bluuebunny/crossref_metadata_2025_split huggingface dataset:
Molecular targets of doxazosin in human prostatic stromal cells
Authors: Zhao Hongjuan , Lai Frank , Nonn Larisa , Brooks James D. , Peehl Donna M. 
Published: September 2004

AbstractBACKGROUNDWe used cDNA microarray analysis to obtain insights into the mechanisms of action of doxazosin, an α1‐adrenergic receptor antagonist used to treat benign prostatic hyperplasia (BPH).METHODSHierarchical clustering analysis and significance analysis of microarray (SAM) were performed to identify genes differentially expressed between untreated stromal cells cultured from normal tissue and BPH, and changes in gene expression induced by doxazosin. Transcript levels of selected genes were validated by real‐time reverse‐transcription polymerase chain reaction (RT‐PCR).RESULTSHierarchical clustering analyses separated untreated normal and BPH cells. Sixty‐seven genes whose expression varied at least twofold after doxazosin treatment in both normal and BPH cells were identified, as were 93 genes differentially regulated in normal versus BPH cells. Molecular targets consistent with tumor necrosis factor (TNF)‐α‐related activity were identified.CONCLUSIONSNormal versus BPH stromal cells differ in global gene transcription. Doxazosin induced gene expression changes relevant to proliferation/apoptosis, immune defense, cell–cell signaling/signal transduction, and transcriptional regulation. © 2004 Wiley‐Liss, Inc.
Ambiguities in the calculation of dislocation self energies
Authors: LeSar R. 
Published: September 2004

AbstractVarious forms for the interactions between dislocations have been given in the literature. While arising from the same basic expression, they differ in terms that vanish when integrating over an entire dis‐location loop and thus yield the same value for the interaction energy between distinct dislocations. In this paper, however, we show that when applied to dislocation self energies, which because of a core cutoff do not involve integrations over the entire loop, these expressions may not yield equivalent results. (© 2004 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
11th International Conference on High‐Pressure Semiconductor Physics (HPSP‐11), Berkeley, USA, 2–5 August 2004
Authors: Cardona M. 
Published: September 2004

AbstractConference Reports are meant to offer an authoritative view on a recently held scientific meeting rather than a comprehensive list of the conference presentations. Authors are invited to describe what they feel were the most interesting contributions.The Proceedings of the 11th International Conference on High‐Pressure Semiconductor Physics (HPSP‐11) will be published in phys. stat. sol. (b) in November 2004.
Quantitative evaluation of the atomic structure of defects and composition fluctuations at the nanometer scale inside InGaN/GaN heterostructures
Authors: Ruterana P. , Singh P. , Kret S. , Jurczak G. , Maciejewski G. , Dluzewski P. , Cho H. K. , Choi R. J. , Lee H. J. , Suh E. K. 
Published: September 2004

AbstractThe cover picture of this issue depicts indium composition fluctuations in InGaN/GaN multi quantum wells. The coded color strain distribution (left) was derived from finite element method calculations of the strain relaxation process and high‐resolution transmission electron microscopy (HRTEM) image simulations, superimposed on the HRTEM image of the quantum wells. The possible corresponding shape and εxx strain profiles in the indium rich clusters (right) hint at a concentration close to pure InN in their core. The paper by Pierre Ruterana et al. [1] was presented at the 5th International Symposium on Blue Laser and Light Emitting Diodes (ISBLLED‐2004), held in Gyeongju, Korea, 15–19 March 2004.Further papers from ISBLLED‐2004 are published in phys. stat. sol. (a) 201, No. 12 (2004) and phys. stat. sol. (c) 1, No. 10 (2004).
Synthesis, Screening and Evaluation of a Combined Library of Tweezer‐ and Tripodal Synthetic Receptors
Authors: Monnee Menno C. F. , Brouwer Arwin J. , Liskamp Rob M. J. 
Published: September 2004

