bluuebunny/crossref_metadata_2025_split huggingface dataset:
Histamine H4 receptor mediates eosinophil chemotaxis with cell shape change and adhesion molecule upregulation
Authors: Ling Ping , Ngo Karen , Nguyen Steven , Thurmond Robin L , Edwards James P , Karlsson Lars , Fung‐Leung Wai‐Ping 
Published: May 2004

During mast cell degranulation, histamine is released in large quantities. Human eosinophils were found to express histamine H4 but not H3 receptors. The possible effects of histamine on eosinophils and the receptor mediating these effects were investigated in our studies.
Histamine (0.01–30 μM) induced a rapid and transient cell shape change in human eosinophils, but had no effects on neutrophils. The maximal shape change was at 0.3 μM histamine with EC50 at 19 nM. After 60 min incubation with 1 μM histamine, eosinophils were desensitized and were refractory to shape change response upon histamine restimulation. Histamine (0.01–1 μM) also enhanced the eosinophil shape change induced by other chemokines.
Histamine‐induced eosinophil shape change was mediated by the H4 receptor. This effect was completely inhibited by H4 receptor‐specific antagonist JNJ 7777120 (IC50 0.3 μM) and H3/H4 receptor antagonist thioperamide (IC50 1.4 μM), but not by selective H1, H2 or H3 receptor antagonists. H4 receptor agonists imetit (EC50 25 nM) and clobenpropit (EC50 72 nM) could mimic histamine effect in inducing eosinophil shape change.
Histamine (0.01–100 μM) induced upregulation of adhesion molecules CD11b/CD18 (Mac‐1) and CD54 (ICAM‐1) on eosinophils. This effect was mediated by the H4 receptor and could be blocked by H4 receptor antagonists JNJ 7777120 and thioperamide.
Histamine (0.01–10 μM) induced eosinophil chemotaxis with an EC50 of 83 nM. This effect was mediated by the H4 receptor and could be blocked by H4 receptor antagonists JNJ 7777120 (IC50 86 nM) and thioperamide (IC50 519 nM). Histamine (0.5 μM) also enhanced the eosinophil shape change induced by other chemokines.
In conclusion, we have demonstrated a new mechanism of eosinophil recruitment driven by mast cells via the release of histamine. Using specific histamine receptor ligands, we have provided a definitive proof that the H4 receptor mediates eosinophil chemotaxis, cell shape change and upregulation of adhesion molecules. The effect of H4 receptor antagonists in blocking eosinophil infiltration could be valuable for the treatment of allergic diseases. The histamine‐induced shape change and upregulation of adhesion molecules on eosinophils can serve as biomarkers for clinical studies of H4 receptor antagonists.

British Journal of Pharmacology (2004) 142, 161–171. doi:10.1038/sj.bjp.0705729
The balloon catheter induces an increase in contralateral carotid artery reactivity to angiotensin II and phenylephrine
Authors: Accorsi‐Mendonça D , Corrêa F M A , Paiva T B , De Souza H P , Laurindo F R M , De Oliveira A M 
Published: May 2004

The effects of balloon injury on the reactivity of ipsilateral and contralateral carotid arteries were compared to those observed in arteries from intact animals (control arteries).
Carotid arteries were obtained from Wistar rats 2, 4, 7, 15, 30 or 45 days after injury and mounted in an isolated organ bath. Reactivity to angiotensin II (Ang II), phenylephrine (Phe) and bradykinin (BK) was studied. Curves were constructed in the absence or presence of endothelium or after incubation with 10 μM indomethacin, 500 μM valeryl salicylate or 0.1 μM celecoxib.
Phe, Ang II and BK maximum effects (Emax) were decreased in ipsilateral arteries when compared to control arteries. No differences were observed among pD2 or Hill coefficient.
Emax to Phe (4 and 7 days) and to Ang II (15 and 30 days) increased in the contralateral artery. In addition, Phe or Ang II reactivity was not significantly different in aorta rings from control or carotid‐injured animals.
The increased responsiveness of contralateral artery was not due to changes in carotid blood flow or resting membrane potential. The endothelium‐dependent inhibitory component is not present in the contraction of contralateral arteries and it is not related to superoxide anion production.
Indomethacin decreased contralateral artery responsiveness to Phe and Ang II. Valeryl salicylate reduced the Ang II response in contralateral and control arteries. Celecoxib decreased the Phe Emax of contralateral artery.
In conclusion, decreased endothelium‐derived factors and increased prostanoids appear to be responsible for the increased reactivity of contralateral arteries after injury.

