bluuebunny/crossref_metadata_2025 huggingface dataset:
Observation of surface structure of 1-alkyl-3-methylimidazolium bis(trifluoromethanesulfonyl)imide using high-resolution Rutherford backscattering spectroscopy
Authors: Nakajima Kaoru , Ohno Atsushi , Hashimoto Hiroki , Suzuki Motofumi , Kimura Kenji
Published: July 2010

The surface structures of 1-alkyl-3-methylimidazolium bis(trifluoromethanesulfonyl)imide ([CnMIM][TFSI], n=2,4,6) are studied by high-resolution Rutherford backscattering spectroscopy. The average composition of the surface molecular layer is very close to the stoichiometric composition, showing that neither ion is enriched in the surface layer. A detailed analysis indicates that both cations and anions have preferential molecular orientations at the surface. The alkyl chains of the [CnMIM] cations protrude to the vacuum and the CF3 groups of the [TFSI] anions are also pointing toward the vacuum. While the orientation of the [TFSI] anion becomes weaker with increasing alkyl-chain length, the protrusion of the alkyl chain occurs irrespective of the chain length. It was also found that the N(SO2)2 moiety is located nearly at the same depth as the imidazolium ring, suggesting that one of oxygen atoms in [TFSI] is bonded to the hydrogen of the C2 carbon atom of the imidazolium ring.
Ab initio statistical mechanics of surface adsorption and desorption. II. Nuclear quantum effects
Authors: Alfè D. , Gillan M. J.
Published: July 2010

We show how the path-integral formulation of quantum statistical mechanics can be used to construct practical ab initio techniques for computing the chemical potential of molecules adsorbed on surfaces, with full inclusion of quantum nuclear effects. The techniques we describe are based on the computation of the potential of mean force on a chosen molecule and generalize the techniques developed recently for classical nuclei. We present practical calculations based on density functional theory with a generalized-gradient exchange-correlation functional for the case of H2O on the MgO (001) surface at low coverage. We note that the very high vibrational frequencies of the H2O molecule would normally require very large numbers of time slices (beads) in path-integral calculations, but we show that this requirement can be dramatically reduced by employing the idea of thermodynamic integration with respect to the number of beads. The validity and correctness of our path-integral calculations on the H2O/MgO(001) system are demonstrated by supporting calculations on a set of simple model systems for which quantum contributions to the free energy are known exactly from analytic arguments.
Ultralow-frequency photocurrent oscillation in ZnO nanowires
Authors: Liao Zhi-Min , Zhang Hong-Zhou , Yu Da-Peng
Published: July 2010

We report experimental results of ultralow frequency photocurrent oscillation in individual ZnO nanowires. Consecutive photocurrent and photoluminescence measurements corroborate the process of capture and release of photogenerated holes by surface trap states. The dynamic process results in the oscillation of the thickness of surface depletion region, which is believed to be responsible for the observed photocurrent oscillation.
Computing Walking Distances within Buildings Using the Universal Circulation Network
Authors: Lee Jin-Kook , Eastman Charles M , Lee Jaemin , Kannala Matti , Jeong Yeon-Suk
Published: July 2010

In this paper we define a computational method for measuring walking distances within buildings based on a length-weighted graph structure for a given building model. We name it the universal circulation network (UCN) and it has been implemented as plug-in software in Solibri Model Checker using building information modeling technologies. It provides a new explicitly defined method for representing circulation paths on top of building models supporting further circulation-related analysis as a network application. We define the computing algorithms and how we realize them. We focus not only on the implementation issues, but also on other intrinsic aspects that need to be considered while dealing with pedestrian circulation within buildings. The UCN is determined mainly by the spatial topology and geometry of a given building, and it returns consistent and accurate scalar quantities. It takes into consideration people-movement patterns, reflecting that people tend to walk along the shortest, easiest, and most visible paths. In several actual-design review projects, the UCN has proved that it is of practical benefit, not only to the distance measurement but also the visualization of pedestrian circulation, especially in reviewing building circulation.
A Dichoptic Study of the Oblique Effect
Authors: Borra Tobias , Hooge Ignace T C , Verstraten Frans A J
Published: July 2010

The oblique effect is a decreased sensitivity for oblique orientations compared with horizontal/vertical orientations. We investigated whether orientation-matching acuity for binocularly presented stimuli is dependent on orientations of retinal projections or on the perceived orientation of the stimulus. Using a stereoscope, we constructed a stimulus, such that retinal orientations were oblique, while the perceived orientation was vertical. We then used this stimulus to test observers in an orientation-matching task. If orientation matching depends on the orientations of retinal projections, low matching performance would be expected, since retinal projections are oblique. However, if orientation matching depends on perceived orientation (vertical), high matching performance would be expected. We found that observers' performance can only be predicted from the perceived orientation, not the orientations of retinal projections, implying that in binocular viewing the oblique effect occurs after binocular fusion.
Effect of Temporal Separation on Synchronization in Rhythmic Performance
Authors: Chafe Chris , Cáceres Juan-Pablo , Gurevich Michael
Published: July 2010

