bluuebunny/crossref_metadata_2025_split huggingface dataset:
The hepatotoxicity of non‐steroidal anti‐inflammatory drugs
Authors: Rubenstein J. H. , Laine L. 
Published: August 2004

SummaryBackground : Non‐steroidal anti‐inflammatory drugs have been implicated in reports of liver injury. However, the precise risk of non‐steroidal anti‐inflammatory drugs for this rare complication is unknown.Aim : To review systematically the published literature of population‐based epidemiological studies reporting the incidence or comparative risk of non‐steroidal anti‐inflammatory drugs for liver injury resulting in clinically significant events, defined as hospitalization or death.Data extraction : Duplicate extraction of the methodological quality, design, source, population, years studied, particular non‐steroidal anti‐inflammatory drugs studied, definitions, patient counts and follow‐up, and the adjustment for confounders.Results : Seven articles met inclusion criteria. The comparative risk of liver injury resulting in hospitalization for current non‐steroidal anti‐inflammatory drug users compared with past non‐steroidal anti‐inflammatory drug users ranged from 1.2 to 1.7, but none was statistically significant. The incidence of liver injury resulting in hospitalization ranged from 3.1 to 23.4/100 000 patient‐years of current use of non‐steroidal anti‐inflammatory drugs, with an excess risk compared with past non‐steroidal anti‐inflammatory drugs users of 4.8–8.6/100 000 patient‐years of exposure. There were zero deaths from liver injury associated with non‐steroidal anti‐inflammatory drugs use in over 396 392 patient‐years of cumulative exposure.Conclusion : These findings allow for the possibility of a small increase in the risk of clinically relevant hepatotoxicity with non‐steroidal anti‐inflammatory drugs use, but do not document that such a risk occurs.
Treatment of gastro‐oesophageal reflux disease with rabeprazole in primary and secondary care: does Helicobacter pylori infection affect proton pump inhibitor effectiveness?
Authors: de Wit N. J. , de Boer W. A. , Geldof H. , Hazelhoff B. , Bergmans P. , Tytgat G. N. J. , Smout A. J. P. M. 
Published: August 2004

SummaryBackground : The presence of the gastric pathogen, Helicobacter pylori influences acid suppression by proton pump inhibitors and treatment outcome in patients with gastro‐oesophageal reflux disease.Aim : To determine the influence of H. pylori infection on effectiveness of rabeprazole in primary and secondary care patients with gastro‐oesophageal reflux disease.Methods : Patients from primary and secondary care centres with uninvestigated gastro‐oesophageal reflux disease (based on symptoms only) and investigated gastro‐oesophageal reflux disease (endoscopically confirmed oesophagitis or endoscopy‐negative reflux disease) were tested for H. pylori and treated with rabeprazole 20 mg once daily for 4–8 weeks in a non‐randomized, multicentre, open‐label study. Primary end‐point for treatment effectiveness was complete resolution of both heartburn and acid regurgitation at 4–8 weeks; secondary end‐point was quality of life as registered with the Psychological General Well‐being Index.Results : Data of 1787 patients could be analysed; mean duration of treatment was 36.3 days. At the evaluation visit 76.9% were heartburn‐free, 77.7% regurgitation‐free and 71% had complete symptom resolution. Overall Psychological General Well‐being Index scores improved accordingly. Treatment was equally effective in patients with or without H. pylori infection, but more effective in patients with oesophagitis when compared with symptomatic gastro‐oesophageal reflux disease.Conclusions : The effectiveness of rabeprazole in gastro‐oesophageal reflux disease is not affected by the presence of H. pylori infection.
IS911 partial transposition products and their processing by the Escherichia coli RecG helicase
Authors: Turlan Catherine , Loot Celine , Chandler Michael 
Published: August 2004

SummaryInsertion of bacterial insertion sequence IS911 can often be directed to sequences resembling its ends. We have investigated this type of transposition and shown that it can occur via cleavage of a single end and its targeted transfer next to another end. The single end transfer (SET) events generate branched DNA molecules that contain a nicked Holliday junction and can be considered as partial transposition products. Our results indicate that these can be processed by the Escherichia coli host independently of IS911‐encoded proteins. Such resolution depends on the presence of homologous DNA regions neighbouring the cross‐over point in the SET molecule. Processing is often accompanied by sequence conversion between donor and target sequences, suggesting that branch migration is involved. We show that resolution is greatly reduced in a recG host. Thus, the branched DNA‐specific helicase, RecG, involved in processing of potentially lethal DNA structures such as stalled replication forks, also intervenes in the resolution of partial IS911 transposition products.
Targeting of the chemotaxis methylesterase/deamidase CheB to the polar receptor–kinase cluster in an Escherichia coli cell
Authors: Banno Satomi , Shiomi Daisuke , Homma Michio , Kawagishi Ikuro 
Published: August 2004

