bluuebunny/crossref_metadata_2025_split huggingface dataset:
Polyanionic Agents as Inhibitors of Phagosome-Lysosome Fusion in Cultured Macrophages: Evolution of an Alternative Interpretation
Authors: Goren Mayer B , Vatter Albert E , Rscus Judith 
Published: January 2018

Abstract
Various natural and synthetic substances classified as polyanlonics have been Implicated in antagonizing phagosome-lysosome fusion in cultured macrophages. The phenomsnon has been Judged by comparing the transfer of selected markera from secondary lysosomes to phagosomes in control and in “polyanion” cells. Our earlier studies showed that use of one of the markers, the membrane per mealing acridine orange, was plagued with artifacts that were especially misleading in the presence of polyanionic agents. We now question the validity of data obtained by the alternative technique, electron microscopy. Our present evidence shows that nonionic hydrocolloids of sufficiently high molecular weight prevent the transfer of various colloidal electron-opaque markers from lysosomes to phagosomes in the same manner as does the powerful polyanionic “fusion inhibitor” dextran sulfate. Both kinds of hydrocolloids, however, allow delivery of lysosomal, low-molecular-weight highly charged non-permeant fluorescent markera to phagosomes, probably by a fusion process. We propose that neither type of hydrocolloid inhibits fusion; instead, when sufficiently concentrated, they trap particulate electron-opaque markers in a gelatinous matrix, which may move only slowly out of lysosomes. The potyanionics trap the electron-opaque markers physically and acridine orange ionically. Hence, the semblance of “fusion inhibition.”
Relationship of Glucocorticoid Suppression of Arachidonic Acid Metabolism to Alteration of Neutrophil Function
Authors: Webb Deborah S A , Roth James A 
Published: January 2018

Abstract
The row of arachidonic acid metabolism in glucocorticold-inducod suppression of neutrophil function was investigated. In vivo treatment of cattle with doxamethasone decreased the production of lipoxygenase products of arachidonic acid metabolism (leukotriene B4 (LTB4) and H-5-hvdroxy-6,8,11,14-eicosatetraenoic acid [5-HETE]) in neutrophils. We previously reported that in vivo dexamethasone treatment resulted in alteration of in vitro neutrophil oxidative metabolism, iodination, antibody-dependent cell-mediated cytotoxicity (ADCC), and random migration. To determine if the decrease in production of LTB4 and 5-HETE were responsible for the changes in neutrophil function, neutrophils were treated In vitro with inhibitors of the lipoxygenase enzyme (BW755c and nordihydroguaiaretic acid), and their function was evaluated. A decrease in neutrophil oxidative metabolism and iodinstion was observed, but there was no effect on neutrophil random migration or ADCC. The results suggest that in vivo trealment with glucocorticoids inhibit neutrophil oxidative metabolism and iodination by decreasing the formation of lipoxygenase products of arachidonic acid metabolism but after neutrophil random migration and ADCC by a mechanism independent of arechidonic add metabolism.
Immunophenotypic and functional characterization of human tonsillar mast cells
Authors: Füreder Wolfgang , Bankl Hans Christian , Toth Josef , Walchshofer Sabine , Sperr Wolfgang , Agis Hermine , Semper Hans , Sillaber Christian , Lechner Klaus , Valent Peter 
Published: January 2018

Abstract
Mast cells (MC) are proinflammatory immune cells residing in various organs. Tissue-specific heterogeneity of MC has been described. The aim of this study was to establish the phenotype and functional profile of human tonsillar mast cells (ToMC) and to compare ToMC with lung-, skin-, and uterus MC. Tonsillar tissue was obtained from 23 patients suffering from hyperplastic tonsils and dispersed by enzymatic digestion. With the use of a combined toluidine blue/immunofluorescence staining technique, isolated ToMC were found to react with monoclonal antibodies (mAb) to immunoglobulin E, CD9, CD43, CD44, CD46, CD54, CD55, and CD59, as well as mAb to stem cell factor (SCF) receptor (CD117/c-kit). ToMC were not recognized by mAb to other cytokine receptors or mAb to CD3, CD11b, CD14, CDw17, the skin MC marker CD88 (C5aR) or CD89 (FcαR). Activation of ToMC by recombinant human (rh) SCF or anti-IgE resulted in histamine secretion, whereas no effects were seen with rhC5a, rh granulocyte-macrophage colony-stimulating factor, or rh interleukin-1 through -10. In summary, ToMC exhibit functional and phenotypic properties similar to lung- or uterus MC. Unlike skin MC, ToMC lack C5aR and are unresponsive to rhC5a.
CSF-1 signal transduction
Authors: Hamilton John A 
Published: January 2018

