0.19), the latter particularly among nonadherers (p < 0.01, η
p
2
= 0.10).

Conclusions
Patients’ initial necessity–concern beliefs about the AET and early severity of side effects affect long-term adherence. Expecting poor management of side effects may also facilitate nonadherence. We suggest that discussing benefits, addressing concerns of AET, and providing side-effect coping strategies could constitute a feasible and promising option to improve adherence in clinical practice.
Risk factors for nasal bleeding in patients undergoing transnasal gastrointestinal endoscopy
Authors: Mieda Mitsuyo , Miyashita Hiroshi , Osawa Hiroyuki , Hirasawa Tomosuke , Makino Nobuko , Toma Sachiko , Tomiyama Takeshi , Miura Yoshimasa , Lefor Alan K. , Yamamoto Hironori 
Published: January 2018

AbstractTransnasal endoscopy is widely used in screening for upper gastrointestinal lesions because of less associated pain. Nasal bleeding is the most severe adverse effect, but specific risk factors have not been identified. The aim of this study is to identify risk factors for nasal bleeding during transnasal endoscopy. Nasal bleeding occurred in 160/3035 (5.3%) of patients undergoing transnasal endoscopy as part of health checkups. Patient data were retrospectively evaluated including anthropometric, medical, and life‐style parameters with multiple logistic regression analysis. Multiple logistic regression revealed that nasal bleeding was significantly associated with age in decades [odds ratio/10 years 0.78, 95% confidence interval (CI) 0.63–0.97, p = 0.027], female gender (2.15, 95% CI 1.48–3.12, p < 0.001), a history of previous upper gastrointestinal endoscopy (0.55, 95% CI 0.36–0.82, p = 0.004), and chronic/allergic rhinitis (0.60, 95% CI 0.36–0.98, p = 0.043). Other factors including the use of antiplatelet and/or anticoagulant drugs were not significantly associated with nasal bleeding. Female and young patients are significantly associated with an increased risk of bleeding from transnasal endoscopy, but antiplatelet and/or anticoagulant medications and a history of chronic/allergic rhinitis may not be associated.