bluuebunny/crossref_metadata_2025_split huggingface dataset:
The limited utility of electrocardiography variables used to predict arrhythmia in psychotropic drug overdose
Authors: Buckley Nicholas A , Chevalier Stephan , Leditschke I Anne , O'Connell Dianne L , Leitch James , Pond Susan M 
Published: August 2003

Abstract
Objective
The aim of the present study was to examine the relationship between serious arrhythmias in patients with psychotropic drug overdose and electrocardiography (ECG) findings that have been suggested previously to predict this complication.

Methods
Thirty-nine patients with serious arrhythmias (ventricular tachycardia, supraventricular tachycardia or cardiac arrest) after tricyclic antidepressant overdose or thioridazine overdose were compared with 117 controls with clinically significant overdose matched to each case for the drug ingested. These patients with psychotropic drug overdose had presented for treatment to the Department of Clinical Toxicology, Newcastle and to the Princess Alexandra Hospital, Brisbane. The heart rate, the QRS width, the QTc and QT intervals, the QT dispersion, and the R wave and R/S ratios in aVR on the initial ECGs were compared in cases and controls.

Results
The cases had taken dothiepin (16 patients), doxepin (six patients), thioridazine (five patients), amitriptyline (five patients), nortriptyline (three patients), imipramine (one patient) and a combination of dothiepin and thioridazine (three patients). In 20 of the 39 patients with arrhythmias, the arrhythmia had been a presumed ventricular tachycardia. Of the other 19 patients, 15 patients had a supraventricular tachycardia, two patients had cardiac arrests (one asystole, one without ECG monitoring) and two patients had insufficient data recorded to make classification of the arrhythmias possible. The QRS was ≥ 100 ms in 82% of cases but also in 76% of controls. QRS ≥ 160 ms had a sensitivity of only 13% and occurred in 2% of controls. QRS > 120 ms, QTc > 500 and the R/S ratio in aVR appeared to have a stronger association with the occurrence of arrhythmia: QRS > 120 ms (odds ratio [OR], 3.56; 95% confidence interval [CI], 1.46–8.68), QTc > 500 (OR, 3.07; 95% CI, 1.33–7.07), and R/S ratio in aVR > 0.7 (OR, 16; 95% CI, 3.47–74). Excluding thioridazine overdoses and performing the analysis for tricyclic antidepressant overdoses alone gave increased odds ratios for QRS > 120 ms (OR, 4.83; 95% CI, 1.73–13.5) and QTc > 500 (OR, 4.5; 95% CI, 1.56–13) but had little effect on that for the R/S ratio in aVR > 0.7 (OR, 14.5; 95% CI, 3.10–68).

Conclusion
ECG measurements were generally weakly related to the occurrence of arrhythmia and should not be used as the sole criteria for risk assessment in tricyclic antidepressant overdose. The frequently recommended practice of using either QRS ≥ 100 ms or QRS ≥ 160 ms to predict arrhythmias is not supported by our study. R/S ratio in aVR > 0.7 was most strongly related to arrhythmia but had estimated positive and negative predictive values of only 41% and 95%, respectively. The use of these specific predictors in other drug overdoses is not recommended without specific studies.
Estradiol Increases Pre- and Post-Synaptic Proteins in the CA1 Region of the Hippocampus in Female Rhesus Macaques (Macaca mulatta)
Authors: Choi Janet M. , Romeo Russell D. , Brake Wayne G. , Bethea Cynthia L. , Rosenwaks Zev , McEwen Bruce S. 
Published: August 2003

Abstract
The role of estrogen (E) in promoting learning and memory in females has been well studied in both rodent and primate models. In female rats, E increases dendritic spine number, synaptogenesis, and synaptic proteins in the CA1 region of the hippocampus, an area of the brain that mediates learning and memory. In the present study, we used radioimmunocytochemistry to examine whether E and progesterone were capable of modulating the levels of pre- and postsynaptic proteins in the CA1 region of the female nonhuman primate hippocampus. It was found that E increased syntaxin, synaptophysin (presynaptic), and spinophilin (postsynaptic) levels in the stratum oriens and radiatum of the CA1 region, whereas combined E and progesterone treatment decreased these synaptic proteins to the levels found in untreated, spayed controls. Furthermore, progesterone treatment alone significantly increased synaptophysin levels in the stratum oriens and radiatum of the CA1 region. The levels of these synaptic proteins were unaltered by hormone treatment in the dentate gyrus, suggesting that this steroid-induced plasticity is hippocampal region specific. As these synaptic proteins are important components of the synaptic apparatus and reliable markers of synaptogenesis, it appears that E-induced increases in cognitive function of higher order mammals may be mediated in part by the effect of E on hippocampal synaptogenesis and synaptic plasticity.
The Constitutively Active N111G-AT1 Receptor for Angiotensin II Maintains a High Affinity Conformation Despite Being Uncoupled from Its Cognate G Protein Gq/11α
Authors: Auger-Messier Mannix , Clement Martin , Lanctot Pascal M. , Leclerc Patrice C. , Leduc Richard , Escher Emanuel , Guillemette Gaetan 
Published: August 2003

