bluuebunny/crossref_metadata_2025 huggingface dataset:
T helper 2 biased de novo immune response to Keyhole Limpet Hemocyanin in humans
Authors: Spazierer D. , Skvara H. , Dawid M. , Fallahi N. , Gruber K. , Rose K. , Lloyd P. , Heuerding S. , Stingl G. , Jung T.
Published: February 2009

Background
Allergen‐specific T helper 2 (Th2) cells play an important role in the pathogenesis of atopic disorders. To date, no model system exists in humans that would allow the monitoring of a developing de novo Th2 immune response in vivo.

Objective
The aim of the experiment was to establish an immunization protocol inducing a de novo Th2 response in humans using Keyhole Limpet Hemocyanin (KLH) as neo‐antigen.

Methods
The double‐blind placebo‐controlled, parallel‐group study was conducted in two groups of subjects (16 healthy volunteers and 16 patients with allergic rhinitis). Subjects received three i.m. injections of 100 μg KLH adsorbed to aluminium hydroxide or matching placebo (alum alone) in intervals of 2 weeks. On day 43, KLH alone (10 μg) was given intra‐dermally (i.d.) to all subjects to assess immediate and late‐phase skin responses.

Results
The immunization protocol was well tolerated, highly specific and efficient. Antigen‐specific production of Th2‐cytokines (mainly IL‐5 and IL‐13) by PBMCs suggested a Th2 pattern, as did the presence of KLH‐specific IgG4 in sera. Intra‐dermal KLH challenge induced an immediate‐type of response predominantly in atopic subjects followed by a late‐phase skin reaction. The latter was accompanied by the presence of IgE+ cells, eosinophils and a strong up‐regulation of IL‐4 and IL‐13 along with the absence of Th1 transcripts in biopsies taken from the site of antigen challenge. IL‐17 and IL‐22 transcripts were detected only in healthy subjects skin following KLH challenge, while IL‐1β and IL‐33 expression did not differ between the healthy and the atopics.

Conclusions
The immunization protocol resulted in the elicitation of a local and peripheral Th2 immune response in both healthy and atopic individuals. This may permit the investigation and monitoring of novel immunomodulatory strategies aiming to interfere with Th2 responses in man. The relevance of lack of Th17 cells in atopic skin in this model remains to be determined.
Assessment of the tolerance to lupine‐enriched pasta in peanut‐allergic children
Authors: Fiocchi A. , Sarratud P. , Terracciano L. , Vacca E. , Bernardini R. , Fuggetta D. , Ballabio C. , Duranti M. , Magni C. , Restani P.
Published: February 2009

Background
Reports of allergy to lupine derivatives (as de novo sensitization or cross‐reactivity in subjects allergic to peanut) are increasing as their use in food products increases.

Objectives
The aim of this study was to assess: (1) lupine tolerance in a group of children allergic to peanut, using lupine enriched‐pasta instead of raw flour as has been done in previous clinical studies; (2) whether technological treatments of lupine modify its cross‐reactivity or co‐sensitization with peanut; (3) the role of lupine seed proteins in sensitization, and (4) to identify the eliciting doses (EDs) by using double‐blind, placebo‐controlled food challenges (DBPCFC).

Methods
Twelve patients with a history of clinical allergic reactions to peanut were evaluated by skin prick tests (SPTs), the ImmunoCAP® test, immunoblotting, and DBPCFC. The 12 selected subjects were included in a trial where lupine‐enriched pasta and placebo pasta were administered in a DBPCFC protocol.

Results
Positive clinical reactions were observed in two children, the EDs being 0.2 and 6.4 g of pasta, corresponding to 50 mg and 1.6 g of lupine proteins, respectively. β‐conglutin was the protein most involved in SPT positivity.

Conclusion
Lupine‐enriched pasta can be tolerated by most subjects suffering from peanut allergy, but a sizeable minority (2/12 of them in this case) can develop potentially dangerous clinical reactions. Information about possible reactions to lupine derivatives by those allergic to peanuts must be included in the labelling of lupine‐enriched products to protect consumers at risk.
Vascular endothelial growth factor in allergen‐induced nasal inflammation
Authors: Choi G‐S , Park H‐J , Hur G‐Y , Choi S‐J , Shin S‐Y , Ye Y‐M , Park H‐S
Published: February 2009

Background
Increased vessel number and permeability are important features of the nasal mucosa in allergic rhinitis (AR), and are mediated in part by the cytokine vascular endothelial growth factor (VEGF). Eosinophils are the major effector cells in the nasal secretions of patients with AR during the responses to allergen challenges. To evaluate the involvement of VEGF in nasal allergic inflammation, we monitored the levels of VEGF, eosinophil cationic protein (ECP), and specific antibodies in the nasal lavage fluids (NLFs) of patients with AR in response to Dermatophagoides pteronyssinus (Dpt).

Methods
Sixty‐three subjects with sensitization to Dpt were enrolled: 29 patients with AR (group I) who showed positive responses in a nasal provocation test (NPT) with Dpt; and 34 asymptomatic controls (group II) who showed sensitization to Dpt but negative NPT results. NLF samples were collected at baseline, 10, 30, and 60 min, and at 3, 6, and 24 h during the NPT. The ECP levels in the NLF samples were measured using the ImmunoCAP system. VEGF and Dpt‐specific IgE, IgA, and IgG in the NLF samples were detected by ELISA.

