bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification and pharmacological characterization of native, functional human urotensin‐II receptors in rhabdomyosarcoma cell lines
Authors: Douglas Stephen A , Naselsky Diane , Ao Zhaohui , Disa Jyoti , Herold Christopher L , Lynch Frank , Aiyar Nambi V 
Published: July 2004

In an effort to identify endogenous, native mammalian urotensin‐II (U‐II) receptors (UT), a diverse range of human, primate and rodent cell lines (49 in total) were screened for the presence of detectable [125I]hU‐II binding sites.
UT mRNA (Northern blot, PCR) and protein (immunocytochemistry) were evident in human skeletal muscle tissue and cells.
[125I]hU‐II bound to a homogenous population of high‐affinity, saturable (Kd 67.0±11.8 pM, Bmax 9687±843 sites cell−1) receptors in the skeletal muscle (rhabdomyosarcoma) cell line SJRH30. Radiolabel was characteristically slow to dissociate (15% dissociation 90 min). A lower density of high‐affinity U‐II binding sites was also evident in the rhabdomyosarcoma cell line TE671 (1667±165 sites cell−1, Kd 74±8 pM).
Consistent with the profile recorded in human recombinant UT‐HEK293 cells, [125I]hU‐II binding to SJRH30 cells was selectively displaced by both mammalian and fish U‐II isopeptides (Kis 0.5±0.1–1.2±0.3 nM) and related analogues (hU‐II[4‐11]>[Cys5,10]Acm hU‐II; Kis 0.4±0.1 and 864±193 nM, respectively).
U‐II receptor activation was functionally coupled to phospholipase C‐mediated [Ca2+]i mobilization (EC50 6.9±2.2 nM) in SJRH30 cells.
The present study is the first to identify the presence of ‘endogenous’ U‐II receptors in SJRH30 and TE671 cells. SJRH30 cells, in particular, might prove to be of utility for (a) investigating the pharmacological properties of hU‐II and related small molecule antagonists at native human UT and (b) delineating the role of this neuropeptide in the (patho)physiological regulation of mammalian neuromuscular function.

British Journal of Pharmacology (2004) 142, 921–932. doi:10.1038/sj.bjp.0705743
Interactions between NMDA receptors and mGlu5 receptors expressed in HEK293 cells
Authors: Collett Valerie J , Collingridge Graham L 
Published: July 2004

Ca2+ imaging was used to investigate interactions between responses induced by N‐methyl‐D‐aspartate (NMDA; 15 μM) and (RS)‐3,5‐dihydroxyphenyl‐glycine (DHPG; 30 μM) in human embryonic kidney (HEK) 293 cells, transiently transfected with rat recombinant NR1a, NR2A and mGlu5a cDNA.
Responses to NMDA were reversibly depressed by DHPG from 244±14 to 194±12% of baseline. Treatment with thapsigargin (1 μM, 10 min) prevented this effect.
After thapsigargin pretreatment, repeated applications of NMDA showed a gradual rundown in amplitude over a period of several hours, and were unaffected by DHPG.
Continuous perfusion with staurosporine (0.1 μM), after thapsigargin pretreatment, converted the run‐down to a small increase in NMDA responses to 123±6 % of baseline. DHPG induced a further and sustained potentiation of NMDA responses to 174±12% of the initial baseline.
The protein tyrosine kinase (PTK) inhibitors genistein (50 μM) and 3‐(4‐chlorophenyl)1‐(1,1‐dimethylethyl)‐1H‐pyrazolo[3,4‐d]pyrimidin‐4‐amine (PP2; 1 μM) inhibited the staurosporine‐ and DHPG‐induced potentiation of NMDA responses.
The protein phosphatase (PTP) inhibitors orthovanadate (100 μM) and phenyl arsine oxide (PAO, 1 μM) facilitated the staurosporine‐evoked potentiation of NMDA responses and occluded DHPG‐induced potentiation.
In conclusion, complex interactions can be demonstrated between mGlu5 and NMDA receptors expressed in HEK293 cells. There is a negative inhibitory influence of Ca2+ release and PKC activation. Inhibition of these processes reveals a tonic, mGlu5 receptor and PTK‐dependent potentiation of NMDA receptors that can be augmented by either stimulating mGlu5 receptors or by inhibiting PTPs.