A variety of short time delays inserted between pairs of subjects were found to affect their ability to synchronize a musical task. The subjects performed a clapping rhythm together from separate sound-isolated rooms via headphones and without visual contact. One-way time delays between pairs were manipulated electronically in the range of 3 to 78 ms. We are interested in quantifying the envelope of time delay within which two individuals produce synchronous performances. The results indicate that there are distinct regimes of mutually coupled behavior, and that ‘natural time delay’—delay within the narrow range associated with travel times across spatial arrangements of groups and ensembles—supports the most stable performance. Conditions outside of this envelope, with time delays both below and above it, create characteristic interaction dynamics in the mutually coupled actions of the duo. Trials at extremely short delays (corresponding to unnaturally close proximity) had a tendency to accelerate from anticipation. Synchronization lagged at longer delays (larger than usual physical distances) and produced an increasingly severe deceleration and then deterioration of performed rhythms. The study has implications for music collaboration over the Internet and suggests that stable rhythmic performance can be achieved by ‘wired ensembles’ across distances of thousands of kilometers.
Hydrocarbon double-stapling remedies the proteolytic instability of a lengthy peptide therapeutic
Authors: Bird Gregory H. , Madani Navid , Perry Alisa F. , Princiotto Amy M. , Supko Jeffrey G. , He Xiaoying , Gavathiotis Evripidis , Sodroski Joseph G. , Walensky Loren D.
Published: July 2010

The pharmacologic utility of lengthy peptides can be hindered by loss of bioactive structure and rapid proteolysis, which limits bioavailability. For example, enfuvirtide (Fuzeon, T20, DP178), a 36-amino acid peptide that inhibits human immunodeficiency virus type 1 (HIV-1) infection by effectively targeting the viral fusion apparatus, has been relegated to a salvage treatment option mostly due to poor in vivo stability and lack of oral bioavailability. To overcome the proteolytic shortcomings of long peptides as therapeutics, we examined the biophysical, biological, and pharmacologic impact of inserting all-hydrocarbon staples into an HIV-1 fusion inhibitor. We find that peptide double-stapling confers striking protease resistance that translates into markedly improved pharmacokinetic properties, including oral absorption. We determined that the hydrocarbon staples create a proteolytic shield by combining reinforcement of overall α-helical structure, which slows the kinetics of proteolysis, with complete blockade of peptide cleavage at constrained sites in the immediate vicinity of the staple. Importantly, double-stapling also optimizes the antiviral activity of HIV-1 fusion peptides and the antiproteolytic feature extends to other therapeutic peptide templates, such as the diabetes drug exenatide (Byetta). Thus, hydrocarbon double-stapling may unlock the therapeutic potential of natural bioactive polypeptides by transforming them into structurally fortified agents with enhanced bioavailability.
The Roles of Cyclin A2, B1, and B2 in Early and Late Mitotic Events
Authors: Gong Delquin , Ferrell James E.
Published: July 2010

Here we have used siRNAs and time-lapse epifluorescence microscopy to examine the roles of various candidate mitotic cyclins in chromatin condensation in HeLa cells. Knocking down cyclin A2 resulted in a substantial (∼7 h) delay in chromatin condensation and histone H3 phosphorylation, and expressing an siRNA-resistant form of cyclin A2 partially rescued chromatin condensation. There was no detectable delay in DNA replication in the cyclin A2 knockdowns, arguing that the delay in chromatin condensation is not secondary to a delay in S-phase completion. Cyclin A2 is required for the activation and nuclear accumulation of cyclin B1-Cdk1, raising the possibility that cyclin B1-Cdk1 mediates the effects of cyclin A2. Consistent with this possibility, we found that chromatin condensation was tightly associated temporally with the redistribution of cyclin B1 to the nucleus. Moreover, a constitutively nuclear cyclin B1 rescued chromatin condensation in cyclin A2 knockdown cells. On the other hand, knocking down cyclin B1 delayed chromatin condensation by only about one hour. Our working hypothesis is that active, nuclear cyclin B1-Cdk1 normally cooperates with cyclin A2 to bring about early mitotic events. Because cyclin A2 is present only during the early stages of mitosis, we asked whether cyclin B knockdown might have more dramatic defects on late mitotic events. Consistent with this possibility, we found that cyclin B1- and cyclin B1/B2-knockdown cells had difficulty in maintaining a mitotic arrest in the presence of nocodazole. Taken together, these data suggest that cyclin A2 helps initiate mitosis, in part through its effects on cyclin B1, and that cyclins B1 and B2 are particularly critical for the maintenance of the mitotic state.
Integrative classification and analysis of multiple arrayCGH datasets with probe alignment
Authors: Tian Ze , Kuang Rui
Published: July 2010

Motivation: Array comparative genomic hybridization (arrayCGH) is widely used to measure DNA copy numbers in cancer research. ArrayCGH data report log-ratio intensities of thousands of probes sampled along the chromosomes. Typically, the choices of the locations and the lengths of the probes vary in different experiments. This discrepancy in choosing probes poses a challenge in integrated classification or analysis across multiple arrayCGH datasets. We propose an alignment-based framework to integrate arrayCGH samples generated from different probe sets. The alignment framework seeks an optimal alignment between the probe series of one arrayCGH sample and the probe series of another sample, intended to find the maximum possible overlap of DNA copy number variations between the two measured chromosomes. An alignment kernel is introduced for integrative patient sample classification and a multiple alignment algorithm is also introduced for identifying common regions with copy number aberrations.

