bluuebunny/crossref_metadata_2025 huggingface dataset:
Involvement of the sigma1(σ1) receptor in the anti‐amnesic, but not antidepressant‐like, effects of the aminotetrahydrofuran derivative ANAVEX1‐41
Authors: Espallergues J , Lapalud P , Christopoulos A , Avlani V A , Sexton P M , Vamvakides A , Maurice T
Published: July 2007

Background and purpose:

Tetrahydro‐N, N‐dimethyl‐5, 5‐diphenyl‐3‐furanmethanamine hydrochloride (ANAVEX1‐41) is a potent muscarinic and sigma1(σ1) receptor ligand. Theσ1receptor modulates glutamatergic and cholinergic responses in the forebrain and selective agonists are potent anti‐amnesic and antidepressant drugs. We have here analysed theσ1component in the behavioural effects of ANAVEX1‐41.

Experimental approach:

Binding of ANAVEX1‐41 to muscarinic andσ1receptors were measured using cell membranes. Behavioural effects of ANAVEX1‐41 were tested in mice using memory (spontaneous alternation, passive avoidance, water‐maze) and antidepressant‐like activity (forced swimming) procedures.

Key results:

In vitro, ANAVEX1‐41 was a potent muscarinic (M1>M3, M4>M2with Kiranging from 18 to 114 nM) and selectiveσ1ligand (σ1, Ki=44 nM;σ2, Ki=4 μM). In mice, ANAVEX1‐41 failed to affect learning when injected alone (0.03–1 mg kg−1), but attenuated scopolamine‐induced amnesia with a bell‐shaped dose response (maximum at 0.1 mg kg−1). Theσ1antagonist BD1047 blocked the anti‐amnesic effect of ANAVEX1‐41 on both short‐ and long‐term memories. Pretreatment with aσ1receptor‐directed antisense oligodeoxynucleotide prevented effects of ANAVEX1‐41 only in the passive avoidance procedure, measuring long‐term memory. ANAVEX1‐41 reduced behavioural despair at 30 and 60 mg kg−1, without involving theσ1receptor, as it was not blocked by BD1047 or the antisense oligodeoxynucleotide.

Conclusions and implications:

ANAVEX1‐41 is a potent anti‐amnesic drug, acting through muscarinic andσ1receptors. The latter component may be involved in the enhancing effects of the drug on long‐term memory processes.

British Journal of Pharmacology(2007)152, 267–279; doi:10.1038/sj.bjp.0707386
Imbalanced synthesis of cyclooxygenase‐derived thromboxane A2 and prostacyclin compromises vasomotor function of the thoracic aorta in Marfan syndrome
Authors: Chung A W Y , Yang H H C , van Breemen C
Published: July 2007

Background and purpose:

Thoracic aortic dissection is a life‐threatening complication of Marfan syndrome, a connective tissue disorder caused by mutations in the gene encoding fibrillin‐1. We have demonstrated that nitric oxide‐mediated endothelial‐dependent relaxation is impaired in the thoracic aorta in Marfan syndrome. In the present study, we determined whether the cyclooxygenase (COX)‐pathway is involved in the compromised aortic vasomotor function.

Experimental approach:

Thoracic aortae from mice at 3, 6 and 9 months of age, heterozygous for the Fbn1 allele encoding a cysteine substitution (Fbn1
C1039G/+, ‘Marfan’, n=35), were compared with those from age‐matched controls (n=35).

Key results:

Isometric force measurement revealed that preincubation with indomethacin, a non‐specific COX inhibitor, but not valeryl salicylate, a specific COX‐1 inhibitor, improved the phenylephrine‐induced contractions (at 6 months, EC50 and Emax were increased 4.5‐fold and by 45%, respectively) in Marfan aortae. Sensitivity to acetylcholine‐induced relaxation was improved 10‐fold. Blockade of the thromboxane‐endoperoxide receptor by SQ‐29548 did not affect phenylephrine‐mediated contractions in Marfan aortae, although they did respond to the thromboxane analogue, U46619. From 6 months on, phenylephrine‐induced secretion of prostacyclin and thromboxane A2 in Marfan aortae was 200% and 40%, respectively, of those in controls. Reduced COX‐1 expression was detected in Marfan aortae at 3 and 9 months, whilst COX‐2 expression was increased from 3 months on.

Conclusions and implications:

The compromised vasomotor function in Marfan thoracic aortae is associated with an imbalanced synthesis of thromboxane A2 and prostacyclin resulting from the differential protein expression of COX‐1 and COX‐2.

British Journal of Pharmacology (2007) 152, 305–312; doi:10.1038/sj.bjp.0707391; published online 16 July 2007
Mechanisms of endothelin‐1‐induced decrease in contractility in adult mouse ventricular myocytes
Authors: Nishimaru K , Miura Y , Endoh M
Published: July 2007

Background and purpose:

The potent vasoconstrictor polypeptide endothelin‐1 (ET‐1) plays an important pathophysiological role in progression of cardiovascular diseases and elicits prominent effects on myocardial contractility. Although ET‐1 produces a positive inotropy in cardiac muscle of most mammalian species, it induces a sustained negative inotropy in mice. This study was performed to gain an insight into the cellular mechanisms underlying the negative inotropy in adult mouse ventricular myocytes.

Experimental approach:

Cell shortening and Ca2+ transients were simultaneously recorded from isolated mouse ventricular myocytes loaded with the Ca2+‐sensitive fluorescent dye indo‐1.