British Journal of Pharmacology (2004) 142, 991–1001. doi:10.1038/sj.bjp.0705861
Antidiabetic drug miglitol inhibits myocardial apoptosis involving decreased hydroxyl radical production and Bax expression in an ischaemia/reperfusion rabbit heart
Authors: Wang Ningyuan , Minatoguchi Shinya , Chen Xuehai , Uno Yoshihiro , Arai Masazumi , Lu ChuanJiang , Takemura Genzou , Fujiwara Takako , Fujiwara Hisayoshi 
Published: July 2004

We examined whether antidiabetic drug miglitol could reduce ischaemia/reperfusion‐induced myocardial apoptosis by attenuating production.
Japanese white rabbits were subjected to 30‐min coronary occlusion followed by 4‐h reperfusion with miglitol (10 mg kg−1, i.v., n=20) or saline (n=20). The infarct area was determined by myoglobin staining, and the infarct size (IS) was expressed as a percentage of the area at risk. DNA fragmentation was assessed by TUNEL method and DNA ladder formation. The expression of Bcl‐XL and Bax was detected by immunohistochemical analysis and Western blot analysis. Myocardial interstitial 2,5‐DHBA levels, an indicator of hydroxyl radicals, were measured during 30‐min ischaemia and 30‐min reperfusion in the absence (n=10) or presence of miglitol (10 mg kg−1, i.v., n=10) using a microdialysis technique.
The IS was significantly reduced in the miglitol group (22.4±3.4%, n=10) compared to the control group (52.8±3.5%, n=10). Miglitol significantly decreased the 2,5‐DHBA level during ischaemia and reperfusion and suppressed the incidence of TUNEL‐positive myocytes in the ischaemic region (from 10.7±3.4 to 4.1±3.0%) and the intensity of DNA ladder formation. Miglitol significantly decreased the incidence of Bax‐positive myocytes in the ischaemic region (7.4±1.7 vs 13.7±1.9% of the control) and significantly attenuated the upregulation of Bax protein in the ischaemic regions (from 179±17 to 90±12% of sham). There was no difference in the expression of Bcl‐XL between the two groups.
These data suggest that miglitol reduces myocardial apoptosis by attenuating production of hydroxyl radicals and suppressing the upregulation of the expression of Bax protein.

British Journal of Pharmacology (2004) 142, 983–990. doi:10.1038/sj.bjp.0705863
Regulation of metalloproteinases and NF‐κB activation in rabbit synovial fibroblasts via E prostaglandins and Erk: contrasting effects of nabumetone and 6MNA
Authors: Pillinger Michael H , Dinsell Victoria , Apsel Beth , Tolani Sonia N , Marjanovic Nada , Chan Edwin S L , Gomez Paul , Clancy Robert , Chang Lih‐Fan , Abramson Steven B 
Published: July 2004

Nabumetone is a prodrug that is converted in vivo into 6‐methoxy‐2‐naphthylacetic acid (6MNA), a cyclooxygenase inhibitor with anti‐inflammatory properties. We tested the effects of nabumetone and 6MNA on the inflammatory responses of synovial fibroblasts (SFs).
Brief exposures to 6MNA (50–150 μM) had no effect on IL‐1β/TNF‐α (each 20 ng ml−1)‐stimulated Erk activation. Longer exposures depleted prostaglandin E1 (PGE1) as much as 70%, and stimulated Erk as much as 300%. Nabumetone (150 μM) inhibited Erk activation by 60–80%.
6MNA (50–150 μM) stimulated (∼200%) and nabumetone (150 μM) inhibited (∼50%) matrix metalloproteinase (MMP)‐1, but not MMP‐13 secretion from SFs. 6MNA stimulation of MMP‐1 secretion was inhibited ∼30% by PGE1 (1 μM) and ∼80% by the Erk pathway inhibitor UO126 (10 μM), confirming that PGE depletion and Erk activation mediate MMP‐1 secretion by 6MNA.
Consistent with its role as an Erk inhibitor, nabumetone (150 μM) abrogated 6MNA enhancement of MMP‐1 secretion.
UO126 (10 μM) and nabumetone (150 μM) inhibited (∼70 and 40%, respectively), but 6MNA (150 μM) enhanced (∼40%), NF‐κB activation.
Our data indicate that 6MNA shares with other COX inhibitors several proinflammatory effects on synovial fibroblasts. In contrast, nabumetone demonstrates anti‐inflammatory and potentially arthroprotective effects that have not been previously appreciated.

