bluuebunny/crossref_metadata_2025_split huggingface dataset:
Interleukin‐8 production by the human colon epithelial cell line HT‐29: modulation by interleukin‐13
Authors: Kolios George , Robertson Duncan A.F. , Jordan Nicola J. , Minty Adrian , Caput Daniel , Ferrara Pascal , Westwick John 
Published: July 2012

We have determined which cytokines induce and modulate the production of the chemokine interleukin‐8 (IL‐8) by the human colonic epithelial cell line HT‐29.
Growth arrested cell cultures were stimulated with the human recombinant cytokines interleukin‐1α (IL‐1α), tumour necrosis factor‐α (TNF‐α), interferon‐γ (IFN‐γ), interleukin‐13 (IL‐13), interleukin‐10 (IL‐10) or vehicle added alone or in combination. The production of IL‐8 was determined by enzyme‐linked immunosorbent assay (ELISA) and IL‐8 messenger RNA expression by Northern blot analysis.
The production of IL‐8 in unstimulated cells was undetectable by both ELISA and Northern blot analysis.
HT‐29 cells produced IL‐8 following stimulation with IL‐1α or TNF‐α in a time‐ and a concentration‐dependent manner, while IFN‐γ, IL‐10 and IL‐13 did not induce IL‐8 production by HT‐29 cells.
IL‐13 was found to up‐regulate significantly (P < 0.01) the IL‐1α but not the TNF‐α‐induced IL‐8 generation by HT‐29 cells. In contrast, IL‐10 had no effect on either IL‐1α or TNF‐α‐induced IL‐8 production.
Experiments using cycloheximide demonstrated that this synergistic effect of IL‐13 and IL‐1α on IL‐8 secretion was not through de novo protein synthesis. Using actinomycin‐D, we demonstrated that the IL‐13 up‐regulation was at the level of transcription rather than messenger RNA stability.
These findings suggest that colonic epithelial cells have a functional IL‐13 receptor, which is coupled to an up‐regulation of IL‐1α, but not TNF‐α induced IL‐8 generation.
Analogues of diverse structure are unable to differentiate native melatonin receptors in the chicken retina, sheep pars tuberalis and Xenopus melanophores
Authors: Pickering Hannah , Sword Susan , Vonhoff Stefan , Jones Rob , Sugden David 
Published: July 2012

The pineal hormone melatonin exerts its biological effects through specific, high affinity G‐protein coupled receptors. Recently, three melatonin receptor subtypes (Mel1a, Mel1b and Mel1c) have been cloned. Neither the cloned subtypes, nor the native receptors have yet been compared in a detailed pharmacological analysis.
The present study examined the structure‐activity relationships of a series of 21 melatonin analogues, by comparing their potency on the pigment aggregation response in Xenopus laevis melanophores with their affinity in radioligand binding competition studies in chicken retina and sheep pars tuberalis (PT), two tissues in which melatonin is known to mediate a biological response.
All but four of the analogues were full melatonin receptor agonists producing a concentration‐related redistribution of pigment granules in cultured Xenopus melanophores. The remaining analogues produced little pigment aggregation at 10 μm.
Saturation studies with 2‐[125I]‐iodomelatonin identified a single binding site in the chicken retina and sheep PT membranes, with a KD of 36.6 ± 2.8 and 37.3 ± 4.3 pM, and a maximal number of binding sites (Bmax) of 16.6 ± 0.5, and 40.1 ± 1.7 fmol mg−1 protein, respectively.
Comparison of the potency/affinity of the analogues for the binding sites gave a highly significant correlation in each case, retina/melanophore, r = 0.97 (P < 0.001, n = 17), PT/melanophore, r = 0.97 (P < 0.001, n = 17) and PT/retina, r = 0.98 (P < 0.001, n = 21).
Despite their large range in affinity and structural diversity these melatonin agonists were unable to distinguish between melatonin receptors in the chicken retina, sheep pars tuberalis and Xenopus melanophores.
Pharmacological and functional characterization of bradykinin receptors in canine cultured tracheal epithelial cells
Authors: Luo Shue‐Fen , Tsai Chuen‐Tao , Wu Wen‐Bin , Pan Shiow‐Lin , Tsai Yih‐Jeng , Yang Chuen‐Mao 
Published: July 2012

