bluuebunny/crossref_metadata_2025_split huggingface dataset:
c-Kit and c-kit mutations in mastocytosis and other hematological diseases
Authors: Boissan Mathieu , Feger Frédéric , Guillosson Jean-Jacques , Arock Michel 
Published: January 2018

Abstract
Mast cells (MC) are tissue elements derived from hematopoietic stem cells. Their differentiation and proliferation processes are under the influence of cytokines, including one of utmost importance known as stem cell factor (SCF). SCF receptor is encoded by the protooncogene c-kit, belongs to the type III receptor tyrosine kinase subfamily, and is also expressed on other hematopoietic or non-hematopoietic cells. Ligation of c-kit receptor by SCF induces its dimerization, followed by induction of multiple intracellular signaling pathways leading to cell proliferation and activation. Mastocytosis, a relatively rare group of diseases characterized by accumulation of MC in various tissues, are found isolated or sometimes associated with other hematological malignancies in humans. Although the initial events leading to mastocytosis are not yet unraveled, alterations of the c-kit gene have been described. Particularly interesting are acquired mutations resulting in a constitutively activated receptor, possibly involved in the increased numbers of MC in tissues. For this reason, future strategies might be envisaged to target specifically the mutated c-kit and/or its intracellular signaling. J. Leukoc. Biol. 67: 135–148; 2000.
Differential role of tyrosine phosphorylation in adhesion-induced transcription, mRNA stability, and cytoskeletal organization in human monocytes
Authors: Mondal Krishna , Sirenko Oksana I , Lofquist Alan K , Morris John S , Haskill J Stephen , Watson Joanna M 
Published: January 2018

Abstract
Monocyte adhesion resulted in rapid tyrosine phosphorylation and subsequent cytokine mRNA induction. The objective of this study was to determine the role of specific tyrosine phosphorylation events, particularly those involving members of the MAP kinase family, in regulating adhesion-induced cytokine expression. Using nuclear run-on analyses, we demonstrated that on adhesion, monocytes rapidly transcriptionally activated numerous cytokine mRNAs, coincident with the activation of the transcription factors NF-κB and AP-1. Both an inhibitor of tyrosine phosphorylation, genistein, and the cytoplasmic tyrosine phosphatase PTP1B, were unable to prevent adhesion-mediated transcriptional activation. However, both blocked adhesion-induced ERK and JNK but not p38 kinase activation and at the same time decreased the stability of interleukin-1β (IL-1β) and IL-8 transcripts. In addition, whereas adhesive events occurred in the presence of genistein and PTP1B, monocyte spreading was markedly inhibited. Our results suggest that the majority of protein phosphorylation events are associated with adhesion-induced cytokine expression through transcript stabilization and cytoskeletal organization. A minority of protein phosphorylation events, not sensitive to genistein or PTP1B exposure, may be instrumental in regulating transcription. Thus the spectrum of protein tyrosine kinases required for transcription appear distinct from those involved in maintaining the stability of some cytokine mRNAs and the integrity of the cytoskeleton to which mRNA destined for translation must be associated. J. Leukoc. Biol. 67: 216–225; 2000.
Regulatory roles for FcγRIII (CD16) and FcγRII (CD32) in the development of T- and B-lineage lymphoid cells
Authors: Lynch Richard G 
Published: January 2018

Abstract
IgG Fc receptors (FcγR) occur on all hematopoietic lineages and participate in a diversity of functions that reflect the combined effects of the molecular heterogeneity of FcγR and the inherent specialization of the FcγR + cells. An extensive literature describes the functions of FcγR on mature myeloid and lymphoid cells in humans and mice but little has been published about FcγR on lineage progenitor cells. Several studies suggest that FcγR can influence leukocyte development and that FcγRII (CD32) and FcγRIII (CD16) can regulate murine T- and B-lineage development at stages before the expression of clonal antigen receptors. The nominal ligand of FcγR is IgG and the physiologically relevant ligand is the IgG-antigen complex, but it is also known that alternative, non-Ig ligands exist for Fc receptors. A role for FcγR in the regulation of leukocyte development has potential relevance for clinical situations in which the levels of nominal and/or alternative ligands of FcγR are elevated, or the production of soluble forms of FcγR is increased. J. Leukoc. Biol. 67: 279–284; 2000.
Increased expression of the tetraspanins CD53 and CD63 on apoptotic human neutrophils
Authors: Beinert Thomas , Münzing Silvia , Possinger K , Krombach Fritz 
Published: January 2018