AbstractThe split‐mix synthesis of a 6912‐member combined library of tweezer‐ and tripodal synthetic receptors is described. This library was prepared by solid phase attachment of a tweezer hinge, a “locked” tweezer hinge and two triazacyclophane (“TAC”) tripodal scaffold, followed by three split‐mix cycles using twelve α‐amino acid (Gly, Ala, Val, Leu, Pro, Phe, Tyr, Lys, Ser, Asp, Gln, His) derivatives. Using fluorescence microscopy and image analysis, the resulting library was screened in aqueous phosphate buffer with fluorescent fragments of the cell wall of Gram‐positive Staphylococcus aureus i.e. Ds‐Gly‐D‐Ala‐D‐Ala‐OH and Ds‐Gly‐D‐Ala‐D‐Lac‐OH as well as FITC‐labeled peptidoglycan fragments. Decoding of selected beads by Edman degradation gave the structures of the possible synthetic receptors, of which thirteen were resynthesized on the solid phase, including one using a cleavable linker containing resin for confirmation of the quality of the resynthesized receptor. Remarkable binding selectivities were observed, for example the presence of Lys (AA3) in almost half of the sequenced receptors arms binding to Ds‐Gly‐D‐Ala‐D‐Ala‐OH, which is less the case in the receptors binding Ds‐Gly‐D‐Ala‐D‐Lac‐OH. Especially prominent was the presence of a Pro residue as AA3 in more than half of the arms of the sequenced receptors. The observed selectivities were not reflected in the binding constants of representative resynthesized synthetic receptors attached to beads, which were all in the range of 500 M−1 in phosphate buffer. Moreover, this showed that, in contrast to an non‐aqueous system, the third arm of the tripod did not contribute to the binding of Ds‐Gly‐D‐Ala‐D‐Lac‐OH, since in chloroform binding constants ‐also determined on the beads‐ were observed of 11,700 M−1 and 5,400 M−1 for a tripod and tweezer receptor, respectively.
Application of QSARs: Correlation of Acute Toxicity in the Rat Following Oral or Inhalation Exposure
Authors: de Wolf Watze , Lieder Paul H. , Walker John D. 
Published: September 2004

AbstractQuantitative Structure‐Activity Relationships (QSARs) based upon a lethal narcosis mechanism represent baseline or minimum toxicity, i.e. unless a chemical acts by a more specific mechanism, its toxicity will be predicted by such models. Baseline toxicity should be independent of exposure route. A toxicity ratio (TR) is defined as the ratio of the calculated baseline toxicity over the experimentally determined value. A TR‐value of approx. 1 indicates baseline toxicity. A TR‐value greater than 1 indicates excess toxicity due to the existence of a more specific mechanism of action. We investigated the possibility of extrapolation from the inhalation route to the oral route by applying the above concepts.
Strain Energies as a Steric Descriptor in QSAR Calculations
Authors: Williford Catherine J. , Stevens Erland P. 
Published: September 2004

AbstractThe difference between the calculated heats of formation of gauche and anti conformers of monosubstituted propanes was determined and used as a new steric parameter (AG60 value) in QSAR calculations. The dihedral angle of the gauche conformation was fixed at 60° during the calculation to force interaction of the gauche groups. AG60 values are a thermodynamically determined steric measure in contrast to the Taft steric parameter, which is based upon kinetic measurements of ester hydrolyses. In comparisons to published QSAR studies, AG60 values correlated steric effects and biological activities very similarly to the Taft parameter. The average of r2 values from five QSAR studies for the Taft parameter was 0.887, while AG60 values averaged 0.883. Direct comparison of the Taft parameter and AG60 values showed a poor correlation (r2=0.300), indicating the two parameters are fundamentally different methods of measuring steric bulk.
Molecular Dynamics of Complexes of Atosiban with Neurohypophyseal Receptors in the Fully Hydrated Phospholipid Bilayer
Authors: Ślusarz Magdalena J. , Ślusarz Rafał , Meadows Robert , Trojnar Jerzy , Ciarkowski Jerzy 
Published: September 2004