Key results:

ET‐1 decreased cell shortening in a concentration‐dependent manner (pD2 value of 10.1). The ET‐1‐induced decrease in cell shortening was associated with a decrease in Ca2+ transients. In addition, the Ca2+ transient/cell‐shortening relationship was shifted to the right by ET‐1, indicating decreased myofilament Ca2+ sensitivity. The instantaneous relationship of the rising phase of the Ca2+ transient and cell shortening was shifted to the right by ET‐1. Decreased Ca2+ transients and cell shortening induced by ET‐1 were markedly attenuated by the specific Na+/Ca2+ exchange inhibitor SEA0400.

Conclusions and implications:

ET‐1‐induced negative inotropy in mouse ventricular myocytes was mediated by decreased Ca2+ transients and myofilament Ca2+ sensitivity. These data are entirely consistent with the involvement of increased Ca2+ extrusion via the Na+/Ca2+ exchanger in the ET‐1‐mediated decrease in Ca2+ transients. Decreased Ca2+ sensitivity may be due to retardation of cell shortening in response to a rise in Ca2+ transients.

British Journal of Pharmacology (2007) 152, 456–463; doi:10.1038/sj.bjp.0707392; published online 16 July 2007
Building a better aspirin: gaseous solutions to a century‐old problem
Authors: Wallace J L
Published: July 2007

The gastrointestinal adverse effects of nonsteroidal anti‐inflammatory drugs (NSAIDs) have been recognized since shortly after the introduction of aspirin to the marketplace over a century ago. However, the underlying pathogenesis of NSAID‐induced gastropathy remains incompletely understood. Advances in understanding some of the factors that contribute to the mucosal injury have provided clues for the development of safer NSAIDs. The inhibitory effects of nitric oxide (NO) on NSAID‐induced leukocyte adherence were exploited in the development of NO‐releasing NSAIDs. As well as eliciting less gastrointestinal damage than conventional NSAIDs, these drugs do not elevate blood pressure and show anti‐inflammatory effects, additional to those of the parent drugs. Modification of other drugs in a similar manner (i.e., NO‐releasing derivatives) has similarly resulted in more effective drugs. More recently, hydrogen sulphide‐releasing derivatives of NSAIDs and of other drugs, have been developed, based on the observed ability of H2S to reduce inflammation and pain in experimental models. H2S‐releasing NSAIDs produce negligible gastric damage and exhibit enhanced anti‐inflammatory potency as compared to the parent drugs. The NO‐NSAIDs and H2S‐releasing NSAIDs represent examples of new anti‐inflammatory drugs with greatly reduced toxicity and improved therapeutic activity, both created through the concept of exploiting the beneficial effects of endogenous gaseous mediators.

British Journal of Pharmacology(2007)152, 421–428; doi:10.1038/sj.bjp.0707396; published online 16 July 2007
Cannabinoids inhibit noradrenergic and purinergic sympathetic cotransmission in the rat isolated mesenteric arterial bed
Authors: Pakdeechote P , Dunn W R , Ralevic V
Published: July 2007

Background and purpose:

Noradrenaline and ATP are sympathetic co‐transmitters. In the rat perfused mesenteric bed cannabinoids have been shown to modify the overall response to sympathetic nerve stimulation. This study has assessed whether cannabinoid receptor activation modulates differentially the noradrenergic and purinergic components of sympathetic vasoconstriction.

Experimental approach:

Rat mesenteric beds were perfused with physiological salt solution and the effects of cannabinoids on responses to nerve stimulation, or exogenous noradrenaline orα,β‐methylene ATP (α,β‐meATP; P2X receptor agonist) were determined after raising tone with U46619. The effects of cannabinoids on the noradrenaline and ATP components of sympathetic neurotransmission were assessed using theα1‐adrenoceptor antagonist, prazosin, or after P2X receptor desensitization withα,β‐meATP.

Key results:

Anandamide, WIN 55,212‐2 and CP55,940 attenuated sympathetic neurogenic vasoconstrictor responses. The inhibitory actions of anandamide and WIN 55,212‐2 were blocked by LY320135, a CB1receptor antagonist, but not by SR144528, a CB2receptor antagonist. The inhibitory actions of CP55,940 were unaffected by LY320135 and SR144528. WIN 55,212‐3, the inactive S(−) enantiomer of WIN 55,212‐2, had no effect on sympathetic neurogenic responses. None of the cannabinoids affected contractile responses to exogenous noradrenaline orα,β‐meATP. Anandamide and WIN 55,212‐2 inhibited both the noradrenaline and ATP components of the sympathetic neurogenic contractile responses, with effects on the ATP component being most marked.

Conclusions and implications:

These results indicate that prejunctional CB1‐like receptors mediate the sympathoinhibitory action of anandamide and WIN 55,212‐2, but not CP55,940, in the rat mesenteric bed. Cannabinoids inhibit both the noradrenergic and purinergic components of sympathetic neurotransmission.

