bluuebunny/crossref_metadata_2025 huggingface dataset:
Inhibition of preadipocyte proliferation by mitochondrial reactive oxygen species
Authors: Carrière Audrey , Fernandez Yvette , Rigoulet Michel , Pénicaud Luc , Casteilla Louis
Published: August 2003

Preadipocytes are present and can proliferate to increase fat mass throughout adult life. The importance of mitochondria in these cells has never been investigated, although we recently reported that mitochondrial oxidative metabolism is non‐negligible in white preadipocytes. Mitochondrial reactive oxygen species generation is intimately associated with respiratory chain function. An increasing number of reports support their role as signalling molecules. The aim of this work was to study the effects of mitochondrial reactive oxygen species on proliferation of white preadipocytes. Rotenone and oligomycin, inhibitors of complex I and of ATP synthase respectively, increased H2O2 and inhibited cell growth of preadipocytes (without inducing necrosis or apoptosis). These effects were partly prevented by addition of radical scavengers. A chemical uncoupler had opposite effects on reactive oxygen species generation and cell growth. Propofol, which inhibits complex I but also scavenges free radicals, had effects similar to those of the uncoupler on both parameters. Thus, mitochondrial reactive oxygen species can influence development of adipose tissue by affecting the size of the white preadipocyte pool.
Changing moisture sources over the last 330,000 years in Northern Oman from fluid-inclusion evidence in speleothems
Authors: Fleitmann Dominik , Burns Stephen J. , Neff Ulrich , Mangini Augusto , Matter Albert
Published: August 2003

Speleothems from Hoti Cave in northern Oman provide a record of continental pluvial periods over the last 330,000 yr. Periods of rapid speleothem deposition occurred from 6000 to 10,500, 78,000 to 82,000, 120,000 to 135,000, 180,000 to 200,000, and 300,000 to 330,000 yr ago, with little or no growth during the intervening periods. During each of these five pluvial periods, δD values of water extracted from speleothem fluid inclusions (δDFI) are between −60 and −20‰ (VSMOW) and δ18O values of speleothem calcite (δ18OC) are between −12 and −4‰ to (VPDB). These values are much more negative than modern rainfall (for δD) or modern stalagmites (for δ18O). Previous work on the isotopic composition of rainfall in Oman has shown that northern and southern moisture sources are isotopically distinct. Combined measurements of the δD values of fluid-inclusion water with calculated δ18O values from peak interglacial speleothems indicate that groundwater was predominantly recharged by the southern (Indian Ocean) moisture source, when the monsoon rainfall belt moved northward and reached Northern Oman during each of these periods.
How the Confocal Laser Scanning Microscope entered Biological Research
Authors: Amos W.B. , White J.G.
Published: August 2003

A history of the early development of the confocal laser scanning microscope in the MRC Laboratory of Molecular Biology in Cambridge is presented. The rapid uptake of this technology is explained by the wide use of fluorescence in the 80s. The key innovations were the scanning of the light beam over the specimen rather than vice‐versa and a high magnification at the level of the detector, allowing the use of a macroscopic iris. These were followed by an achromatic all‐reflective relay system, a non‐confocal transmission detector and novel software for control and basic image processing. This design was commercialized successfully and has been produced and developed over 17 years, surviving challenges from alternative technologies, including solid‐state scanning systems. Lessons are pointed out from the unusual nature of the original funding and research environment. Attention is drawn to the slow adoption of the instrument in diagnostic medicine, despite promising applications.
Assessment of metabolites and AhR and CYP1A1 mRNA expression subsequent to prenatal exposure to inhaled benzo(a)pyrene
Authors: Wu Jie , Ramesh Aramandla , Nayyar Tultul , Hood Darryl B.
Published: August 2003

Few studies have focused on environmental aerosol contaminant, mechanistically‐based, dose‐related neurotoxicity with respect to development of the central nervous system. To fill this important data gap and to highlight possible mechanistic pathways, a study was undertaken to determine metabolite concentrations associated with the transplacental disposition of inhaled benzo(a)pyrene (B(a)P) and the resulting effects on the status of aryl hydrocarbon receptor (AhR), and cytochrome P450 1A1 (CYP1A1) mRNA in preweaning F1 generation animals. In this study, laparotomy on GD 8 was performed on timed‐pregnant rats followed by dosing via nose‐only exposure for 4 h a day for 10 days (GD 11–GD 20) to three concentrations of a B(a)P: carbon black aerosol (25, 75 and 100 μg/m3). A dose‐dependent decrease in birth index was observed in the B(a)P exposed group as compared to the controls (P<0.05). Analysis of cerebrocortical extracts from F1 generation pups revealed a dose‐dependent (P<0.05) increase in total B(a)P metabolites. Analysis of cerebrocortical and hippocampal mRNA developmental expression profiles for AhR and CYP1A1 using 18sRNA as the internal standard, revealed that inhaled B(a)P upregulates AhR during the first postnatal month. The present study suggest that prenatal exposure to inhaled B(a)P upregulates hepatic aryl hydrocarbon receptor dependent mechanisms in the F1 generation. Hepatic upregulation of the aryl hydrocarbon receptor may modulate the potential for benzo(a)pyrene toxicity via the activation of cytochrome P450 and the subsequent deposition of lipophillic metabolites to developing central nervous system structures such as cerebral cortex and hippocampus.
High affinity neurotrophin receptors in the human pre‐term newborn, infant, and adult cerebellum
Authors: Quartu Marina , Serra Maria Pina , Manca Annalisa , Follesa Paolo , Ambu Rossano , Del Fiacco Marina
Published: August 2003