Results
The eosinophil counts and ECP levels in the samples were significantly increased in group I, but not in group II, during the early and late responses. Although the baseline VEGF level was not significantly different between groups I and II, increased VEGF production was noted in group I after the NPT, especially during the early response. The level of Dpt‐specific IgA was significantly increased in group I during the NPT. A relationship was found between the levels of VEGF and ECP or Dpt‐specific IgA in the NLF samples collected at 10 min and at 3–6 h (P<0.05, respectively).

Conclusion
Nasal VEGF secretion in response to allergen exposure may augment eosinophilic inflammation in the nasal mucosa of patients with AR.
Aligned vertical fractures, HTI reservoir symmetry and Thomsen seismic anisotropy parameters for polar media
Authors: Berryman James G.
Published: February 2009

Certain crack‐influence parameters of Sayers and Kachanov are shown to be directly related to Thomsen's weak‐anisotropy seismic parameters for fractured reservoirs when the crack/fracture density is small enough. These results are then applied to the problem of seismic wave propagation in polar reservoirs, i.e., those anisotropic reservoirs having two axes that are equivalent but distinct from the third axis), especially for horizontal transversely isotropic seismic wave symmetry due to the presence of aligned vertical fractures and resulting in azimuthal seismic wave symmetry at the Earth's surface. The approach presented suggests one method of inverting for fracture density from wave speed data. A significant fraction of the technical effort in the paper is devoted to showing how to predict the angular location of the true peak (or trough) of the quasi‐SV‐wave for polar media and especially how this peak is related to another angle that is very easy to compute. The axis of symmetry is always treated here as the x3‐axis for either vertical transversely isotropic symmetry (due, for example, to horizontal cracks), or horizontal transversely isotropic symmetry (due to aligned vertical cracks). Then, the meaning of the stiffnesses is derived from the fracture analysis in the same way for vertical transversely isotropic and horizontal transversely isotropic media, but for horizontal transverse isotropy the wave speeds relative to the Earth's surface are shifted by 90o in the plane perpendicular to the aligned vertical fractures. Skempton's poroelastic coefficient B is used as a general means of quantifying the effects of fluids inside the fractures. Explicit Biot‐Gassmann‐consistent formulas for Thomsen's parameters are also obtained for either drained or undrained fractures resulting in either vertical transversely isotropic or horizontal transversely isotropic symmetry of the reservoir.
Vertically fractured transversely isotropic media: dimensionality and deconstruction
Authors: Schoenberg Michael A.
Published: February 2009

A vertically fractured transversely isotropic (VFTI) elastic medium is one in which any number of sets of vertical aligned fractures (each set has its normal lying in the horizontal x1, x2‐plane) pervade the medium and the sets of aligned fractures are the only features of the medium disturbing the axi‐symmetry about the x3‐axis implying that in the absence of fractures, the background medium is transversely isotropic (TI). Under the assumptions of long wavelength equivalent medium theory, the compliance matrix of a fractured medium is the sum of the background medium's compliance matrix and a fracture compliance matrix. For sets of parallel rotationally symmetric fractures (on average), the fracture compliance matrix is dependent on 3 parameters − its normal and tangential compliance and its strike direction. When one fracture set is present, the medium is orthorhombic and the analysis is straightforward. When two (non‐orthogonal) or more sets are present, the overall medium is in general elastically monoclinic; its compliance tensor components are subject to two equalities yielding an 11 parameter monoclinic medium. Constructing a monoclinic VFTI medium with n embedded vertical fracture sets, requires 5 TI parameters plus 3×n fracture set parameters. A deconstruction of such an 11 parameter monoclinic medium involves using its compliance tensor to find a background transversely isotropic medium and several sets of vertical fractures which, in the long wavelength limit, will behave exactly as the original 11 parameter monoclinic medium. A minimal deconstruction, would be to determine, from the 11 independent components, the transversely isotropic background (5 parameters) and two fracture sets (specified by 2 × 3 = 6 parameters). Two of the background TI medium's compliance matrix components are known immediately by inspection, leaving nine monoclinic components to be used in the minimal deconstruction of the VFTI medium. The use of the properties of a TI medium, which are linear relations on its compliance components, allows the deconstruction to be reduced to solving a pair of non‐linear equations on the orientations of two fracture sets. A single root yielding a physically meaningful minimum deconstruction yields a unique minimal representation of the monoclinic medium as a VFTI medium. When no such root exists, deconstruction requires an additional fracture set and uniqueness is lost. The boundary between those monoclinic media that have a unique minimal representation and those that do not is yet to be determined.
P‐wave dispersion and attenuation in fractured and porous reservoirs – poroelasticity approach
Authors: Gurevich Boris , Brajanovski Miroslav , Galvin Robert J. , Müller Tobias M. , Toms‐Stewart Julianna
Published: February 2009

Natural fractures in hydrocarbon reservoirs can cause significant seismic attenuation and dispersion due to wave induced fluid flow between pores and fractures. We present two theoretical models explicitly based on the solution of Biot's equations of poroelasticity. The first model considers fractures as planes of weakness (or highly compliant and very thin layers) of infinite extent. In the second model fractures are modelled as thin penny‐shaped voids of finite radius. In both models attenuation is a result of conversion of the incident compressional wave energy into the diffusive Biot slow wave at the fracture surface and exhibits a typical relaxation peak around a normalized frequency of about 1. This corresponds to a frequency where the fluid diffusion length is of the order of crack spacing for the first model and the crack diameter for the second. This is consistent with an intuitive understanding of the nature of attenuation: when fractures are closely and regularly spaced, the Biot's slow waves produced by cracks interfere with each other, with the interference pattern controlled by the fracture spacing. Conversely, if fractures are of finite length, which is smaller than spacing, then fractures act as independent scatterers and the attenuation resembles the pattern of scattering by isolated cracks. An approximate mathematical approach based on the use of a branching function gives a unified analytical framework for both models.
Geomechanical simulation to predict open subsurface fractures
Authors: Lewis Helen , Hall Stephen A. , Couples Gary D.
Published: February 2009