British Journal of Pharmacology(2007)152, 725–733; doi:10.1038/sj.bjp.0707397; published online 16 July 2007
Plastidic trnFUUC Pseudogenes in North American Genus Boechera (Brassicaceae): Mechanistic Aspects of Evolution
Authors: Dobeš C. , Kiefer C. , Kiefer M. , Koch M. A.
Published: July 2007

Abstract: The origin and maintenance of a plastidic tandem repeat next to the trnFUUC gene were analyzed in the genus Boechera in a phylogenetic context and were compared to published analogous examples that emerged in parallel in the Asteraceae and Juncaceae, respectively. Although we identified some features common to these taxonomic groups with respect to structure and origin of the region, obvious differences were encountered, which argue against a specific mechanism or evolutionary principle underlying the parallel origin and maintenance of the trnF‐tandem repeats in those families. In contrast to the situation in the Asteraceae, no reciprocal recombinant repeat types have been observed in the Brassicaceae. Forty copy types, classified into three groups, were isolated from 103 chloroplast haplotypes of Boechera and it was demonstrated that they are composed of four subregions of various origins. We discuss various mutation mechanisms such as DNA replication slippage, and inter‐ and intrachromosomal recombination which were reported to mediate variation in copy numbers and other types of observed sequence length polymorphism. It is shown that the observed molecular structure of the tandem repeat region did not fully fit the particular patterns expected under a scenario of evolution including any of the known mechanisms. Nevertheless, it appeared that intermolecular unequal crossing‐over is most likely the driving force in the evolution of this tandem repeat. However, it remains to be explained, why no reciprocal recombinant copy types have been observed. The reconstructed phylogenetic relationships among copies reflected different evolutionary scenarios as follows: (1) A single and ancient origin of copies pre‐dates the radiation of Boechera. (2) Parallel expansion and shortening of the tandem repeat within different Boechera lineages. (3) Conservation of the first copy, as it was the only one present in all chloroplast haplotypes.
Genetic Structure of Araucaria angustifolia (Araucariaceae) Populations in Brazil: Implications for the in situ Conservation of Genetic Resources
Authors: Stefenon V. M. , Gailing O. , Finkeldey R.
Published: July 2007

Abstract: The distribution of the genetic variation within and among natural populations of A. angustifolia growing in different regions in Brazil was assessed at microsatellite and AFLP markers. Both markers revealed high gene diversity (H= 0.65; AR= 9.1 for microsatellites and H= 0.27; P= 77.8 % for AFLPs), moderate overall differentiation (RST= 0.13 for microsatellites and FST= 0.10 for AFLPs), but high divergence of the northernmost, geographically isolated population. In a Bayesian analysis, microsatellite data suggested population structure at two levels: at K= 2 and at K= 3 in agreement to the geographical distribution of populations. This result was confirmed by the UPGMA dendrogram based on microsatellite data (bootstrap support > 95 %). Non‐hierarchical AMOVA revealed high variation among populations from different a posteriori defined geographical groups. The genetic distance between sample locations increased with geographical distance for microsatellites (r= 0.62; p= 0.003) and AFLPs (r= 0.32; p= 0.09). This pattern of population differentiation may be correlated with population history such as geographical isolation and postglacial colonization of highlands. Implications of the population genetic structure for the conservation of genetic resources are discussed.
Pair interaction potentials with explicit polarization for molecular dynamics simulations of La3+ in bulk water
Authors: Duvail Magali , Souaille Marc , Spezia Riccardo , Cartailler Thierry , Vitorge Pierre
Published: July 2007

Pair interaction potentials (IPs) were defined to describe the La3+–OH2 interaction for simulating the La3+ hydration in aqueous solution. La3+–OH2 IPs are taken from the literature or parametrized essentially to reproduce ab initio calculations at the second-order Møller-Plesset level of theory on La(H2O)83+. The IPs are compared and used with molecular dynamics (MD) including explicit polarization, periodic boundary conditions of La(H2O)2163+ boxes, and TIP3P water model modified to include explicit polarization. As expected, explicit polarization is crucial for obtaining both correct La–O distances (rLa–O) and La3+ coordination number (CN). Including polarization also modifies hydration structure up to the second hydration shell and decreases the number of water exchanges between the La3+ first and second hydration shells. rLa–O(1)=2.52Å and CN(1)=9.02 are obtained here for our best potential. These values are in good agreement with experimental data. The tested La–O IPs appear to essentially account for the La–O short distance repulsion. As a consequence, we propose that most of the multibody effects are correctly described by the explicit polarization contributions even in the first La3+ hydration shell. The MD simulation results are slightly improved by adding a—typically negative 1∕r6—slightly attractive contribution to the—typically exponential–repulsive term of the La–O IP. Mean residence times are obtained from MD simulations for a water molecule in the first (1082ps) and second (7.6ps) hydration shells of La3+. The corresponding water exchange is a concerted mechanism: a water molecule leaving La(H2O)93+ in the opposite direction to the incoming water molecule. La(H2O)93+ has a slightly distorded “6+3” tricapped trigonal prism D3h structure, and the weakest bonding is in the medium triangle, where water exchanges take place.
Monitoring ultrashort pulses by transverse frequency doubling of counterpropagating pulses in random media
Authors: Fischer Robert , Neshev Dragomir N. , Saltiel Solomon M. , Sukhorukov Andrey A. , Krolikowski Wieslaw , Kivshar Yuri S.
Published: July 2007

The authors study experimentally the transverse second-harmonic generation of counterpropagating pulses by a quasi-phase-matching in a medium with a random ferroelectric domain structure. The authors show that this parametric process results in a direct realization of the cross correlation of two optical signals and, therefore, it can be employed for direct characterizations of ultrashort pulses including their temporal structure and pulse front tilt.
Single-photon experiments at telecommunication wavelengths using nanowire superconducting detectors
Authors: Zinoni C. , Alloing B. , Li L. H. , Marsili F. , Fiore A. , Lunghi L. , Gerardino A. , Vakhtomin Yu. B. , Smirnov K. V. , Gol’tsman G. N.
Published: July 2007