The immunohistochemical occurrence of the high affinity neurotrophin (NT) receptors trkA, trkB, and trkC is shown in the pre‐term newborn, infant, and adult human post‐mortem cerebellum. Immunoreactive neuronal perikarya and processes were observed in all specimens examined, where they appeared unevenly distributed in the cerebellar cortical layers and deep nuclei, and showed regional differences among cerebellar lobules and folia. The trk receptor‐antibodies, tested by Western blot on human cerebellum homogenates, revealed multiple immunoreactive bands for trkA and single bands for trkB and trkC. The results obtained show the tissue localization of the trk receptor‐like immunoreactivity in the human cerebellum from prenatal to adult age. The analysis for codistribution of the receptors with the relevant ligand and among the receptors in discrete cortical and deep nuclei tissue fields shows a wide variety of conditions, from a good similarity in terms of type and density of labeled structures, to a lack of correspondence, and suggests the possibility of colocalization of trk receptors with the relevant neurotrophin and among them in the cerebellar cortex. These results sustain the concept that the neurotrophin trophic system participates in the development, differentiation, and maintenance of the human cerebellar connectivity and support the possibility of a multifactorial trophic support for the neurotrophins through target‐derived and local mechanisms.
Cardioverter‐defibrillators after MADIT‐II: the balance between weight of evidence and treatment costs
Authors: Boriani Giuseppe , Biffi Mauro , Martignani Cristian , Camanini Claudia , Grigioni Francesco , Rapezzi Claudio , Branzi Angelo
Published: August 2003

The possibility of using implantable cardioverter‐defibrillators (ICDs) for primary prevention of sudden death in selected high‐risk patients has prompted a series of prospective controlled studies. Recently, the MADIT II study highlighted the possibility of effective primary prevention of sudden death in patients with coronary artery disease selected by straightforward clinical data and without expensive screening (electrophysiological study). For patients with previous myocardial infarction and low left ventricular ejection fraction (≤30%), ICD implantation may reduce mortality risk by approximately 31% in the following 2 years. Implementation of this therapeutic strategy threatens to impact on public health‐care spending. Possible cost‐limiting mechanisms include price cuts because of increasing usage (market forces); identification of subgroups at higher risk of sudden death and use of cheaper devices with limited diagnostic and therapeutic options. Further long‐term evaluation of the cost‐effectiveness and cost‐utility of ICDs should identify subgroups of patients for whom implantation is affordable despite current economic constraints. For heart failure patients, randomized controlled trials are currently evaluating the effects on overall survival of both conventional ICDs and devices with biventricular pacing capabilities. In this perspective, data from the COMPANION trial are expected to stimulate the use of devices with defibrillation back‐up in candidates for biventricular pacing.
VALsartan In Acute myocardial iNfarcTion (VALIANT) trial: baseline characteristics in context
Authors: Velazquez Eric J. , Pfeffer Marc A. , McMurray John V. , Maggioni Aldo P. , Rouleau Jean‐Lucien , Van de Werf Frans , Kober Lars , White Harvey D. , Swedberg Karl , Leimberger Jeffrey D. , Gallo Paul , Sellers Mary Ann , Edwards Susan , Henis Marc , Califf Robert M. ,   for the VALIANT Investigators
Published: August 2003

Background:

The VALsartan In Acute myocardial iNfarcTion (VALIANT) trial compared outcomes with: (1) angiotensin‐converting enzyme inhibition (ACEI) with the reference agent captopril; (2) angiotensin‐receptor blockade (ARB) with valsartan; or (3) both in patients with heart failure (HF) and/or left ventricular systolic dysfunction (LVSD) after myocardial infarction (MI).

Aims:

A goal of this active‐control trial was to simulate conditions that would lead current practitioners to use ACEIs. Thus, we compared characteristics of VALIANT patients with those of patients in placebo‐controlled trials that established ACEIs as standard treatment.

Methods and Results:

We collected demographic, clinical, medication and imaging information from 14703 patients in 24 countries. This high‐risk population was a median 65.8 years old, and 31.1% were female. Most (51.8%) showed imaging evidence of LVSD at enrollment. Most (72%) had Killip class≥II HF. Patients received evidence‐based therapies at rates similar to those of contemporary MI trials and at an improved rate compared with prior placebo‐controlled ACEI trials.