AbstractThe aim of our research was to get insight into the molecular mechanism of binding atosiban, a strong selective oxytocin (OT) antagonist by OT receptor (OTR) versus vasopressin V1a and V2 receptors (V1aR and V2R, respectively). The docking of ligand and interaction with receptor are dynamic events and Molecular Dynamics (MD) seems to be a proper tool for studying the mentioned processes. Therefore we describe MD of three pairs of atosiban‐receptor complexes, two complexes per each receptor, conducted in the fully hydrated 1‐palmitoyl‐2‐oleoyl‐sn‐glycero‐3‐phosphatidylcholine lipid bilayer, simulating G protein‐coupled receptors environment. We confirmed strong and specific binding of atosiban in OTR and a weaker binding of it in V1aR, on the contrary to its less specific binding in V2R, in the agreement with our preliminary results [Ślusarz et al. 2003].
QSTR with Extended Topochemical Atom Indices. 4. Modeling of the Acute Toxicity of Phenylsulfonyl Carboxylates toVibrio fischeriusing Principal Component Factor Analysis and Principal Component Regression Analysis
Authors: Roy Kunal , Ghosh Gopinath 
Published: September 2004

AbstractThe present paper deals with modeling of the acute toxicity of 56 phenylsulfonyl carboxylates toVibrio fischeri.Principal component factor analysis has been used as the data‐preprocessing step for the selection of independent variables for the subsequent multiple regression analysis. The statistical quality of the best model using ETA descriptors is as follows:n=56,Q2=0.726,Ra2=0.837,R=0.923,F=57.4 (df5, 50),s=0.186, AVRES=0.136. Attempt has also been made to model the data set with different non‐ETA parameters (topological indices including Wiener, HosoyaZ, molecular connectivity, kappa shape, BalabanJand E‐State parameters apart from physicochemical parameters like AlogP98, MolRef and H‐bond‐acceptor) and the best model shows the following quality:n=56,Q2=0.763,Ra2=0.798,R=0.903,F=44.3 (df 5, 50),s=0.207, AVRES=0.139. An attempt to use both ETA and non‐ETA parameters has lead to an equation which is somewhat better in statistical quality than the best ETA model:n=56,Q2=0.779,Ra2=0.861,R=0.935,F=69.4 (df5, 50),s=0.172, AVRES=0.127. Use of the ETA indices has suggested that negative contributions of steric bulk, branching, functionality of C10, functionality of chloro substituent at X1position and presence of unsaturation at the substituent(s) on C10, and positive contributions of functionality of O13and presence of substituents with electronegative atoms at R2and R3positions. Using factor scores as independent variables, principal component regression analysis has been performed and the derived relations are of excellent statistical qualities (Q2values being 0.816, 0.828 and 0.848 whileR2values being 0.894, 0.871 and 0.905 for factor scores derived from ETA, non‐ETA and combined matrices respectively) which are comparable to that (Q2andR2values being 0.790 and 0.920 respectively) of the relation generated from comparative molecular field analysis on the same data set.
Negative ion graphitised carbon nano‐liquid chromatography/mass spectrometry increases sensitivity for glycoprotein oligosaccharide analysis
Authors: Karlsson Niclas G. , Wilson Nicole L. , Wirth Hans‐Jürgen , Dawes Peter , Joshi Hiren , Packer Nicolle H. 
Published: September 2004