The authors report fiber-coupled superconducting single-photon detectors with specifications that exceed those of avalanche photodiodes, operating at telecommunication wavelength, in sensitivity, temporal resolution, and repetition frequency. The improved performance is demonstrated by measuring the intensity correlation function g(2)(τ) of single-photon states at 1300nm produced by single semiconductor quantum dots.
Three dimensional mapping of thermal and tunneling electron emission from InAs∕GaAs quantum dots
Authors: Engström O. , Kaniewska M. , Jung W. , Kaczmarczyk M.
Published: July 2007

Using a three dimensional representation of data from deep level transient spectroscopy (DLTS) in a parameter space given by temperature, applied sample voltage, and DLTS signal, a method is demonstrated for interpreting a complex set of basic properties of quantum dots. Experimental results on InAs∕GaAs quantum dots are compared with theoretical calculations presented in the same parameter space. From such a comparison, different regimes dominated by charge carrier tunneling and thermal emission and mixture of these can be identified, thus resolving the complex emission data from this kind of systems into its component parts.
Grain boundary fine structure of ultrananocrystalline diamond thin films measured by Raman scattering
Authors: Veres M. , Tóth S. , Koós M.
Published: July 2007

Structural units of the grain boundaries in ultrananocrystalline diamond thin films with different grain sizes were investigated using Raman spectroscopy. Characteristic peaks of well-defined molecular structural building blocks were detected in the near-infrared excited Raman spectra of these materials by limiting the excitation volume to the size of the crystallites using an optical microscope and surface enhanced Raman spectroscopy. The analysis of the spectra provides evidence for the presence of aromatic hydrocarbons and different sp3 CHx groups in grain boundaries of these materials.
Improved thermal stability of ruthenium oxide metal gate electrode on hafnium oxide gate dielectric
Authors: Hasan Musarrat , Park Hokyung , Lee Joon-myong , Hwang Hyunsang
Published: July 2007

This study focused on the detailed understanding of the thermal stability of ruthenium oxide metal gate electrode for hafnium oxide gate dielectric. A sample with ruthenium oxide electrode shows reduction of capacitance and flatband voltage shift after high temperature annealing. The degradation of device parameter can be explained by the reduction of amorphous ruthenium oxide phase into ruthenium metallic phase and oxygen. With the introduction of an additional ruthenium metal layer between ruthenium oxide and hafnium oxide, the authors can minimize oxygen diffusion from ruthenium oxide electrode toward silicon/hafnium oxide interface which in turn improves the thermal stability of hafnium oxide devices.
Sign Language Peoples as Indigenous Minorities: Implications for Research and Policy
Authors: Batterbury Sarah C E , Ladd Paddy , Gulliver Mike
Published: July 2007

In this paper we draw strong parallels between Sign Language Peoples (SLPs) and First Nation peoples. We argue that SLPs (communities defining themselves by shared membership in physical and metaphysical aspects of language, culture, epistemology, and ontology) can be considered indigenous groups in need of legal protection in respect of educational, linguistic, and cultural rights accorded to other First Nation indigenous communities. We challenge the assumption that SLPs should be primarily categorised within concepts of disability. The disability label denies the unique spatial culturolinguistic phenomenon of SLP collectivist identity by replicating traditional colonialist perspectives, and actively contributing to their ongoing oppression. Rather, SLPs are defined spatially as a locus for performing, building, and reproducing a collective topography expressed through a common language and a shared culture and history.
The UK Geography of the e-Society: A National Classification
Authors: Longley Paul A , Webber Richard , Li Chao
Published: July 2007

It is simplistic to think of the impacts of new information and communication technologies (NICTs) in terms of a single ‘digital divide’, or even a small number of them. As developments in what has been termed the ‘e-society’ reach wider and more generalised audiences, so it becomes appropriate to think of digital media as having wider-ranging but differentiated impacts upon consumer transactions, information gathering, and citizen participation. This paper describes the development of a detailed, nationwide household classification based on levels of awareness of different NICTs; levels of use of NICTs; and their perceived impacts upon human capital formation and the quality of life. It discusses how multivariate classification of individuals and households makes it possible to provide a context for detailed case studies, and hence to identify how policy might best improve both the quality and degree of society's access to NICTs. The primary focus of the paper is to describe how this bespoke classification is developed, but it also illustrates how it may be used to investigate a range of regional and subregional policy issues. As such, we illustrate how the classification provides a valuable context for study of the e-society and for people's engagement with NICT In more general terms, we anticipate the likely net benefits of combining the most appropriate methods, techniques, datasets, and practices that are used in the public and private sectors.
Sanitation in Mumbai's Informal Settlements: State, ‘Slum’, and Infrastructure
Authors: McFarlane Colin
Published: July 2007

This paper examines an ongoing intervention in sanitation in informal settlements in Mumbai, India. The Slum Sanitation Programme (SSP) is premised upon ‘partnership’, ‘participation’, and ‘cost recovery’ in the delivery of large toilet blocks as a practical solution to the stark lack and inadequacy of sanitation, and offers an opportunity to interrogate a growing consensus on sanitation provision among mainstream development agencies. In the paper, I argue for a more flexible approach to policy infrastructure, technical infrastructure, and cost recovery in urban sanitation interventions. I also consider whether the SSP, as the largest city project of its nature in Indian history, marks a shift in the relationship between the state and the ‘slum’ in Mumbai. I suggest that, despite constituting a change from ad hoc sanitation provision to a more sustained and universal policy, informal settlements in the SSP remain populations outside the sphere of citizenship and notions of the clean, ordered modern city.
Natural polymorphism affecting learning and memory in
Drosophila
Authors: Mery Frederic , Belay Amsale T. , So Anthony K.-C. , Sokolowski Marla B. , Kawecki Tadeusz J.
Published: July 2007