SummaryChemotactic adaptation to persisting stimulation involves reversible methylation of the chemoreceptors that form complexes with the histidine kinase CheA at a cell pole. The methyltransferase CheR targets to the C‐terminal NWETF sequence of the chemoreceptor. In contrast, localization of the methylesterase CheB is largely unknown, although regulation of its activity via phosphorylation is central to adaptation. In this study, green fluorescent protein was fused to full‐length CheB or its various parts: the N‐terminal regulatory domain (N), the C‐terminal catalytic domain (C) and the linker (L). The full‐length and NL fusions and, to a lesser extent, the LC fusion localized to a pole. Deletion of the P2 domain from CheA abolished polar localization of the full‐length and NL fusions, but did not affect that of the LC fusion. Pull‐down assays demonstrated that the NL fragment, but not the LC fragment, binds to the P2 fragment of CheA. These results indicate that binding of the NL domain to the P2 domain targets CheB to the polar signalling complex. The LC fusion, like the chemoreceptor, partially localized in the absence of CheA, suggesting that the LC domain may interact with its substrate sites, either as part of the protein or as a proteolytic fragment.
Coupling of the pathway of sulphur oxidation to dioxygen reduction: characterization of a novel membrane‐bound thiosulphate:quinone oxidoreductase
Authors: Müller Fabian H. , Bandeiras Tiago M. , Urich Tim , Teixeira Miguel , Gomes Cláudio M. , Kletzin Arnulf 
Published: August 2004

SummaryThiosulphate is one of the products of the initial step of the elemental sulphur oxidation pathway in the thermoacidophilic archaeon Acidianus ambivalens. A novel thiosulphate:quinone oxidoreductase (TQO) activity was found in the membrane extracts of aerobically grown cells of this organism. The enzyme was purified 21‐fold from the solubilized membrane fraction. The TQO oxidized thiosulphate with tetrathionate as product and ferricyanide or decyl ubiquinone (DQ) as electron acceptors. The maximum specific activity with ferricyanide was 73.4 U (mg protein)−1 at 92°C and pH 6, with DQ it was 397 mU (mg protein)−1 at 80°C. The Km values were 2.6 mM for thiosulphate (kcat = 167 s−1),  3.4 mM  for  ferricyanide  and  5.87 µM for DQ. The enzymic activity was inhibited by sulphite (Ki = 5 µM), metabisulphite, dithionite and TritonX‐100, but not by sulphate or tetrathionate. A mixture of caldariella quinone, sulfolobus quinone and menaquinone was non‐covalently bound to the protein. No other cofactors were detected. Oxygen consumption was measured in membrane fractions upon thiosulphate addition, thus linking thiosulphate oxidation to dioxygen reduction, in what constitutes a novel activity among Archaea. The holoenzyme was composed of two subunits of apparent molecular masses of 28 and 16 kDa. The larger subunit appeared to be glycosylated and was identical to DoxA, and the smaller was identical to DoxD. Both subunits had been described previously as a part of the terminal quinol:oxygen oxidoreductase complex (cytochrome aa3).
The gate controlling cell wall synthesis in Staphylococcus aureus
Authors: Komatsuzawa Hitoshi , Fujiwara Tamaki , Nishi Hiromi , Yamada Sakuo , Ohara Masaru , McCallum Nadine , Berger‐Bächi Brigitte , Sugai Motoyuki 
Published: August 2004