Results: The probe alignment kernel and the MPA algorithm were experimented to integrate three bladder cancer datasets as well as artificial datasets. In the experiments, by integrating arrayCGH samples from multiple datasets, the probe alignment kernel used with support vector machines significantly improved patient sample classification accuracy over other baseline kernels. The experiments also demonstrated that the multiple probe alignment (MPA) algorithm can find common DNA aberrations that cannot be identified with the standard interpolation method. Furthermore, the MPA algorithm also identified many known bladder cancer DNA aberrations containing four known bladder cancer genes, three of which cannot be detected by interpolation.

Availability:  http://www.cs.umn.edu/compbio/ProbeAlign

Contact:  kuang@cs.umn.edu

Supplementary information:  Supplementary data are available at Bioinformatics online.
Physical, Compositional, and Wet Milling Characteristics of Grain from Crosses of Corn Inbreds with Exotic and Nonexotic Background
Authors: Taboada‐Gaytan Oswaldo , Pollak Linda M. , Johnson Lawrence A. , Fox Steven R. , Montgomery Kevin T.
Published: July 2010

Corn breeders have developed hybrids with enhanced compositional characteristics, but exotic germplasm represents little of the germplasm base used to produce these hybrids. Effects of the exotic germplasm on physical, compositional, and wet‐milling properties as well as the proximate composition of recovered fractions need to be determined before these materials are of value to the corn processing industry. Ten lines from the Germplasm Enhancement of Maize (GEM) project with exotic germplasm introgressed from Argentina, Chile, Uruguay, Cuba, and Florida were crossed to three adapted inbred lines (testers) and grain from the resulting 30 hybrids were evaluated for physical, compositional, and wet‐milling characteristics and the expression of heterosis in these variables. The B73xMo17 adapted public hybrid was used as control. Grain obtained by self‐pollination of the hybrid plants was analyzed using near‐infrared transmittance (NIT) technology and a 100‐g wet‐milling procedure. There was great variation among physical, compositional, and wet‐milling characteristics, and some of the experimental hybrids with exotic origin had better starch yield and starch recovery than B73xMo17, which suggests that wet‐milling characteristics of U.S. hybrids can be improved by breeding with exotic germplasm. In particular, GEM breeding crosses AR16035:S19, CH05015:N15, CUBA117:S1520, and FS8B(T):N1802 could be valuable germplasm sources to produce inbreds with good milling properties. Testers varied in ability to produce hybrids with good milling properties, indicating that choice of tester is an important factor when evaluating this end use. Although general trait trends for mid‐ and high‐parent heterosis were revealed, individual variation among hybrids and testers was large for most traits. This demonstrates the importance of analyzing individual hybrids that are intended for the wet‐milling industry when breeding with exotic introgressed lines.
Effects of Acute Low-Temperature Events on Development ofErysiphe necatorand Susceptibility ofVitis vinifera
Authors: Moyer Michelle M. , Gadoury David M. , Cadle-Davidson Lance , Dry Ian B. , Magarey Peter A. , Wilcox Wayne F. , Seem Robert C.
Published: July 2010

Growth and development of Erysiphe necator (syn. Uncinula necator) has been extensively studied under controlled conditions, primarily with a focus on development of grapevine powdery mildew within the optimal temperature range and the lethal effects of high temperatures. However, little is known of the effect of cold temperatures (above freezing but <8°C) on pathogen development or host resistance. Pretreatment of susceptible Vitis vinifera leaf tissue by exposure to cold temperatures (2 to ≤8°C for 2 to 8 h) reduced infection efficiency and colony expansion when tissues were subsequently inoculated. Furthermore, nascent colonies exposed to similar cold events exhibited hyphal mortality, reduced expansion, and increased latent periods. Historical weather data and an analysis of the radiational cooling of leaf tissues in the field indicated that early-season cold events capable of inducing the foregoing responses occur commonly and frequently across many if not most viticultural regions worldwide. These phenomena may partially explain (i) the unexpectedly slow development of powdery mildew during the first month after budbreak in some regions and (ii) the sudden increase in epidemic development once seasonal temperatures increase above the threshold for acute cold events.
Host Effect on the Genetic Diversification of Beet necrotic yellow vein virus Single-Plant Populations
Authors: Acosta-Leal Rodolfo , Bryan Becky K. , Rush Charles M.
Published: July 2010

Theoretical models predict that, under restrictive host conditions, virus populations will exhibit greater genetic variability. This virus response has been experimentally demonstrated in a few cases but its relation with a virus's capability to overcome plant resistance is unknown. To explore the genetic host effects on Beet necrotic yellow vein virus (BNYVV) populations that might be related to resistance durability, a wild-type virus isolate was vector inoculated into partially resistant Rz1, Rz2, and susceptible sugar beet cultivars during a serial planting experiment. Cloning and sequencing a region of the viral RNA-3, involving the pathogenic determinant p25, revealed that virus diversity significantly increased in direct proportion to the strength of host resistance. Thus, whereas virus titers were highest, intermediate, and lowest in susceptible, Rz1, and Rz2 plants, respectively; the average number of nucleotide differences among single-plant populations was 0.8 (±0.1) in susceptible, 1.4 (±0.1) in Rz1, and 2.4 (±0.2) in Rz2 genotypes. A similar relationship between host restriction to BNYVV root accumulation and virus genetic variability was detected in fields of sugar beet where these specific Rz1- and Rz2-mediated resistances have been defeated.
Yolk testosterone reduces oxidative damages during postnatal development
Authors: Noguera José Carlos , Alonso-Alvarez Carlos , Kim Sin-Yeon , Morales Judith , Velando Alberto
Published: July 2010