Geomechanical simulation of the evolution of a geological structure can play an important role in predicting open fracture development for all stages in that structure's development. In this work, three such geomechanical simulations are used to predict the evolving stress and strain fields, including dilational and compactional changes in the rock fabric in developing fault and fold systems. Their consequences for open fracture development and flow are addressed. These simulated stress and strain fields show considerable spatial and temporal heterogeneity that is consistent with deformation patterns observed in both natural examples and in laboratory‐deformed analogues. But the stress and strain states that develop are neither co‐axial nor do they bear a simple relationship to one another. The dilational and compactional strains, manifest as open fracturing or sealing, represent some significantly increased or significantly decreased flow rates. However, open‐fracture predictions based on such geomechanical simulations are extremely difficult to validate with any degree of confidence as there is little direct evidence of sub‐surface fracture distributions. In this context we also discuss possible integration of seismic anisotropy measurements, as an independent measure of open fracture alignment, to support the geomechanically derived fracture predictions. The focus of this work is on volumetric strains in fault zone evolution, though folding is also addressed.
Variable temperature sensitivity of soil organic carbon in North American forests
Authors: FISSORE CINZIA , GIARDINA CHRISTIAN P. , SWANSTON CHRISTOPHER W. , KING GARY M. , KOLKA RANDALL K.
Published: February 2009

We investigated mean residence time (MRT) for soil organic carbon (SOC) sampled from paired hardwood and pine forests located along a 22 °C mean annual temperature (MAT) gradient in North America. We used acid hydrolysis fractionation, radiocarbon analyses, long‐term laboratory incubations (525‐d), and a three‐pool model to describe the size and kinetics of the acid insoluble C (AIC), active and slow SOC fractions in soil. We found that active SOC was 2 ± 0.2% (mean ± SE) of total SOC, with an MRT of 33 ± 6 days that decreased strongly with increasing MAT. In contrast, MRT for slow SOC and AIC (70 ± 6% and 27 ± 6% of total SOC, respectively) ranged from decades to thousands of years, and neither was significantly related to MAT. The accumulation of AIC (as a percent of total SOC) was greater in hardwood than pine stands (36% and 21%, respectively) although the MRT for AIC was longer in pine stands. Based on these results, we suggest that the responsiveness of most SOC decomposition in upland forests to global warming will be less than currently modeled, but any shifts in vegetation from hardwood to pine may alter the size and MRT of SOC fractions.
Spatial modelling of nitrous oxide emissions at the national scale using soil, climate and land use information
Authors: LILLY A. , BALL B. C. , MCTAGGART I. P. , DEGROOTE J.
Published: February 2009

Nitrous oxide (N2O) is a powerful greenhouse gas. The UK government is committed to reducing all greenhouse gas emissions and is required to make an inventory of the sources and emissions of these gases. Here, we extend work from a pilot study at the catchment scale reported in an earlier paper. This paper reports on the upscaling measurements of emissions to derive annual emission rates for specific combinations of soil type, land management and fertiliser practices to the national scale. Digital soil, climate and land use maps were combined within Geographic Information Systems (GIS) software. Upscaling of field emissions measurements involves adjusting measured annual N2O emissions to fit combinations of crop growth cycles, soil wetness and the amount and timing of fertiliser applications. We have also taken account of the differences in emission rates from grazed pasture land due to differences in land management between land utilised for dairy production and land utilised for beef production. Calculated annual emission rates were then spatially scaled to derive national figures through the use of a GIS modelling framework, termed NitOx. The annual emission of N2O from Scotland was determined as approximately 6 000 000 kg N yr−1 (2.8 Mt carbon dioxide (CO2) equivalents) and compares favourably with other national scale estimates such as the IPCC (1997). The combination of animal grazing, high N inputs, climatic warmth and poorly drained soils means that the south west contributes significantly to the national total N2O emissions. Localised areas of high emission can also be identified, but identification could be improved by applying this modelling approach at a larger scale. It would be beneficial to target these areas with mitigation strategies.
Biogeographical patterns of marine larval trematode parasites in two intermediate snail hosts in Europe
Authors: Thieltges David W. , Ferguson MacNeill A. D. , Jones Cathy S. , Noble Leslie R. , Poulin Robert
Published: February 2009

Aim  We used published inventories of trematodes in Littorina littorea (L.) and Hydrobia ulvae (Pennant) in European seas to search for two basic biogeographical patterns in the spatial occurrence of various trematode species: (1) do parasite distribution and richness patterns in the two host snails overlap with known ecoregions of free‐living organisms; and (2) does trematode species richness in the snails follow latitudinal or longitudinal gradients?

Location  North East Atlantic.

Methods  We used multidimensional scaling (MDS), analysis of similarity (ANOSIM) and analysis of variance (ANOVA) to test whether there were overlaps of parasite distribution and richness with known ecoregions of free‐living organisms. In addition, we used linear regression analyses to test whether trematode richness in snails (corrected for sampling effort) was correlated with the latitude or longitude of the sampling sites.