Abstract
The recently discovered tetraspanin superfamily comprises a group of cell-surface proteins that are suggested to be involved in cell activation and signal transduction as well as in cell adhesion, motility, and metastasis. In this study, we have assessed the expression of two tetraspanins, CD53 and CD63, and two principal leukocyte adhesion molecules, CD11b and CD62L, on human apoptotic neutrophils. After aging of human neutrophils for 20 and 40 h in vitro, apoptosis was analyzed by light microscopy and flow cytometry. The binding of monoclonal antibodies directed against CD11b, CD62L, CD53, and CD63 on apoptotic and nonapoptotic cells was determined by dual-color flow cytometry. Aging of neutrophils in vitro resulted in a significant (P &lt; 0.05) down-regulation of expression of the selectin CD62L, and a significantly increased expression of the two tetraspanins CD53 and CD63. The selective analysis of apoptotic versus nonapoptotic cells proved that both the increased expression of the tetraspanins and the loss of CD62L were restricted to the apoptotic subpopulation. An identical pattern of surface molecule expression was detected at 12 h after induction of apoptosis by an agonistic anti-Fas IgM monoclonal antibody. Further studies are required to clarify whether tetraspanins participate in the recognition of apoptotic circulating or extrava-sated neutrophils by macrophages. J. Leukoc. Biol. 67: 369–373; 2000.
Receptor reserve analysis of the human CCR3 receptor in eosinophils and CCR3-transfected cells
Authors: Umland Shelby P , Wan Yuntao , Shortall Jennifer , Shah Himanshu , Jakway James , Garlisi Charles G , Tian Fang , Egan Robert W , Billah M Motasim 
Published: January 2018

Abstract
A novel pharmacological study of CCR3 receptor reserve in a CCR3-transfected cell (CREM3) and human eosinophils was done; functional responses measured were increases in intracellular calcium and chemotaxis. Eotaxin, eotaxin-2, monocyte chemoattractant protein-4 (MCP-4), RANTES, and MCP-3 induced similar maximal eosinophil chemotaxis, whereas MCP-3 and RANTES induced submaximal calcium responses in eosinophils compared to eotaxin, MCP-4, and eotaxin-2. This suggested a receptor reserve in the chemotaxis response. Receptor reserve was quantitated for eotaxin. Occupancy of all CCR3 receptors was required for a maximal calcium response in both CREM3 and eosinophils (reserve = 1.0 or 0.17, respectively); the stimulus-calcium response relationship was linear, indicating no receptor reserve. In contrast, in eosinophils a large receptor reserve (6.5) was found for chemotaxis, where occupancy of 15% receptors drove half-maximal responses. These studies indicate that CCR3 interacts with G-proteins that are poorly coupled to the calcium response, whereas coupling efficiency and/or amplification to the chemotaxis apparatus in human eosinophils is significantly greater. J. Leukoc. Biol. 67: 441–447; 2000.
Does innate immune privilege exist?
Authors: Streilein J Wayne , Stein-Streilein Joan 
Published: January 2018