Conclusion:

VALIANT represents the largest globally representative cohort enrolled with HF and/or LVSD after MI. Patients were similar to those in placebo‐controlled ACEI trials while reflecting improvements in evidence‐based care. With enrollment complete, VALIANT is poised to define the optimal strategy for renin–angiotensin system blockade after MI to improve cardiovascular outcomes.
Breakstructures
Authors: THRANE TORBEN
Published: August 2003

Addressing current generative concerns over the Left Periphery of clause structure, this paper proposes a categorial distinction, based on the choice of value for the feature [±FINITE], between two functional heads, C° and Top°, which project into CP and TopP, respectively. The choice is responsible for a principled distinction between structural (TopP) and rhetorical (CP) topicalization. Primary data are Det-clefts, Hv-clefts and so-called sikke-expressions in Danish. The latter are peripheral to the core of Danish grammar, but are nevertheless – or perhaps therefore – a mine of evidence for the distinction argued for. Criterial evidence is a conjunction of three diagnostics: lack of V2 word order, so-called ‘pleonastic’ complementizers and the syntactic behaviour of expletive der. It is argued that normal (left) movement principles cannot account for the sharing of information between the Specifier and the Complement of Top°. Instead, two possibilities for interpretation are tentatively explored, involving various kinds of Right Periphery phenomena. Since the Specifier and the Complement of Top° each provides the structural basis for independent, clause-like utterances, TopPs are seen as clear cases of BREAKSTRUCTURES.
‘The first thing to know about God’: Kretzmann and Aquinas on the meaning and necessity of arguments for the existence of God
Authors: TE VELDE RUDI A.
Published: August 2003

This paper examines critically Kretzmann's reconstruction of the project of natural theology as exemplified by Aquinas's Summa Contra Gentiles. It is argued that the notion of natural theology, as understood and advocated by Kretzmann, is particularly indebted to the epistemologically biased natural theology of modernity with its focus on rational justification of theistic belief. As a consequence, Kretzmann's view of the arguments for the existence of God and their place within Aquinas's theological project is insufficiently sensitive to the ontological conception of truth and intelligibility which underlies the argumentation. From his epistemological point of view Kretzmann differs from Aquinas in two aspects. First, he contends that it is not necessary to establish the existence of God with absolute certainty at the outset; one may begin with the hypothesis that there is a God. Second, the arguments do not yet conclude to the existence of God in the specific theistic sense; they show at most the existence of a primary explanatory entity, which may be identified with God later on. Both claims are criticized in the light of a discussion of Aquinas's theological method.
Robert E. Hudec 1934–2003
Authors:   The Editor and the Members of the Editorial Board
Published: August 2003

Bob Hudec passed away on 12 March at the age of 68. In the world of GATT and WTO legal scholarship he was a towering intellectual figure of his generation.
Probing the magnetic polarity structure of the heliospheric current sheet
Authors: Kahler S. W. , Crooker N. U. , Larson D. E.
Published: August 2003

We use solar wind heat‐flux electrons to determine the solar magnetic polarities of the interplanetary magnetic field (IMF) close to the heliospheric current sheet (HCS) around the time of the last solar minimum in 1995–1996. At that time the tilt angle of the HCS was very low and solar activity was minimal, allowing the Wind spacecraft to probe the polarities of the fields close to the HCS during a time relatively free of transient interplanetary coronal mass ejections (ICMEs). During the three periods we examined, all solar polarity boundaries predicted from Stanford source surface (SS) maps were observed. During 34 days in which the SS magnetic neutral line skimmed within 3° of the ecliptic, only six tangential excursions into opposite solar polarities were observed. The distribution of the durations of magnetic polarity sectors was very similar to that reported earlier for solar maximum in 1978–1982, showing no increase in sectors which might be expected for a spacecraft trajectory roughly tangential to a corrugated HCS separating regions of opposite polarity. The heat‐flux electron pitch angle distributions, intervals of magnetic false polarities, high‐latitude field excursions, and orientations of minimum variance vectors at polarity boundaries were all similar to those observed away from the boundaries. About one third of the polarity boundaries were displaced from the large‐angle changes of the IMF direction usually thought to define the HCS. These observations suggest a single, globally smooth HCS in the form of a corrugated ribbon much less complex than and often separated from a thicker and more structured surrounding current sheet system formed by IMF discontinuities.
Air‐sea interaction and circulation changes in the northeast Atlantic
Authors: Holliday N. P.
Published: August 2003

The upper ocean of the Rockall Trough exhibits coherent interannual variations in temperature and salinity over the past 26 years, with highs in the mid‐1980s and late 1990s and lows in the late 1970s and early 1990s, and with ranges of ±0.5°C and ±0.05 in salinity. The origins of the interannual changes are discussed, covering three potential influencing factors: the propagation of anomalies developed upstream of the basin, the effect of local air‐sea interaction, and the result of changes of regional circulation bringing different water masses into the region. The changes in heat and freshwater content of the upper ocean are directly compared to observed variations in air‐sea heat and freshwater fluxes over the period of the time series. It is shown that the role of the atmosphere in locally altering the oceanic properties, particularly salinity, is relatively small and insufficient to explain the changes. Two recent hydrographic surveys are analyzed to ascertain how the distribution of water masses to the south of the basin may influence the properties of the northern Rockall Trough upper ocean, and the results are reviewed in the context of historical analyses. It is found that the critical factor in determining the properties is the varying amount of relatively cool and fresh North Atlantic Current water mixing with the dominant water mass, the warm saline Eastern North Atlantic Central Water at the entrance to the basin. Variations of inflowing water masses are caused by east‐west changes in the location of the subpolar front, and the relationship of these changes in regional circulation to the North Atlantic wind stress field is discussed.
Mixing and recirculation in two‐layer exchange flows
Authors: Stenström Petter
Published: August 2003