AbstractNegative ion nano‐liquid chromatography/mass spectrometry (nano‐LC/MS) and tandem mass spectrometry (nano‐LC/MS2), using graphitised carbon as separating medium, were explored for analysing neutral and acidic O‐linked and N‐linked oligosaccharide alditols. Compared to the sensitivity of capillary LC/MS (flow rate of 6 μL/min) coupled with a conventional electrospray ionisation source, the nano‐LC/MS (flow rate of 0.6 μL/min) with a nanoflow ion source was shown to increase the sensitivity ten‐fold with a detection limit in the low‐femtomole range. The absolute signals for the [MnH]n− ions of the oligosaccharides were increased 100‐fold, enabling accumulation of high‐quality fragmentation data in MS2 mode, in which detection of low abundant sequence ions is necessary for characterisation of highly sialylated N‐linked oligosaccharides. Oligosaccharides with high numbers of sialic acid residues gave dominant fragments arising from the loss of sialic acid, and less abundant fragments from cleavage of other glycosidic bonds. Enzymatic off‐line desialylation of oligosaccharides in the low‐femtomole range prior to MS2 analysis was shown to increase the quality of the spectra. Automated glycofragment mass fingerprinting using the GlycosidIQ software confirmed the oligosaccharide sequence for both neutral desialylated as well as sialylated structures. Furthermore, the use of graphitised carbon nano‐LC/MS enabled the detection of four sialylated O‐linked oligosaccharides on membrane proteins from ovarian tissue (5 μg of total amount of protein). Copyright © 2004 John Wiley & Sons, Ltd.
Ultra‐performance liquid chromatography coupled to quadrupole‐orthogonal time‐of‐flight mass spectrometry
Authors: Plumb Robert , Castro‐Perez Jose , Granger Jennifer , Beattie Iain , Joncour Karine , Wright Andrew 
Published: September 2004

AbstractUltra‐performance liquid chromatography (UPLC) utilizes sub‐2 μm particles with high linear solvent velocities to effect dramatic increases in resolution, sensitivity and speed of analysis. The reduction in particle size to below 2 μm requires instrumentation that can operate at pressures in the 6000–15 000 psi range. The typical peak widths generated by the UPLC system are in the order of 1–2 s for a 10‐min separation. In the present work this technology has been applied to the study of in vivo drug metabolism, in particular the analysis of drug metabolites in bile. The reduction in peak width significantly increases analytical sensitivity by three‐ to five‐fold, and the reduction in peak width, and concomitant increase in peak capacity, significantly reduces spectral overlap resulting in superior spectral quality in both MS and MS/MS modes. The application of UPLC/MS resulted in the detection of additional drug metabolites, superior separation and improved spectral quality. Copyright © 2004 John Wiley & Sons, Ltd.
Maintenance of bone mass and architecture in denning black bears (Ursus americanus)
Authors: Pardy Connor K. , Wohl Gregory R. , Ukrainetz Philip J. , Sawers Andrew , Boyd Steven K. , Zernicke Ronald F. 
Published: September 2004

AbstractBone mass is dramatically compromised during periods of weightlessness, inactivity, or bed rest. Animals that hibernate reduce their body temperature, heart rate and metabolic activity, and likewise lower bone turnover activity during their immobile state. Black bears Ursus americanus, however, do not hibernate, but rather overwinter by denning during which they maintain a nearly normal functional heart rate, cardiac output and temperature. Furthermore, markers of bone turnover in black bears are maintained during denning periods. Thus, the purpose of this work was to determine if the denning state of relative immobility in black bears results in changes in bone mass and bone architectural structure. Harvested forelimbs (ulna and radius) were compared between pre‐ and post‐denning black bears using X‐ray imaging, dual energy X‐ray absorptiometry, and micro‐computed tomography to quantify total distal forelimb bone mineral density, cancellous bone mineral density, bone mineral content, bone volume fraction, degree of anisotropy, structure model index, and trabecular thickness. No significant differences in any of the measured parameters were found in comparing radius and ulna from autumn and spring bears in this cross‐sectional sample, suggesting that black bears did not experience a significant change in bone mass or architecture during denning. The statistical power for detecting a significant difference (P≤ 0.05) for this sample was 0.8. The specific mechanism by which the preservation of bone was attained may be related to skeletal muscle interaction or circulating systemic hormones.
Sphingosine 1‐phosphate‐induced vasoconstriction is elevated in mesenteric resistance arteries from aged female rats
Authors: Hemmings D G , Xu Y , Davidge S T 
Published: September 2004