A direct [3H]‐bradykinin ([3H]‐BK) binding assay has been used to characterize the BK receptors in canine cultured tracheal epithelial cells (TECs). Based on receptor binding assay, TECs have specific, saturable, high‐affinity binding sites for [3H]‐BK.
The specific [3H]‐BK binding was time‐ and temperature‐dependent. Equilibrium of association of [3H]‐BK with the BK receptors was attained within 30 min at room temperature and 1 h at 4°C, respectively.
Analysis of binding isotherms yielded an apparent equilibrium dissociation constant (KD) of 1.5 ± 0.2 nM and a maximum receptor density (Bmax) of 53.2 ± 5.2 fmol mg−1 protein. The Hill coefficient for [3H]‐BK binding was 1.00 ± 0.02. The association (K1 and dissociation (K‐1) rate constants were (7.6 ± 1.1) × 106 M−1 min−1 and (9.2 ± 1.5) × 10 M−3 min−1, respectively. KD, calculated from the ratio of K‐1 and K1 was 1.2 ± 0.3 nM, a value close to that calculated from Scatchard plots of binding isotherms.
Neither a B1 receptor selective agonist (des‐Arg9‐BK, 0.1 nM‐10 μm) nor antagonist ([Leu8, des‐Arg9]‐BK, 0.1 nM‐10 μm) significantly inhibited [3H]‐BK binding to TECs, which excludes the presence of B1 receptors in canine TECs.
The specific binding of [3H]‐BK to canine TECs was inhibited by the B2 receptor selective antagonists ([D‐Arg0, Hyp3, Thi5, D‐Tic7, Oic8]‐BK (Hoe 140, 0.1 nM‐10 μm) and [D‐Arg0, Hyp3, Thi5,8, D‐Phe7]‐BK, 0.1 nM‐10 μm) and agonists (BK and kallidin, 0.1 nM‐10 μm) with a best fit by a one‐binding site model. The order of potency for the inhibition of [3H]‐BK binding was kallidin = BK = Hoe 140 > [D‐Arg0, Hyp3, Thi5,8, D‐Phe7]‐BK.
BK and kallidin significantly induced concentration‐dependent accumulation of IPs with a half‐maximal response (EC50) at 17.6 ± 3.5 and 26.6 ± 5.3 nM, respectively, while the B1‐selective agonist, des‐Arg9‐BK did not stimulate IPs accumulation and the B1‐selective antagonist [Leu8, des‐Arg9‐BK did not inhibit BK‐induced IPs accumulation. Two B2‐selective antagonists, Hoe 140 and [D‐Arg0, Hyp3, Thi5,8, D‐Phe7]‐BK, inhibited BK‐stimulated IPs accumulation with apparent pKB values of 8.8 ± 0.3 and 7.0 ± 0.3, respectively.
It is concluded that the pharmacological characteristics of the BK receptors in canine cultured TECs are primarily of the B2 receptor subtype which might regulate the function of tracheal epithelium through the activation of this receptor subtype coupling to PI hydrolysis.
Regulation of nitric oxide synthesis by dimethylarginine dimethylaminohydrolase
Authors: MacAllister Raymond J. , Parry Heather , Kimoto Masumi , Ogawa Tadashi , Russell Rachel J. , Hodson Harold , Whitley Guy St.J. , Vallance Patrick 
Published: July 2012