Results  When corrected for sampling effort, mean trematode species richness per site did not differ among the different ecoregions in L. littorea. In contrast, in H. ulvae, mean species richness was much lower for sites from the Celtic Sea compared with sites from the Baltic Sea and the North Sea. Based on the results of MDS analyses, trematode species composition was distinct among ecoregions; in particular, communities from the Baltic Sea differed markedly from communities in the Celtic Sea, for both snail species. Latitude and longitude were not significantly correlated with parasite species richness in either snail species. Most trematode species had restricted distributions, and only three species in L. littorea and five species in H. ulvae occurred at more than 50% of the sites.

Main conclusions  There is more structure in the large‐scale distribution of trematodes in gastropods than one would expect from the large‐scale dispersal capabilities of their bird and fish final hosts. We propose mechanisms based both on limited dispersal via fish and bird final hosts and on gradients in environmental factors to explain the observed patterns.
Prospects and challenges for parametric models in historical biogeographical inference
Authors: Ree Richard H. , Sanmartín Isabel
Published: February 2009

In historical biogeography, phylogenetic trees have long been used as tools for addressing a wide range of inference problems, from explaining common distribution patterns of species to reconstructing ancestral geographic ranges on branches of the tree of life. However, the potential utility of phylogenies for this purpose has yet to be fully realized, due in part to a lack of explicit conceptual links between processes underlying the evolution of geographic ranges and processes of phylogenetic tree growth. We suggest that statistical approaches that use parametric models to forge such links will stimulate integration and propel hypothesis‐driven biogeographical inquiry in new directions. We highlight here two such approaches and describe how they represent early steps towards a more general framework for model‐based historical biogeography that is based on likelihood as an optimality criterion, rather than having the traditional reliance on parsimony. The development of this framework will not be without significant challenges, particularly in balancing model complexity with statistical power, and these will be most apparent in studies of regions with many component areas and complex geological histories, such as the Mediterranean Basin.
Multi‐stemmed trees in montane rain forests: their frequency and demography in relation to elevation, soil nutrients and disturbance
Authors: Bellingham Peter J. , Sparrow Ashley D.
Published: February 2009

Multi‐stemmed trees are a common component of tropical and temperate montane rain forests, where they co‐occur with single‐stemmed trees. We hypothesized that multi‐stemmed architecture should predominate in less productive sites (such as at high elevation or with low soil nutrient availability) and that, because it frequently results from sprouting, it should prevail in sites that are frequently disturbed. We also hypothesized that where multi‐stemmed architecture predominates, there should be lower rates of mortality and recruitment of individuals.

We tested these hypotheses using data from permanent plots in tropical montane rain forests in Jamaica (14 years) and in temperate montane rain forests in New Zealand (19 years). The frequency of multi‐stemmed trees varied across plots in both forests (4–34% in Jamaica; 0–21% in New Zealand) along gradients of elevation and soil nutrients.

Analyses examined the direct and indirect effects of the various environmental variables that are likely to drive site productivity and disturbance. We showed contrasting predictors of the frequency of multi‐stemmed trees in the tropical and temperate forests. Multi‐stemmed trees in Jamaican forests were most frequent on sites of low soil nutrient status (especially available soil phosphorus, P) whereas in New Zealand they were most frequent at high elevation sites, especially towards tree line. In both forests there was no relationship between multi‐stemmed tree frequency and slope.

Turnover (the mean of mortality and recruitment rates) of multi‐stemmed trees in Jamaican forests was lowest on sites of low soil nutrient status (especially available P) but was unrelated to environmental predictors in New Zealand. In both forests, turnover rates of multi‐stemmed trees overall were 60% lower than those for co‐occurring single‐stemmed trees, offering support for the hypothesis that multi‐stemmed architecture favours persistence.

Synthesis. Our study demonstrates that multi‐stemmed trees can predominate in low productivity sites in montane rain forests. Their low turnover compared with co‐occurring single‐stemmed trees confirms the importance of evaluating the persistence niche as a mechanism promoting woody species coexistence in forests.
Streptococcosis on a red tilapia, Oreochromis sp., farm: a case study
Authors: Hernández E , Figueroa J , Iregui C
Published: February 2009

A commercial red tilapia farm was diagnosed with Streptococcus agalactiae infection using histopathology, microbiology and immunohistochemistry. One hundred fish were randomly taken from different weight/age groups including broodstock, market fish (larger than 150 g), on‐growing fish between 20 and 150 g, juveniles and larvae. Fish were clinically examined, anaesthetised and necropsied. Samples were taken from brain, liver, spleen, eyes and kidney for microbiology. All organs were processed for histopathology and an indirect immunoperoxidase test (IIP). Organs from wild fish and birds found in close proximity to the farm were also sampled for microbiology and IIP. The prevalence of lesions or infection found by IIP, histopathology and microbiology was 16%, 29% and 7% respectively. Clinical disease, lesions or infection were not seen in larvae or juveniles. By contrast, infection and disease were found in fish larger than 20 g, suggesting that the condition was linked to the intensive culture conditions of broodstock, on‐growing and market fish. S. agalactiae was not found in wild fish, or in birds, by microbiology and IIP.
Delivering oxytetracycline to first‐feeding zebrafish, Danio rerio (Hamilton), and goby, Asterropteryx semipunctata Rüppell, larvae using lipid spray beads
Authors: Temple E , Langdon C
Published: February 2009