AbstractAsn111, localized in the third transmembrane domain of the AT1 receptor for angiotensin II, plays a critical role in stabilizing the inactive conformation of the receptor. We evaluated the functional and G protein-coupling properties of mutant AT1 receptors in which Asn111 was substituted with smaller (Ala or Gly) or larger residues (Gln or Trp). All four mutants were expressed at high levels in COS-7 cells and, except for N111W-AT1, recognized 125I-Ang II with high affinities comparable to that of the wild-type AT1 receptor. In phospholipase C assays, the four mutants encompassed the entire spectrum of functional states, ranging from constitutive activity (without agonist) for N111A-AT1 and N111G-AT1 to a significant loss of activity (upon maximal stimulation) for N111Q-AT1 and a major loss of activity for N111W-AT1. In Ca2+ mobilization studies, N111W-AT1 produced a weak Ca2+ transient and, unexpectedly, N111G-AT1 also produced a Ca2+ transient that was much weaker than that of the wild-type AT1. The agonist binding affinity of N111W-AT1 was not modified in the presence of GTPγ S, suggesting that this receptor is not basally coupled to a G protein. GTPγ S did not modify the high agonist-binding affinity of N111G-AT1 but abolished the coimmunoprecipitation of Gq/11α with this constitutively active mutant receptor. These results are a direct demonstration that the N111G-AT1 receptor maintains a high affinity conformation despite being uncoupled from the G protein Gq/11.
Steroidogenic Factor-1 and The Gonadotrope-Specific Element Enhance Basal and Pituitary Adenylate Cyclase-Activating Polypeptide-Stimulated Transcription of the Human Glycoprotein Hormone α-Subunit Gene in Gonadotropes
Authors: Fowkes Robert C. , Desclozeaux Marion , Patel Mayur V. , Aylwin Simon J. B. , King Peter , Ingraham Holly A. , Burrin Jacky M. 
Published: August 2003

Abstract
In the anterior pituitary, expression of the common glycoprotein hormone α-subunit (αGSU) is mediated in part by multiple response elements residing in the distal promoter (−435 bp). One such site is the gonadotrope-specific element (GSE), which is bound by the orphan nuclear receptor steroidogenic factor-1 (SF-1) and confers pituitary adenylate cyclase-activating polypeptide (PACAP)-stimulated αGSU expression. Here we investigated the functional importance of the GSE and SF-1 phosphorylation in both basal and stimulated αGSU transcription. Mutation of the GSE reduced basal and PACAP-stimulated αGSU promoter activity in the αT3-1 gonadotrope cell line. Overexpression of wild-type SF-1, but not an S203A mutant form of SF-1, enhanced basal and PACAP-stimulated αGSU promoter activity. The effect of PACAP on αGSU promoter activity was inhibited after overexpression of MAPK phosphatase. Helix assembly of the SF-1 ligand-binding domain was stimulated by PACAP in vitro via a MAPK-dependent pathway, as determined using a mammalian two-hybrid assay. PACAP quickly activated MAPK (within 5 min) and also resulted in elevated levels of phospho-cAMP response element-binding protein and phospho-SF-1, as judged by a specific antiphospho-S203 antibody; this effect was blocked by the MAPK kinase inhibitor, UO126. Collectively, these data demonstrate that SF-1 binds to the GSE and activates both basal and PACAP-stimulated αGSU transcription, which is further increased by phosphorylation at Ser203 via MAPK. These data suggest strongly that the induction of αGSU gene expression by peptide hormone signaling is coupled directly to the posttranslational status of SF-1.
Discovery in Silico and Characterization in Vitro of Novel Genes Exclusively Expressed in the Mouse Epididymis
Authors: Penttinen Jenni , Pujianto Dwi Ari , Sipilä Petra , Huhtaniemi Ilpo , Poutanen Matti 
Published: August 2003