Dimethylarginine dimethylaminohydrolase (DDAH), an enzyme that metabolizes the endogenous nitric oxide synthase inhibitors NG‐monomethyl‐L‐arginine and NG, NG‐dimethy‐L‐arginine to citrulline, was identified by Western blotting in rat and human tissue homogenates.
S‐2‐amino‐4(3‐methylguanidino)butanoic acid (4124W) inhibited the metabolism of [14C]‐NG‐monomethyl‐L‐arginine to [14C]‐citrulline by rat liver homogenates (IC50 416 ± 66μm; n = 9), human cultured endothelial cells (IC50 250 ± 34 μm; n = 9)and isolated purified dimethylarginine dimethylaminohydrolase.
Addition of 4124W to culture medium increased the accumulation of endogenously‐generated NG, NG‐dimethy‐L‐arginine in the supernatant of human cultured endothelial cells from 3.1 ± 0.3 to 5 ± 0.7 μm (n=15; P < 0.005).
4124W (1 μm‐1 mM) had no direct effect on endothelial nitric oxide synthase activity but caused endothelium‐dependent contraction of rat aortic rings (1 mM 4124W increased tone by 81.5 ± 9.6% of that caused by phenylephrine 100 nM). This effect was reversed by L‐arginine (100 μm). 4124W reversed endothelium‐dependent relaxation of human saphenous vein (19.2 ± 6.7% reversal of bradykinin‐induced relaxation at 1 mM 4124W).
These data suggest that inhibition of dimethylarginine dimethylaminohydrolase increases the intracellular concentration of NG, NG‐dimethyl‐L‐arginine sufficiently to inhibit nitric oxide synthesis. Inhibiting the activity of DDAH may provide an alternative mechanism for inhibition of nitric oxide synthases and changes in the activity of DDAH could contribute to pathophysiological alterations in NO generation.
Analysis of relaxation and repolarization mechanisms of nicorandil in rat mesenteric artery
Authors: Fujiwara Toshimasa , Angus Jarnes A. 
Published: July 2012

The mechanism by which nicorandil causes relaxation of rat isolated small mesenteric arteries mounted on a Mulvany myograph was investigated by use of a combination of putatively mechanism‐specific antagonists.
In arteries precontracted by the thromboxane‐mimetic, U46619, the EC50 for cromakalim and levcromakalim‐induced relaxation curves were raised by 36 and 17 fold by glibenclamide (3 μm) while the EC50 for nicorandil‐induced relaxation was unaffected by either glibenclamide or methylene blue (10 μm). A combination of these antagonists raised the EC50 for nicorandil by 8 fold.
In U46619‐contracted arteries, nifedipine (100 nM) did not affect the cromakalim relaxation curve but it raised the EC50 for nicorandil by 5 fold. The combination of methylene blue, glibenclamide and nifedipine further inhibited the maximum relaxation to nicorandil.
In separate experiments, membrane potential (Em) and force responses were measured simultaneously. In arteries depolarized and contracted by U46619 both nicorandil and cromakalim repolarized (δEm, 35mV) and relaxed (100%) the vessels. Glibenclamide (3μm) did not alter the relaxation‐concentration curve to nicorandil but reduced the maximum repolarization to A10.8 mV. In contrast the Em and relaxation‐response curves to cromakalim were shifted to the right by glibenclamide by 30–100 fold.
In unstimulated arteries, nicorandil (but not cromakalim) ‐induced hyperpolarization was significantly antagonized by methylene blue (10 μm) (6.6 fold rightward shift) or nifedipine (100 nM) (2.6 fold). In depolarized arteries (U46619), nifedipine but not methylene blue inhibited the nicorandil‐induced hyperpolarization.
In arteries precontracted to 50% tissue maximum by either KCl or U46619, nifedipine (100 nM) relaxed the artery but failed to repolarize the Em. Presumably voltage‐operated calcium channels (VOCC) were blocked preventing contraction but the artery remained depolarized, presumably through non VOCC mechanisms.
These data suggest that nicorandil may relax small arteries through 3 parallel pathways, (i) NO‐donor mediated stimulation of guanylate cyclase and increase in cyclic GMP, (ii) K+ATP channel opening, and (iii) nifedipine‐sensitive VOCC inhibition. Em data suggest that nicorandil‐induced repolarization is caused principally through opening K+ATP channels. Blockade of this hyperpolarization by glibenclamide is not sufficient to alter the relaxation, indicating dissociation of nicorandil‐induced changes in membrane potential and relaxation.
These results highlight the ‘chameleon’ actions of nicorandil where there is no apparent association of Em repolarization with relaxation, in contrast to the parallel responses for cromakalim.
A possible structural determinant of selectivity of boldine and derivatives for the α1A‐adrenoceptor subtype
Authors: Madrero Y. , Elorriaga M. , Martinez S. , Noguera M.A. , Cassels B.K. , D'Ocon P. , Ivorra M.D. 
Published: July 2012