Sphingosine 1‐phosphate (S1P), a bioactive lipid, signals through cell surface receptors to induce vasoconstriction and activate endothelial nitric oxide synthase (eNOS), suggesting a role for S1P in vascular tone modulation.
Using a model of aging in female rats, we investigated the vasoactivity of S1P and the roles of eNOS and estrogen replacement in modulation of that vasoactivity.
Mesenteric arteries from aged female rats were significantly more sensitive to S1P‐induced vasoconstriction than arteries from young female rats, and reached greater maximum constriction (58.2±2.98 vs 34.8±4.44%; P<0.005). Modulation of this vasoconstriction by pretreating vessels with the NOS inhibitor L‐NAME occurred only in young vessels.
Ovariectomy reduced the maximum S1P‐induced vasoconstriction observed in intact aged rats. Estrogen replacement did not appear to have an independent beneficial effect. However, estrogen replacement did restore nitric oxide modulation of S1P‐induced vasoconstriction.
Expression of the S1P1 receptor, through which eNOS can be activated, was reduced in vessels from aged rats. S1P1 receptor expression was restored in vessels from the estrogen‐replaced group.
S1P is a novel mediator of vascular tone through induction of both vasoconstriction and vasodilation. Reduced S1P1 receptor expression on aging vessels may explain reduced eNOS activity, which results in greater sensitivity to S1P‐induced vasoconstriction. Estrogen replacement in aging female rats restores both S1P1 receptor expression and NOS activity, suggesting an important role for estrogen in this novel pathway of vascular tone modulation.

British Journal of Pharmacology (2004) 143, 276–284. doi:10.1038/sj.bjp.0705752
Role of PDE4 in superoxide anion generation through p44/42MAPK regulation: a cAMP and a PKA‐independent mechanism
Authors: Jacob Claire , Szilagyi Corinne , Allen Janet M , Bertrand Claude , Lagente Vincent 
Published: September 2004

We investigated the generation of reactive oxygen species (ROS) from bronchoalveolar lavage (BAL) cells of either control or LPS‐exposed rats and the effects of PDE4 inhibitors on ROS production.
The PDE4 inhibitors, rolipram and Ariflo (cilomilast, SB 207499) dose‐dependently (0.1–10 μM) inhibited fMLP‐induced superoxide anion (O2•−) production (IC50s: 0.03 and 0.55 μM, respectively) in BAL cells of Wistar rats collected 3 h after an LPS‐aerosol (200 μg ml−1, 1 h). These BAL contained 85–95% neutrophils (BAL cells enriched in neutrophils).
In contrast, BAL cells collected at the end of the challenge contained only macrophages and in these conditions, rolipram and Ariflo (0.1–10 μM) could only inhibit 25 and 45% of fMLP‐induced O2•− release, respectively.
We also observed that the inhibition of p44/42MAPK by PD98059 (1–10 μM) increased O2•− release by BAL cells enriched in neutrophils, but not by macrophages, and prevented the inhibition of O2•− production induced by PDE4 inhibitors.
Western blot analysis showed that PDE4 inhibitors strongly activated p44/42MAPK in BAL cells enriched in neutrophils but not in macrophages. And in these cells, PDE4 and p44/42MAPK were co‐immunoprecipitated by a polyclonal anti‐PDE4 antibody.
The following cell permeable‐cAMP analogues, dbcAMP (10 μM–1 mM), 8‐CPT‐cAMP (1 mM) and 8‐pMeOPT‐2′‐O‐Me‐cAMP (0.5 mM), could not reduce fMLP‐induced O2•− production and both PKA inhibitors, PKA inhibitor 14–22 amide myristoylated (50 nM–1 μM) and H‐89 (100 nM–1 μM), did not affect the decrease of O2•− release induced by PDE4 inhibitors in BAL cells enriched in neutrophils.
These data suggest that PDE4 inhibitors decreased fMLP‐induced O2•− release in BAL cells enriched in neutrophils but not in macrophages, through p44/42MAPK activation by a cAMP‐ and a PKA‐independent mechanism.