Abstract
Immune privilege in the eye is believed to originate from the eye's need to avoid the sight-destroying consequences of inflammation. Over the past 25 years, many of the anatomical, cellular, and molecular mechanisms by which the eye avoids inflammation secondary to adaptive immune responses have been elucidated. In the recent past, it has become increasingly clear that innate immune responses play a critical role in activating the adaptive immune response. Moreover, innate immunity itself carries a heavy burden of inflammation, thereby posing a threat to vision if it should occur intraocularly. Ocular immunologists have now begun to inquire into the extent to which the eye regulates the expression of innate immunity in oculi. Evidence is presented which indicates that factors found in normal aqueous humor (1) prevent NK cells from lysing their targets, (2) inhibit neutrophil activation by CD95 ligand, (3) suppress nitric oxide production by activated macrophages, and (4) interfere with complement activation via the alternative pathway. These factors include transforming growth factor-β2, α-melanocyte-stimulating hormone, calcitonin gene-related peptide, and migration inhibitory factor. The ability of the eye to prevent intraocular activation of innate immune effectors spares the corneal endothelium (which expresses CD95 ligand constitutively, but low levels of MHC class I molecules) from destruction by NK cells and neutrophils, and protects the visual axis from distortion by macrophage and complement-mediated inflammation. Thus, privilege exists in the eye for both adaptive and innate immunity. J. Leukoc. Biol. 67: 479–487; 2000.
Neutrophil chemotaxis in moving gradients of fMLP
Authors: Ebrahimzadeh P R , Högfors C , Braide M 
Published: January 2018

Abstract
In this study the fluid gradient chamber, a modified version of the Boyden chamber that enables mobile gradients, was used to study the migration of human granulocytes in gradients of fMLP. Temporal chemotactic gradients were created by moving density-stabilized spatial gradients at different velocities in relation to migrating cells. Random and directed cell migration was quantified by applying a theoretical population distribution model to experimental cell distributions obtained from cell counts at different depths in the filters. Rates of random and directed migration generally increased with gradient velocity. At negative gradient velocities, i.e., when the gradients were moved in a direction opposite to that of cell migration to decrease fMLP concentration over time, random and directed migration was inhibited. At positive gradient velocities, migration rates were not significantly different from those seen in immobile gradients. The fact that the rate of directed migration was smaller at negative gradient velocities indicates that negative temporal gradients reduced the average speed and/or orientation of the chemotactically migrating cells. In immobile gradients, the cells generated a small concentration increase over time when they migrated in the up-gradient direction. Consequently, a positive temporal gradient as perceived by the cells may act as a positive feedback signal to maintain chemotactic migration. J. Leukoc. Biol. 67: 651–661; 2000.
Role of mast cell leukotrienes in neutrophil recruitment and bacterial clearance in infectious peritonitis
Authors: Malaviya Ravi , Abraham Soman N 
Published: January 2018

Abstract
Stimulated mast cells release a variety of chemotactic factors such as tumor necrosis factor α (TNF-α) and leukotriene B4. Recent studies have shown that mast cell-derived TNF-α plays a critical role in host defense against Gram negative bacterial infections by the recruitment of neutrophils to the sites of infection. In the present study, we sought to investigate if mast cells release leukotriene (LT) B4 in response to bacteria and, if so, to establish its in vivo relevance. We show that mast cells release significant amounts of LTB4 and LTC4 in response to exposure to FimH-expressing type 1 fimbriated Escherichia coli in vitro. To test the functional significance of mast cell-derived LTs during an E. coli infection in vivo, we examined the effect of a LT-synthesis inhibitor, A-63162, on bacterial clearance and neutrophil influx in an infectious peritonitis model in mast cell-deficient mice (WBB6F1-W/WV) and their normal congenic control (WBB6F1-+/+) mice. Our results show that a treatment with A-63162 reduced neutrophil influx and bacterial clearance in the peritoneal cavities of mast cell-sufficient but not -deficient mice. Thus, mast cell-derived LTs contribute to host defense by mediating early neutrophil influx and bacterial clearance at sites of infection. J. Leukoc. Biol. 67:841–846; 2000.
Aspirin-induced increases in soluble IL-1 receptor type II concentrations in vitro and in vivo
Authors: McHugh Shannon L , Yamamoto Yoshimasa , Klein Thomas W , Friedman Herman 
Published: January 2018