Lipid spray beads (LSB) were evaluated for delivery of the low‐molecular weight, water‐soluble antibiotic, oxytetracycline·HCl (OTC) to fish larvae. Various OTC core‐to‐lipid ratios and OTC core concentrations were evaluated to maximize OTC delivery efficiency by LSB. Acceptability and digestion of LSB containing OTC and riboflavin by larval zebrafish, Danio rerio (Hamilton), and larval gobies, Asterropteryx semipunctata Rüppell, were also evaluated. Increasing LSB core‐to‐lipid ratios from 1:3 to 1:1 v/v resulted in an increase in encapsulation efficiency (EE) from 2.33 to 3.68% w/w. Increasing OTC concentrations of core solutions from 0.1 to 0.5 g OTC mL−1 increased EE from 3.95 to 18.77% w/w, respectively. Although retention efficiency (RE) was unaffected by this increase, delivery efficiency was increased to 7.9 ± 0.7% w/w, after correcting for leakage losses because of the suspension of beads in water for 60 min. Consumption of LSB containing OTC by first‐feeding zebrafish and goby larvae was confirmed by analysis of feeding incidence and gut fullness. Visual observations of larvae fed on LSB containing riboflavin indicated that larvae of both species digested LSB. Zebrafish larvae fed on OTC LSB contained 39.3 ± 2.5 ng OTC after purging LSB from their guts. Use of LSB provides an effective means of delivering therapeutics to fish larvae and could greatly reduce required doses compared with current methods of immersing larvae in solutions of therapeutic agents.
Investigation of the role of adrenergic and non‐nitrergic, non‐adrenergic neurotransmission in the sheep isolated internal anal sphincter
Authors: Acheson A. , Rayment S. , Eames T. , Mundey M. , Nisar P. , Scholefield J , Wilson V. G.
Published: February 2009

Abstract Nitric oxide is widely established as an important neurotransmitter in the control of anal sphincter tone; although, a number of other transmitters have also been tentatively implicated. Whilst α‐adrenoceptor antagonists reduce anal sphincter pressure in man, the role of noradrenaline as a possible transmitter is poorly characterised. We have investigated the contribution of these transmitters to neurogenic relaxations, and evaluated the possible role of a non‐nitrergic, non‐adrenergic transmitter. The magnitude and duration of neurogenic responses were examined by measuring responses to electrical field stimulation (EFS) in segments of sheep internal anal sphincter following the development of spontaneous myogenic tone. Neurogenic relaxations induced by EFS were significantly reduced in the presence ofNG‐nitro‐L‐arginine methyl ester (l‐NAME) suggesting major involvement of nitric oxide as a neurotransmitter. The duration of neurogenic relaxations was inversely related to the frequency of EFS, with contractile responses often manifest at higher frequencies. The duration of relaxations at high frequencies of EFS was increased by bretylium (adrenergic neurone blocker) and prazosin (α1‐adrenoceptor antagonist). At higher frequencies of EFS, 60% of preparations also produced a residual non‐nitrergic, non‐adrenergic, apamin‐sensitive relaxation which was unaffected by vasoactive intestinal polypeptide (VIP) and inhibitors of purinergic responses [suramin, pyridoxal‐phosphate‐6‐azophenyl 2′,4′ disulfonic acid (PPADS) and α,β‐methylene adenosine triphosphate (ATP)]. However, MRS2179 (P2Y1receptor antagonist) showed a modest inhibitory effect. We conclude that endogenous noradrenaline acts via postjunctional α1‐adrenoceptors to antagonize neurogenic relaxations that are largely mediated by nitric oxide. Our results indicate the involvement of a non‐nitrergic, non‐adrenergic, apamin‐sensitive transmitter which is inhibited by MRS2179, suggesting a possible role for purines.
A dose‐ranging, placebo‐controlled, pilot trial of Acotiamide in patients with functional dyspepsia
Authors: Tack J. , Masclee A. , Heading R. , Berstad A. , Piessevaux H. , Popiela T. , Vandenberghe A. , Kato H.
Published: February 2009

Abstract Impaired gastric accommodation, hypersensitivity to distension and delayed gastric emptying are major pathophysiological mechanisms in functional dyspepsia (FD). Acotiamide (Z‐338) was well‐tolerated in healthy volunteers. To determine the effect of three doses of Acotiamide on major pathophysiological mechanisms, symptoms, quality of life (QOL) and safety in functional dyspeptics. A phase IIa, randomized, double‐blind, placebo‐controlled study (14, 21 and 28 days, respectively, for run‐in, study drug administration and follow‐up). Gastric accommodation, sensitivity to distension and gastric emptying were assessed by barostat and13C breath test, symptoms by daily diary cards and QOL by SF‐36. A total of 71 patients were enrolled (62 evaluable). There was no effect on gastric emptying and sensitivity to distension. 300 mg was better than placebo for meal accommodation (P = 0.024). 100 mg was better than placebo at week 2 for upper abdominal bloating (P = 0.001) and overall symptom score (P = 0.022), and at week 3 for bloating (P = 0.008) and heartburn (P = 0.041). 100 mg was also better than placebo for QOL (physical function) (P = 0.003). Acotiamide was safe and well‐tolerated in patients with FD. The involved mechanism could at least in part depend on an effect on meal‐induced accommodation. 100 mg Acotiamide exhibited the potential to improve FD symptoms and QOL. Further studies are indicated.
Embryo nutrition in parthenogenetic viviparous aphids
Authors: BERMINGHAM JOHN , WILKINSON TOM L.
Published: February 2009