Mixing and recirculation due to interfacial friction in two‐layer exchange flows through topographic constrictions are investigated using a nonhydrostatic, three‐dimensional numerical model. The simulated exchange flows are always lower than what inviscid hydraulic theory predicts; the reduction is greater for a contraction than for a sill, with intermediate values for sill‐contraction combinations. A large fraction of a tracer flux in one layer is lost to the other layer from an inflow section at the entrance of the contraction (foot of the sill) up to the throat of the contraction (sill crest). For a contraction this fraction is about equal for the two layers, whereas for a sill the loss from the upper to the lower layer is about 6 times as high as the loss from the lower to the upper layer. Sill‐contraction combinations show similar behavior to a contraction toward the dense reservoir and to a sill toward the light reservoir. The variation in recirculation fractions over a tidal cycle is small for flow over a sill, but greater for flow through a contraction. The peak rate of loss from a layer occurs when the flow in the other layer has its maximum, i.e., at maximum negative barotropic flow for the lower layer and at maximum positive barotropic flow for the upper layer.
Seasonal dependence of the long‐range transport and vertical distribution of free tropospheric aerosols over east Asia: On the basis of aircraft and lidar measurements and isentropic trajectory analysis
Authors: Matsuki Atsushi , Iwasaka Yasunobu , Osada Kazuo , Matsunaga Katsuji , Kido Mizuka , Inomata Yayoi , Trochkine Dmitri , Nishita Chiharu , Nezuka Takayoshi , Sakai Tetsu , Zhang Daizhou , Kwon Soung‐An
Published: August 2003

Seasonal changes in the vertical structure of free tropospheric aerosols over east Asia, on the basis of aircraft‐borne and lidar measurements, and on the pathway of the long‐range transport of Asian dust particles inferred from isentropic trajectory analysis are discussed. Aircraft‐borne measurements held in situ in the free troposphere over central Japan in 2000–2001 revealed a small in scale yet steady transport of dust in the lower‐middle free troposphere (2–6 km altitude) during spring including days with no evident dust outbreak. Such dust, found as background, was observed even in summer in the regions higher than 4 km under the influence of remaining westerly winds but not in the lower regions. From a series of lidar observations over Nagoya (35°N, 137°E), Japan, noticeable changes in aerosol characteristics were obtained in the free troposphere from spring to summer. Taklimakan desert is suggested as possible important source of the background dust.
Self‐potential, soil CO2 flux, and temperature on Masaya volcano, Nicaragua
Authors: Lewicki J. L. , Connor C. , St‐Amand K. , Stix J. , Spinner W.
Published: August 2003

We investigate the spatial relationship between self‐potential (SP), soil CO2 flux, and temperature and the mechanisms that produce SP anomalies on the flanks of Masaya volcano, Nicaragua. We measured SP, soil CO2 fluxes (<1 to 5.0 × 104 g m−2 d−1), and temperatures (26 to 80°C) within an area surrounding a normal fault, adjacent to Comalito cinder cone (2002–2003). These variables are well spatially correlated. Wavelengths of SP anomalies are ≤100 m, and high horizontal SP gradients flank the region of elevated flux and temperature. Carbon isotopic compositions of soil CO2 (δ13C = −3.3 to −1.1‰) indicate a deep gas origin. Given the presence of a deep water table (100 to 150 m), high gas flow rates, and subsurface temperatures above liquid boiling points, we suggest that rapid fluid disruption is primarily responsible for positive SP anomalies here. Concurrent measurement of SP, soil CO2 flux, and temperature may be a useful tool to monitor intrusive activity.
Complete and accurate mass spectrometric isotope analysis of tropospheric nitrous oxide
Authors: Kaiser Jan , Röckmann Thomas , Brenninkmeijer Carl A. M.
Published: August 2003

We describe a manual extraction and purification method for mass spectrometric isotope analyses of tropospheric N2O. A theoretical framework to correct for (hydro)fluorocarbon and CO2 interferences is developed and verified experimentally. The standard deviation for analysis of one sample on a single day is 0.05‰ for δ15N and δ18O and 0.2‰ for the relative enrichment of the terminal (1δ5N) and central (2δ5N) nitrogen atoms. The isotopic composition of N2O in tropospheric background air could thus be measured with unprecedented precision on samples from six locations. We obtained overall average values of δ15N = (6.72 ± 0.12)‰ versus air N2 and δ18O = (44.62 ± 0.21)‰ versus Vienna Standard Mean Ocean Water. Neither a clear spatial pattern from 28°N to 79°N, nor a temporal trend over the course of 2 years was found. Within the experimental uncertainties, this is in line with small trends of 0.02 to 0.04‰/a derived from analyses of Antarctic firn air and isotopic budget calculations. Using an independent 2δ15N calibration of our working standard versus air N2, we find large differences in the position‐dependent 15N/14N ratios: The mean for all samples is 1δ15N = (−15.8 ± 0.6)‰ and 2δ15N = (29.2 ± 0.6)‰ versus air N2. In light of a new definition for oxygen isotope anomalies, we reevaluate the existing measurements and derive a 17O excess of Δ17O = (0.9 ± 0.1)‰.
PMX2B, a new candidate gene for Hirschsprung's disease
Authors: Benailly HK , Lapierre JM , Laudier B , Amiel J , Attié T , De Blois MC , Vekemans M , Romana SP
Published: August 2003