Abstract
Virulent Legionella pneumophila replicate readily in thioglycollate-elicited peritoneal macrophages from genetically permissive A/J mice, but avirulent L. pneumophila do not. The production of cytokines by macrophages infected with L. pneumophila has been studied, but the correlation of bacterial virulence with immune responses of macrophages, such as proinflammatory cytokine production, is not well understood. In this regard, production of the cytokines tumor necrosis factor α (TNF-α), interleukin (IL)-1α, IL-1β, and IL-6 were examined in macrophage cultures infected in vitro with virulent vs. avirulent L. pneumophila. Infection of macrophages from A/J mice with the virulent L. pneumophila up-regulated mRNA expression for these cytokines, whereas avirulent bacteria resulted in only a slight or no detectable increase in cytokine mRNA. Similarly, virulent L. pneumophila induced the macrophages to produce relatively high levels of TNF-α, IL-1α, IL-1β, and IL-6 proteins as measured by enzyme-linked immunosorbent assays, whereas avirulent bacteria induced only low or often undetectable amounts of these cytokines. Thus, these results show the murine macrophages from susceptible A/J mice are readily infected with virulent L. pneumophila in vitro and stimulated to produce the proinflammatory acute-phase cytokines TNF-α, IL-1α, IL-1β, and IL-6, but avirulent L. pneumophila did not. Such differences in induction of these proinflammatory cytokines by macrophages in response to virulent vs. avirulent L. pneumophila infections may be an important factor in the pathogenesis induced by these intracellular bacteria. J. Leukoc. Biol. 67: 863–868; 2000.
Vermicomposting: A sustainable tool for environmental equilibria
Authors: Singh Archana , Singh Gopal Shankar 
Published: January 2018

ABSTRACTImproperly managed organic waste constitutes a serious environment threat across the globe. This has led to a worldwide struggle to strike a balance between the rapid generation of such wastes and protection of the environment. With the unique advantages of lower operational and maintenance costs compared with other waste management technologies, the use of vermicomposting to manage organic wastes has been increasing rapidly in recent years. Still, some factors (e.g., characteristics of substrate composition before and after treatment) are in need of additional, specific studies so that researchers can better understand the metabolism involved in the process. Vermicomposting provides employment opportunities as it protects the environment, augmenting crop productivity when it is used as a fertilizer supplement and helping to maintain ecological balance. Thus, vermicompost plays an important role in the circular economy. This article provides an overview of the research activities that have been conducted on the use of vermicomposts to remove pollutants from the soil, in wastewater treatment, and in organic waste recycling throughout the world. Circular economic assessment has revealed that vermicomposting technology is usually feasible except in certain cases. Most other methods of waste disposal lead to soil deterioration, toxic effects, and increased pollution affecting land, air, water, and living beings, in addition to the sometimes considerable expense of their implementation. Thus, an eco‐friendly method that removes waste in one step is needed. Determining the long‐term performance and sustainable operation of vermicomposting systems still poses a challenge, however, as treatment performance is affected by design parameters, operational conditions, and environmental factors. This article summarizes the factors influencing pollutant removal through the vermicomposting process. Finally, this article highlights additional research that should be conducted on these issues to improve the performance of vermicomposting.
Changing Forms of Corruption in India
Authors: GUPTA AKHIL 
Published: January 2018

AbstractThis article has four important goals. First, I want to ask why liberalization and market-friendly reforms failed to curb corruption in India. Indeed, confounding the predictions of most proponents of reform, corruption seems to have increased after the neoliberal reforms of 1991. Second, I aim to develop a typology in which the importance of particular sectors to corrupt practices is highlighted and explained. Third, I point out that India has failed to make the ‘transition’ historically seen in low-income countries as they develop. Nation-states have in the past moved from a system of vertical corruption—marked by the extraction of small sums from a large number of transactions with citizens in everyday life—to a system of horizontal corruption, in which governmental elites extract large sums in a small number of transactions from corporate and commercial bodies. Finally, I argue that anti-corruption movements cannot be understood without paying attention to the affective and emotional ties that bind citizens to the state. We have to take account of contradictory feelings about the state: cynicism about the state and popular anger against corruption on one side, and an attachment to popular sovereignty and patronage on the other. These contradictory sentiments will better enable us to understand the conjunctures that lead to effective institutional change.
OP30 Health Technology Assessment And The Decision-Making Process Of New Drug Listing In Hong Kong
Authors: Wong Carlos , Wu Olivia , Cheung Bernard 
Published: January 2018