Abstract The reproductive potential of aphids is well known and is the basis for their considerable economic importance. Reproductive output is ultimately fuelled by nutrients derived from the maternal haemolymph but mechanisms of embryo provisioning are poorly understood. Here, the morphological features of the reproductive system that have a critical role in nutrient transfer are reviewed, and the contribution of the symbiotic bacteria Buchnera to embryo nutrition is considered. In particular, the importance of the ovariole sheath as the selective barrier for nutrient exchange between the maternal haemolymph and the embryo tissue is highlighted, along with the division of the bacterial population into distinct embryo and maternal compartments. Three models are proposed to explain the relative contribution of the symbiotic compartments to embryo nutrition and the review concludes by highlighting experimental studies that have directly examined nutrient transfer from the maternal haemolymph to the developing embryos.
Smoke exposure interacts withADAM33polymorphisms in the development of lung function and hyperresponsiveness
Authors: Reijmerink N. E. , Kerkhof M. , Koppelman G. H. , Gerritsen J. , De Jongste J. C. , Smit H. A. , Brunekreef B. , Postma D. S.
Published: February 2009

Introduction: ADAM33is the first identified asthma gene by positional cloning, especially asthma combined with bronchial hyperresponsiveness (BHR). Moreover,ADAM33is associated with early‐life lung function and decline of forced expiratory volume in 1 s (FEV1) in the general population.In uteroand postnatal cigarette smoke exposure (CSE) are associated with reduced lung function, and development of BHR and asthma. We hypothesized that this may occur via interaction withADAM33.

Aim: To replicate the role ofADAM33in childhood lung function and development of BHR and asthma. Furthermore, we investigated gene–environment interaction ofADAM33within uteroand postnatal CSE in the Dutch PIAMA cohort.

Methods: SixADAM33single‐nucleotide polymorphisms (SNPs) were genotyped. Rint was measured at age 4 and 8 years, FEV1and BHR at age 8 years; asthma was based on questionnaire data at age 8.

Results: In the total cohort, the rs511898 A, rs528557 C, and rs2280090 A alleles increased the risk to develop asthma (+BHR). There existed interaction betweenin uterobut not postnatal CSE and the rs528557 and rs3918396 SNPs with respect to development of BHR, the rs3918396 SNP with Rint at age 8 and the rs528557 SNP with FEV1% predicted.

Conclusions: We confirm associations betweenADAM33and the development of asthma (+BHR). This is the first study suggesting that interaction ofin uteroCSE withADAM33results in reduced lung function and the development of BHR, which needs further confirmation.
A new HLA‐A*26 variant, A*2637 identified by haplotype‐specific extraction and sequencing‐based typing
Authors: Ulrich S. , Sorantin S. , Posch U. , Helmberg W. , Lanzer G.
Published: February 2009

The novel allele A*2637 differs from the common A*260101 by a single nucleotide substitution in exon 2 (position 186 C>G) causing an amino acid exchange (SER>ARG).
Identification of a novel HLA‐B allele HLA‐B*9526 in a Chinese donor
Authors: Wang Q.‐S. , Li J.‐P. , Chen Y. , Li X.‐F. , Liu X.‐Z.
Published: February 2009

A novel human leukocyte antigen‐B (HLA‐B) allele, B*9526, was identified. The B*9526 allele has one nucleotide change from the closest matching allele B*1507 resulting in an amino acid change from Y(TAC) to C(TGC) at codon 142.
Identification of the novel HLA‐G*010112 allele by sequencing genomic DNA of Korean individuals
Authors: Kim J.‐G. , Yun H.‐S. , Lee J.‐K. , Kwack K.
Published: February 2009

Human leukocyte antigen (HLA)‐G is an immune modulator that inhibits the functions of cytotoxic T lymphocytes and natural killer cells. Immune modulation of HLA‐G plays an important role in the prevention of fetal rejection. We found a novel substitution at nucleotide position 195 (G–T), codon 41 (Ala), in exon 2 of HLA‐G. This substitution does not change the amino acid (GCG→GCT).
Domestic and foreign donor candidates result in differential probability of matching minor histocompatibility antigens – relevance of selection for hematopoietic stem cell transplantation
Authors: Turpeinen H. , Volin L. , Partanen J.
Published: February 2009

Mismatches between patient and donor at minor histocompatibility antigens (minor H antigens) account for most of the genetic component of histocompatibility problems in human leukocyte antigen (HLA)‐matched hematopoietic stem cell transplantations (HSCTs). There are usually more genetic differences outside the matched HLA region between unrelated donors and patients than in transplantations between related individuals. Also, foreign unrelated donors may differ from domestic donors at several loci as allele frequencies vary between populations. To unravel differences in minor H antigen matching when using unrelated donors from various registries worldwide, we genotyped 10 minor H antigen loci for 143 consecutive Finnish patients and 424 unrelated donor candidates. We observed that probability of matching specific minor H antigens was different for domestic and foreign donor candidates. HA‐2 and HA‐3 minor H antigens were significantly more often mismatched with Finnish donor candidates (P = 0.0003 for HA‐2 and P= 0.004 for HA‐3), whereas ACC1 and ACC2 minor H antigens were significantly more often mismatched with foreign donor candidates (P = 0.04 for ACC1 and P = 0.03 for ACC2). This observation is of clinical importance when specific minor H antigens are intended to match or mismatch in the future to minimize the risk for graft‐vs‐host disease or to maximize the graft‐vs‐malignancy effect in HLA‐matched HSCT from an unrelated donor.
Trends in invasive disease due to Candida species following heart and lung transplantation
Authors: Schaenman J.M. , Rosso F. , Austin J.M. , Baron E.J. , Gamberg P. , Miller J. , Oyer P.E. , Robbins R.C. , Montoya J.G.
Published: February 2009