Abstract
Colony-stimulating factor-1 (CSF-1) or macrophage-CSF (M-CSF) is a growth factor involved in the proliferation, differentiation, and activation of cells of the monocyte/macrophage lineage. Its receptor is the homodimeric, tyrosine kinase product of the c-fms proto-oncogene, which contains a so-called kinase insert domain. This review focuses mainly on recent studies of signal transduction events that are initiated on interaction of CSF-1 and its receptor. A summary is given of the tyrosine autophosphorylation sites on c-Fms identified to date, including their interaction with various substrates and their possible significance for signal transduction and cellular function. In addition, the signal transduction pathways that have been identified to lie downstream of activated c-Fms are reviewed. Although it is apparent that there have been many recent significant developments in our understanding of CSF-1 signaling, a number of examples are mentioned of significant discrepancies in the literature, some possible reasons for which can sometimes be offered. It is also apparent that any particular biochemical response or signal transduction pathway, even though widespread in other ligand receptor/cellular systems, including those with similar receptor structures to c-Fms, may not be relevant to CSF-1 signaling. The relevance of any potentially important molecular signaling pathway activated by CSF-1 in cells in vitro will ultimately have to be related to the functions of monocytes/macrophages in vivo.
The CD28-B7 costimulatory pathway and its role in autoimmune disease
Authors: Daikh David , Wofsy David , Imbodent John B 
Published: January 2018

Abstract
The activation of naive CD4+ T cells requires two discrete signals: a signal delivered by the T cell receptor following recognition of antigen and an accessory signal transduced when costimulatory receptors interact with their ligands. Particularly important in the development of an immune response to foreign antigens is the T cell molecule CD28, which delivers a potent costimulus when engaged by ligands, B7-1 and B7-2, on antigen-presenting cells. It is interesting that blockade of B7 molecules, which disrupts interactions with CD28 and prevents delivery of the CD28 costimulus, also alters the immune responses to self antigens and prevents the development of clinical disease in murine models of systemic and organ-specific autoimunity. Herein we review the roles of CD28 and its B7 ligands in the pathogenesis of autoimmunity, discuss efforts to treat animal models of autoimmunity by modifying the CD28 signal, and consider the mechanisms by which manipulation of the CD28 signal alters the course of experimental autoimmune disease.
Leukotriene B4-activated human endothelial cells promote transendothelial neutrophil migration
Authors: Nohgawa Masaharu , Sasada Masataka , Maeda Akinori , Asagoe Kohsuke , Harakawa Nari , Takano Kuniko , Yamamoto Kokichi , Okuma Minoru 
Published: January 2018

Abstract
We explored the effect of leukotriene B4 (LTB4) on endothelial cells in LTB4-induced transendothelial migration (TEM) of neutrophils as an in vitro model of neutrophil extravasation. Chemotactic response of human neutrophils to LTB4 was significantly lower than that in response to N-formyl-methionyl-leucyl-phenylalanine (fMLP), whereas the extent of TEM in response to LTB4 was significantly higher than that to fMLP. The study on random migration induced by LTB4 and fMLP also showed similar results, which indicated that LTB4 might affect the human umbilical cord vein endothelial cell (HUVEC) barrier. Neutrophil TEM was induced by pretreatment of HUVEC monolayer with LTB4 but not with fMLP. Treatment of endothelial cells by ONO-4057, a LTB4 receptor antagonist, abolished the effect of LTB4 almost completely whereas neutrophils treated with ONO-4057 could transmigrate through HUVEC treated with LTB4. These findings indicated that LTB4 could induce neutrophil TEM by acting on HUVEC.
Oral administration of unsaturated fatty acids: effects on human peripheral blood T lymphocyte proliferation
Authors: Rossetti Ronald G , Seiler Christina M , DeLuca Pamela , Laposata Michael , Zurier Robert B 
Published: January 2018