AbstractEpididymal proteins interact with sperm during their passage through the epididymis and thus contribute to the maturation and fertilizing capacity of the spermatozoa. In the present study we have discovered five novel epididymis-specific genes through in silico analysis of expressed sequence tags (ESTs) at the UniGene library collection. The strategy used is a powerful way to discover novel epididymis-specific genes. The full-length cDNA sequences were determined, and computational tools were used to characterize the genomic structures and to predict putative functions for the encoded proteins. In vitro analyses revealed that all five genes characterized were highly expressed in the defined areas of the epididymis, and they were not expressed at significant levels in any other tissue. Three of the genes were named on the basis of their putative functions: Spint4 (serine protease inhibitor, Kunitz type 4), and Rnase9 and Rnase10 (ribonuclease, Rnase A family 9 and 10), while for the ESTs AV381130 and AV381126 no putative functions could be predicted. The expression of Spint4, Rnase9, and AV381130 was found to be under a direct or indirect regulation by androgens, while the expression of Rnase10 is regulated by a testicular factor(s) other than androgen. None of the genes were expressed in the immature epididymis, while mRNAs were detected from d 17 onward, at the time of maturation of epididymal epithelium. However, the expression of AV381130 was not detected until d 30 after birth, indicating a close connection between gene expression and puberty.
Identification of a Novel Glucocorticoid Receptor Mutation in Budesonide-Resistant Human Bronchial Epithelial Cells
Authors: Kunz Susan , Sandoval Robert , Carlsson Peter , Carlstedt-Duke Jan , Bloom John W. , Miesfeld Roger L. 
Published: August 2003

AbstractWe developed a molecular genetic model to investigate glucocorticoid receptor (GR) signaling in human bronchial epithelial cells in response to the therapeutic steroid budesonide. Based on a genetic selection scheme using the human Chago K1 cell line and integrated copies of a glucocorticoid-responsive herpes simplex virus thymidine kinase gene and a green fluorescent protein gene, we isolated five Chago K1 variants that grew in media containing budesonide and ganciclovir. Three spontaneous budesonide-resistant subclones were found to express low levels of GR, whereas two mutants isolated from ethylmethane sulfonate-treated cultures contained normal levels of GR protein. Analysis of the GR coding sequence in the budesonide-resistant subclone Ch-BdE5 identified a novel Val to Met mutation at amino acid position 575 (GRV575M) which caused an 80% decrease in transcriptional regulatory functions with only a minimal effect on ligand binding activity. Homology modeling of the GR structure in this region of the hormone binding domain and molecular dynamic simulations suggested that the GRV575M mutation would have a decreased affinity for the LXXLL motif of p160 coactivators. To test this prediction, we performed transactivation and glutathione-S-transferase pull-down assays using the p160 coactivator glucocorticoid interacting protein 1 (GRIP1)/transcriptional intermediary factor 2 and found that GRV575M transcriptional activity was not enhanced by GRIP1 in transfected cells nor was it able to bind GRIP1 in vitro. Identification of the novel GRV575M variant in human bronchial epithelial cells using a molecular genetic selection scheme suggests that functional assays performed in relevant cell types could identify subtle defects in GR signaling that contribute to reduced steroid sensitivities in vivo.
The Lutropin/Choriogonadotropin Receptor-Induced Phosphorylation of the Extracellular Signal-Regulated Kinases in Leydig Cells Is Mediated by a Protein Kinase A-Dependent Activation of Ras
Authors: Hirakawa Takashi , Ascoli Mario 
Published: August 2003