Abstract: Although invasive candidiasis (IC) causes significant morbidity and mortality in patients who undergo heart, lung, or heart–lung transplantation, a systematic study in a large cohort of thoracic organ transplant recipients has not been reported to date. Clinical and microbiological data were reviewed for 1305 patients who underwent thoracic organ transplantation at Stanford University Medical Center between 1980 and 2004. We identified and analyzed 76 episodes of IC in 68 patients (overall incidence 5.2% per patient). The incidence of IC was higher in lung (LTx) and heart–lung transplant (HLTx) recipients as compared with heart transplant (HTx) recipients (risk ratio [RR] 1.7, 95% confidence interval [CI] 1.1–2.7). The incidence of IC decreased over time in all thoracic organ transplant recipients, decreasing from 6.1% in the 1980–1986 time period to 2.1% in the 2001–2004 era in the HTx recipients, and from 20% in the 1980–1986 period to 1.8% in the 2001–2004 period in the LTx and HLTx recipients. The most common site of infection differed between the HTx and LTx cohorts, with bloodstream or disseminated disease in the former and tracheobronchitis in the latter. IC in the first year after transplant was significantly associated with death in both HTx (RR 2.9, 95% CI 1.8–4.6, P=0.001) and LTx and HLTx patients (RR 3.0, 95% CI 1.9–4.6, P<0.001). The attributable mortality from IC decreased during the 25‐year period of observation, from 36% to 20% in the HTx recipients and from 39% to 15% in the LTx and HLTx recipients. There were a significant number of cases caused by non‐albicans Candida species in all patients, with a trend toward higher mortality in the HTx group. In conclusion, the incidence and attributable mortality of IC in thoracic organ transplant recipients has significantly declined over the past 25 years. The use of newer antifungal agents for prophylaxis and treatment, the decrease in the incidence of cytomegalovirus disease, and the use of more selective immunosuppression, among other factors, may have been responsible for this change.
Cytomegalovirus infection and disease in the new era of immunosuppression following solid organ transplantation
Authors: Fisher R.A.
Published: February 2009

Abstract: As the most prevalent pathogen among transplant patients, cytomegalovirus (CMV) affects up to three‐quarters of all solid organ transplant recipients. While we have made great strides in preventing CMV infection and disease in the early post‐transplant period, late CMV infection and indirect effects due to viral immunomodulation remain problematic. Changing immunosuppression practices, including the increasing use of T‐cell depleting induction antibodies, have the potential to affect the risk for CMV infection and disease, even in the face of good prophylactic and preemptive therapy. The purpose of this review article is to discuss the impact of CMV infection on long‐term allograft outcomes and to re‐evaluate the risks and management strategies for prevention of CMV in the framework of evolving modern immunosuppressive strategies.
Population Dynamics of Pseudomonas syringae pv. tomato Strains on Tomato Cultivars Rio Grande and Rio Grande‐Pto under Field Conditions
Authors: Willis David K. , Kinscherf Thomas G.
Published: February 2009

We examined the effects of the Pto resistance locus on the population dynamics of Pseudomonas syringae pv. tomato (Pst) strains in field experiments with the nearly isogenic tomato lines Rio Grande (RG, susceptible to Pst races 0 and 1) and Rio Grande‐Pto (RG‐Pto, resistant to Pst race 0, susceptible to Pst race 1). Pst strain SM78‐1Smr (race 0) grew well under field conditions and caused ample bacterial speck disease on susceptible RG plants. In contrast, strain DC3000 failed to establish large populations when inoculated onto field grown RG plants. Mean population sizes of SM78‐1Smr were 4–5 orders of magnitude larger on RG than RG‐Pto plants indicating that RG‐Pto plants were highly effective in attenuating pathogen population development. Most of the sampled leaflets from RG‐Pto field plots harboured small numbers of SM78‐1Smr. However, population sizes SM78‐1Smr as large as 105–106 CFU were found on a few leaflets. Bacteria isolated from these leaflets had phenotypes characteristic of Pst race 1 strains. In growth chamber plant assays, the bacterial strains grew well and caused typical speck lesions on RG‐Pto plants. The strains appeared to be race‐shift mutants of SM SM78‐1Smr. Interestingly, results from DNA hybridization experiments demonstrated that the race‐shift mutants were deleted for the avirulence gene, avrPto but not for avrPtoB.
Treatment of diabetic hypertension
Authors: Bell David S. H.
Published: February 2009

Insulin resistance and hyperglycaemia combine to make hypertension more prevalent in the type 2 diabetic patient. Blood pressure goals below those for the non‐diabetic subject have been shown to be more effective in lowering mortality and cardiovascular events in the diabetic patient. To achieve these goals in most cases, three to five antihypertensives from different therapeutic groups need to be utilized. Suppression of the renin–angiotensin system (RAS) with angiotensin‐converting enzyme inhibitors, angiotensin 2 receptor blockers or a renin inhibitor should be the primary therapy. A second goal should be suppression of the sympathetic nervous system utilizing a beta‐blocker that does not increase insulin resistance. The addition of a diuretic, calcium channel blocker or a vasodilator to suppressors of the RAS and sympathetic nervous system aid in achieving hypertensive goals in the diabetic patient. Achieving hypertensive goals with suppression of the RAS and sympathetic nervous system should result in a decrease in mortality and cardiovascular events in the diabetic hypertensive patient. In this review article, the benefits and disadvantages of the different antihypertensive therapies in the diabetic patient are discussed.
Antioxidants attenuate hyperglycaemia‐mediated brain endothelial cell dysfunction and blood–brain barrier hyperpermeability
Authors: Allen C. L. , Bayraktutan U.
Published: February 2009