The selectivity of action of boldine and the related aporphine alkaloids, predicentrine (9‐O‐methylboldine) and glaucine (2,9‐O‐dimethylboldine) on α1‐adrenoceptor subtypes was studied by examining [3H]‐prazosin competition binding in rat cerebral cortex. WB 4101 and benoxathian were used as selective α1A‐adrenoceptor antagonists.
In the competition experiments [3H]‐prazosin (0.2 nM) binding was inhibited by WB 4101 and benoxathian. The inhibition curves displayed shallow slopes which could be subdivided into high and low affinity components (pKi = 9.92 and 8.29 for WB 4101, 9.35 and 7.94 for benoxathian). The two antagonists recognized approximately 37% of the sites with high affinity from among the total [3H]‐prazosin specific binding sites.
Boldine, predicentrine and glaucine also competed for [3H]‐prazosin (0.2 nM) binding with shallow and biphasic curves recognizing 30–40% of the sites with high affinity. Drug affinities (pKi) at the high and low affinity sites were, 8.31 and 6.50, respectively, for boldine, 8.13 and 6.39 for predicentrine, and 7.12 and 5.92 for glaucine. The relative order of selectivity for α1A‐adrenoceptors was boldine (70 fold α1A‐selective) = predicentrine (60 fold, α1A‐selective) > glaucine (15 fold, α1A‐selective).
Pretreatment of rat cerebral cortex membranes with chloroethylclonidine (CEC, 10 μm) for 30 min at 37°C followed by thorough washing out reduced specific [3H]‐prazosin binding by approximately 70%. The CEC‐insensitive [3H]‐prazosin binding was inhibited by boldine monophasically (Hill slope = 0.93) with a single pKi value (7.76).
These results suggest that whereas the aporphine structure shared by these alkaloids is responsible for their selectivity of action for the a α1A‐adrenoceptor subtype in rat cerebral cortex, defined functional groups, namely the 2‐hydroxy function, induces a significant increase in α1A‐subtype selectivity and affinity.
A cyclic GMP‐dependent housekeeping Cl− channel in rabbit gastric parietal cells activated by a vasodilator ecabapide
Authors: Sakai Hideki , Ikari Akira , Kumano Eiichi , Takeguchi Noriaki 
Published: July 2012