Knowing which genes contribute to natural variation in learning and memory would help us understand how differences in these cognitive traits evolve among populations and species. We show that a natural polymorphism at the
foraging
(
for
) locus, which encodes a cGMP-dependent protein kinase (PKG), affects associative olfactory learning in
Drosophila melanogaster
. In an assay that tests the ability to associate an odor with mechanical shock, flies homozygous for one natural allelic variant of this gene (

for
R

) showed better short-term but poorer long-term memory than flies homozygous for another natural allele (

for
s

). The

for
s

allele is characterized by reduced PKG activity. We showed that

for
R

-like levels of both short-term learning and long-term memory can be induced in

for
s

flies by selectively increasing the level of PKG in the mushroom bodies, which are centers of olfactory learning in the fly brain. Thus, the natural polymorphism at
for
may mediate an evolutionary tradeoff between short- and long-term memory. The respective strengths of learning performance of the two genotypes seem coadapted with their effects on foraging behavior:

for
R

flies move more between food patches and so could particularly benefit from fast learning, whereas

for
s

flies are more sedentary, which should favor good long-term memory.
Reevaluating the relationship between EPR spectra and enzyme structure for the iron–sulfur clusters in NADH:quinone oxidoreductase
Authors: Yakovlev Gregory , Reda Torsten , Hirst Judy
Published: July 2007

NADH:quinone oxidoreductase (complex I) plays a pivotal role in cellular energy production. It employs a series of redox cofactors to couple electron transfer to the generation of a proton-motive force across the inner mitochondrial or bacterial cytoplasmic membrane. Complex I contains a noncovalently bound flavin mononucleotide at the active site for NADH oxidation and eight or nine iron–sulfur clusters to transfer electrons between the flavin and a quinone-binding site. Understanding the mechanism of complex I requires the properties of these clusters to be defined, both individually and as an ensemble. Most functional information on the clusters has been gained from EPR spectroscopy, but some clusters are not observed by EPR and attributing the observed signals to the structurally defined clusters is difficult. The current consensus picture relies on correlating the spectra from overexpressed subunits (containing one to four clusters) with those from intact complexes I. Here, we analyze spectra from the overexpressed NuoG subunit from
Escherichia coli
complex I and compare them with spectra from the intact enzyme. Consequently, we propose that EPR signals N4 and N5 have been misassigned: signal N4 is from NuoI (not NuoG) and signal N5 is from the conserved cysteine-ligated [4Fe-4S] cluster in NuoG (not from the cluster with a histidine ligand). The consequences of reassigning the EPR signals and their associated functional information on the free energy profile for electron transfer through complex I are discussed.
Helicobacter pylori and Helicobacter heilmannii in untreated Bulgarian children over a period of 10 years
Authors: Boyanova Lyudmila , Lazarova Elena , Jelev Christo , Gergova Galina , Mitov Ivan
Published: July 2007

The aims of the study were to evaluate the incidence of Helicobacter pylori and Helicobacter heilmannii in untreated Bulgarian children from 1996 to 2006, to analyse the performance of diagnostic tests, and to look at H. pylori density in specimens by culture. Antral specimens from children with chronic gastritis (n=513), peptic ulcers (n=54) and other diseases (n=91) were evaluated by direct Gram staining (DGS), in-house rapid urease test (RUT) and culture. The living environment and semi-quantitative H. pylori density were assessed in 188 and 328 children, respectively. H. pylori infection was found in children with ulcers (77.8  %), chronic gastritis (64.5  %) and other diseases (36.3  %). Half (51.4  %) of patients aged 1–5 years and 77.4  % of those aged 16–17 years were H. pylori-positive. Of all children, 328 (49.8  %) showed positive DGS, 184 (28  %) had a positive RUT, and 386 (58.7  %) were culture-positive. Unlike gastric mucus specimens, frozen biopsy specimens provided reliable diagnosis. H. heilmannii was observed in two (0.3  %) children. High H. pylori density (growth into all quadrants of plates) was found in 18  % of 328 children evaluated, involving 31  % of ulcer and 16.7  % of non-ulcer patients. H. pylori infection was more common in rural children with chronic gastritis (91.3  %) than in the remainder (66.7  %). In conclusion, H. pylori infection was common in symptomatic Bulgarian children. The infection prevalence was >77  % in patients aged 16–17 years, in children with a duodenal ulcer, and in rural patients. H. heilmannii infection was uncommon. The performance of the bacterial culture was good. The impact of H. pylori density on the clinical expression and eradication of the infection requires further evaluation. The results highlight the need for routine H. pylori diagnosis in rural children with chronic gastritis.
A synthetic polypeptide based on human E-cadherin inhibits invasion of human intestinal and liver cell lines by Listeria monocytogenes
Authors: Sahu Saura C. , Gaines Dennis W. , Williams Kristina M. , Raybourne Richard B.
Published: July 2007

Internalin A is a surface protein of the facultative intracellular pathogen Listeria monocytogenes that interacts with the human host cell protein E-cadherin to facilitate invasion of epithelial cells. A single amino acid substitution at position 16 in mouse E-cadherin prevents this interaction. Synthetic polypeptides of 30 aa encompassing position 16 of human and mouse E-cadherin were tested for their ability to inhibit in vitro invasion of Caco-2, HepG2 and TIB73 cell lines by L. monocytogenes. Only the human-derived peptide was capable of inhibiting invasion in the human-origin Caco-2 and HepG2 cell lines. These findings demonstrate that small polypeptides can inhibit invasion of biologically relevant cell types by L. monocytogenes in vitro and may be potentially useful as therapeutic agents in vivo.
A potyvirus P1 protein interacts with the Rieske Fe/S protein of its host
Authors: SHI YUHONG , CHEN JIONG , HONG XUEYU , CHEN JIANPING , ADAMS MICHAEL J.
Published: July 2007