British Journal of Pharmacology (2004) 143, 257–268. doi:10.1038/sj.bjp.0705927
Marijuana and cannabinoid regulation of brain reward circuits
Authors: Lupica Carl R , Riegel Arthur C , Hoffman Alexander F 
Published: September 2004

The reward circuitry of the brain consists of neurons that synaptically connect a wide variety of nuclei. Of these brain regions, the ventral tegmental area (VTA) and the nucleus accumbens (NAc) play central roles in the processing of rewarding environmental stimuli and in drug addiction. The psychoactive properties of marijuana are mediated by the active constituent, Δ9‐THC, interacting primarily with CB1 cannabinoid receptors in a large number of brain areas. However, it is the activation of these receptors located within the central brain reward circuits that is thought to play an important role in sustaining the self‐administration of marijuana in humans, and in mediating the anxiolytic and pleasurable effects of the drug. Here we describe the cellular circuitry of the VTA and the NAc, define the sites within these areas at which cannabinoids alter synaptic processes, and discuss the relevance of these actions to the regulation of reinforcement and reward. In addition, we compare the effects of Δ9‐THC with those of other commonly abused drugs on these reward circuits, and we discuss the roles that endogenous cannabinoids may play within these brain pathways, and their possible involvement in regulating ongoing brain function, independently of marijuana consumption. We conclude that, whereas Δ9‐THC alters the activity of these central reward pathways in a manner that is consistent with other abused drugs, the cellular mechanism through which this occurs is likely different, relying upon the combined regulation of several afferent pathways to the VTA.British Journal of Pharmacology (2004) 143, 227–234. doi:10.1038/sj.bjp.0705931
Loss of endothelial KATP channel‐dependent, NO‐mediated dilation of endocardial resistance coronary arteries in pigs with left ventricular hypertrophy
Authors: Gendron Marie‐Eve , Thorin Eric , Perrault Louis P 
Published: September 2004

The influence of left ventricular hypertrophy (LVH) on the endothelial function of resistance endocardial arteries is not well established. The aim of this study was to characterise the mechanisms responsible for UK‐14,304 (α2‐adrenoreceptor agonist)‐induced endothelium‐dependent dilation in pig endocardial arteries isolated from hearts with or without LVH.
LVH was induced by aortic banding 2 months before determining endothelial function. Following euthanasia, hearts were harvested and endocardial resistance arteries were isolated and pressurised to 100 mmHg in no‐flow conditions. Vessels were preconstricted with acetylcholine (ACh) or high external K+ (40 mmol l−1 KCl). Results are expressed as mean±s.e.m.
UK‐14,304 induced a maximal dilation representing 79±6% (n=8) of the maximal diameter. NO synthase (L‐NNA, 10 μmol l−1, n=7) or guanylate cyclase (ODQ, 10 μmol l−1, n=4) inhibition reduced (P<0.05) UK‐14,304‐dependent dilation to 35±6 and 18±7%, respectively. Apamin and charybdotoxin reduced (P<0.05) to 39±8% (n=4) the dilation induced by UK‐14,304. In depolarised conditions, however, this dilation was prevented (P<0.05).
UK‐14,304‐induced dilation was reduced (P<0.05) by glibenclamide (Glib, 1 μmol l−1), a KATP channel blocker, either alone (35±10%, n=5) or in combination with L‐NNA (34±9%, n=4).
In LVH, UK‐14,304‐induced maximal dilation was markedly reduced (25±4%, P<0.05) compared to control; it was insensitive to L‐NNA (21±5%) but prevented either by the combination of L‐NNA, apamin and charybdotoxin, or by 40 mmol l−1 KCl.
Activation of endothelial α2‐adrenoreceptor induces an endothelium‐dependent dilation of pig endocardial resistance arteries. This dilation is in part dependent on NO, the release of which appears to be dependent on the activation of endothelial KATP channels. This mechanism is blunted in LVH, leading to a profound reduction in UK‐14,304‐dependent dilation.

British Journal of Pharmacology (2004) 143, 285–291. doi:10.1038/sj.bjp.0705937