Aims:  Hyperglycaemia (HG), in stroke patients, is associated with worse neurological outcome by compromising endothelial cell function and the blood–brain barrier (BBB) integrity. We have studied the contribution of HG‐mediated generation of oxidative stress to these pathologies and examined whether antioxidants as well as normalization of glucose levels following hyperglycaemic insult reverse these phenomena.

Methods:  Human brain microvascular endothelial cell (HBMEC) and human astrocyte co‐cultures were used to simulate the human BBB. The integrity of the BBB was measured by transendothelial electrical resistance using STX electrodes and an EVOM resistance meter, while enzyme activities were measured by specific spectrophotometric assays.

Results:  After 5 days of hyperglycaemic insult, there was a significant increase in BBB permeability that was reversed by glucose normalization. Co‐treatment of cells with HG and a number of antioxidants including vitamin C, free radical scavengers and antioxidant enzymes including catalase and superoxide dismutase mimetics attenuated the detrimental effects of HG. Inhibition of p38 mitogen‐activated protein kinase (p38MAPK) and protein kinase C but not phosphoinositide 3 kinase (PI3 kinase) also reversed HG‐induced BBB hyperpermeability. In HBMEC, HG enhanced pro‐oxidant (NAD(P)H oxidase) enzyme activity and expression that were normalized by reverting to normoglycaemia.

Conclusions:  HG impairs brain microvascular endothelial function through involvements of oxidative stress and several signal transduction pathways.
Treatment choice and effectiveness of adding sulphonylurea or glitazones to metformin for the treatment of type 2 diabetes mellitus
Authors: Stargardt T. , Yin D. D. , Alexander C. M.
Published: February 2009

Aim:  This study investigates the treatment choice between, and the effectiveness of, adding sulphonylurea or glitazone to ongoing metformin therapy for patients with type 2 diabetes mellitus in the clinical practice setting.

Methods:  A multicentre observational study using data from clinical records was conducted in Finland, France, Germany, Norway, Poland, Spain and the UK. Data were collected for patients who added sulphonylurea or glitazone to metformin. Effectiveness was defined as a change in haemoglobin A1c (HbA1c) from baseline to approximately 1 year after the initiation of additional therapy. To allow for comparisons between the two medication regimens, propensity score matching was employed. Treatment choice was analysed using a probit regression model. We hypothesized that treatment choice was associated with factors reflecting patient’s characteristics, patient’s experience with diabetes, patient‘s health or to physician’s characteristics at baseline.

Results:  Compared with baseline, adding sulphonylurea to metformin reduced HbA1c by 0.8% (p < 0.0001), while adding glitazone to metformin reduced HbA1c by 0.9% (p < 0.0001). Percentage at HbA1c goal (6.5%) increased from 6.9 to 23.8% for the sulphonylurea group and 8.3 to 33.3% for the glitazone group. Both groups had similar changes in high‐density lipoprotein cholesterol, low‐density lipoprotein cholesterol and triglycerides. In the probit regression model, age, HbA1c, weight, treatment for weight reduction, history of macrovascular complications and type of physician were significant factors associated with treatment choice.

Conclusions:  This study is consistent with the results of long‐term randomized clinical trials in a clinical practice setting. Both regimens were able to reduce HbA1c by about 1%.
The Save the Children Fund and the Russian Famine of 1921–23: Claims and Counter‐Claims about Feeding “Bolshevik” Children*
Authors: MAHOOD LINDA , SATZEWICH VIC
Published: February 2009

Drawing on literature on the social construction of social problems, this paper examines the British Save the Children Fund's claims making activities regarding support for child famine victims in Russia in 1921–23. It examines 1) how the Fund constructed famine in Russia as a social problem that was worthy of British, and wider international, support and attention; 2) the rhetorical strategies used by the Fund to construct the causes of the famine for the British public; and 3) the claims the Fund made about why Britons should care about starving children in Russia. We also attend to counter‐claims made about the Fund and its involvement with Russia. We used unpublished letters, memos and reports from The Save the Children Fund archives to examine how the Fund responded to attacks on its activities coming from Russian émigrés and from The Daily Express. We suggest that the examination of this case through the concept of claims making offers a lens to understand how children in distress in the early 20th century became the objects of British, and wider international aid.
MIMESIS AND ICONOCLASM
Authors: MOXEY KEITH
Published: February 2009

What is the enduring power of mimesis? What hold do paintings that mimic perception have over our imagination? This essay analyses Hans Holbein the Younger's portrait of The Ambassadors to assess its magic both for ourselves in the present and for those who first beheld it. The very structure of the work, its facture, is invested with an iconic vitality that we often overlook. Its surface is alive with a thoroughly medieval sense of pictorial presence that Reformation image theory sought to destroy. The shadow of iconoclasm that hangs over these pictures lends them a particular poignancy, for the illusionism that once endowed the dead with afterlife continues to invest them with remarkable ontological power. The to‐and‐fro of our perceptual encounter with the world insists that we ascribe such paintings an agency that exceeds our own.