bluuebunny/crossref_metadata_2025_split huggingface dataset:
Activation of microglia with zymosan promotes excitatory amino acid release via volume‐regulated anion channels: the role of NADPH oxidases
Authors: Harrigan Timothy J. , Abdullaev Iskandar F. , Jourd’heuil David , Mongin Alexander A. 
Published: July 2008

AbstractMicroglia are the resident immune cells of the CNS, which are important for preserving neural tissue functions, but may also contribute to neurodegeneration. Activation of these cells in infection, inflammation, or trauma leads to the release of various toxic molecules, including reactive oxygen species (ROS) and the excitatory amino acid glutamate. In this study, we used an electrophysiologic approach and a d‐[3H]aspartate (glutamate) release assay to explore the ROS‐dependent regulation of glutamate‐permeable volume‐regulated anion channels (VRACs). Exposure of rat microglia to hypo‐osmotic media stimulated Cl− currents and d‐[3H]aspartate release, both of which were inhibited by the selective VRAC blocker, DCPIB. Exogenously applied H2O2 potently increased swelling‐activated glutamate release. Stimulation of microglia with zymosan triggered production of endogenous ROS and strongly enhanced glutamate release via VRAC in swollen cells. The effects of zymosan were attenuated by the ROS scavenger, MnTMPyP, and by two inhibitors of NADPH oxidase (NOX), diphenyliodonium and thioridazine. However, zymosan‐stimulated glutamate release was insensitive to other NOX blockers, apocynin and HEBSF. This pharmacologic profile pointed to the potential involvement of apocynin‐insensitive NOX4. Using RT‐PCR we confirmed that NOX4 is expressed in rat microglial cells along with NOX1 and NOX2. To check for potential involvement of phagocytic NOX2, we stimulated this isoform using protein kinase C (PKC) activator, phorbol 12‐myristate 13‐acetate or inhibited it with the broad spectrum PKC blocker, Gö6983. Both agents potently modulated endogenous ROS production by NOX2 but not VRAC activity. Taken together, these data suggest that the anion channel VRAC may contribute to microglial glutamate release and that its activity is regulated by endogenous ROS originating from NOX4.
Sweet taste receptor interacting protein CIB1 is a general inhibitor of InsP3‐dependent Ca2+ release in vivo
Authors: Hennigs Jan K. , Burhenne Nicole , Stähler Frauke , Winnig Marcel , Walter Bettina , Meyerhof Wolfgang , Schmale Hartwig 
Published: July 2008

AbstractIn a search for sweet taste receptor interacting proteins, we have identified the calcium‐ and integrin‐binding protein 1 (CIB1) as specific binding partner of the intracellular carboxyterminal domain of the rat sweet taste receptor subunit Tas1r2. In heterologous human embryonic kidney 293 (HEK293) cells, the G protein chimeras Gα16gust44 and Gα15i3 link the sweet taste receptor dimer TAS1R2/TAS1R3 to an inositol 1,4,5‐trisphosphate (InsP3)‐dependent Ca2+ release pathway. To demonstrate the influence of CIB1 on the cytosolic Ca2+ concentration, we used sweet and umami compounds as well as other InsP3‐generating ligands in FURA‐2‐based Ca2+ assays in wild‐type HEK293 cells and HEK293 cells expressing functional human sweet and umami taste receptor dimers. Stable and transient depletion of CIB1 by short‐hairpin RNA increased the Ca2+ response of HEK293 cells to the InsP3‐generating ligands ATP, UTP and carbachol. Over‐expression of CIB1 had the opposite effect as shown for the sweet ligand saccharin, the umami receptor ligand monosodium glutamate and UTP. The CIB1 effect was dependent on the thapsigargin‐sensitive Ca2+ store of the endoplasmic reticulum (ER) and independent of extracellular Ca2+. The function of CIB1 on InsP3‐evoked Ca2+ release from the ER is most likely mediated by its interaction with the InsP3 receptor. Thus, CIB1 seems to be an inhibitor of InsP3‐dependent Ca2+ release in vivo.
Pilot study of Japanese cedar pollen exposure using a novel artificial exposure chamber (OHIO Chamber)
Authors: Hashiguchi K. , Tang H. , Fujita T. , Suematsu K. , Tsubaki S. , Nagakura H. , Kitajima S. , Gotoh M. , Okubo K. 
Published: July 2008