Yeast two‐hybrid (Y2H) screens were used to test for interactions between the P1 protein ofSoybean mosaic virusPinellia isolate (SMV‐P) and a cDNA expression library of its host, the aroidPinellia ternata.Of the 13 independent interacting clones identified, ten were identical and had an open reading frame predicted to encode a 23.7‐kDa protein closely related to the cytochromeb6/fcomplex Rieske Fe/S genes of plants. The interaction between SMV‐P‐P1 and the mature Rieske Fe/S protein (without transit peptide) of the host was confirmed byin vitroco‐immunoprecipitation of the two proteins. Y2H assays using different parts of the two proteins showed that only the N‐terminal part (amino acids 1–82) of SMV‐P P1 was responsible for the interaction with the Rieske Fe/S protein and that amino acids 1–33 interacted only with the transit peptide, while amino acids 34–82 could interact with the entire Rieske Fe/S protein. SMV‐P P1 also interacted moderately with the Rieske Fe/S protein of its other hosts, soybean andZantedeschia aethiopica, but weakly with that of the non‐hostArabidopsis thaliana. The P1‐Rieske Fe/S protein interactions are likely to be involved in symptom development, and the very variable N‐terminus of P1 may play an important role in host adaptation.
Surgical interventions in a cohort of patients with haemophilia A and inhibitors: an experiential retrospective chart review
Authors: KRAUT E. H. , ALEDORT L. M. , ARKIN S. , STINE K. C. , WONG W.‐Y.
Published: July 2007

Summary.  Strategies for the management of perioperative bleeding in patients with haemophilia and inhibitors have evolved rapidly as a result of the development of the bypassing agents Factor Eight Inhibitor Bypassing Activity, Anti‐inhibitor Coagulant Complex (FEIBATM) and activated recombinant factor VII (rFVIIa). However, there are currently no established guidelines for perioperative use of bypassing agents, and few controlled clinical studies have been carried out. Thus, case reports, such as those presented here, provide useful anecdotal evidence to guide the treatment of inhibitor patients. The purpose of this report was to describe experiences in the use of bypassing agents in a small cohort of patients with haemophilia A and inhibitors undergoing surgical procedures. Cases from five treatment centres were reviewed. Twenty‐two procedures using FEIBATM, rFVIIa or a combination of both agents were compiled from seven inhibitor patients (six with an alloantibody inhibitor and one with an acquired autoantibody inhibitor). Eleven procedures used FEIBATM monotherapy, two employed rFVIIa monotherapy and nine were performed using combination therapy. Supplemental therapies were required to manage bleeding in some cases. Haemostatic control was achieved in all cases, and treatment regimens were generally well tolerated. One thrombotic adverse event was reported: evidence of disseminated intravascular coagulation (DIC) was found after rFVIIa use in one case, although the direct cause of DIC was unknown. The experiences in this case review demonstrate that both major and minor surgical procedures can be safely performed in patients with haemophilia and high‐titre inhibitors under the cover of bypassing agents, with a high expectation of success.
Enhanced antitumour immunity by combined use of temozolomide and TAT‐survivin pulsed dendritic cells in a murine glioma
Authors: Kim Chang‐Hyun , Woo Sun‐Je , Park Jung‐Sun , Kim Hye‐Sung , Park Mi‐Young , Park Sung‐Dong , Hong Yong‐Kil , Kim Tai‐Gyu
Published: July 2007

Although chemotherapy remains among the best treatment options for most cancers, adjuvant therapies such as dendritic cell (DC)‐based immunotherapy have been added to treatment protocols to destroy residual tumour cells. Combination treatment with low‐dose temozolomide (TMZ) chemotherapy followed by vaccination with TAT‐survivin‐pulsed DCs enhanced T‐cell responses specific for survivin and improved survival rate, as compared with DC alone or TMZ alone. Moreover, antigen‐specific immunity appears to be mediated by CD8+ T cells, as determined by in vitro T‐cell subset depletion. These studies demonstrated that a combination of low‐dose TMZ chemotherapy and TAT‐based DC immunotherapy may be a novel strategy for safe and effective treatment of malignant gliomas.
A qualitative investigation of the influence of time since graduation on English dentists’ approach to the care of young children
Authors: DAILEY YVONNE‐MARIE , MILSOM KEITH MARTIN , PILKINGTON LAURA , BLINKHORN ANTHONY STEPHENSON , THRELFALL ANTHONY GEORGE , TICKLE MARTIN
Published: July 2007

Background.  In the UK, general dental practitioners (GDPs) provide the majority of dental care to young children. The approach to undergraduate teaching of paediatric dentistry varies across UK dental schools. There is no understanding of how undergraduate teaching influences practice in the first few years after qualification and how this influence behaves over time as dentists mature as clinicians.

Objective.  The aim of this paper is to gain a deeper understanding of the influence of time since graduation on how GDPs manage the dental care of their child patients.

Design.  A qualitative study, with three interviewers conducted 93 interviews with GDPs practising in the north‐west of England. Interviews were transcribed verbatim and content analysis was used with the purpose of identifying themes from the data.

Results.  Findings showed that formal postgraduate education was not a great influence upon the GDPs’ approach to care over time. Change in approach was influenced by experiential learning over a GDP's career and external influences such as policy change, but this was not underpinned by any formal reflective practice.