British Journal of Pharmacology (2004) 142, 973–982. doi:10.1038/sj.bjp.0705864
Possible mechanism of action of the histone deacetylase inhibitors for the induction of differentiation of HL‐60 clone 15 cells into eosinophils
Authors: Ishihara Kenji , Hong JangJa , Zee OkPyo , Ohuchi Kazuo 
Published: July 2004

We have examined the effect of the histone deacetylase inhibitors apicidin, trichostatin A (TSA) and n‐butyrate on the histone acetylation and the differentiation of human eosinophilic leukemia HL‐60 clone 15 cells into eosinophils.
Viability of the cells incubated with apicidin (100 nM), TSA (30 nM) or n‐butyrate (500 μM) did not change significantly, but higher concentrations of apicidin (300 nM) or TSA (100 nM) decreased the viability when examined at day 1.
Apicidin (100 nM) as well as n‐butyrate (500 μM) induced continuous acetylations of histone H4 and lysine14 residue on histone H3, while TSA (30 nM) induced transient acetylations.
After 6 days incubation, eosinophilic cells stained by Luxol‐fast‐blue were generated by apicidin (100 nM) and n‐butyrate (500 μM) but not by TSA (30 nM). Other markers for differentiation into eosinophils such as changes in intracellular structure, and expressions of integrin β7 and major basic protein, and the inhibition of cell proliferation were also induced by apicidin and n‐butyrate but not by TSA.
Continuous acetylation of histone H4 achieved by repeated treatment with TSA (30 nM) at an interval of 12 h for more than three times induced such changes when examined on day 6. In addition, the induction was impaired by shortening the period of incubation with apicidin (100 nM) or n‐butyrate (500 μM).
CCAAT/enhancer binding protein was continuously activated by apicidin (100 nM) and n‐butyrate (500 μM), but was transiently activated by TSA (30 nM).
These findings suggest that the continuous acetylation of histones H3 and H4 is necessary for the differentiation of HL‐60 clone 15 cells into eosinophils.

British Journal of Pharmacology (2004) 142, 1020–1030. doi:10.1038/sj.bjp.0705869
Inhibition of c‐Jun N‐terminal kinase decreases cardiomyocyte apoptosis and infarct size after myocardial ischemia and reperfusion in anaesthetized rats
Authors: Ferrandi Chiara , Ballerio Rossana , Gaillard Pascale , Giachetti Claudio , Carboni Sonia , Vitte Pierre‐Alain , Gotteland Jean‐Pierre , Cirillo Rocco 
Published: July 2004

Myocardial ischemia/reperfusion is associated with inflammation, apoptosis and necrosis. During this process, c‐jun N‐terminal kinase is activated in cardiac myocytes resulting in apoptosis.
This study investigates the effects of AS601245, a nonpeptide ATP competitive JNK inhibitor, on infarct size caused by myocardial ischemia/reperfusion in anaesthetized rats. The left descending coronary artery of anaesthetized rats was occluded for 30 min and then reperfused for 3 h. AS601245 was administered 5 min before the end of the ischemia period as an i.v. bolus (1.5, 4.5 or 15 mg kg−1 i.v.) followed by continuous i.v. infusion (18, 55 and 183 μg kg−1 min−1, respectively) during reperfusion. Controls received saline only. 3‐Aminobenzamide, a poly(ADP‐ribose) polymerase inhibitor, was used as reference compound at 10 mg kg−1 i.v. bolus plus 0.17 mg kg−1 min−1 continuous infusion.
AS601245 significantly reduced infarct size at 4.5 mg kg−1 (−44%; P<0.001) and 15 mg kg−1 i.v. (−40.3%; P<0.001) similarly to 3‐aminobenzamide (−44.2%; P<0.001). This protective effect was obtained without affecting hemodinamics or reducing ST‐segment displacement.
The beneficial effects on infarct size correlated well with the reduction of c‐jun phosphorylation (−85%; P<0.001 versus control) and of TUNEL‐positive cells (−82.1%; P<0.001) in post‐ischemic cardiomyocytes. No change in the phosphorylation state of p38 MAPK and ERK in post‐ischemic heart was observed in the presence of AS601245 in comparison to the vehicle‐treated group.
These results demonstrate that blocking the JNK pathway may represent a novel therapeutic approach for treating myocardial ischemia/reperfusion‐induced cardiomyocyte death.