The membrane potential of rabbit gastric parietal cells is dominated by a Cl− channel with a sub‐picosiemens single channel conductance in the basolateral membrane. The effects of 3‐[[[2‐(3,4‐dimethoxyphenyl)ethyl]carbamoyl]methyl]amino‐N‐methylbenzamide (DQ‐2511: ecabapide), a vasodilator, on the opening of this Cl− channel, the cyclic GMP content and the intracellular free Ca2+ concentration ([Ca2+]i) of parietal cells were investigated by whole‐cell patch‐clamp technique, enzyme immunoassay and Fura 2‐fluorescence measurement.
Ecabapide stimulated the opening of the Cl− channel as determined by the reversal potential. This stimulation was concentration‐dependent, and its EC50 value was 0.2 μm. Both the basal and ecabapide‐induced openings of the channel were inhibited by 5‐nitro‐2‐(3‐phenylpropylamino)‐benzoate (NPPB, 500 μm), a Cl− channel blocker. Another Cl− channel blocker, niflumic acid (500 μm) was much less effective.
The power spectra of the currents before and after the addition of ecabapide (10 μm) were analysed. Both spectra contained only one Lorentzian (1/f2) component.
6‐Anilino‐5,8‐quinolinedione (LY83583; 5 μm), which prevents activation of soluble guanylate cyclase, significantly inhibited both the basal and ecabapide (10 μm)‐induced openings of the Cl− channel.
Ecabapide (0.01 −100 μm) concentration‐dependently elevated the cyclic GMP content in the parietal cell‐rich suspension. The EC50 value was 0.2 μm.
In single Fura 2‐loaded parietal cells, ecabapide (10–100 μm) did not increase [Ca2+]i.
These results indicate that ecabapide stimulates an intracellular production of cyclic GMP in the parietal cell without increasing [Ca2+]i, and leads to an activation of the housekeeping Cl− channel.
Inhibition of ecto‐ATPase by PPADS, suramin and reactive blue in endothelial cells, C6 glioma cells and RAW 264.7 macrophages
Authors: Chen Bin C. , Lee Chii‐M. , Lin Wan‐W. 
Published: July 2012

Previous studies have shown that bovine pulmonary artery endothelium (CPAE) has P2Y and P2U purinoceptors, rat C6 glioma cells have P2u purinoceptors and mouse RAW 264.7 cells have pyrimidinoceptors, all of which are coupled to phosphoinositide‐specific phospholipase C (PI‐PLC). The dual actions of PPADS, suramin and reactive blue as antagonists of receptor subtypes and ecto‐ATPase inhibitors were studied in these three cell types.
In CPAE, suramin, at 3–100 μm, competitively inhibited the PI responses induced by 2MeSATP and UTP, with pA2 values of 5.5 ± 0.3 and 4.4 ± 0.4, respectively. Reactive blue, at 1–3 μm, produced shifts to the right of the 2MeSATP and UTP curves, but no further right shift at 10 μm. PPADS, at 10 μm, caused a 3 fold right shift of the 2MeSATP curve, but no further shift at concentrations up to 100 μm. In contrast, a dose‐dependent shift to the left of the UTP curve and a weak inhibition of the ATP response were seen with PPADS.
In RAW 264.7 cells, suramin and reactive blue, but not PPADS, competitively inhibited the UTP response, with pA2 values of 4.8 ± 0.5 and 5.8 ± 0.7, respectively.
In C6 glioma cells, although suramin and reactive blue inhibited the ATP response, a potentiation effect on ATP and UTP responses was seen with PPADS.
The ecto‐ATPase inhibitory activity of these three receptor antagonists were determined. All three inhibited ecto‐ATPase present in CPAE, C6 and RAW 264.7 cells, with IC50 values of 4, 4.8 and 4.7 for PPADS, 4, 4.4 and > > 4 for suramin, and 4.5, 4.7 and 4.7 for reactive blue.
This study indicates that PPADS, suramin and reactive blue are ecto‐ATPase inhibitors. This property, combined with their antagonistic selectivity for receptor subtypes, can result in inhibition of, potentiation of, or lack of effect on agonist‐mediated PI responses. Reactive blue is a more potent antagonist than suramin on P2Y, P2U and pyrimidinoceptors, and PPADS is a weak antagonist for P2Y receptors.
Early Exercise of Put Options on Stocks
Authors: BARRACLOUGH KATHRYN , WHALEY ROBERT E. 
Published: July 2012

ABSTRACTU.S. exchange‐traded stock options are exercisable before expiration. While put options should frequently be exercised early to earn interest, they are not. In this paper, we derive an early exercise decision rule and then examine actual exercise behavior during the period January 1996 through September 2008. We find that more than 3.96 million puts that should have been exercised early remain unexercised, representing over 3.7% of all outstanding puts. We also find that failure to exercise cost put option holders $1.9 billion in forgone interest income and that this interest is systematically captured by market makers and proprietary firms.
Nurse‐Physician Relationships in Ambulatory Oncology Settings
Authors: Friese Christopher R. , Manojlovich Milisa 
Published: July 2012