British Journal of Pharmacology (2004) 142, 79–88. doi:10.1038/sj.bjp.0705732
Vascular hyper‐reactivity following arterial balloon injury: distant and delayed effects
Authors: Wilson Andrew J 
Published: May 2004

The adverse functional effects of balloon angioplasty include simple procedure failure, compromise of vessel lumen (rupture), and restenosis. A much less well‐defined repercussion of balloon injury to arteries is a paradoxical alteration in vascular reactivity at an anatomically distant site. The paper by Accorsi‐Mendonça in the current issue presents new data showing that, following balloon injury to the rat left common carotid artery, there is a delayed hyperreactivity to both phenylephrine and angiotensin II in the contralateral artery. The pharmacological basis of these effects is unknown, although the authors demonstrate that products of cyclooxygenase (COX) 1 or 2 are responsible for the hyperreactivity to angiotensin II and phenylephrine, respectively. The absence of delayed hyperreactivity to these agents in the aorta of injured rats would suggest that a humoral factor is not involved.British Journal of Pharmacology (2004) 142, 3–4. doi:10.1038/sj.bjp.0705734
Comparison of functional profiles at human recombinant somatostatin sst2 receptor: simultaneous determination of intracellular Ca2+ and luciferase expression in CHO‐K1 cells
Authors: Nunn Caroline , Cervia Davide , Langenegger Daniel , Tenaillon Laurent , Bouhelal Rochdi , Hoyer Daniel 
Published: May 2004

Somatostatin (somatotropin release inhibiting factor; SRIF) acts via five G protein‐coupled receptors (sst1–sst5) that modulate multiple cellular effectors. The aim of this study was to compare two functional effects of the human sst2 receptor stably expressed in CHO‐K1 cells in a single experiment using a duplex assay for intracellular calcium and serum response element (SRE)‐driven luciferase expression.
Intracellular calcium was measured using a fluorometric imaging plate reader II (FLIPR II). SRIF‐14 rapidly and transiently increased intracellular calcium with a pEC50 of 8.74±0.03 (n=52). At 5 h after FLIPR II measurements, luciferase expression was determined. SRIF‐14 concentration‐dependently increased luciferase expression (pEC50=9.06±0.03, n=52).
Natural and synthetic agonist/antagonist ligands for SRIF receptors were tested in the duplex assay. Correlation of agonist potencies and efficacies between the two responses were significant (r2=0.83 and 0.90, pEC50 and Emax, respectively).
Pertussis toxin pretreatment reduced SRIF‐14/octreotide‐mediated intracellular calcium increases by 45–47% and luciferase expression by 95–98%.
Thapsigargin pretreatment abolished the SRIF‐14/octreotide‐mediated intracellular calcium increase but had no effect on luciferase expression.
In conclusion, SRIF stimulates an increase in intracellular calcium and SRE‐luciferase expression via human sst2 receptors in CHO‐K1 cells. The increase in luciferase is mediated via Gi/Go while intracellular calcium increase is mediated by both Gi/Go proteins and pertussis toxin‐insensitive G proteins, and is mainly via release of calcium from intracellular stores. SRIF ligands display a similar recognition profile suggesting that the ligand/receptor/G protein/effector interaction is similar for the two parameters.

British Journal of Pharmacology (2004) 142, 150–160. doi:10.1038/sj.bjp.0705735
Raloxifene acutely suppresses ventricular myocyte contractility through inhibition of the L‐type calcium current
Authors: Liew Reginald , Stagg Mark A , MacLeod Kenneth T , Collins Peter 
Published: May 2004

The selective oestrogen (ER) receptor modulator, raloxifene, is widely used in the treatment of postmenopausal osteoporosis, but may also possess cardioprotective properties. We investigated whether it directly suppresses myocyte contractility through Ca2+ channel antagonism in a similar way to 17β‐oestradiol.
Cell shortening and Ca2+ transients were measured in single guinea‐pig ventricular myocytes field‐stimulated (1 Hz, 37°C) in a superfusion chamber. Electrophysiological recordings were performed using single electrode voltage‐clamp.
Raloxifene decreased cell shortening (EC50 2.4 μM) and the Ca2+ transient amplitude (EC50 6.4 μM) in a concentration‐dependent manner. At a concentration of 1 μM, raloxifene produced a 33±2% (mean±s.e.m) and 24±2% reduction, respectively (P<0.001, n=14 for both parameters).
These inhibitory actions were not observed in myocytes that had been incubated with the specific antagonist, ICI 182,780 (10 μM) (n=11).
Raloxifene (1 μM) shortened action potential durations at 50 and 90% repolarisation (P<0.05 and <0.001, respectively; n=27) and decreased peak L‐type Ca2+ current by 45%, from −5.1±0.5 pA/pF to −2.8±0.3 pA/pF (P<0.001, n=18).
Raloxifene did not significantly alter sarcoplasmic reticulum Ca2+ content, as assessed by integrating the Na+/Ca2+ exchanger currents following rapid caffeine application.
The present study provides evidence for direct inhibitory actions of raloxifene on ventricular myocyte contractility, mediated through Ca2+ channel antagonism.