Conditions experienced during early life can influence the development of an organism and several physiological traits, even in adulthood. An important factor is the level of oxidative stress experienced during early life. In birds, extra-genomic egg substances, such as the testosterone hormone, may exert a widespread influence over the offspring phenotype. Interestingly, testosterone can also upregulate the bioavailability of certain antioxidants but simultaneously increases the susceptibility to oxidative stress in adulthood. However, little is known about the effects of maternally derived yolk testosterone on oxidative stress in developing birds. Here, we investigated the role of yolk testosterone on oxidative stress of yellow-legged gull chicks during their early development by experimentally increasing yolk testosterone levels. Levels of antioxidants, reactive oxygen species and lipid oxidative damage were determined in plasma during nestlings' growth. Our results revealed that, contrary to control chicks, birds hatched from testosterone-treated eggs did not show an increase in the levels of oxidative damage during postnatal development. Moreover, the same birds showed a transient increase in plasma antioxidant levels. Our results suggest that yolk testosterone may shape the oxidative stress-resistance phenotype of the chicks during early development owing to an increase in antioxidant defences and repair processes.
Hippocampal neurogenesis is associated with migratory behaviour in adult but not juvenile sparrows (
Zonotrichia leucophrys
ssp.)
Authors: LaDage Lara D. , Roth Timothy C. , Pravosudov Vladimir V.
Published: July 2010

It has been hypothesized that individuals who have higher demands for spatially based behaviours should show increases in hippocampal attributes. Some avian species have been shown to use a spatially based representation of their environment during migration. Further, differences in hippocampal attributes have been shown between migratory and non-migratory subspecies as well as between individuals with and without migratory experience (juveniles versus adults). We tested whether migratory behaviour might also be associated with increased hippocampal neurogenesis, and whether potential differences track previously reported differences in hippocampal attributes between a migratory (
Zonotrichia leucophrys gambelii
) and non-migratory subspecies (
Z. l. nuttalli
) of white-crowned sparrows. We found that non-migratory adults had relatively fewer numbers of immature hippocampal neurons than adult migratory birds, while adult non-migrants had a lower density of new hippocampal neurons than adult and juvenile migratory birds and juvenile non-migratory birds. Our results suggest that neurogenesis decreases with age, as juveniles, regardless of migratory status, exhibit similar and higher levels of neurogenesis than non-migratory adults. However, our results also suggest that adult migrants may either seasonally increase or maintain neurogenesis levels comparable to those found in juveniles. Our results thus suggest that migratory behaviour in adults is associated with maintained or increased neurogenesis and the differential production of new neurons may be the mechanism underpinning changes in the hippocampal architecture between adult migratory and non-migratory birds.
Evolutionary demography and quantitative genetics: age-specific survival as a threshold trait
Authors: Moorad Jacob A. , Promislow Daniel E. L.
Published: July 2010

Researchers must understand how mutations affect survival at various ages to understand how ageing evolves. Many models linking mutation to age-specific survival have been proposed but there is little evidence to indicate which model is most appropriate. This is a serious problem because the predicted evolutionary endpoints of ageing depend upon the details of the specific model. We apply an explicitly quantitative genetic perspective to the problem. To determine the inheritance of dichotomous traits (such as survival), quantitative genetics has long employed a threshold model. Beginning from first principles, we show how this is the most defensible mutational model for age-specific survival and how this, relative to the standard model, predicts delayed senescence and mortality deceleration at late age. These are commonly observed patterns of ageing that heretofore have required more complicated survival models. We also show how this model can be developed further to unify quantitative genetics and evolutionary demography into a more complete conceptual framework for understanding the evolution of ageing.
Src inhibition reduces NR2B surface expression and synaptic plasticity in the amygdala
Authors: Sinai Laleh , Duffy Steven , Roder John C.
Published: July 2010

The Src protein tyrosine kinase plays a central role in the regulation of N-methyl-d-aspartate receptor (NMDAR) activity by regulating NMDAR subunit 2B (NR2B) surface expression. In the amygdala, NMDA-dependent synaptic plasticity resulting from convergent somatosensory and auditory inputs contributes to emotional memory; however, the role of Src tyrosine kinase has not been investigated. We have synthesized a Src-derived peptide, Tat-Src (40–58), that crosses the blood–brain barrier following injection and accumulates intracellularly. Tat-Src (40–58) blocks the interaction of Src with NMDA receptors. Following injection, mice demonstrate impaired amygdala-dependent cued fear conditioning, as well as impairments in an amygdala-dependent nonassociative social recognition task. The Src inhibitor decreased NR2B phosphorylation in amygdala tissue and reduced NR2B surface expression in cultured amygdala neurons with a concomitant reduction in NMDA multimer-containing dendritic puncta. In addition, preincubation of this inhibitory peptide blocked amygdalar long-term potentiation in the lateral to basolateral pathway in vitro. These results indicate that Src is a key regulator of NMDAR trafficking in the amygdala. Furthermore, Src-dependent phosphorylation of NR2B supports amygdala plasticity and amygdalar-dependent learning.
Acrodermatitis enteropathica with anorexia nervosa
Authors: KIM Sang Tae , KANG Jin Seuk , BAEK Jae Woo , KIM Tae Kwon , LEE Jin Woo , JEON Young Seung , SUH Kee Suck
Published: July 2010