British Journal of Pharmacology (2004) 142, 953–960. doi:10.1038/sj.bjp.0705873
Central effects of the cannabinoid receptor agonist WIN55212‐2 on respiratory and cardiovascular regulation in anaesthetised rats
Authors: Pfitzer Torsten , Niederhoffer Nathalie , Szabo Bela 
Published: July 2004

The primary aim was to study the central respiratory effects of cannabinoids (CB). To this end, the cannabinoid receptor agonist WIN55212‐2 was injected into the cisterna magna of urethane‐anaesthetised rats and changes in respiratory parameters were observed. The secondary aim was to observe the centrally elicited cardiovascular actions of WIN55212‐2. Involvement of opioid mechanisms in the central effects of WIN55212‐2 was also studied.
Intracisternal (i.c.) application of WIN55212‐2 (1, 3, 10 and 30 μg kg−1) dose‐dependently decreased the respiratory rate and minute volume. Tidal volume was slightly increased, whereas peak inspiratory flow remained unchanged. In addition, WIN55212‐2 increased mean arterial pressure and the plasma noradrenaline concentration and decreased heart rate. I.c. injection of WIN55212‐3 (1, 3, 10 and 30 μg kg−1), an enantiomer of WIN55212‐2 lacking affinity for cannabinoid receptors, elicited no effects. All effects of WIN55212‐2 were prevented by the CB1 receptor antagonist SR141716 (2 mg kg−1 i.v.).
I.c. administration of the opioid receptor agonist DAMGO (0.1, 0.3, 1 and 3 μg kg−1) markedly lowered the respiratory rate, tidal volume, minute volume and peak inspiratory flow. These effects were attenuated by the opioid receptor antagonist naloxone (0.2 mg kg−1 i.v.). In contrast, naloxone did not affect the respiratory and cardiovascular effects of i.c. administered WIN55212‐2.
Our results show that activation of CB1 cannabinoid receptors in the brain stem depresses respiration and enhances sympathetic tone and cardiac vagal tone. Opioid mechanisms are not involved in these central cannabinoid effects.

British Journal of Pharmacology (2004) 142, 943–952. doi:10.1038/sj.bjp.0705874
Peripheral GABAB agonists stimulate gastric acid secretion in mice
Authors: Piqueras Laura , Martinez Vicente 
Published: July 2004

We characterized the effects of intravenous GABA and preferential GABAA (muscimol), GABAB (R‐baclofen and SKF‐97541) and GABAC agonists (imidazole‐4‐acetic acid) on gastric acid secretion in urethane‐anesthetized mice implanted with a gastric cannula, and determined the role of vagal cholinergic mechanisms, and gastrin and somatostatin by using peptide immunoneutralization, the SSTR2 antgonist, PRL‐2903, and SSTR2 knockout mice.
The selective GABAB agonists R‐baclofen (0.1–3 mg kg−1, i.v.) and SKF‐97541 (0.01–0.3 mg kg−1, i.v.) induced a dose‐related stimulation of gastric acid secretion. SKF‐97541 was about 10 times more potent than R‐baclofen stimulating gastric acid secretion. Neither GABA (0.1–100 mg kg−1, i.v.) nor muscimol (0.1–3 mg kg−1) nor imidazole‐4‐acetic acid (0.1–10 mg kg−1) affected basal gastric acid secretion.
Stimulatory effects of SKF‐97541 (0.1 mg kg−1, i.v.) were blocked by the selective GABAB antagonist, 2‐hydroxysaclofen, cholinergic blockade with atropine, subdiaphragmatic vagotomy or gastrin immunoneutralization.
Somatostatin immunoneutralization or SSTR2 blockade with PRL‐2903 enhanced the secretory response to SKF‐97541 (0.1 mg kg−1, i.v.) by 78 and 105%, respectively.
In SSTR2 knockout mice, SKF‐97541 (0.1 mg kg−1, i.v.) increased basal gastric acid secretion by 48%. Neither GABA nor muscimol nor imidazole‐4‐acetic acid modified basal gastric acid secretion in SSTR2 knockout mice.
These results indicate that, in mice, stimulation of GABAB receptors increases gastric acid secretion through vagal‐ and gastrin‐dependent mechanisms. Somatostatin implication might be secondary to the release of gastrin and the increase in gastric luminal acidity.