SummaryGlucosamine‐6‐P occupies a central position between cell wall synthesis and glycolysis. In the initial steps leading to peptidoglycan precursor formation glucosamine‐6‐P is processed sequentially to UDP‐N‐acetylglucosamine, while to enter the glycolysis pathway, glucosamine‐6‐P is isomerized by NagB to fructose‐6‐P. Although we could not demonstrate NagB activity, nagB inactivation significantly reduced growth. Mutational analysis showed that NagA was involved in glucosamine‐6‐P formation from N‐acetylglucosamine‐6‐P, and GlmS in that from fructose‐6‐P. Inactivation of glmS prevented growth on glucose as sole carbon source, which resumed after complementation with N‐acetylglucosamine. Transcription of glmS as well as the amount of GlmS was reduced in the presence of N‐acetylglucosamine. This and the preferential incorporation of N‐acetylglucosamine over glucose into cell wall material showed that N‐acetylglucosamine was used exclusively for cell wall synthesis, while glucose served both cell wall synthesis and glycolysis. These observations suggest furthermore GlmS to be the key and only enzyme leading from glucose to cell wall synthesis in Staphylococcus aureus, and show that there exists a tight regulation and hierarchy in sugar utilization. Inactivation of nagA, nagB or glmS affected the susceptibility of S. aureus to cell wall synthesis inhibitors, suggesting an interdependence between efficiency of cell wall precursor formation and resistance levels.
Bacteriophage T7 DNA ejection into cells is initiated by an enzyme‐like mechanism
Authors: Kemp Priscilla , Gupta Manisha , Molineux Ian J. 
Published: August 2004

SummaryIn a normal infection about 850 bp of the bacteriophage T7 genome is ejected into the cell, the remainder of the genome is internalized through transcription by Escherichia coli and then T7 RNA polymerase. Rates of T7 DNA internalization by the E. coli enzyme in vivo are constant across the whole genome. As expected for an enzyme‐catalysed reaction, rates vary with temperature and can be fitted to Arrhenius kinetics. Phage virions containing a mutant gp16, a protein known to be ejected from the phage capsid into the cell at the initiation of infection, allow complete entry of the T7 genome in the absence of transcription. The kinetics of DNA ejection from such a mutant virion into the bacterial cytoplasm have also been measured at different temperatures in vivo. Between 15 and 43°C the entire 40 kb T7 genome is translocated into the cell at a constant rate that is characteristic for each temperature, and the temperature‐dependence of DNA translocation rates can be fitted to Arrhenius kinetics. The data are consistent with the idea that transcription‐independent DNA translocation from the T7 virion is also enzyme‐catalysed. The proton motive force is necessary for this mode of DNA translocation, because collapsing the membrane potential while the T7 genome is entering the cell abruptly halts further DNA transfer.
Haemophore‐mediated signalling in Serratia marcescens: a new mode of regulation for an extra cytoplasmic function (ECF) sigma factor involved in haem acquisition
Authors: Biville Francis , Cwerman Hélène , Létoffé Sylvie , Rossi Maria‐Silvia , Drouet Valérie , Ghigo J. M. , Wandersman Cécile 
Published: August 2004

SummaryBacterial extra cytoplasmic function (ECF) sigma factors control a wide range of cell envelope activities including iron and haem uptake systems. Sigma activity is usually inhibited by membrane‐bound antisigma. An extra cytoplasmic signal modulates sigma–antisigma interactions and thereby leads to the transcription of the target operon. Sigma and antisigma genes generally belong to one autoregulated operon. However, ECF sigma and antisigma genes involved in iron acquisition, also called iron starvation ECF, are non‐autoregulated exceptions to this rule.We fully reconstituted the has signalling cascade of Serratia marcescens in Escherichia coli. Binding of the haem‐loaded haemophore to the outer membrane receptor, HasR, inactivates the antisigma HasS, turning on HasI and thereby allowing has operon transcription. Deletion of the HasR N‐terminal extension, present in all characterized outer membrane receptors endowed with signal transduction capacity, abolished the inducing activity but not the transport activity. Induction required the TonB‐ExbB‐ExbD complex. HasI, like the other iron starvation sigma, is iron repressed but not autoregulated. We found an entirely new regulation for the antisigma hasS gene, the transcription of which is HasI dependent. We suggest that the has system is both activated and repressed by the availability of external haem. When there is enough haem, the HasS antisigma activity is turned off and HasI induces the transcription of hasS. This leads to the storage of inactive HasS molecules which become active when HasR is not occupied by holo‐haemophore ligand molecules: as soon as there is a haem shortage transcription is turned off. Positive autoregulation of ECF sigma and antisigma genes is usually considered as a mechanism for amplifying a perceived signal. However, our findings suggest, on the contrary, that antisigma regulation allows fine‐tuning to the external signal. The biological significance of ECF sigma and antisigma autoregulation may need to be reconsidered.
The East Asian Dollar Standard, Fear of Floating, and Original Sin
Authors: McKinnon Ronald , Schnabl Gunther 
Published: August 2004