Acrodermatitis enteropathica is a rare hereditary or acquired disorder of hypozincemia. It is characterized by acral and periorificial dermatitis, alopecia, diarrhea and growth retardation. Anorexia nervosa is characterized by low body weight, body image distortion with an obsessive fear and is also associated with various cutaneous findings including acrodermatitis enteropathica. We report a 37‐year‐old female with acrodermatitis enteropathica showing acquired zinc deficiency with anorexia nervosa.
Opposite effects of two nonstructural proteins of Theiler's murine encephalomyelitis virus regulates apoptotic cell death in BHK‐21 cells
Authors: Okuwa Takako , Taniura Naoko , Saito Mineki , Himeda Toshiki , Ohara Yoshiro
Published: July 2010

Theiler's murine encephalomyelitis virus is divided into two subgroups, TO and GDVII, inducing subgroup‐specific diseases. In order to investigate the role(s) of nonstructural proteins of TMEV, L and L*, leaders of two subgroups, were separately expressed with or without L* in BHK‐21 cells. Expression of L increased the number of apoptotic cells. L*/BHK‐21 cells constitutively expressing L* showed the decrease in cell death induced by L. These results suggest that L and L* regulate apoptosis during viral infection and contribute to TMEV subgroup‐specific biological activities.
Inhibition of prostanoid synthesis by human gastric mucosa
Authors: TAVARES I. A. , COLLINS P. O. , BENNETT A.
Published: July 2010

Non‐steroidal anti‐inflammatory drugs (NSAIDs) damage the gastric mucosa, and an important part of this effect is probably due to inhibition of prostaglandin synthesis. We have therefore studied various drugs for their ability to reduce prostaglandin and thromboxane formation by human isolated gastric mucosa. The overall relative potencies for inhibiting the endogenous production of PGE, 6‐keto‐PGF1α and thromboxane B2 by mucosal pieces was generally: indomethacin = naproxen > ibuprofen > piroxicam; diflunisal, the prodrug sulindac, and the analgesic paracetamol usually had small or variable effects. This rank order was mainly similar to the inhibition of gastric microsomal PGE2 formation from exogenous arachidonic acid, the relative potencies being: indomethacin > naproxen > ibuprofen = piroxicam = diflunisal; again sulindac and paracetamol had little or no effect. The relative propensity of NSAIDs to cause gastric mucosal damage is controversial, but aspirin and indomethacin may be worst, and ibuprofen seems to be among the safest. Potency as an inhibitor of prostaglandin synthesis correlates better with the reported propensity for damage than does potency dose. For reasons that are given in the discussion, this may indicate that gastric mucosal damage by NSAIDs with short or moderate half‐lives is due largely to locally absorbed drug. Whereas inhibition of prostaglandin synthesis is probably the major cause of the damage, the simultaneous reduction of thromboxane formation might be advantageous for gastric mucosal integrity. Various implications arise from our hypotheses concerning the design of anti‐inflammatory drugs.
Effect of omeprazole on lower oesophageal function in normal subjects
Authors: CHAKRABORTY T. K. , DE CAESTECKER J. S. , PRYDE A. , HEADING R. C.
Published: July 2010

In a double‐blind crossover study, lower oesophageal sphincter pressure (LOSP) and distal oesophageal motility were studied in eight healthy volunteers following a single intravenous dose of omeprazole or placebo. Lower oesophageal sphincter pressure was determined before and at intervals up to 120 min after intravenous administration of 40 mg omeprazole or placebo. No effects on LOSP or distal oesophageal motility were observed.
Review article: antibiotics and the gut
Authors: PITHIE A. D. , ELLIS C. J.
Published: July 2010

Antibiotics have an important place in the management of gastrointestinal disease. Recent studies have demonstrated efficacy in acute bacterial gastroenteritis caused by salmonellae and campylobacteriaceae, shigellae and enterotoxigenic strains of E coli (ETEC). Tetracycline remains effective in cholera.

Antibiotic resistance is widespread amongst the enteric pathogens and can quickly spread during epidemics of infective diarrhoeas. It is important that antibiotics are reserved for the treatment of serious infections lest their effectiveness in these conditions be lost. Campylobacter pylori appears to be an important cause of chronic active gastritis and is amenable to treatment with antibiotics and bismuth salts. The role of C. pylori in the pathogenesis of peptic ulcer disease is not yet established but there is mounting evidence that antibiotic treatment will have a place in the treatment of this common condition. The effect of antibiotics on the normal intestinal microflora can have serious consequences. It is a major cause of resistance in urinary tract pathogens, can result in outbreaks of hospital infection with resistant organisms and frequently results in C. difficile associated diarrhoea.
Early histological features of small intestinal injury induced by indomethacin
Authors: ANTHONY A. , DHILLON A. P. , NYGARD G. , HUDSON M. , PIASECKI C. , STRONG P. , TREVETHICK M. A. , CLAYTON N. M. , JORDAN C. C. , POUNDER R. E. , WAKEFIELD A. J.
Published: July 2010