Hirschsprung's (HSCR) disease is a congenital intestinal malformation of the enteric nervous system. It is a multigenic malformation and until now, eight genes have been involved in the etiology of this disease: genes encoding proteins of the RET signaling pathway (RET, GDNFandNTN), genes participating in the endothelin (EDN) type B receptor pathway (EDNRB, EDN3andECE‐1), theSOX10gene and theSIP1gene that is mutated in syndromic forms of HSCR. Mutations of these genes are found in not more than 50–60% of affected individuals. Here, we report on the results of a molecular cytogenetic study performed in a girl who presented with a syndromic short segment HSCR associated with ade novot(4;8)(p13;p22) translocation. A comparative genomic hybridization (CGH) study found a 4p12p13 deletion. A molecular characterization of this rearrangement showed that the 4p13 deletion was 5 Mb in length and included the paired mesoderm homeobox gene (PMX2B) (MIM 603851), a gene expressed in the human embryonic gut and essential for the development of autonomic neural crest derivatives. The present observation suggests that PMX2B haploinsuffciency might predispose to HSCR.
Anaphylaxis induced by pine nuts in two young girls
Authors: Ibáñez M. Dolores , Lombardero Manuel , San Ireneo Mercedes Martinez , Muñoz M. Carmen
Published: August 2003

Pine nuts are the seeds of Pinus pinea. There are few reported cases of allergy to pine nut. We describe two young girls with anaphylaxis caused by small amounts of pine nuts. Specific IgE to pine nut was demonstrated by skin prick tests and RAST but no IgE to other nuts and pine pollen was detected. The patients had IgE against a pine nut protein band with apparent molecular weights of ∼17 kDa that could be considered as the main allergen. Our patients were monosensitized to pine nut and the 17‐kDa protein could be correlated with the severe clinical symptoms.
Yeast Functional Analysis: Identification of Two Essential Genes Involved in ER to Golgi Trafficking
Authors: Belgareh‐Touzé Naïma , Corral‐Debrinski Marisol , Launhardt Heike , Galan Jean‐Marc , Munder Thomas , Le Panse Sophie , Haguenauer‐Tsapis Rosine
Published: August 2003

We screened for genes potentially involved in the secretory and vacuolar pathways a collection of 61 yeast strains, each bearing an essential orphan gene regulated by the tetO7‐CYC1 promoter that can be down‐regulated by doxycycline. After down‐regulating the expression of these genes, we performed systematic Western blot analysis for markers of the secretory and vacuolar pathways that undergo post‐translational modifications in their intracellular trafficking. Accumulation of protein precursors, revealed by Western immunoblot analysis, indicates defects in the secretory pathway or in associated biochemical modifications. After screening the whole collection, we identified two genes involved in ER to Golgi trafficking: RER2, a cis‐prenyl transferase, and USE1, the function of which was unknown. We demonstrated that repression of USE1 also leads to BiP secretion, and therefore likely affects retrograde, in addition to anterograde, ER to Golgi trafficking. The collection also includes two essential genes involved in intracellular trafficking that were conveniently repressed without resulting growth or trafficking defects.
Incorporating socio‐political health promotion activities in clinical practice
Authors: Whitehead Dean
Published: August 2003

• A criticism laid at the door of many nurses in relation to their health promotion activity is that they almost exclusively adopt a biomedical/preventative health education approach. When it comes to adopting socio‐political health promotion approaches, there is scant evidence that nurses implement these activities in clinical practice.

• This article is designed to raise awareness and signpost the types of activities that nurses could be involved with if they wish to influence the broader social and political health promotion agenda. In doing so, it has developed an ‘effect’ programme model for socio‐political health promotion practice as a framework for those practitioners who wish to review their current health‐related activities and/or who are seeking to extend their range of health promotional practice.

• This article draws upon a critical review of the literature in order to develop an evolving theoretical perspective for health promotion practice. The proposed model was developed from this new perspective as were recommendations for practice.
A comparison of pain and health‐related quality of life between two groups of cancer patients with differing average levels of pain
Authors: Boström Barbro , Sandh Marie , Lundberg Dag , Fridlund Bengt
Published: August 2003

• A study was performed to describe and compare pain and Health‐Related Quality of Life (HRQOL) in two groups of cancer patients in palliative care as well as to describe the correlation between pain and HRQOL.

• Forty‐seven patients with mild average pain [Visual Analogue Scale (VAS) ≤ 3] and 28 patients with moderate to severe average pain (VAS > 3) were included. Medical Outcomes Study Short Form (SF‐36) was used to evaluate HRQOL, pain intensity levels were measured with the VAS on Pain‐O‐Meter.

• Compared to patients with mild pain, patients with moderate to severe pain had statistically significant, higher pain intensity for the items ‘pain at time of interview’, ‘worst pain in the past 24 hours’ and ‘pain interrupting sleep.’ They also had the lowest scores of the SF‐36 dimensions: physical functioning, role‐physical, and bodily pain. Patients with moderate to severe pain had statistically significant, fewer months of survival. There were statistically significant positive correlations between pain items and negative correlation between pain and SF‐36 dimensions.