SummaryFor basic and clinical studies of Japanese cedar (JC) pollinosis and its treatment, experimental facilities for exposure to pollen under stable environmental conditions are becoming increasingly desirable. We developed an artificial exposure chamber (OHIO Chamber) that allows the dispersal of fixed concentrations of JC pollen in stable environments with a unique pollen supply system, air flow system for fixing the concentration of JC pollen, system for monitoring the number of pollen grains, and automated pure water washing and drying system. In the chamber, temperature and relative humidity (RH) could be successfully maintained at 22±1.1 °C and 45±5%, respectively. The spatial distribution of pollen concentrations in the chamber was within 10% of target, including when subjects were present. Only a few or no pollen grains were detected in the chamber after automatic washing and drying. We conducted a pilot tolerability and safety study in 15 JC pollinosis patients who were exposed to 15 000 pollen grains/m3 for 2 h. Symptoms manifested on average 33 min after start of exposure. The subjects experienced no serious side‐effects, and pollen exposure at 15 000 grains/m3 was confirmed safe. After exposure, the number of intranasal and intraocular pollen grains was 469 and 602, respectively. The lower number of pollen grains in the nose than in the eyes was considered due to sneezing and nasal discharge. Further studies are needed to clarify the number of pollen grains required for the occurrence of symptoms in the OHIO Chamber.
Management of persistent allergic rhinitis in the tropics: Singapore experiences
Authors: Wang D‐Y. , Gordon B. R. 
Published: July 2008

SummaryAllergic rhinitis (AR) is a common manifestation of allergic diseases, affecting 10–25% of the world's population. In the tropics, the majority of AR is persistent. The year‐round warm, humid climate is conducive for the proliferation of dust mites and moulds, two of the most common aeroallergens implicated in persistent allergic rhinitis (PAR). The management of AR includes patient education, allergen avoidance, pharmacological treatment, and specific immunotherapy. Patient education, especially regarding dust and mould exposure reduction, can be effective but is often under‐utilized. Second generation, non‐sedating H1‐antihistamines rapidly relieve most nasal symptoms because they effectively block the histamine H1‐receptors that trigger plasma exudation and oedema. Congestion is most effectively controlled by intranasal glucocorticosteroids (INSs), which are currently the most potent AR drug treatment. The beneficial effects of steroids depend on their long‐term, multi‐pathway anti‐inflammatory effects, unlike H1‐antihistamines, which directly block neural and vascular H1 receptors. However, especially in PAR, patients' compliance with INS therapy has a significant impact on treatment efficacy, because year‐round treatment is required. Subcutaneous inhalant allergen immunotherapy (SCIT) is effective against a broad range of AR symptoms, and may be able to alter the natural course of allergy and prevent asthma onset. SCIT can significantly reduce the severity of allergic disease, including nasal obstruction, and decrease the need for anti‐allergic drugs. Immunotherapy (IT) can also be given as sublingual drops (SLIT). Recent studies have shown the SLIT to be effective in reducing AR symptoms and medication use. Both types of IT require long‐term patient compliance for successful treatment. Drug and IT interventions may not be economically feasible in certain patients. In conclusion, the type of AR most prevalent in the tropics is PAR, which must be treated year round. Improvement of educational programmes for the public and physicians alike seems to be the most effective treatment strategy.
Pharmacogenetics of anti‐leukotriene drugs
Authors: Asano K. , Ishizaka A. 
Published: July 2008

SummaryCysteinyl leukotrienes, a group of compounds with potent bioactivity to constrict bronchial smooth muscle cells and recruit eosinophils and other inflammatory cells into the airways, act as key modulators of the pathophysiology of allergic rhinitis and asthma. Drugs targeting leukotriene‐related molecules such as leukotriene synthase inhibitors and CysLT1‐receptor antagonists are widely used as safe and effective agents for the treatment of these diseases. The main limitation of anti‐leukotriene drugs, however, is that there is a substantial proportion of patients who do not respond to these drugs. Therefore, identification of genetic and non‐genetic factors that determine the pharmacologic response should further increase the usefulness of anti‐leukotriene drugs. We undertook a multidirectional approach based on the assumption that the pharmacologic response to anti‐leukotriene drugs is determined by factors related to pharmacokinetics such as drug metabolism, and pharmacodynamics such as the expression and function of leukotriene synthases and receptors. Among patients with asthma, we identified two genetic variations (polymorphisms) in the promoter of arachidonate 5‐lipoxygenase and leukotriene C4 synthase as possible factors to distinguish responders from non‐responders to anti‐leukotriene drugs. This pharmacogenetic approach might be useful to establish the basis of individualized treatment for patients with asthma as well as those with allergic rhinitis.
Competitive Pricing in Markets with Different Overhead Costs: Concealment or Leakage of Cost Information?
Authors: CARDINAELS EDDY , ROODHOOFT FILIP , WARLOP LUK , VAN HERCK GUSTAAF 
Published: July 2008