AbstractBefore the crisis of 1997/98, the East Asian economies—except for Japan but including China—pegged their currencies to the US dollar. To avoid further turmoil, the IMF argues that these currencies should float more freely. However, the authors’ econometric estimations show that the dollar's predominant weight in East Asian currency baskets has returned to its pre‐crisis levels. By 2002, the day‐to‐day volatility of each country's exchange rate against the dollar had again become negligible. Most governments were rapidly accumulating a “war chest” of official dollar reserves, which portends that this exchange rate stabilization will come to extend over months or quarters. From the doctrine of “original sin” applied to emerging‐market economies, the authors argue that this fear of floating is entirely rational from the perspective of each individual country. And their joint pegging to the dollar benefits the East Asian dollar bloc as a whole, although Japan remains an important outlier.
R&D‐induced Growth in the OECD?
Authors: Zachariadis Marios 
Published: August 2004

AbstractThe study uses aggregate and manufacturing sector data for a group of ten OECD countries for the period 1971 to 1995 to estimate a system of two equations implied by a model of R&D‐induced growth in steady state. These equations relate R&D intensity to productivity growth and the latter to output growth. The author finds evidence of a positive impact of aggregate R&D intensity on the growth rates of productivity and output. The null hypothesis that growth is not induced by R&D is rejected in favor of the Schumpeterian endogenous growth framework without scale effects. The R&D impact for the aggregate economy is distinctly larger than for the manufacturing sector. Finally, an extension of the empirical model shows that openness has a positive impact on productivity growth.
Reexamination of Economic Growth, Tax Policy, and Distributive Politics
Authors: Bao Yong , Guo Jang‐Ting 
Published: August 2004

AbstractThe paper examines the relationship between economic growth, tax policy, and distribution of capital and labor ownership in a one‐sector political‐economy model of endogenous growth with productive government spending financed by a proportional tax on capital income. The analysis shows that inequality in wealth and income can be positively or negatively related to the optimal tax rate. In either environment, higher inequality leads to a lower after‐tax return to capital, thereby reducing the economy's growth rate.
ARDL Approach to Test the Productivity Bias Hypothesis
Authors: Bahmani‐Oskooee Mohsen , Nasir A. B. M. 
Published: August 2004

AbstractThe productivity bias hypothesis states that a relatively more productive country should experience a real appreciation of its currency. Most studies in the literature that have tested the hypothesis have employed cross‐sectional data. Only a few studies have used time‐series data and they have tested the hypothesis for only a small number of countries. In this paper the authors test the hypothesis by using time‐series data over the 1960–90 period for a sample of 44 countries and with a relatively new method of cointegration known as the ARDL approach. For most countries there is strong evidence supporting the hypothesis.
Filial Obligations and Child Labor
Authors: López‐Calva Luis Felipe , Miyamoto Koji 
Published: August 2004

AbstractThe model presented here reproduces the empirical fact that poorer countries show a higher incidence of child labor and time‐intensive care of retired parents, whereas richer countries have negligible child labor and people indulge in money‐intensive care of the old. For that purpose, the effect of social norms of filial obligations on child labor and schooling decisions is analyzed. It is shown that norms of filial obligations are sustainable as an equilibrium in the intergenerational game. Widely discussed contracting problems à la Becker, which allegedly explain underinvestment in schooling by poor households, are thus solved. However, this alone does not induce the elimination of child labor. Technological parameters and relative returns to schooling also play a fundamental role.
Mechanism of Ba2+ block of a mouse inwardly rectifying K+ channel: differential contribution by two discrete residues
Authors: Alagem Noga , Dvir Miri , Reuveny Eitan 
Published: August 2004

The block of the IRK1/Kir2.1 inwardly rectifying K+ channel by a Ba2+ ion is highly voltage dependent, where the ion binds approximately half‐way within the membrane electrical field. The mechanism by which two distinct mutations, E125N and T141A, affect Ba2+ block of Kir2.1 was investigated using heterologous expression in Xenopus oocytes.
Analysis of the blocking kinetics showed that E125 and T141 affect the entry and binding of Ba2+ to the channel, respectively. Replacing the glutamate at position 125 with an asparagine greatly decreased the rate at which the Ba2+ ions enter and leave the pore. In contrast, replacing the polar threonine at position 141 with an alanine affected the entry rate of the Ba2+ ions while leaving the exit rate unchanged.
Acidification of the extracellular solution slowed the exit rate of the Ba2+ from the wild‐type channel, but had no such effect on the Kir2.1(E125N) mutant.
These results thus reveal two unique roles for the amino acids at positions 125 and 141 in aiding the interaction of Ba2+ with the channel. Their possible roles in K+ permeation are discussed.
Serotonin facilitates AMPA‐type responses in isolated siphon motor neurons of Aplysia in culture
Authors: Chitwood Raymond A. , Li Quan , Glanzman David L. 
Published: August 2004