• The conclusion is that pain has a negative impact on HRQOL, especially on physical health and that pain increases towards the final stages of life. Even if patients have to endure symptoms such as fatigue and anxiety during their short survival time, dealing with pain is an unnecessary burden, which can be prevented.
The reality of clinical learning in critical care settings: a practitioner:student gap?
Authors: Endacott Ruth , Scholes Julie , Freeman Marnie , Cooper Simon
Published: August 2003

• This article reports on the clinical phase of a study commissioned by the English National Board for Nursing, Midwifery and Health Visiting to evaluate the effectiveness of educational preparation for critical care nursing [Scholes & Endacott (2002) Evaluation of the Effectiveness of Educational Preparation for Critical Care Nursing. ENB, London]. The authors draw on observation and interview data from clinical settings (general and paediatric intensive care units; operating theatre departments; accident and emergency departments and coronary care units), focusing specifically on the way in which curricular intentions were made a reality in clinical practice. The reality of learning in practice is examined, with evidence from the data to illustrate the real world of clinical practice.

• Different models of support and supervision are identified, alongside strategies used to create different learning opportunities. The majority of students remained in their own workplace when undertaking the English National Board for Nursing, Midwifery and Health Visiting clinical course. This raised a number of issues for the students and their colleagues which we have labelled the practitioner:student gap. The authors discuss the impact this has on supernumerary status, perceptions of learning and opportunities to undertake placements.
Expression of single copies of a strongly expressed 35S transgene can be silenced post‐transcriptionally
Authors: Elmayan Taline , Vaucheret Hervé
Published: August 2003

The bacterial UidA gene cloned between the 35S promoter with a double enhancer and the terminator sequences of the pea rbcS 9C gene was introduced into tobacco plants. All 11 transformants carrying the transgene at a single locus showed silencing at each generation, but the timing of silencing occurred at different rates in the different transformants. Two plants showed high levels of UidA mRNA accumulation and GUS activity in young seedlings and a rapid decline of these levels during the first month of growth irrespective of the allelic state of the T‐DNA. The other plants showed high levels of UidA mRNA accumulation and GUS activity in young seedlings and a slow decline of these levels during the first 4 months of growth in homozygous plants, whereas these levels decline only after 1 year of growth in hemizygous plants. Haploids showed the same kinetics of silencing as the homozygous plants from which they derived. Silencing correlated with a strong decrease of the steady‐state level of UidA mRNA, while the transcription of the transgene in the nucleus was not affected. Since haploids and hemizygous plants derived from transformants carrying a single copy of the T‐DNA show silencing, and since all the plants express the transgene at a very high level before the triggering of silencing, the results suggest that post‐transcriptional silencing occurs through a dose effect and not through DNA‐DNA interaction.
Identification with a photoaffinity reagent of a tonoplast protein involved in vacuolar malate transport of Catharanthus roseus
Authors: Lahjouji Karim , Carrasco Antoine , Bouyssou Huguette , Cazaux Louis , Marigo Gérard , Canut Hervé
Published: August 2003

The effect of N‐(4‐azido‐salicylyl) aspartic acid (AzSA), a photolysable analogue of malate, was tested on the malate transport activity of tonoplast vesicles isolated from Catharanthus roseus cell suspension cultures. AzSA inhibited malate uptake in a competitive manner with a Kti of 1.7 millimolar. When iodinated, the malate analogue was found to be still photolysable and a competitive inhibitor of malate uptake. Photolysis of 125I‐labelled AzSA in the presence of purified tonoplast vesicles led to label incorporation into several polypeptides after analysis by gel electrophoresis. Only one polypeptide, with an apparent molecular mass of 37 kDa, was totally protected by the inclusion of 50 millimolar malate, the original substrate, in the photolysis medium. The labelled polypeptide is therefore apparently a specific malate‐binding protein. Diethylpyrocarbonate (DEPC), a very potent inhibitor of malate transport acting at the active site of the transporter, also protected the 37 kDa polypeptide from labelling. Citrate and, to a lesser extent, quinate afforded protection from labelling whilst other organic acids or aspartic acid (100 millimolar) did not. These photoprotection results are in good agreement with the data concerning the specificity of malate transport across the tonoplast. Polyclonal antibodies against the 37 kDa polypeptide strongly inhibited malate uptake both in tonoplast vesicles and in isolated vacuoles. These results suggest the involvement of the 37 kDa polypeptide in vacuolar malate transport.
A second form of adenine phosphoribosyltransferase in Arabidopsis thaliana with relative specificity towards cytokinins
Authors: Schnorr Kirk Matthew , Gaillard Catherine , Biget Elisabeth , Nygaard Per , Laloue Michel
Published: August 2003

Adenine phosphoribosyltransferase (APRTase) is an important enzyme for its ability to convert adenine, a by‐product of many biochemical reactions, into AMP. By functional complementation of an Escherichia coli mutant, cDNAs encoding two APRTases have been cloned from Arabidopsis thaliana. One of the cDNAs (ATapt1)has been previously identified while the second (ATapt2) is of a previously unknown type. Kinetic analysis of the two enzymes purified from E. coli expressing the two cDNAs indicates that ATapt2 has a higher affinity for cytokinin than the ATapt1. RNase protection studies indicate that the ATapt2, is not expressed in leaves. Analysis of the gene structure indicates that ATapt2 has identical intron positions to ATapt1, but neither the intron sequence nor intron size are conserved between the two genes. The implications of a second, differentially expressed APRTase with affinity for both adenine and cytokinin are discussed.
A role for arabinogalactan‐proteins in plant cell expansion: evidence from studies on the interaction of β‐glucosyl Yariv reagent with seedlings of Arabidopsis thaliana
Authors: Willats William G.T. , Knox J. Paul
Published: August 2003