ABSTRACTThis paper experimentally investigates how leaders and followers in a duopoly set prices for two product markets that have different overhead costs. In a fully crossed two‐by‐two design, we manipulate the participants' private cost report quality as either low or high, representing the extent to which these reports reveal that product markets have different overhead costs. We show that when only the leader is given a high‐quality cost report, private cost information of higher quality is better incorporated into market prices (that are observable to participants). Both the leader and follower improve in profits and their prices better reflect the differences in overhead costs because the follower infers information from the leader's prices (information leakage). In contrast, when only the follower receives a high‐quality cost report, the leader's profits and prices do not improve. This occurs because the follower conceals cost information when the leader has a low‐quality cost report.
Keynesian Beauty Contest, Accounting Disclosure, and Market Efficiency
Authors: GAO PINGYANG 
Published: July 2008

ABSTRACTThis paper examines the market efficiency consequences of accounting disclosure in the context of stock markets as a Keynesian beauty contest, an influential metaphor originally proposed by Keynes [1936] and recently formalized by Allen, Morris, and Shin [2006]. In such markets, public information plays an additional commonality role, biasing stock prices away from the consensus fundamental value toward public information. Despite this bias, I demonstrate that provisions of public information always drive stock prices closer to the fundamental value. Hence, as a main source of public information, accounting disclosure enhances market efficiency, and transparency should not be compromised on grounds of the Keynesian‐beauty‐contest effect.
Accuracy assessment of lidar‐derived digital elevation models
Authors: Aguilar Fernando J. , Mills Jon. P. 
Published: July 2008

AbstractDespite the relatively high cost of airborne lidar‐derived digital elevation models (DEMs), such products are usually presented without a satisfactory associated estimate of accuracy. For the most part, DEM accuracy estimates are typically provided by comparing lidar heights against a finite sample of check point coordinates from an independent source of higher accuracy, supposing a normal distribution of the derived height differences or errors. This paper proposes a new methodology to assess the vertical accuracy of lidar DEMs using confidence intervals constructed from a finite sample of errors computed at check points. A non‐parametric approach has been tested where no particular error distribution is assumed, making the proposed methodology especially applicable to non‐normal error distributions of the type usually found in DEMs derived from lidar. The performance of the proposed model was experimentally validated using Monte Carlo simulation on 18 vertical error data‐sets. Fifteen of these data‐sets were computed from original lidar data provided by the International Society for Photogrammetry and Remote Sensing Working Group III/3, using their respective filtered reference data as ground truth. The three remaining data‐sets were provided by the Natural Environment Research Council’s Airborne Research and Survey Facility lidar system, together with check points acquired using high precision kinematic GPS. The results proved promising, the proposed models reproducing the statistical behaviour of vertical errors of lidar using a favourable number of check points, even in the cases of data‐sets with non‐normally distributed residuals. This research can therefore be considered as a potentially important step towards improving the quality control of lidar‐derived DEMs.
Mapping tooth surface loss with a fixed‐base stereo camera
Authors: Grenness Malcolm J. , Osborn Jon E. , Tyas Martin J. 
Published: July 2008

AbstractChange detection of tooth surface loss in the cervical region of a tooth replica has been performed using a fixed‐base stereoscopic camera, consisting of two SLR digital cameras with lenses of fixed focal length. Commercial digital photogrammetric and calibration software was used to perform a convergent multi‐station calibration with an artefact comprising a transilluminated planar array and a tiered object exhibiting optical texture. Digital surface models of a tiered test object and a tooth surface containing a non‐carious cervical lesion were generated from stereo‐imagery. The accuracy of automatic mass point measurement of a planar surface was 4 ± 13 μm in Z. The sensitivity of change detection on mapped tooth replicas was 0·03 mm with change ranging from 0·03 to 0·07 mm per annum. Different rates of change were clearly evident in different areas at different times. The results of this investigation suggest that annual change detection studies will provide a clearer picture of the pattern of tooth surface loss and, in combination with other analytical techniques, a more detailed explanation of the natural history of these lesions.
A model‐based approach for reconstructing a terrain surface from airborne LIDAR data
Authors: Sohn Gunho , Dowman Ian J. 
Published: July 2008