British Journal of Pharmacology (2004) 142, 89–96. doi:10.1038/sj.bjp.0705736
R‐citalopram functionally antagonises escitalopram in vivo and in vitro: evidence for kinetic interaction at the serotonin transporter
Authors: Stórustovu Signe í , Sánchez Connie , Pörzgen Peter , Brennum Lise T , Larsen Anna Kirstine , Pulis Monica , Ebert Bjarke 
Published: May 2004

Clinical observations with the selective serotonin reuptake inhibitor (SSRI), S‐citalopram, indicate that S‐citalopram is more efficacious and produces earlier symptom relief than RS‐citalopram. Since R‐citalopram is at least 20‐fold weaker than S‐citalopram as inhibitor of the 5‐HT transporter (SERT) in preclinical studies, the clinical data suggest an unexpected antagonistic interaction between the two enantiomers. We therefore characterised the interaction of R‐ and S‐citalopram with the SERT in in vivo and in vitro assays.
In both behavioural (potentiation of 5‐hydroxytryptophan (5‐HTP)‐induced behaviour) and electrophysiological studies (inhibition of 5‐HT‐elicited ion currents in Xenopus oocytes expressing the human SERT (hSERT) R‐citalopram inhibited the effects of S‐citalopram in a dose‐dependent manner. With S‐citalopram : R‐citalopram ratios of 1 : 2 and 1 : 4, 5‐HTP potentiation was significantly smaller than with S‐citalopram alone.
emsp;R‐citalopram did not antagonise the effects of another SSRI (fluoxetine) in either behavioural or electrophysiological studies.
In oocytes, inhibition of hSERT‐mediated currents by R‐citalopram was almost completely reversible and characterised by fast on‐ and off‐sets of action. In contrast, the off‐set for S‐citalopram was 35‐fold slower than for R‐citalopram.
Kinetic analysis of the oocyte experiments suggests that S‐citalopram binding to SERT induces a long‐lasting, inhibited state of the transporter and that coapplication of R‐citalopram partially relieves SERT of this persistent inhibition.
We propose that the kinetic interaction of R‐ and S‐citalopram with SERT is a critical factor contributing to the antagonistic effects of R‐citalopram on S‐citalopram in vitro and in vivo.

British Journal of Pharmacology (2004) 142, 172–180. doi:10.1038/sj.bjp.0705738
Cardioprotective efficacy of zoniporide, a potent and selective inhibitor of Na+/H+ exchanger isoform 1, in an experimental model of cardiopulmonary bypass
Authors: Clements‐Jewery Hugh , Sutherland Fiona J , Allen Mary C , Tracey W Ross , Avkiran Metin 
Published: May 2004

We determined (1) the inhibitory potency of zoniporide against the native Na+/H+ exchanger isoform 1 (NHE1) that is expressed in adult rat ventricular myocytes and platelets, and (2) the cardioprotective efficacy of zoniporide in isolated, blood‐perfused adult rat hearts subjected to cardioplegic arrest, hypothermic ischaemia (150 min at 25°C) and normothermic reperfusion (60 min at 37°C).
In isolated myocytes, in which NHE1 activity was determined directly by measurement of H+ efflux rate following intracellular acidification, zoniporide produced a dose‐dependent inhibition of such activity (IC50 73 nM at 25°C). A comparable NHE1‐inhibitory potency was retained at 37°C.
In platelets, in which the rate of cell swelling was used as a surrogate index of NHE1 activity, this was again inhibited by zoniporide (IC50 67 nM at 25°C).
In the isolated heart model, administration of zoniporide (loading bolus of 1 mg kg−1 i.v. plus continuous infusion at 1.98 mg kg−1 h−1 i.v.) to the support animal achieved a free plasma drug concentration of 1 μM. At this dose, zoniporide afforded significant cardioprotective benefit relative to vehicle treatment, with improved preservation of left ventricular end‐diastolic and developed pressures and coronary perfusion pressure during reperfusion. Myocardial myeloperoxidase activity was also attenuated by zoniporide treatment, indicating reduced neutrophil accumulation.
These data show that zoniporide (1) is a potent inhibitor of native NHE1 activity in ventricular myocytes and platelets, and (2) affords significant cardioprotective benefit during ischaemia and reperfusion in an experimental model that mimics several distinctive features of human cardioplegic arrest with cardiopulmonary bypass.