Conclusions.  Education is just one of many influences on clinical practice over the whole of a clinician's career. A gradual change in clinical practice is influenced by the personal experience of dentists treating children.
One‐week versus two‐week furazolidone‐based quadruple therapy as the first‐line treatment for Helicobacter pylori infection in Iran
Authors: Daghaghzadeh Hamed , Emami Mohammad Hasan , Karimi Somayeh , Raeisi Mostafa
Published: July 2007

Background and Aim:  Furazolidone‐based regimens for the eradication of Helicobacter pylori are low cost and effective although less tolerable. Our aim was to compare the efficacy and compliance of 1‐week furazolidone‐based quadruple therapy (furazolidone, amoxicillin, bismuth subcitrate, omeprazole; FABO) with 2‐week quadruple therapy using the same drugs.

Methods:  One hundred and fifty‐six consecutive patients with H. pylori related diseases were enrolled in our study. The patients were randomized into two groups of FABO1 and FABO2 groups receiving, 1 or 2 weeks' quadruple H. pylori eradication therapies, respectively, as follows: furazolidone (200 mg twice daily), amoxicillin (1 g twice daily), bismuth (240 mg twice daily) and omeprazole (20 mg twice daily). The χ2 test was used to compare the efficacy of the therapies.

Results:  The per‐protocol eradication rate in FABO1 and FABO2 groups were 56/66 (84.8%) and 57/69 (82.6%), respectively. The intention‐to‐treat eradication rate was 56/78 (71.8%) in FABO1 group and 57/78 (73.1%) in FABO2 group. There was not any significant statistical difference between two groups. A significant decrease in compliance in FABO2 group was seen.

Conclusion:  This is an encouraging report showing a therapy with possible success in decreasing the duration of H. pylori infection as well as reaching the eradication rate of 80%.
Directly observed therapy for the treatment of hepatitis C virus infection in current and former injection drug users
Authors: Grebely Jason , Raffa Jesse D , Meagher Caite , Duncan Fiona , Genoway Krista A , Khara Milan , McLean Mark , Mead Annabel , Viljoen Mark , DeVlaming Stanley , Fraser Chris , Conway Brian
Published: July 2007

Background and Aim: There are few studies investigating the treatment of hepatitis C virus (HCV) infection in current and former drug users. With this in mind, we sought to evaluate the antiviral efficacy of interferon alpha‐2b (IFN α‐2b) or pegylated‐interferon alpha‐2b (PEG‐IFN α‐2b) and ribavirin (RBV) in injection drug users (IDU) enrolled in a directly observed therapy (DOT) program, as measured by sustained virologic response (SVR).

Methods: Viremic HCV‐infected IDU, with alanine aminotransferase (ALT) >1.5× upper limit of normal (ULN) were offered 24–48 week (based on HCV genotype) therapy with RBV (800–1200 mg/day, based on weight) along with IFN α‐2b (3 million IU thrice weekly) replaced by PEG‐IFN α‐2b (1.5 ìg/kg once weekly) as it became available. All injections were directly observed. The primary endpoint was SVR.

Results: Overall, 40 patients (33 males) received IFN α‐2b (12) or PEG‐IFN α‐2b (28), 55% with HCV genotypes 2 or 3. Only 14 discontinued therapy, 5 due to toxicity, 6 due to illicit drug use and 3 did not achieve an early virologic response. In an intent‐to‐treat analysis, the overall SVR was 55% (22/40), 64% (14/22) in subjects with genotypes 2/3. There was no significant difference in response rates among those with >6 (50%) or ≤6 months (64%) drug abstinence (P = 0.51) or among those with (53%) and without (57%) intercurrent drug use (P = 0.99); however, frequent users (n = 9) had a decreased SVR (22%) when compared with occasional users (n = 10, 80%,P = 0.12).

Conclusion: Treatment of HCV in current and former IDU within a multidisciplinary DOT program can be successfully undertaken, resulting in SVR similar to those in randomized controlled trials.
Comparison of low‐dose pegylated interferon versus standard high‐dose pegylated interferon in combination with ribavirin in patients with chronic hepatitis C with genotype 3: An Indian experience
Authors: Sood Ajit , Midha Vandana , Hissar Syed , Kumar Manoj , Suneetha Pothakamuri V , Bansal Manu , Sood Nina , Sakhuja Puja , Sarin Shiv K
Published: July 2007

Background and Aims:  In chronic hepatitis C virus (HCV) infection with genotype 3, therapy with pegylated interferon (peg‐IFN) alfa‐2b in a dose of 1.5 μg/kg/week and ribavirin (800–1000 mg/day) is recommended for 24 weeks. Reduced doses of peg‐IFN may increase compliance and decrease cost and adverse events. This study aimed to assess the safety and efficacy of two different regimens of peg‐IFN alfa‐2b, in combination with ribavirin, in genotype 3 patients.

Methods:  A total of 103 liver biopsy–proven chronic HCV patients with genotype 3, having alanine aminotransferase levels >1.2 × ULN and positive HCV‐RNA were randomized into two groups: group I (n = 76; age, 43.1 ± 11.4 years; male/female, 67/9) received peg‐IFN 1.0 μg/kg/week + ribavirin 10.6 mg/kg/day, while group II (n = 27; age, 37.3 ± 11.6 years; male/female, 21/6) received peg‐IFN 1.5 μg/kg/week + ribavirin 10.6 mg/kg/day. Patients in both groups were treated for 24 weeks. End of treatment viral response (ETVR) and sustained viral response (SVR) after a 6‐month follow‐up period were assessed.