AbstractA lidar filtering technique is used to differentiate on‐terrain points and off‐terrain points from a cloud of 3D point data collected by a lidar system. A major issue of concern in this low‐level filter is to design a methodology to ensure a continual adaptation to variations of terrain slopes and object scales. In this paper, a new lidar filtering technique which hierarchically fragments lidar data into piecewise planar terrain models is introduced. Once a number of hypothetical planar terrain models are generated to fit the terrain surface of the underlying area, the optimal terrain model to produce the minimum labelling errors is determined based on minimum description length (MDL) principles. This hypothesis‐verification optimisation is achieved in a coarse‐to‐fine strategy by which the entire terrain surface is incrementally reconstructed by increasing the number of planar terrain models fitted. The proposed technique was successfully applied to a digital surface model provided within an OEEPE lidar trial, showing 0·94% of Type I errors and 6·75% of Type II errors compared to manually classified reference data.
The role of topical negative pressure in wound repair: Expression of biochemical markers in wound fluid during wound healing
Authors: Mouës Chantal M. , Van Toorenenbergen Albert W. , Heule Freerk , Hop Wim C. , Hovius Steven E. R. 
Published: July 2008

ABSTRACTThe clinical effects of topical negative pressure therapy (TNP) on wound healing are well described in numerous articles. While the mechanism(s) of action are not completely understood, it is postulated that reduction of local and interstitial tissue edema, increased perfusion of the (peri‐) wound area, changed bacterial composition, and mechanical stimulation of the woundbed contribute to the clinical success. Our hypothesis is that with the removal of excessive fluid, proteolytic enzymes negatively influencing the healing process are removed. Our aim was to assess whether the concentrations of albumin, matrixmetalloproteinase‐9 (MMP‐9), and tissue inhibitor of metalloproteinase (TIMP‐1) were different between wounds treated with TNP and conventional gauze therapy. We analyzed wound fluid samples of 33 wounds treated with either TNP therapy (n=15) or conventional therapy (n=18) on albumin, pro‐ and activated MMP‐9, TIMP‐1, and the ratio of total MMP‐9/TIMP‐1. Albumin levels were found to increase significantly in acute wounds compared with chronic wounds; however, no difference could be found on comparing TNP with conventional therapy. We did find significantly lower levels of pro‐MMP‐9 and lower total MMP‐9/TIMP‐1 ratio in TNP‐treated wounds during the follow‐up of 10 days. These data strongly suggest that TNP therapy influences the microenvironment of the wound.
Evaluation of dermal pericapillary fibrin cuffs in venous ulceration using confocal microscopy
Authors: Kobrin Kendra L. , Thompson Paul J. , Scheur Martijn van de , Kwak Tae‐Hee , Kim Saerom , Falanga Vincent 
Published: July 2008

ABSTRACTDermal pericapillary fibrin is a hallmark of venous disease and is thought to play a pathogenic role in the development of ulceration. However, the actual spatial configuration of pericapillary fibrin is unknown, and it remains unclear whether it truly represents a barrier that can impair physiological exchanges between the blood and dermis. Using confocal microscopy on tissue specimens taken from the edges of venous ulcers in six patients, we report a detailed analysis of dermal pericapillary fibrin deposits. Sections were evaluated with an antibody to human fibrinogen/fibrin and viewed, vertically and horizontally, with confocal microscopy. The distribution of fibrin deposition was highly variable and patchy, with areas of great intensity next to others of marginal intensity. Vertical cut sections showed the highest concentration of fluorescent material next to the lumen of dermal capillaries. Horizontal sections showed that maximal fluorescence was distributed at random. Our findings indicate that fibrin deposits in venous ulcers are patchy and discontinuous around dermal vessels. As such, these deposits are unlikely to act as a true and stable anatomic barrier as originally proposed. However, pericapillary fibrin may still act as a physiological barrier under conditions of poor blood flow where even marginal or patchy fibrin deposition might have a greater effect on the exchange of oxygen and other nutrients between blood and dermis.
Epidermal growth factor protects fibroblasts from apoptosis via PI3 kinase and Rac signaling pathways
Authors: Shao Hanshuang , Yi Xiao‐Ming , Wells Alan 
Published: July 2008