INTRODUCTION:In Hong Kong, the Drug Advisory Committee (DAC) has had the role of evaluating and advising new drugs to be included in the listing of the Hospital Authority Drug Formulary since July 2005. The drug review process was subject to challenge due to a lack of transparency to members of the public and documentation of the scientific basis for decision making. The purpose of this review was to describe the process, evaluation criteria and possible outcomes of decision making for new drugs listed in the Hong Kong Hospital Authority Drug Formulary in comparison to Health Technology Assessment (HTA) policies in overseas countries.METHODS:Details of the decision-making processes including new drug listing submissions, the DAC meeting, procedures before and after the meeting, were extracted from the official Hong Kong Hospital Authority drug formulary management website and manual. Publicly available information related to new drug decision making processes for four HTA agencies (National Institute for Health and Clinical Excellence (NICE), Scottish Medicines Consortium (SMC), Australian Pharmaceutical Benefits Advisory Committee (PBAC), and Canadian Agency for Drugs and Technologies in Health (CADTH)) were reviewed and retrieved from official documents on their public domains.RESULTS:The DAC is in charge of the systematical and critical appraisal of new drugs for listing on the formulary, reviewing submitted applications, and making decisions of drug listing based on scientific evidence in which safety, efficacy and cost-effectiveness are primary considerations. When compared to other HTA agencies, transparency of decision-making processes of the DAC, relevance of clinical and health economic evidence, and lack of health economic and methodological input to submissions were major challenges of the new drug listing policy in Hong Kong.CONCLUSIONS:Despite the challenges identifed, this review provided suggestions for establishing a more transparent, credible, evidence-based decision-making process for the Hong Kong Hospital Authority Drug Formulary. Proposals for improvement in the listing of new drugs in the formulary should be a priority in healthcare reform.
OP131 Cost-Effectiveness Of Dexamethasone And Adalimumab For Uveitis
Authors: Bermejo Inigo , Squires Hazel , Poku Edith , Cooper Katy , Stevens John , Hamilton Jean , Wong Ruth 
Published: January 2018

INTRODUCTION:Uveitis is inflammation inside the eye whose underlying cause may be infectious or non-infectious. The objective of our study was to assess the cost-effectiveness of the dexamethasone implant and adalimumab compared with current practice (immunosuppressants and systemic corticosteroids) in patients with non-infectious intermediate, posterior or pan-uveitis.METHODS:A Markov model was built to estimate costs and benefits of the interventions. Systematic reviews were performed to identify the relevant evidence. Quality of life data collected in three key randomized-controlled trials (1-3) was used to estimate the interventions effectiveness compared with the trials comparator arms, which consisted of placebo plus limited current practice (LCP). An indirect treatment comparison between adalimumab and dexamethasone was considered inappropriate due to lack of necessary evidence. For adalimumab, patients with active and inactive uveitis were considered separately. Due to the short duration of the trials, the rate of blindness, an important complication of uveitis, was highly uncertain. Substantial exploratory analyses were therefore undertaken. The analysis was performed from the perspective of the National Health Service (NHS) and Personal Social Services (PSS). Costs were calculated based on standard United Kingdom sources.RESULTS:The estimated incremental cost-effectiveness (ICER) of dexamethasone compared with LCP was GBP19,509 per quality-adjusted life year (QALY) gained. The estimated ICER of adalimumab compared with LCP was GBP94,523 and GBP317,547 per QALY in patients with active and inactive uveitis respectively. The factors with the largest impact upon the ICERs were the rate of blindness and the proportion of cases of blindness avoided by interventions.CONCLUSIONS:Dexamethasone and adalimumab resulted in health gains, but at significant extra costs, especially adalimumab which is unlikely to be considered a cost-effective use of NHS resources. The results of the analysis are highly uncertain due to the limited availability of evidence on: the comparative effectiveness of dexamethasone, adalimumab and current practice; the effectiveness of treatments in avoiding blindness; and, the effectiveness of interventions in different subgroups.