Abstract
Oils enriched in certain polyunsaturated fatty acids suppress joint pain and swelling in rheumatoid arthritis (RA) patients. Because T lymphocyte activation is important to propagation of joint tissue injury in patients with RA, we examined the effects of fatty acids administered by mouth in vivo on proliferation of human lymphocytes activated through the T cell receptor complex. T cell proliferation was reduced after oral administration of 2.4 g gammalinolenic acid in capsules of borage seed oil. Oral administration of oils enriched in linoleic acid, the parent n-6 fatty acid, and alpha linolenic acid, the parent n-3 fatty acid, did not influence growth of stimulated cells. Fatty acid analyses indicated that suppression of lymphocyte proliferation after gammalinolenic acid administration was associated with increased plasma and peripheral blood mononuclear cell concentrations of gammalinolenic acid and dihomogammalinolenic acid.
Increased monocyte TNF-α message stability contributes to trauma patients' increased TNF production
Authors: Furse Robert Kyle , Kodys Karen , Zhu Di , Miller-Graziano Carol L 
Published: January 2018

Abstract
Post-trauma elevation of tumor necrosis factor α (TNF-α) appears to be critical in mediating many symptoms of systemic inflammatory response syndrome (SIRS), resulting in late mortality. Although increased monocyte (mø) TNF-α production plays a pivotal role in this TNF-α elevation, the molecular mechanisms leading to increased mø TNF-α production have yet to be elucidated. We demonstrate that, although TNF-α mRNA levels are increased in all trauma patients' mø, which produce elevated levels of TNF-α protein, in the majority of patients, these increased TNF-α mRNA levels are under normal transcriptional and posttranscriptional control. Consequently, the increased TNF-α production by these patients' mø is probably due to preactivation of these mø by trauma-released mediators. However, a small minority of patients, whose mortality rate was 57%, produce TNF-α of primarily the membrane-associated type. The mø TNF-α mRNA accumulation of these patients in response to in vitro stimulation is significantly augmented. All of these patients experienced SIRS. In this subset of patients' mø, TNF-α mRNA stability was aberrantly increased. Such an increase in TNF-α mRNA stability could lead to devastatingly prolonged production of TNF-α protein. This demonstration of increased TNF-α mRNA stability in post-trauma mø represents a novel correlation of elevated membrane-associated TNF-α protein, increased mortality, and a mechanism for this occurrence.
Cell-to-cell and cell-to-matrix interactions mediate chemokine expression: an important component of the inflammatory lesion
Authors: Smith R E , Hogaboam C M , Strieter R M , Lukacs N W , Kunkel S L 
Published: January 2018

Abstract
Although many studies have characterized soluble factors that stimulate or inhibit chemokine secretion, in this review we focus on the event of cellular adhesion as a novel mechanism for stimulating chemokine expression. Recent work has demonstrated chemokine expression following cell-to-cell and cell-to-matrix adhesion. The specificity of this finding was demonstrated utilizing various techniques that illustrate that adhesion, and not a soluble stimulus, is in some cases responsible for initiating or augmenting chemokine expression. For example, co-cultures of peripheral blood monocytes and endothelial cells secreted elevated levels of IL-8 and MCP-1 compared with either cell type alone. When co-cultured in transwells, this effect was significantly attenuated. In other experiments, neutralizing monoclonal antibodies to various adhesion molecules inhibited chemokine expression. The effects of adhesion were not limited to leukocytes. Both immune and non-immune cell types were evaluated as potential sources of adhesion-mediated chemokine expression. Not suprisingly, expression of some chemokines was associated with adhesion, whereas others were not, supporting the notion that adhesion differentially signals chemokine secretion during the inflammatory response. We hypothesize that as a recruited leukocyte encounters different adhesion substrates such as endothelial cells, basement membrane, extracellular matrix, and fibroblasts, the expression of chemokines from both the leukocyte and the substrate may be initiated, inhibited, or augmented. Careful characterization of the contribution of adhesion to regulation of chemokine expression will provide insight into the pathogenesis of many human diseases where chemokines have a central role.
Novel lymphocyte-specific CC chemokines and their receptors
Authors: Yoshie Osamu , Imai Toshio , Nomiyama Hisayuki 
Published: January 2018