ABSTRACTThe fibroplasia noted during wound repair is resolved by fibroblast cell death. How fibroblasts undergo death and how this is prevented by trophic growth factors present during the regenerative phase are unknown at the molecular level. We examined a model of staurosporine‐induced apoptosis in fibroblasts. We demonstrated that epidermal growth factor (EGF) stimulation of fibroblast NR6WT expressing human EGF receptors blocks staurosporine‐induced apoptosis by inhibiting the activation of caspase‐3. The survival effect of EGF on rescuing apoptotic NR6WT involves signaling pathways that derive from PI3K and Rac; the blockade of apoptosis is abolished when PI3K and Rac signals are inhibited simultaneously. Furthermore, by using KP372‐1, a specific Akt inhibitor, we found that downstream of Akt signaling pathways is absolutely required for the EGF rescue from staurosporine‐induced apoptosis in NR6WT. Interestingly, EGF prevention of apoptosis induced by tumor necrosis factor‐α in the face of cycloheximide blockade of protein translation occurs via a different set of pathways as the simultaneous inhibition of extracellular signal‐regulated kinase, Rac, and PI3K signaling did not eliminate EGF from rescuing fibroblasts in the face of this cytokine. These findings indicate that EGF receptor activation provides survival response against staurosporine‐induced apoptosis through signal pathways of PI3K and Rac, which then may prevent the activation of caspase‐3.
The use of a semiocclusive dressing reduces epidermal inflammatory cytokine expression and mitigates dermal proliferation and inflammation in a rat incisional model
Authors: Kloeters Oliver , Schierle Clark , Tandara Andrea , Mustoe Thomas A. 
Published: July 2008

ABSTRACTOcclusive wound dressings are utilized clinically to accelerate wound healing and improve the final appearance of scars. In vivo and in vitro evidence suggests that one mechanism for this effect is maintenance of normal hydration in the epidermis, although the molecular signals remain uncharacterized. We sought to elucidate histological changes and some of the molecular signals involved in this effect in a rat model of wound semiocclusion. We utilized a rat linear incision model with surgical tape occlusion. Histological stains and quantitative real‐time PCR analysis were used to characterize the cellular and molecular effects of semiocclusion on the wound healing response. Semioccluded wounds demonstrated decreased epidermal thickness and cellularity and less mitotic epidermal activity when compared with nonoccluded control wounds. Associated dermal cellularity was similarly attenuated by semiocclusion. Finally, levels of proinflammatory cytokines interleukin‐1‐α and tumor necrosis factor‐α were significantly decreased on postoperative day 3 at the transcriptional level when compared with nonoccluded wounds. Semiocclusive wound treatments significantly decrease epidermal thickness, cellularity, mitotic activity, and dermal cellularity as well as transcriptional levels of important epidermal mediators of inflammation in a rat incisional wound model.
NON‐CORONARY HEART DISEASE IN DIALYSIS PATIENTS: Sympathetic Overactivity—The Cinderella of Cardiovascular Risk Factors in Dialysis Patients
Authors: Vonend Oliver , Rump L. Christian , Ritz Eberhard 
Published: July 2008

AbstractCardiovascular morbidity and mortality is exceedingly high in patients with chronic renal failure. Sympathetic overactivity is an important pathomechanism contributing to progression of renal disease as well as cardiovascular complications. For more than 30 years it has been known that plasma levels of norepinephrine are elevated in chronic renal failure pointing to increased sympathetic nerve activity. The kidneys are richly innervated by efferent sympathetic and afferent sensory nerves. They participate in many reflex adjustments of renal function. Initially, this finding had not been attributed to increased efferent sympathetic drive, but rather to reduced renal clearance and defective neuronal reuptake of norepinephrine.At this time, however, the evidence for increased sympathetic drive is solid. Interventions to reduce sympathetic overactivity will provide new therapeutic approaches. The available experimental and clinical evidence to suggest such a pathophysiological role of sympathetic overactivity is summarized in this current review.