British Journal of Pharmacology (2004) 142, 1038–1048. doi:10.1038/sj.bjp.0705876
Ligands of the peroxisome proliferator‐activated receptor‐γ and heart failure
Authors: Thiemermann Christoph 
Published: July 2004

This Commentary originally appeared in the British Journal of Pharmacology in January 2004 (Br J Pharmacol 141 (1), 1–3). That version, regrettably, contained a number of errors and the corrected version is printed here, as an Erratum.Peroxisome proliferator‐activated receptors (PPARs) are members of the nuclear hormone receptor superfamily of ligand‐activated transcription factors that are related to retinoid, steroid and thyroid hormone receptors. The PPAR subfamily comprises of three members, PPAR‐α, PPAR‐β and PPAR‐γ. There is good evidence that ligands of PPAR‐γ, including certain thiazolinediones, reduce myocardial tissue injury and infarct size. The use of PPAR‐γ agonists in the treatment of heart failure is, however, controversial.British Journal of Pharmacology (2004) 142, 1049–1051. doi:10.1038/sj.bjp.0705898
Cyclooxygenasen in der Haut
Authors: Müller‐Decker Karin 
Published: July 2004

ZusammenfassungCyclooxygenasen (COX)‐1 und COX‐2 sind die Schrittmacherenzyme in der Prostaglandinbiosynthese und repräsentieren die molekularen Targets für nicht‐steroidale Entzündungshemmer. In gesunden Geweben von Erwachsenen wird in der Regel COX‐1, nicht jedoch COX‐2 exprimiert. Nach Schnittverletzung der Haut oder Auslösung einer akuten irritativen Kontaktdermatitis wird COX‐2 transient in der Epidermis gebildet. Insbesondere die Entwicklung von UV‐induziertem Erythem und Ödem aber auch von Hauttumoren werden maßgeblich durch die Aktivität von COX‐2 beeinflußt. Plattenepithelkarzinome und aktinische Keratosen der Haut gelten als ein prominentes Beispiel von epithelialen Tumoren, für die eine permanente Überexpression der COX‐2 im Tumorparenchym, im entzündlichen Tumorinfiltrat und in Tumorgefäßen ein hervorstechendes Merkmal ist. Mehrstufenkarzinogeneseversuchen in der Maushaut und Experimenten mit transgenen Mäusen zufolge besteht ein kausaler Zusammenhang zwischen aberranter COX‐2‐Expression und Aktivität im Epithel und der Tumorpromotion und ‐progression. Die transgene Überexpression der COX‐2 verursacht nämlich einen autopromovierten Hautphänotyp, d. h. das Enzym sensibilisiert das Gewebe drastisch für die Entwicklung von Plattenepithelkarzinomen. Umgekehrt führt die genetische Ausschaltung der COX‐2, aber auch der COX‐1, in der Maushaut zu einer reduzierten Tumorlast. Die Störung der terminalen Differenzierung der Epidermis scheint ein Hauptmechanismus zu sein, wie COX‐2 zur epidermalen Tumorbildung beiträgt. Aufgrund dieser Erkenntnisse werden COX‐2‐selektive Inhibitoren als vielversprechende Substanzen zur Prävention und Therapie von Hautkrebs eingestuft.
DNA structure constraint is probably a fundamental factor inducing CpG deficiency in bacteria
Authors: Wang Yong , Leung Frederick C. C. 
Published: July 2004