Seedlings of Arabidopsis thaliana were germinated and grown in medium containing β‐glucosyl Yariv reagent (βGlcY), a synthetic phenyl glycoside that interacts specifically with arabinogalactan‐proteins (AGPs), a class of plant cell surface proteoglycans. The effect of βGlcY on the seedlings was to reduce the overall growth of both the root and the shoot. βGlcY only accumulated in the root tissues and the reduced growth of the shoot appeared to be an indirect effect of impaired root growth. Reduced root growth was a consequence of a reduction in cell elongation during the postproliferation phase of elongation at the root apex and this was associated with extensive radial expansion of root epidermal cells. βGlcY penetrated roots as far as the endodermis and it is suggested that the interaction of βGlcY with AGPs in the load‐bearing cell layers inhibited root elongation. When βGlcY was added to carrot suspension‐cultured cells that had been induced to elongate rather than proliferate, cell elongation was inhibited. The AGP‐unreactive α‐galactosyl Yariv reagent (αGalY) had no biological activity in either of these systems.
Lc as a non‐destructive visual reporter and transposition excision marker gone for tomato
Authors: Goldsbrough Andrew P. , Tong Yusen , Yoder John I.
Published: August 2003

The maize anthocyanin regulatory gone Lc gives rise to greatly enhanced anthocyanin accumulation when introduced into tomato. Under the control of the cauliflower mosaic virus promoter Lc was seen to mediate enhanced pigmentation in all vegetative tissues, including roots, under high light (or sunlight) conditions. This paper demonstrates that the gone can be used as a powerful non‐destructive cell autonomous visual excision marker which will provide a valuable tool for transposon mutagenesis, the study of transposon biology and for studying cell lineages at the whole‐plant level.
Comparative dose‐dependence study of FK506 on transected mouse sciatic nerve repaired by allograft or xenograft
Authors: Udina Esther , Voda Jan , Gold Bruce G. , Navarro Xavier
Published: August 2003

Abstract  We evaluated the effects of FK506, at doses of 0.2, 2, and 5 mg/kg/day, on the response to nerve grafts implanted in outbred mice. A 6 mm long segment of the sciatic nerve was transected and repaired by autograft (the same segment resected), allograft (from another mouse), or xenograft (from a rat nerve). The regenerating nerves were harvested after 3 weeks and studied under light and electron microscope. Allografts of animals treated with the 5 mg/kg/day dose of FK506 appeared similar to those from autografts, demonstrating an equivalent number of myelinated fibers. In mice treated with the 2 mg/kg/day dose, regeneration was slightly hindered, as indicated by the reduced number of myelinated fibers. In contrast, in mice given a 0.2 mg/kg/day dose of FK506, allografts were not different from untreated allografts; both groups showed a marked rejection response with only few unmyelinated axons and no myelinated fibers. Xenografts showed a more severe rejection than allografts, with a marked inflammatory cell reaction throughout the graft. In contrast, in mice treated with the 5 mg/kg/day dose, xenografts exhibited a mild cell reaction and a greater number of regenerated myelinated fibers. In conclusion, effective axonal regeneration is achieved with FK506 administration at doses of 5 mg/kg/day through allografts and, partially, through xenografts.
Mind the Model: Effect of Instrumentation on Inducibility of Atrial Fibrillation in a Sheep Model
Authors: WILLEMS RIK , HOLEMANS PATRICIA , ECTOR HUGO , SIPIDO KARIN R. , VAN DE WERF FRANS , HEIDBÜCHEL HEIN
Published: August 2003

Effect of Instrumentation on AF in a Sheep Model.
Introduction: Atrial electrical remodeling, shortening of the atrial effective refractory period (AERP) underlying atrial fibrillation (AF) has been described in different animal models. However, there remains some controversy regarding the time course of this electrical remodeling and the need for secondary factors in the development of AF. We investigated the effect of instrumentation on the inducibility of AF. We hypothesized that epicardial instrumentation could be a confounding factor that accelerates the development of AF.

Methods and Results: Thirty sheep were rapidly atrially paced at 600 beats/min for 15 weeks: 15 were endocardially instrumented and paced (endo), and 15 were both endocardially and epicardially instrumented. Six of these animals were endocardially paced (sham) and 9 were epicardially paced (epi). The underlying rhythm was determined at regular intervals, and electrophysiologic study was performed. AF developed significantly faster in the epi group. After 3 weeks of pacing, the cumulative incidence of sustained AF (> 1 hour) already was 70% in this group versus only 14% and 20% in the endo and sham groups, respectively. After 15 weeks of pacing, this difference was no longer evident. Baseline AERP and minimal AERP, reached before the development of AF, were not significantly different in the three groups. Epicardial instrumentation (epi and sham) increased baseline left and right atrial pressures, but only epicardial stimulation (epi) led to early development of AF.