The early histological features of indomethacin‐induced jejunal injury in the rat are described in tissues preserved by perfusion‐fixation with 10% formolsaline. After an oral dose of indomethacin (15 mg/kg, known to cause severe multifocal ulceration of the rat jejunum), groups of rats were anaesthetized with subsequent perfusion‐fixation of the gastrointestinal tract at 1, 2, 3, 6 and 48 h after dosing. Using routine light microscopic techniques, we have observed a sequence of four distinct stages, in time, of small intestinal injury. The earliest histological features were shortening of the villi, epithelial stratification, basal lamina degeneration, eosinophil degranulation and infiltration of the epithelium prior to infiltration of the mucosa by neutrophils. We consider that these earliest changes, seen at 1, 2 and 3 h, represent a distinct histological entity termed Type 1 change or villous ‘tufting’. Type 2 change includes all of the features of Type 1 change plus the subsequent infiltration of the mucosa by neutrophils at 2, 3 and 6 h. Type 3 change includes necrosis of the upper‐third of the villi and was mainly seen at 3 and 6 h. Type 4 change describes extreme injury to more than one‐third of the mucosa with severe, acute inflammation and perforation of the bowel wall by 48 h. Although a small number of neutrophils had appeared to infiltrate the mucosa as early as 2 h after dosing, they were only significantly increased at 3, 6 and 48 h. Possible pathogenic mechanisms involved in shortening of villi as a result of smooth muscle contraction and the role of mucosal eosinophils in NSAID‐induced jejunal injury in the rat are discussed.
Enhancement of cytoprotective ability and cell restoration in 70‐kDa heat shock protein gene‐transfected rat gastric mucosal cells
Authors: OTAKA M. , MATSUHASHI T. , ODASHIMA M. , ITOH H. , JIN M. , WADA I. , KOMATSU K. , HORIKAWA Y. , OHBA R. , OYAKE J. , HATAKEYAMA N. , WATANABE S.
Published: July 2010

Background

Many recent studies have indicated the importance of heat shock proteins for cell survival under stress conditions. Some heat shock proteins are known to be involved in cytoprotection against environmental stresses, through their function as ‘molecular chaperones’.

Aim

To examine the biological characteristics of HSP70 gene‐transfected gastric mucosal cells.

Materials and methods

Complimentary DNA of human HSP70 gene was transfected to RGM‐1 cells (rat gastric mucosal cell line) and HSP70 highly‐expressing cells were selected and cloned. A single clone (7018‐RGM‐1), which highly expressed HSP70 compared with RGM‐1, was used in this study. Cytoprotective ability against H2O2 or ethanol was analysed by WST‐assay and LDH‐release. Wound restoration of artificially created wounds was also compared between RGM‐1 and 7018‐RGM‐1 cells.

Results

We successfully cloned HSP70 highly‐expressing gastric mucosal cells, which expressed a level of HSP70 equal to 350% of that of RGM‐1 cells. Over‐expression of HSP70 clearly enhanced cytoprotective ability against H2O2 or ethanol‐induced cell damage. Wound restoration was enhanced in 7018‐RGM‐1 cells compared with RGM‐1 cells.

Conclusion

Our results suggested that expression of HSP70 might play important roles not only in cytoprotection but also in mucosal wound restoration, mediated by the molecular chaperone function of HSP70.
Meta‐analysis: mortality in Crohn’s disease
Authors: CANAVAN C. , ABRAMS K. R. , MAYBERRY J. F.
Published: July 2010

AimTo perform a meta‐analysis is of published literature reporting standardized mortality ratios (SMR) for Crohn’s patients from 1970 to date.

MethodsMedline search identified relevant papers. Exploding references identified additional papers. When two papers reviewed mortality of one patient group at different times, the later publication was used.

ResultsOf 13 papers identified, three studies reported SMR below 1.0, two others had confidence intervals including 1.0. All other studies reported mortality higher than the general population. Meta‐analysis using a random effects model shows the pooled estimate for SMR in Crohn’s disease is 1.52 (95% CI: 1.32 to 1.74 [P < 0.0001]). Meta‐regression shows the SMR for these patients has decreased slightly over the past 30 years, but this decrease is not statistically significant (P = 0.08).

ConclusionAssessing evidence from original studies and conducting a meta‐analysis shows age‐adjusted mortality risk from Crohn’s disease is over 50% greater than the general population. Whilst mortality has improved since the condition was first recognized, further evaluation of the patients studied in the cohorts included here is necessary to assess more recent changes in clinical practice.
Development of a capsule endoscopy scoring index for small bowel mucosal inflammatory change
Authors: GRALNEK I. M. , DEFRANCHIS R. , SEIDMAN E. , LEIGHTON J. A. , LEGNANI P. , LEWIS B. S.
Published: July 2010

Background Capsule endoscopy can identify small bowel mucosal inflammatory change. However, there has been no validated index for capsule endoscopy findings. This manuscript documents the development of such an index.

Aim To develop a capsule endoscopy scoring index for small bowel mucosal inflammatory change.

Methods The index was created in four separate steps. First, parameters and descriptors of inflammatory change were identified. Secondly, blinded readers prospectively graded the presence or absence of each parameter on de‐identified videos and graded a perceived global assessment of overall severity. Thirdly, the individual parameters and descriptors were ranked in order of severity. Fourthly, values for each parameter were created using the descent gradient methodology. The premise was to assure that the final numerical score reflected the global assessment and that the global assessment agreed with the ranking of finding severity. Results were compiled for the three categories: no or clinically insignificant change, mild change, and moderate or severe change. Thresholds were determined.

Results The final index includes three parameters: villous oedema, ulcer and stenosis. A score <135 is designated normal or clinically insignificant mucosal inflammatory change, a score between 135 and 790 is mild, and a score ≥790 is moderate to severe.