Abstract
By using a cloning method termed the signal sequence trap as well as by searching for chemokine homologous sequences in the database of expressed sequence tags, cDNA fragments potentially encoding novel CC chemokines were initially identified. Using these sequences, we have cloned five novel human CC chemokines termed TARC, LARC, ELC, SLC, and PARC. These chemokines are constitutively expressed especially in some lymphoid tissues with individually unique expression patterns. The recombinant proteins are all found to be selectively chemotactic for lymphocytes but not for monocytes or neutrophils. Each chemokine appears to interact with a class of receptors on lymphocytes that is not shared by any other chemokines so far tested. Furthermore, we have identified CCR4 as the specific receptor for TARC, GPR-CY4/DRY6/CKR-L3/STRL22 as that for LARC (CCR6), and EBI1/BLR2 as that for ELC (CCR7). Only the gene for PARC is mapped to the traditional CC chemokine gene cluster at chromosome 17q11.2, whereas those for TARC, LARC, ELC, and SLC are localized at different loci. Collectively, these five CC chemokines may constitute a new category of CC chemokines that are involved in trafficking and homing of particular subsets of lymphocytes in particular lymphoid tissue microenvironments.
LCST‐Type Hyperbranched Poly(oligo(ethylene glycol) with Thermo‐ and CO2‐Responsive Backbone
Authors: Cao Gaixia , Li Guo , Yang Qi , Liu Zhaotie , Liu Zhongwen , Jiang Jinqiang 
Published: January 2018

AbstractA novel hyperbranched lower critical solution temperature (LCST) polymer with sharp temperature and CO2‐responsive behaviors is presented in this study. The target polymer of hyperbranched poly(oligo(ethylene glycol) (HBPOEG) is constructed using POEG as the backbone and tertiary amines as branch points. Phase transition of HBPOEG in aqueous solution is investigated by heating and cooling the system; the results indicate that HBPOEG in aqueous solution has a concentration‐dependent phase transition behavior with excellent repeatability. Moreover, LCST of HBPOEG can be tuned by bubbling CO2 into the solution, as the tertiary amines can be protonated and the solubility of the polymer would increase by bubbling CO2 into the system, leading to an increase of LCST of the polymer. Further bubbling N2 to remove CO2 can reversibly turn back the LCST to its original value. This backbone‐based hyperbranched LCST polymer with both CO2 and temperature responsiveness can be applied in application areas like drug delivery, gene transfection, functional coatings, etc.
Selected health and lifestyle factors, cytosine‐adenine‐guanine status, and phenoconversion in Huntington's disease
Authors: Tanner Caroline , Marder Karen , Eberly Shirley , Biglan Kevin , Oakes David , Shoulson Ira ,   on behalf of the Huntington Study Group Prospective Huntington At‐Risk Observational Study Investigators
Published: January 2018

ABSTRACTBackground: In Huntington's disease, 60% of the variance in onset age is not explained by the huntingtin gene mutation. Huntington's disease onset was earlier in caffeine users.Objective: The objective of this study was to assess the relationship of lifestyle factors with motor phenoconversion among persons at risk for Huntington's disease.Methods: The associations of motor phenoconversion and exposure to selected lifestyle and health factors were examined using Cox proportional hazards analyses adjusted for age, gender, and repeat length.Results: Of 247 participants, 36 (14.6%) phenoconverted. Mean follow‐up was 4.2 years. Greater caffeinated soda use was associated with an increased hazard of phenoconversion: moderate use hazard ratio 2.26 (95% confidence interval 0.59‐8.71), high use hazard ratio 4.05 (95% confidence interval 1.18‐13.96).Conclusions: Huntington's disease onset was earlier among consumers of caffeinated soda, but not other caffeinated beverages. This finding may be spurious or not related to caffeine. © 2018 International Parkinson and Movement Disorder Society
Technical Note: The impact of deformable image registration methods on dose warping
Authors: Qin An , Liang Jian , Han Xiao , O'Connell Nicolette , Yan Di 
Published: January 2018