Abstract
Motivation: It has been speculated that CpG dinucleotide deficiency in genomes is a consequence of DNA methylation. However, this hypothesis does not adequately explain CpG deficiency in bacteria. The hypothesis based on DNA structure constraint as an alternative explanation was therefore examined.
Results: By comparing real bacterial genomes and Markov artificial genomes in the second order, we found that the core structure of a restricted pattern, the TTCGAA pattern, was under represented in low GC content bacterial genomes regardless of CpG dinucleotide level. This is in contrast to the AACGTT pattern, indicating that the counterselection is context-dependent. Further study discovered nine underrepresented patterns that were supposed to be capable of inducing DNA structure constraint. In summary, most of them are in TTCGNA and TTCGAN patterns in both DNA strands. An explanation is also proposed for the strong correlation between GC content and CpG deficiency. The result of random sequence simulation showed that the occurrences of these patterns were correlated with GC content, as well as the percentage of CpG dinucleotides being trapped in these patterns. Finally, we suggest that the degree of counter-selection against these restricted patterns could be influenced by global GC content of a genome.
Importing MAGE-ML format microarray data into BioConductor
Authors: Durinck Steffen , Allemeersch Joke , Carey Vincent J. , Moreau Yves , De Moor Bart 
Published: July 2004

Abstract
The microarray gene expression markup language (MAGE-ML) is a widely used XML (eXtensible Markup Language) standard for describing and exchanging information about microarray experiments. It can describe microarray designs, microarray experiment designs, gene expression data and data analysis results. We describe RMAGEML, a new Bioconductor package that provides a link between cDNA microarray data stored in MAGE-ML format and the Bioconductor framework for preprocessing, visualization and analysis of microarray experiments.
Availability: http://www.bioconductor.org. Open Source
PLPMDB: Pyridoxal-5′-phosphate dependent enzymes mutants database
Authors: Di Giovine Paolo 
Published: July 2004

Abstract
Summary: The searchable mutant database PLPMDB has been developed to provide rapid and simple access to relevant mutant information on pyridoxal-5′-phosphate dependent enzymes. All data have been extracted from publications and publicly available databases, then organized in a relational database to enable searching via a web-based search form. The current version of PLPMDB contains 688 mutants described in 220 research papers. The database is a useful tool for planning mutant experiments and for interpretation of information from such experiments.
Availability: PLPMDB is freely accessible from http://www.studiofmp.com/plpmdb/index.htm
VisRD—visual recombination detection
Authors: Forslund Kristoffer , Huson Daniel H. , Moulton Vincent 
Published: July 2004

Abstract
Summary: VisRD, a program for visual recombination detection in a sequence alignment is presented. VisRD is written in Java and is designed to complement the multi-purpose phylogenetic software package SplitsTree4.
Availability: The software is freely available from http://www.lcb.uu.se/~vmoulton/software/visrd/
DNMAD: web-based diagnosis and normalization for microarray data
Authors: Vaquerizas Juan M. , Dopazo Joaquín , Díaz-Uriarte Ramón 
Published: July 2004

Abstract
Summary: We present a web server for Diagnosis and Normalization of MicroArray Data (DNMAD). DNMAD includes several common data transformations such as spatial and global robust local regression or multiple slide normalization, and allows for detecting several kinds of errors that result from the manipulation and the image analysis of the arrays. This tool offers a user-friendly interface, and is completely integrated within the Gene Expression Pattern Analysis Suite (GEPAS).
Availability: The tool is accessible on-line at http://dnmad.bioinfo.cnio.es
Conserved network motifs allow protein–protein interaction prediction
Authors: Albert István , Albert Réka 
Published: July 2004

Abstract
Motivation: High-throughput protein interaction detection methods are strongly affected by false positive and false negative results. Focused experiments are needed to complement the large-scale methods by validating previously detected interactions but it is often difficult to decide which proteins to probe as interaction partners. Developing reliable computational methods assisting this decision process is a pressing need in bioinformatics.
Results: We show that we can use the conserved properties of the protein network to identify and validate interaction candidates. We apply a number of machine learning algorithms to the protein connectivity information and achieve a surprisingly good overall performance in predicting interacting proteins. Using a ‘leave-one-out’ approach we find average success rates between 20 and 40% for predicting the correct interaction partner of a protein. We demonstrate that the success of these methods is based on the presence of conserved interaction motifs within the network.
Availability: A reference implementation and a table with candidate interacting partners for each yeast protein are available at http://www.protsuggest.org.