Serotonin (5‐HT) facilitates the connections between sensory and motor neurons in Aplysia during behavioural sensitization. The effect of 5‐HT on sensorimotor synapses is believed to be primarily presynaptic. Here we tested whether 5‐HT can have an exclusively postsynaptic facilitatory effect.
Siphon motor neurons were individually dissociated from the abdominal ganglion of Aplysia and placed into cell culture. Brief pulses of glutamate, the putative sensory neuron transmitter, were focally applied (0.1 Hz) to solitary motor neurons in culture, and the glutamate‐evoked postsynaptic potentials (Glu‐PSPs) were recorded.
When 5‐HT was perfused over the motor neuron for 10 min, the amplitude of the Glu‐PSPs was significantly increased. The 5‐HT‐induced enhancement of the Glu‐PSPs persisted for at least 40 min after washout.
Prior injection into the motor neuron of the calcium chelator BAPTA, GDP‐β‐S or GTP‐γ‐S blocked the 5‐HT‐induced facilitation of the Glu‐PSPs. However, the facilitation was not blocked when APV, an NMDA receptor antagonist, was applied together with the 5‐HT.
The enhancement of the Glu‐PSPs by 5‐HT was reversed by the AMPA receptor antagonist DNQX, indicating that 5‐HT increased the functional expression of AMPA‐type receptors in the motor neuron.
The presence of botulinum toxin in the motor neuron blocked the 5‐HT‐induced enhancement of the Glu‐PSPs. As botulinum toxin prevents exocytosis we hypothesize that during sensitization 5‐HT causes the insertion of additional AMPA‐type receptors into the postsynaptic membrane of sensorimotor synapses via exocytosis. This postsynaptic mechanism may contribute to facilitation of the synapses.
Adrenomedullin increases fluid extravasation from the splenic circulation of the rat
Authors: Kaufman S. , Andrew P. , Sultanian R. , Deng Y. 
Published: August 2004

We studied the effect of adrenomedullin (ADM) on fluid efflux from the splenic vasculature into extravascular spaces.
Splenic arterial infusion of ADM (1, 3 and 9 ng min−1; n = 9, 11 and 10, respectively) caused a dose‐dependent increase in intrasplenic fluid efflux (+0.6 ± 0.3 (saline) vs.+2.0 ± 0.3 ml min−1 (9 ng min−1 ADM), P < 0.05), and in splenic (venous minus arterial) haematocrit (+0.8 ± 0.1 (saline, n = 6) vs.+3.1 ± 0.3 % (9 ng min−1 ADM, n = 7), P < 0.05). There was no change in splenic weight (0.99 ± 0.02 (saline, n = 6) vs. 0.99 ± 0.02 g (9 ng min−1 ADM, n = 7), P > 0.05).
There was no change in MAP before (97.5 ± 2.2 mmHg), during (98.4 ± 3.4 mmHg), or after (100.2 ± 2.2 mmHg) intrasplenic infusion of ADM (9 ng min−1) (n = 11, P < 0.05).
ADM (9 ng min−1) caused an increase in intrasplenic microvascular pressure (11.3 ± 0.3 (saline, n = 5) vs. 13.0 ± 0.3 mmHg (9 ng min−1 ADM, n = 6), P < 0.05).
ADM (1 × 10−11 to 1 × 10−6m) induced greater vasorelaxation of isolated preconstricted splenic resistance arteries than veins (maximal relaxation: 60 ± 0.9 (artery, n = 9) vs. 43 ± 1.7 % (vein, n = 8), P < 0.05). l‐NMMA (10−4m) partially inhibited the ADM‐induced relaxation in splenic arteries (maximal relaxation: 38 ± 3 (ADM +l‐NMMA, n = 5) vs. 60 ± 3 % (ADM +d‐NMMA, n = 5), P < 0.05).
It is concluded that ADM increases fluid efflux from the splenic vasculature by differentially reducing pre‐ vs. post‐capillary resistance, thus increasing intrasplenic microvascular pressure.