Conclusion This capsule endoscopy score provides a common language to quantify small bowel inflammatory changes.
Can biological markers act as non‐invasive, sensitive indicators of radiation‐induced effects in the gastrointestinal mucosa?
Authors: WEDLAKE L. , McGOUGH C. , HACKETT C. , THOMAS K. , BLAKE P. , HARRINGTON K. , TAIT D. , KHOO V. , DEARNALEY D. , ANDREYEV H. J. N.
Published: July 2010

Background  Reliable, non‐invasive biological markers of the severity of radiotherapy‐induced damage to the gastrointestinal tract are not available. Clinicians continue to use symptom scores as surrogate indicators of toxicity.

Aim  To determine whether levels of potential biochemical markers of mucosal toxicity change during pelvic radiotherapy.

Methods  Fifty‐nine patients (30:29 males:females) with mixed pelvic malignancies, receiving 45–70 Gy were recruited. At baseline and weeks 4 or 5 of radiotherapy, blood samples for citrulline, C‐reactive protein, eosinophil cationic protein and stool samples for faecal calprotectin were obtained. Symptoms were measured using the Inflammatory Bowel Disease Questionnaire – Bowel Subset, Radiation Therapy Oncology Group and Vaizey Incontinence Questionnaires. Paired t‐tests of change in marker values were calculated.

Results  Citrulline (P = 0.02) and faecal calprotectin (P = 0.01) values changed significantly between baseline and 4/5 weeks. Inflammatory Bowel Disease Questionnaire – Bowel Subset fell significantly (mean fall = 10 points, s.d.: 8.9). Changes in markers did not correlate with symptoms.

Conclusions  Some biochemical markers of mucosal toxicity change significantly during treatment. Further studies must investigate the timing of changes of these biochemical markers, their relationship to gastrointestinal physiological change and the radiotherapy dose delivered to the gastrointestinal tract and whether changes in markers acutely can predict the degree of long‐term gastrointestinal dysfunction.
Review article: current management of non‐alcoholic fatty liver disease and non‐alcoholic steatohepatitis
Authors: YOUNOSSI Z. M.
Published: July 2010

Background Non‐alcoholic fatty liver disease (NAFLD) is the hepatic manifestation of metabolic syndrome.

Aim To assess the epidemiological impact and the current management of patients with NAFLD.

Methods Published peer‐reviewed literature and abstracts concerning NAFLD and non‐alcoholic steatohepatitis (NASH) were reviewed. Articles specifically related to epidemiology, diagnosis and current treatment strategies for NAFLD and NASH are summarized.

Results NAFLD is strongly associated with the epidemic of obesity and type‐2 diabetes mellitus, and is estimated to affect about 20–30% of the population in the US. From the spectrum of NAFLD, only patients with biopsy‐proven NASH (estimated prevalence in the US population is about 3–5%) have been convincingly shown to progress to cirrhosis, liver failure and hepatocellular carcinoma. The clinical manifestation of NAFLD is usually absent or subtle, with abnormal aminotransferases or incidental radiographic findings of fatty liver. The pathogenesis of NAFLD is attributed to a multi‐hit process involving insulin resistance, oxidative stress, apoptotic pathways, and adipocytokines. In 2008, there is no established treatment for NAFLD. Weight loss and treatment for each component of metabolic syndrome. Nevertheless, a large number of agents are being considered in clinical trials of patients with NASH.

Conclusions Awareness of the tremendous impact of NAFLD as an important cause of chronic liver disease is increasing along with a great deal of information about its pathogenesis. Future, well‐designed clinical trials that target specific pathways involved in the pathogenesis of NASH are urgently needed.
Peri‐operative endocrine effects of etomidate
Authors: MOORE R. A. , ALLEN M. C. , WOOD P. J. , REES L. H. , SEAR J. W.
Published: July 2010

This study investigated the effects of etomidate on endocrine responses to anaesthesia and surgery. Patients undergoing abdominal hysterectomy received standard anaesthetics of either etomidate for induction with etomidate infusion, or thiopentone and halo thane. Etomidate suppressed the secretion of cortisol and aldosterone for between 8 and 22 hours after the end of the etomidate infusion; 11‐deoxycortisol secretion was not suppressed during the etomidate infusion, but rose postoperatively; 17α‐hydroxyprogesterone suppression also lasted only as long as the etomidate infiion. There were no effects on plasma oestradiol, A CTH, or prolactin, but growth hormone concentrations were elevated in the etomidate group. Etomidate was concluded to have influenced adrenocortical function only, where it probably inhibits 11 β‐hydroxylation, 17 α‐hydroxylation and other intramitochondrial hydroxylation reactions. There were no clinical sequelae attributable to adrenocortical suppression. The relationship of chemical structure of etomidate and other phenylated imidazoles to inhibition of steroidogenesis is discussed.
Anaesthetic management of glucagonoma
Authors: NICOLL J. M. V. , CATLING S. J.
Published: July 2010

Alpha cell tumours of the pancreatic islets of Langerhans are rare. The glucagonoma syndrome is caused by excess glucagon secretion from such a tumour. Physiologically, glucagon is important in the control of the homeostasis of glucose and certain amino acids. Pharmacologically, it has been used to treat heart failure. Problems with both glucose homeostasis and myocardial function could, therefore, theoretically be anticipated following resection of a glucagonoma. This paper describes the peri‐operative management of such a case, where, despite measured changes in glucagon, no problems of this nature were encountered.
Treatment of acute total atelectasis
Authors: MURRAY J.F.
Published: July 2010