British Journal of Pharmacology (2004) 142, 57–66. doi:10.1038/sj.bjp.0705749
Markedly reduced effects of (−)‐isoprenaline but not of (−)‐CGP12177 and unchanged affinity of β‐blockers at Gly389‐β1‐adrenoceptors compared to Arg389‐β1‐adrenoceptors
Authors: Joseph S S , Lynham J A , Grace A A , Colledge W H , Kaumann A J 
Published: May 2004

Substitution of arginine by glycine at position 389, a frequent β1‐adrenoceptor polymorphism, reduces adenylyl cyclase stimulation by (−)‐isoprenaline. β1‐Adrenoceptors mediate the effects of catecholamines and nonconventional partial agonists ((−)‐CGP12177) through different sites. We investigated the influence of the 389 polymorphism on β blocker affinity, as well as on the responses to (−)‐isoprenaline and the nonconventional partial agonist (−)‐CGP12177 on cyclic AMP levels in CHO cells expressing recombinant Arg389‐β1‐adrenoceptors (101 fmol mg−1 protein) or Gly389‐β1‐adrenoceptors (94 fmol mg−1).
The affinity of β‐blockers and partial agonists, estimated from competition binding with (−)‐[125I]‐cyanopindolol, was not different for Arg389‐β1‐adrenoceptors and Gly389‐β1‐adrenoceptors.
The maximum cAMP increases by (−)‐isoprenaline and (−)‐CGP12177 at Gly389‐β1‐adrenoceptors were reduced by 97 and 46%, but the potencies enhanced 2 and 0.5 log units, respectively, compared to Arg389‐β1‐adrenoceptors. The intrinsic activity of (−)‐CGP12177 with respect to the (−)‐isoprenaline was 0.057 at Arg389‐β1‐adrenoceptors and 1.05 at Gly389‐β1‐adrenoceptors.
We confirm in intact CHO cells that responses to (−)‐isoprenaline are markedly reduced at Gly389‐β1‐adrenoceptors compared to Arg389‐β1‐adrenoceptors. However, the 389 polymorphism reduces considerably less the agonist responses to (−)‐CGP12177, indicating that coupling to Gs protein is different for β1‐adrenoceptors activated by catecholamines than for receptors activated by nonconventional partial agonists. The affinity of β‐blockers is conserved across the Arg389Gly polymorphism.

British Journal of Pharmacology (2004) 142, 51–56. doi:10.1038/sj.bjp.0705753
Hydrogen sulphide: an endogenous stimulant of capsaicin‐sensitive primary afferent neurons?
Authors: Chahl L A 
Published: May 2004

Hydrogen sulphide (H2S) is a gas best known for its rotten egg smell. The toxic effects of high concentrations of H2S have been extensively investigated. It is known that H2S is generated in mammalian systems, but little is known of its effects in physiological concentrations. In the present issue of this journal, Patacchini et al. present evidence that H2S stimulates capsaicin‐sensitive primary afferent neurons to release tachykinins in the rat urinary bladder. The possible significance of this finding is discussed in this commentary.British Journal of Pharmacology (2004) 142, 1–2. doi:10.1038/sj.bjp.0705765
Martingale Approach for Moments of Discounted Aggregate Claims
Authors: Jang Ji‐Wook 
Published: May 2004

AbstractWe examine the Laplace transform of the distribution of the shot noise process using the martingale. Applying the piecewise deterministic Markov processes theory and using the relationship between the shot noise process and the accumulated/discounted aggregate claims process, the Laplace transform of the distribution of the accumulated aggregate claims is obtained. Assuming that the claim arrival process follows the Poisson process and claim sizes are assumed to be exponential and mixture of exponential, we derive the explicit expressions of the actuarial net premiums and variances of the discounted aggregate claims, which are the annuities paid continuously. Numerical examples are also provided based on them.
Incentives for Managing Accounting Information: Property‐Liability Insurer Stock‐Charter Conversions
Authors: Mayers David , Smith Clifford W. 
Published: May 2004

AbstractIncentives to manage accounting information are examined within 63 property‐liability insurance company conversions from mutual ownership to common stock charter. In the conversion process, policyholders' embedded equity claims must be valued. Since mutuals have no separately traded equity, accounting numbers are a critical input in this valuation. Incentives for surplus management vary across firms; the strongest evidence of surplus management is observed among firms where the mutual's executives become the firm's principal stockholders following conversion. The evidence suggests that converting firms manage accounting information primarily by adjusting liabilities and selectively establishing investment losses—not by altering claims settlement policy.
Law and the Determinants of Property‐Casualty Insurance
Authors: Esho Neil , Kirievsky Anatoly , Ward Damian , Zurbruegg Ralf 
Published: May 2004