PurposeThe purpose of this study was to investigate the clinical‐relevant discrepancy between doses warped by pure image based deformable image registration (IM‐DIR) and by biomechanical model based DIR (BM‐DIR) on intensity‐homogeneous organs.Methods and materialsTen patients (5Head&Neck, 5Prostate) were included. A research DIR tool (ADMRIE_v1.12) was utilized for IM‐DIR. After IM‐DIR, BM‐DIR was carried out for organs (parotids, bladder, and rectum) which often encompass sharp dose gradient. Briefly, high‐quality tetrahedron meshes were generated and deformable vector fields (DVF) from IM‐DIR were interpolated to the surface nodes of the volume meshes as boundary condition. Then, a FEM solver (ABAQUS_v6.14) was used to simulate the displacement of internal nodes, which were then interpolated to image‐voxel grids to get the more physically plausible DVF. Both geometrical and subsequent dose warping discrepancies were quantified between the two DIR methods. Target registration discrepancy(TRD) was evaluated to show the geometry difference. The re‐calculated doses on second CT were warped to the pre‐treatment CT via two DIR. Clinical‐relevant dose parameters and γ passing rate were compared between two types of warped dose. The correlation was evaluated between parotid shrinkage and TRD/dose discrepancy.ResultThe parotid shrunk to 75.7% ± 9% of its pre‐treatment volume and the percentage of volume with TRD>1.5 mm) was 6.5% ± 4.7%. The normalized mean‐dose difference (NMDD) of IM‐DIR and BM‐DIR was −0.8% ± 1.5%, with range (−4.7% to 1.5%). 2 mm/2% passing rate was 99.0% ± 1.4%. A moderate correlation was found between parotid shrinkage and TRD and NMDD. The bladder had a NMDD of −9.9% ± 9.7%, with BM‐DIR warped dose systematically higher. Only minor deviation was observed for rectum NMDD (0.5% ± 1.1%).ConclusionImpact of DIR method on treatment dose warping is patient and organ‐specific. Generally, intensity‐homogeneous organs, which undergo larger deformation/shrinkage during treatment and encompass sharp dose gradient, will have greater dose warping uncertainty. For these organs, BM‐DIR could be beneficial to the evaluation of DIR/dose‐warping uncertainty.
A simple model for transit dosimetry based on a water equivalent EPID
Authors: Deshpande S. , Blake S. J. , Xing A. , Metcalfe P. E. , Holloway L. C. , Vial P. 
Published: January 2018

PurposeThe aim of this study was to demonstrate a new model for implementing a transit dosimetry system as a means of in vivo dose verification with a water equivalent electronic portal imaging device (WE‐EPID) and a conventional treatment planning system (TPS).Method and materialsA standard amorphous silicon (a‐Si) EPID was modified to a WE‐EPID configuration by replacing the metal‐plate/phosphor screen situated above the photodiode detector with a 3 cm thick water equivalent plastic x ray converter material. A clinical TPS was used to calculate dose to the WE‐EPID in its conventional EPID position behind the phantom/patient. The “extended phantom” concept was used to facilitate dose calculation at the EPID position, which is outside the CT field of view (FOV). The CT images were manipulated from 512 × 512 into 1024 × 1024 and padded pixels were assigned the density of air before importing to the TPS. The virtual WE‐EPID was added as an RT structure of water density at the EPID plane. The accuracy of TPS dose calculations at the EPID plane in transit geometry was first evaluated for different field sizes and thickness of object in the beam by comparison with the dose measured using a 2D ion chamber array (ICA) and the WE‐EPID. Following basic dose response tests, clinical fields including direct single fields (open and wedged) and modulated fields (integrated or control point by control point doses for VMAT) were measured for 6 MV photons with varying of solid water thickness or an anthropomorphic phantom present in beam. The EPID images were corrected for dark signal and pixel sensitivity and converted to dose using a single dose calibration factor. The 2D dose evaluation was conducted using 3%/3 and 2%/2 mm gamma‐index criteria.ResultsThe measured dose–response with the ICA and WE‐EPID for all basic dose–response tests agreed with TPS dose calculations to within 1.5%. The maximum difference in dose profiles for the largest measured field size of 25 × 25 cm2 was 2.5%. Gamma evaluation showed at least 94% (3%/3 mm criteria) and 90% (2%/2 mm) agreement in both integrated and control‐point doses for all clinical fields acquired by the WE‐EPID and ICA when compared with TPS‐calculated portal dose images.ConclusionA new approach to transit dose verification has been demonstrated utilizing a water equivalent EPID and a commercial TPS. The accuracy of dose calculations at the EPID plane using a commercial TPS beam model was experimentally confirmed. The model proposed in this study provides an accurate method to directly verify doses delivered during treatment without the additional uncertainties inherent in modelling the complex dose–response of standard EPIDs.