Three cases are described of complete collapse of a lung in the absence of bronchial obstruction. The condition was treated by the application of a sustained high pressure (6 kPa) to the aflected lung through one limb of a double lumen bronchial tube whilst intermittent positive pressure ventilation was continued through the other limb.
Severe hypercalcaemia due to a parathyroid‐type hormone‐secreting tumour of the liver treated by hepatic transplantation
Authors: SEALEY M. M.
Published: July 2010

It is very rare for a patient to have to be submitted for surgery and anaesthesia with severe hypercalcaemia unresponsive to medical treatment. Problems which may be anticipated are hypertension, hypotension, cardiac dysrhythmias and renal failure. Anaesthesia for liver transplantation also requires a full appreciation of the biochemical, haematological and haemodynamic problems involved. In the present report a patient scheduled for hepatic transplantation had a consistently raised serum calcium level (4 mmol/litre) due to the secretion of a parathyroid‐type hormone by hepatic tumour cells. The pre‐operative management of hypercalcaemia and intra‐ and postoperative management of liver transplantation in this patient are presented and discussed.
A rate pressure product meter A new module for use with the Simonsen & Weel System 8000 monitors
Authors: LAWLER P. G. , ROYALL R. A. , BURNISTON M. T.
Published: July 2010

A prototype rate pressure product module has been constructed for use with Simonsen and Weel Series 8000 monitors. The importance of method of display of rate pressure product is stressed.
Isoflurane: effect on the encephalogram during carotid endarterectomy
Authors: Campkin T.V. , Honigsberger L. , Smith I.S.
Published: July 2010

The effect of isoflurane on the electroencephalogram was studied in patients monitored during carotid endarterectomy. Increasing concentrations of this agent cause changes, but did not affect the ability to detect the onset of cerebral ischaemia consequent upon temporary occlusion of the internal carotid artery. At 1.0% and 1.5% concentration isopurane caused signijcant decreases in mean arterial pressure which is undesirable in patients undergoing vascular surgery.
Disposable double‐lumen bronchial tubes. A cost‐effectiveness survey
Authors: Linter S.P.K.
Published: July 2010

The use of red rubber double‐lumen‐bronchial tubes was studied in the Regional Cardiothoracic Centre and three large District General Hospitals to assess whether the use of disposable polyvinylchloride tubes was a viable cost‐effective alternative. In the Regional Cardiothoracic Centre red rubber tubes were used frequently throughout their predicted lifespan and were cost eflective. In the district hospitals red rubber tubes were unlikely to be used sufficiently to justify their cost. Many district general hospitals could reduce capital expenditure and annual costs by changing from red rubber to disposable polyvinyl chloride double lumen tubes.
Ventilation, dynamic compliance and ventilatory response to CO2
Authors: OLSSON A.‐K. , LINDAHL S. G. E.
Published: July 2010

Age dependent variations in minute ventilation (V̇E), tidal volume (Vr), respiratory rate and dynamic compliance (Cdyn) as well as ventilatory response to inhalation of carbon dixoide (CO2) were investigated in 20 spontaneously breathing intubated infants and children during halothane anaesthesia. Ages ranged from 6 days to 5 years. Seven patients were younger than 6 months of age. Ventilation volumes were measured by pneumotachography and end tidal carbon dioxide concentration by an in‐line capnograph. Fluid‐filled oesophageal catheters were used for pressure recordings. Measurements were made before surgery (with and without 2.22 and 3.71% of CO2 in inspired gas) and during surgery. Regression analysis of the relationship between V̇E and body weight revealed no direct proportionality. On a weight basis, V̇E was significantly higher in younger than in older patients. Tidal volume was directly proportional to body weight. The mean (SEW value of tidal volume was 4.3 (0.2) ml/kg. Dynamic compliance showed a direct proportionality with weight. The mean (SEM) value of Cdyn was 10 (1.1) ml/kPa/kg. There was no ventilatory response in any patient to inhalation of 2.22% CO2. In the older group of children (>6 months of age) V̇E increased by 34% during inhalation of 3.71% CO2 (p < 0.025). In the younger patients (<6 months of age) no ventilatory response to inhalation of 3.71% of CO2 was found, indicating a more pronounced depression of ventilation in these infants.
Plasma ionized calcium during open‐heart surgery
Authors: HEINING M. P. D. , LINTON R. A. F. , BAND D. M.
Published: July 2010

Plasma ionized calcium has been measured in eighteen patients undergoing open heart surgery. No change in ionized calcium concentration was found during the period of cardiopulmonary bypass. In the early postbypass period, a wide range of ionized calcium concentrations was found, but this did not obviously affect myocardial performance. Factors influencing the ionized calcium concentration under these circumstances are discussed.
Disruption of colonic anastomosis during continuous epidural analgesia
Authors: BIGLER D. , HJORTSØ N‐C , KEHLET H.
Published: July 2010

The clinical presentation is described of partial rupture of a colonic anastomosis two hours after surgery during epidural analgesia. The unusually early presentation of this complication is possibly due to removal of normal intestinal sympathetic activity by epidural analgesia resulting in normal or increased colonic motility. It is not known whether epidural analgesia may precipitate anastomotic breakdown due to increased contractions and strain on the anastomosis, or lead to an earlier presentation of a disruption caused by failure of surgical technique or other factors.