AbstractThis article examines the importance of legal rights and enforcement in influencing property‐casualty insurance (PCI) consumption. We extend the existing literature by examining the role of legal factors in determining insurance density across countries. Also, measures of risk aversion, loss probability, and price, which overcome limitations of proxies used in the existing literature on insurance demand, are analyzed. Using a panel data set, we apply a generalized methods of moments dynamic system estimator, which relaxes the assumption of strict exogeneity of the regressors and produces unbiased and efficient estimates. The results show a strong positive relationship between the protection of property rights and insurance consumption, which is robust to various model specifications and estimation techniques. Moreover, the results show the purchase of PCI is significantly and positively related to loss probability and income, as well as providing weaker evidence of a negative relationship with price.
Dendritic Cell Vaccine Therapy by Immunization with Fusion Cells of Interleukin‐2 Gene‐Transduced, Spleen‐Derived Dendritic Cells and Tumour Cells
Authors: Ogawa F. , Iinuma H. , Okinaga K. 
Published: May 2004

AbstractWe examined the preventive and therapeutic effects of fusion cells prepared from spleen‐derived dendritic cells (DCs) transduced with the interleukin‐2 (IL‐2) gene and QRsP fibrosarcoma cells in a mouse lung metastasis model. The IL‐2 or LacZ gene was introduced into spleen‐derived DCs using an adenoviral vector. Irradiated QRsP tumour cells were fused with IL‐2 gene‐transduced DCs (fusion/IL‐2) or LacZ gene‐transduced DCs (fusion/LacZ) by polyethylene glycol. These fusion cells expressed major histocompatibility complexes (MHC) class I and II, CD86, CD11c and CD8α. Splenocytes from mice vaccinated with fusion cells showed increased production of interferon‐γ (IFN‐γ) and cytotoxic T‐lymphocyte (CTL) activity as compared with those vaccinated with DCs or tumour cells alone, and CTL levels were higher in fusion/IL‐2‐vaccinated mice than in fusion/LacZ‐vaccinated mice. In our experiments on the protective and therapeutic effects on lung metastasis, mice vaccinated with fusion/IL‐2 fusion/LacZ or fusion showed a significant reduction in pulmonary metastasis compared with those given DCs, tumour or phosphate‐buffered saline. The introduction of the IL‐2 gene into fusion cells produced more potent preventive and therapeutic effects. These results suggest that immunization with fusion cells prepared from spleen‐derived DCs and tumour cells is capable of inducing preventive and therapeutic anti‐tumour immunity against lung metastasis, and modification by the IL‐2 gene may increase anti‐tumour efficacy.
Modulation of Adhesion Molecule Expression on Endothelial Cells after Induction by Lipopolysaccharide‐Stimulated Whole Blood
Authors: Nooteboom A. , Van Der Linden C. J. , Hendriks T. 
Published: May 2004

AbstractThe relative contribution of the pro‐inflammatory cytokines tumour necrosis factor (TNF)‐α and interleukin (IL)‐1β and the lipopolysaccharide (LPS)‐induced pathways that result in endothelial activation during sepsis are not fully understood. We have examined the effects of plasma obtained from LPS‐treated human whole blood on the expression of E‐selectin and intercellular adhesion molecule‐1 (ICAM‐1) on human endothelial cells. Stimulation of blood with 10 pg/ml of LPS is sufficient to produce plasma that induces E‐selectin and ICAM‐1 expression, while direct induction by LPS alone requires a 100‐fold higher concentration. Characteristics for the plasma‐induced adhesion molecule expression were similar to the LPS‐induced production of TNF‐α and IL‐1β in blood. A complete inhibition of E‐selectin and ICAM‐1 expression was observed when antibodies against TNF‐α and IL‐1β were added to plasma prior to the incubation to endothelial cultures. Significant inhibition was even observed if antibodies were added to the cultures up until 3 h after LPS‐conditioned plasma. The plasma‐induced adhesion molecule response could also be prevented with inhibitors of nuclear factor (NF)‐κB, such as pyrollidine dithiocarbamate. These findings emphasize the central role of TNF‐α and IL‐1β in LPS‐induced endothelial activation and suggest that simultaneous neutralization of these cytokines or their common pathways may, even after the initial stimulus, prevent endothelial response during sepsis.