Results:  In both groups I and II, one patient was lost to follow‐up, while one patient in group II withdrew due to side‐effects. ETVR was seen in 72/76 (94.7%) of patients in the low dose group and 24/27 (88.9%) of patients in the high dose group (P = 0.375). SVR was seen in 60/76 (78.9%) of patients in the low dose group and 25/27 (92.6%) of patients in the high dose group (P = 0.145). Age (Pearson correlation coefficient = 0.263; P = 0.008) and fibrosis (correlation coefficient, 0.263; P = 0.008) showed a significant correlation with the SVR.

Conclusion:  In patients with genotype 3, peg‐IFN at 1.0 μg/kg/week with ribavirin is as effective as peg‐IFN at 1.5 μg/kg/week with ribavirin.
Comparison of an inflammation‐based prognostic score (GPS) with performance status (ECOG‐ps) in patients receiving palliative chemotherapy for gastroesophageal cancer
Authors: Crumley Andrew B C , Stuart Robert C , McKernan Margaret , McDonald Alexander C , McMillan Donald C
Published: July 2007

Aim:  The aim of the present study was to compare an inflammation‐based prognostic score (Glasgow Prognostic Score, GPS) with performance status (ECOG‐ps) in patients receiving platinum‐based chemotherapy for palliation of gastroesophageal cancer.

Methods:  Sixty‐five patients presenting with gastroesophageal carcinoma to the Royal Infirmary, Glasgow between January 1999 and December 2005 and who received palliative chemotherapy or chemo‐radiotherapy were studied. ECOG‐ps, C‐reactive protein, and albumin were recorded at diagnosis. Patients with both an elevated C‐reactive protein (>10 mg/L) and hypoalbuminemia (<35 g/L) were allocated a GPS of 2. Patients in whom only one of these biochemical abnormalities was present were allocated a GPS of 1 and patients with a normal C‐reactive protein and albumin were allocated a score of 0. Toxicity was recorded using the Common Toxicity Criteria.

Results:  The minimum follow up was 14 months. During the follow‐up period, 59 (91%) of the patients died. On univariate and multivariate survival analysis, only the GPS (hazard ratios 1.65, 95% CI 1.10–2.47, P < 0.05) was a significant independent predictor of cancer survival. In addition, in comparison with patients with GPS of 0, those patients with a GPS of 1 or 2 required more frequent chemotherapy dose reduction (P < 0.05), were less likely to exhibit a clinical response to treatment (P < 0.05), and had shorter survival (P < 0.05).

Conclusion:  The presence of a systemic inflammatory response, as evidenced by the GPS, appears to be superior to the subjective assessment of performance status (ECOG‐ps) in predicting the response to platinum‐based chemotherapy in patients with advanced gastroesophageal cancer.
A RULE‐BASED APPROACH FOR SEMANTIC ANNOTATION EVOLUTION
Authors: Luong P.‐H. , Dieng‐Kuntz R.
Published: July 2007

An approach for managing knowledge in an organization in the new infrastructure of Semantic Web consists of building a corporate semantic web (CSW). The main components of a CSW are (i) evolving resources distributed over an intranet and indexed using (ii) semantic annotations expressed with the vocabulary provided by (iii) a shared ontology. However, changes in the operating environment may lead to some inconsistencies in the system and they result in need of modifications of the CSW components. These changes need to be evolved and well managed. In this paper we present a rule‐based approach allowing us to detect and correct semantic annotation inconsistencies. This rule‐based approach is implemented in the CoSWEM system enabling to manage the evolution of such a CSW, especially to address the evolution of semantic annotations when its underlying ontologies change.
Low‐affinity spermine block mediating outward currents through Kir2.1 and Kir2.2 inward rectifier potassium channels
Authors: Ishihara Keiko , Yan Ding‐Hong
Published: July 2007

The outward component of the strong inward rectifier K+ current (IKir) plays a pivotal role in polarizing the membranes of excitable and non‐excitable cells and is regulated by voltage‐dependent channel block by internal cations. Using the Kir2.1 channel, we previously showed that a small fraction of the conductance susceptible only to a low‐affinity mode of block likely carries a large portion of the outward current. To further examine the relevance of the low‐affinity block to outward IKir and to explore its molecular mechanism, we studied the block of the Kir2.1 and Kir2.2 channels by spermine, which is the principal Kir2 channel blocker. Current–voltage relations of outward Kir2.2 currents showed a peak, a plateau and two peaks in the presence of 10, 1 and 0.1 μm spermine, respectively, which was explained by the presence of two conductances that differ in their susceptibility to spermine block. When the current–voltage relations showed one peak, like those of native IKir, outward Kir2.2 currents were mediated mostly by the conductance susceptible to the low‐affinity block. They also flowed in a narrower range than the corresponding Kir2.1 currents, because of 3‐ to 4‐fold greater susceptibility to the low‐affinity block than in Kir2.1. Reducing external [K+] shifted the voltage dependences of both the high‐ and low‐affinity block of Kir2.1 in parallel with the shift in the reversal potential, confirming the importance of the low‐affinity block in mediating outward IKir. When Kir2.1 mutants known to have reduced sensitivity to internal blockers were examined, the D172N mutation in the transmembrane pore region made almost all of the conductance susceptible only to low‐affinity block, while the E224G mutation in the cytoplasmic pore region reduced the sensitivity to low‐affinity block without markedly altering that to the high‐affinity block or the high/low conductance ratio. The effects of these mutations support the hypothesis that Kir2 channels exist in two states having different susceptibilities to internal cationic blockers.