Conclusion: In this sheep model of AF, the experimental setup is a major determinant of the inducibility of AF. Not epicardial instrumentation per se but epicardial stimulation accelerated the development of AF. Different animal models of AF may represent different clinical entities of AF.
Differentiation of Atrial and Pulmonary Vein Potentials Recorded Circumferentially Within Pulmonary Veins
Authors: TADA HIROSHI , ORAL HAKAN , GREENSTEIN RADMIRA , PELOSI FRANK , KNIGHT BRADLEY P. , STRICKBERGER S. ADAM , MORADY FRED
Published: August 2003

Pulmonary Vein Electrograms.
Introduction: Accurate discrimination of atrial and pulmonary vein potentials recorded circumferentially within the pulmonary veins is important when performing segmental isolation of the pulmonary veins in patients with atrial fibrillation.

Methods and Results: Twenty patients with paroxysmal atrial fibrillation underwent pulmonary vein mapping with a decapolar Lasso catheter during sinus rhythm and during pacing in the distal coronary sinus and left atrial appendage. Bipolar and unipolar electrograms were recorded within the left superior, right superior, and left inferior pulmonary veins. The atrial potentials were larger in the left pulmonary veins than in the right superior pulmonary vein, whereas the pulmonary vein potentials in the superior pulmonary veins were larger than in the left inferior pulmonary vein. The atrial and pulmonary vein potentials usually were readily distinguished during sinus rhythm in the right superior pulmonary vein. Characteristic distribution and morphologies of the atrial potentials as well as the response to distal coronary sinus and left atrial appendage pacing were useful for differentiating the atrial and pulmonary vein potentials in the left pulmonary veins.

Conclusion: Atrial and pulmonary vein potentials recorded circumferentially within the pulmonary veins have characteristic features that are useful in distinguishing them from each other.In the left pulmonary veins, discrimination of the atrial and pulmonary vein potentials is aided by coronary sinus or left atrial appendage pacing.
Class I Antiarrhythmic Drug and Coronary Vasospasm‐Induced T Wave Alternans and Ventricular Tachyarrhythmia in a Patient with Brugada Syndrome and Vasospastic Angina
Authors: CHINUSHI YUKO , CHINUSHI MASAOMI , TOIDA TATUNARI , AIZAWA YOSHIFUSA
Published: August 2003

T Wave Alternans in Brugada Syndrome and Vasospastic Angina. A 50‐year‐old man presented with a history of transient chest pain and palpitations. The 12‐lead ECG at rest showed normal sinus rhythm. A slight ST segment elevation was observed in leads V1 to V3. During hospitalization, atrial fibrillation developed, and oral pilsicainide was administered. Thirty minutes after the drug was given, the ECG showed marked ST segment elevation in leads V1 to V3, and T wave alternans became visible in leads V2 and V3. Self‐terminating ventricular tachycardia was initiated following frequent ventricular premature complexes, which showed a left bundle branch block pattern. The coronary angiogram was normal, but in the provocation test of vasospastic angina, acetylcholine administration into the left coronary artery resulted in complete occlusion of the left anterior descending and circumflex arteries. Marked ST segment elevation developed in leads I, aVL, and V3 to V6 concomitant with visible QT/T alternans in leads V4 and V5, and ventricular tachyarrhythmia was initiated. Brugada syndrome and vasospastic angina coexisted in this patient, and T wave alternans can be used as a predictor of ventricular tachyarrhythmias in such patients.
Mechanisms for Atrial Fibrillation in Patients with Wolff‐Parkinson‐White Syndrome
Authors: HAMADA TAKASHI , HIRAKI TATSURO , IKEDA HISAO , KUBARA ICHIRO , YOSHIDA TERUHISA , OHGA MASANOBU , IMAIZUMI TSUTOMU
Published: August 2003

Atrial Fibrillation and WPW Syndrome.
Introduction: Paroxysmal atrial fibrillation (PAF) frequently occurs in patients with Wolff‐Parkinson‐White (WPW) syndrome. To elucidate the mechanisms for PAF, we performed electrophysiologic studies (EPS) before and after ablation of accessory pathways (APs).

Methods and Results: We investigated 24 patients with WPW syndrome who had AV reciprocating tachycardia and prior PAF and had undergone successful ablation of APs. Patients in whom atrial fibrillation (AF) was induced by EPS at day 7 after ablation were considered the inducible AF group (n = 14), and patients in whom AF was not induced by EPS at day 7 after ablation were considered the noninducible AF group (n = 10). Fifteen patients with AV nodal reentrant tachycardia (AVNRT) but without PAF who underwent ablation of the slow AV nodal pathways served as the control group (AVNRT group). Maximal atrial conduction delay and conduction delay zone, which are indices of atrial vulnerability, were measured before and after ablation. Before ablation, maximal atrial conduction delay and conduction delay zone were significantly greater (P < 0.0001 and P < 0.0001, respectively) in the two WPW syndrome groups than in the AVNRT group, indicating increased atrial vulnerability in WPW syndrome with PAF. After ablation, these parameters did not change in the inducible AF group, whereas they were significantly (P < 0.0001) decreased in the noninducible AF group and were not different from those in the AVNRT group, indicating normalized atrial vulnerability in the noninducible AF group after ablation. The prospective study demonstrated that PAF recurred only in the inducible AF group during long‐term follow‐up (17 ± 7 months).

Conclusion: The findings of this study suggest that there are two mechanisms of PAF in patients with WPW syndrome: one mechanism is reversible and AP‐dependent atrial vulnerability, and the other is intrinsic and AP‐independent atrial vulnerability.