AbstractThe pathways involved in activation of the ERK1/2 cascade in Leydig cells were examined in MA-10 cells expressing the recombinant human LH receptor (hLHR) and in primary cultures of rat Leydig cell precursors. In MA-10 cells expressing the recombinant hLHR, human choriogonadotropin-induced activation of ERK1/2 is effectively inhibited by overexpression of a cAMP phosphodiesterase (a manipulation that blunts the human choriogonadotropin-induced cAMP response), by addition of H89 (a selective inhibitor of protein kinase A), or by overexpression of the heat-stable protein kinase A inhibitor, but not by overexpression of an inactive mutant of this inhibitor. Stimulation of hLHR did not activate Rap1, but activated Ras in an H89-sensitive fashion. Addition of H89 to MA-10 cells that had been cotransfected with a guanosine triphosphatase-deficient mutant of Ras almost completely inhibited the hLHR-mediated activation of ERK1/2. We also show that 8-bromo-cAMP activates Ras and ERK1/2 in MA-10 cells and in primary cultures of rat Leydig cells precursors in an H89-sensitive fashion, whereas a cAMP analog 8-(4-chloro-phenylthio)-2′-O-methyl-cAMP (8CPT-2Me-cAMP) that is selective for cAMP-dependent guanine nucleotide exchange factor has no effect. Collectively, our results show that the hLHR-induced phosphorylation of ERK1/2 in Leydig cells is mediated by a protein kinase A-dependent activation of Ras.
Janus Kinase 2 Determinants for Growth Hormone Receptor Association, Surface Assembly, and Signaling
Authors: He Kai , Wang Xiangdong , Jiang Jing , Guan Ran , Bernstein Kenneth E. , Sayeski Peter P. , Frank Stuart J. 
Published: August 2003

AbstractGH signaling depends on functional interaction of the GH receptor (GHR) and the cytoplasmic tyrosine kinase, Janus kinase 2 (JAK2), which possesses a C-terminal kinase domain, a catalytically inactive pseudokinase domain just N-terminal to the kinase domain, and an N-terminal half shown by us and others to harbor elements for GHR association. Computational analyses indicate that JAKs contain in their N termini (∼450 residues) divergent FERM domains. FERM domains (or subdomains within them) in JAKS may be important for associations with cytokine receptors. For some cytokine receptors, JAK interaction may be required for receptor surface expression. We previously demonstrated that a JAK2 mutant devoid of its N-terminal 239 residues (JAK2-Δ1–239) did not associate with GHR and could not mediate GH- induced signaling. In this report we employ a JAK2-deficient cell line to further define N-terminal JAK2 regions required for physical and functional association with the GHR. We also examine whether JAK2 expression affects cell surface expression of the GHR. Our results suggest that FERM motifs play an important role in the interaction of GHR and JAK2. While JAK2 expression is not required for detectable surface GHR expression, an increased JAK2 level increases the fraction of GHRs that achieves resistance to deglycosylation by endoglycosidase H, suggesting that the GHR-JAK2 association may enhance either the receptor’s efficiency of maturation or its stability. Further, we report evidence for the existence of a novel GH-inducible functional interaction between JAK2 molecules that may be important in the mechanism of GH-triggered JAK2 signaling.
Numerical simulation of ship propulsion transients and full-scale validation
Authors: Campora U , Figari M 
Published: August 2003

The paper describes a mathematical model for the dynamics simulation of ship propulsion systems. The model, developed in a MATLAB-SIMULINK software environment, is structured in modular form; the various elements of the system are described as individuals blocks (hull, prime mover, gear, waterjet, etc.) and linked together to take their interactions into account. In this way it is possible to characterize the dynamic behaviour of both the single component and the whole propulsion plant. The model may be used to analyse the system response at off-design and transient conditions. In particular, the developed computer simulation code may be considered as a useful tool to facilitate the correct matching of the prime mover (diesel or gas turbine) to the propulsor (waterjet or propeller) in a wide range of operating conditions. The paper shows the application of the methodology to a cruise ferry used to validate the model results through a full-scale test campaign conducted by the authors during normal operation of the ship.
A feasibility study of the use of biodiesel in recreational boats in the United Kingdom
Authors: Zhou P L , Fet A M , Michelsen O , Fet K 
Published: August 2003

The paper presents a feasibility study for applying biodiesel in recreational boats in the United Kingdom for the purpose of rational utilization of energy resources and environmental protection. Biodiesel has been widely used to fuel diesel engines for onshore vehicles, particularly for agriculture machinery. Application of biodiesel for merchant ship propulsion on a large scale has been seen as not an option in the near future due to the lack of availability and supply chains of the fuel. However, there has been interest in the possibility of powering recreational boats with biodiesel in order to pursue marine environmental protection. The study reviews the current status of using biodiesel in recreational boats and analyses the market in the United Kingdom. Results on fuel availability for the sector, economic aspects and environmental benefits are presented.
Interfacial Nanochemistry in Liquid–Liquid Extraction Systems
Authors: Watarai Hitoshi , Tsukahara Satoshi , Nagatani Hirohisa , Ohashi Akira 
Published: August 2003