AbstractPurpose: The purpose of this study was to explore nurses’ perceptions of nurse‐physician relationships in ambulatory oncology settings, which are linked to patient safety.Design: This cross‐sectional, descriptive study analyzed survey data collected in 2010 from oncology nurses employed in ambulatory settings. The sampling frame was the nurse licensure database in one state in the Southeastern United States. Nurses completed the Practice Environment Scale of the Nursing Work Index (PES‐NWI), reported on the quality of care in their setting, and commented on factors that promoted or inhibited high‐quality care delivery.Methods: Data analysis used three study variables: empirically derived values from the PES‐NWI, a scale of nurse‐reported quality of care in their setting, and open‐text comments about features in their workplace that promoted or hindered high‐quality care. After categorizing open‐text comments, analysis of variance was used to evaluate differences in PES‐NWI subscales by comment category. Chi‐square test statistics were calculated to examine differences in overall practice environment and quality of care by comment category.Results: Nurses reported their relationships with physicians as generally favorable. Qualitative findings suggest two themes that influence how nurses characterize their working relationships with physicians: (a) physician behaviors and (b) structural factors. Both PES‐NWI scores and quality of care were rated significantly higher by nurses who wrote favorably about physicians.Conclusions: Favorable nurse‐physician relationships in ambulatory settings may reflect positive workplaces and promote high‐quality care.Clinical Relevance: Consistent with findings from inpatient units, nurse‐physician relationships are important to the quality of ambulatory oncology care. Systematic measurement and attention to reported deficits in these relationships may promote higher quality care.Journal of Nursing Scholarship, 2012; 00:0, 1–8. ©2012 Sigma Theta Tau International.
Secular trends in impact factor of neonatology publications over a 10‐year period
Authors: Marom Ronella , Mimouni Francis B. , Cohen Shlomi , Lubetzky Ronit , Mandel Dror 
Published: July 2012

AbstractAim:  To test the hypotheses that published randomized clinical trials (RCTs) in neonatology with negative results (NR) are more likely to be published in journals with lower impact factor (IF) than those with positive results (PR); that there is an increase in the number of yearly published RCTs; that studies with large sample sizes are likely to be published in journals with higher IF.Methods:  We used all English‐written RCTs registered in MEDLINE between 1/1/2001–31/12/2010 in the field of neonatology. Each RCT was classified as having a PR or NR. IF of each journal was determined for the year of publication.Results:  We identified 329 RCTs. Yearly number of RCTs varied between 19 and 46, with no significant consistent linear increase over the years. There was no significant change over the years in average IF or in average patient size. IF and sample size of the studies were not significantly higher in studies with PR than in studies with NR.Conclusion:  The number of RCTs per year in the field of neonatology has stabilized in the past 10 years, and RCTs with positive or negative results are published in journals of similar IF.
Integrated Reporting, Stakeholder Engagement, and Balanced Investing at American Electric Power
Authors: Parrot Katherine W. , Tierney Brian X. 
Published: July 2012

The policies and practices of American Electric Power (AEP) encompass a number of paradoxes in the domain of sustainability. AEP is a large electric power provider with a predominantly coal‐fired power generation portfolio, which puts the company squarely in the center of national debates about global climate change and national air quality. At the same time, AEP is also a leader on several social and environmental fronts: integrated reporting, stakeholder engagement, technology innovation, and policy solutions for climate change.In this article, the authors describe AEP's rationale for providing leadership in these areas and then explore how the company tries to balance stakeholder interests and financial, environmental, and social concerns in its capital investment decisions. Using these examples, the authors expand on and discuss the limitations of Michael Jensen's theory of “enlightened value maximization.”