Abstract
Recent development of the interfacial nanochemistry in the solvent extraction systems is reviewed, as well as the development of measurement methods for interfacial reactions. The studies on specific reactions at the interface of various metal extraction systems have elucidated essential modes of the interfacial reactions, including the interfacial adsorption, the interfacial complexation, and the interfacial aggregation. The catalytic role of the liquid-liquid interface in the solvent extraction kinetics and the molecular recognition ability of the self-assembled metal complexes at the interface were emphasized. Spectroscopic studies on the rotational and translational dynamics of fluorescent molecules, a single molecule in some cases, at the interface are also discussed. The utility of the molecular dynamics simulations is demonstrated in the discussions of the solvent structure in the interfacial region and of the stability of surface active molecules at the interface.
Recent Advances in Phenoxy-Based Catalysts for Olefin Polymerization
Authors: Suzuki Yasuhiko , Terao Hiroshi , Fujita Terunori 
Published: August 2003

Abstract
Olefiin polymerization behavior of phenoxy-based catalysts has been discussed. Phenoxy-based olefin polymerization catalysts are capable of showing high catalytic activities. Moreover, the phenoxy-based catalysts can display unique catalytic properties and thus have offered opportunities to make polyolefinic materials that are difficult or impossible to prepare using conventional catalysts. Therefore, the phenoxy-based catalysts have opened up a new dimension in the fields of olefin polymerization catalysis and polymer synthesis.
Magnetic Studies on Quaternary Iron Sulfides BaLn2FeS5 (Ln = Ce, Pr, Nd, Sm) by Magnetic Susceptibility, Specific Heat, 57Fe Mössbauer Spectrum, and Neutron Diffraction Measurements
Authors: Wakeshima Makoto , Ino Kentaro , Hinatsu Yukio , Ishii Yoshinobu 
Published: August 2003

Abstract
Magnetic properties of quaternary iron sulfides, BaLn2FeS5 (Ln = Ce, Pr, Nd, Sm), have been investigated through magnetic susceptibility, electrical resistivity, specific heat, 57Fe Mössbauer spectrum, and powder neutron diffraction measurements. In these compounds, the Fe2+ ion exhibits an antiferromagnetic ordering at around 40 K. In the Nd and Sm compounds, these lanthanide ions show an antiferromagnetic ordering at 6.5 K for Ln = Nd and at 28 K for Ln = Sm. The reduction of the Fe2+ magnetic moment is observed below 120–170 K for all the compounds. Their electrical conductivities show an Arrhenius temperature-dependence, and the activation energies change at around the moment-reduction temperatures. The 57Fe Mössbauer spectra for BaPr2FeS5 indicate that the FeS4 tetrahedron is distorted prominently below the temperature at which both the magnetic susceptibility and the electrical resistivity show an anomaly in their temperature dependence. The neutron diffraction data collected for BaPr2FeS5 at 10 K show that it has a collinear antiferromagnetic structure and that the magnetic moments of the Fe2+ ions are parallel to the c-axis.
Anodic Behaviour of Antimony and Antimony-Tin Alloys in Alkaline Solutions
Authors: El-Sayed Abd El-Rahman , Shaker Ali Mohamed , El-Kareem Hatem Gad 
Published: August 2003

Abstract
The electrochemical and corrosive behaviour of antimony and antimony-tin alloys (Alloy No./Sb(wt. %); I/90, II/80, III/65, IV/50) as anodes in various aqueous concentrations of KOH have been investigated using galvanostatic, potentiodynamic and potentiostatic techniques. Galvanostatic potential–time curves at 4 mA cm−2 revealed that passivation of both antimony and antimony tin alloys is inhibited by an increase in KOH concentration. The opposite effect was observed with an increase in Sn content in the alloy. At high Sn content and low [OH−] a pseudo passivation potential was observed. (Abnormal early passivation occurring in the active anodic region due to the formation of tin oxides, which dissolve in alkali. Then, potential decreases.) The alloy with 50% Sn exhibited immediate passivation. The potentiodynamic curves were swept from Eo.c up to +1000 mV vs SCE. The results showed an increase in the peak current (Ip) for antimony and its alloys with increasing [OH−] on the oxide film. The first three alloys showed two anodic peaks at −780 and −450 mV, but the forth traced a third peak at −940 mV. X-ray diffraction and SEM micrographs detailed the electrochemical results and morphology of the electrode surface.