bluuebunny/crossref_metadata_2025 huggingface dataset:
Entanglement and alpha entropies for a massive scalar field in two dimensions
Authors: Casini H , Huerta M
Published: December 2005

We find the analytic expression of
tr ρ
n
(L) for a free massive
boson field in 1+1
dimensions, where ρ(L)
is the reduced density matrix corresponding to an interval of length
L. This is given exactly (except for a non-universal factor) in terms of a finite sum of
solutions of non-linear differential equations of the Painlevé V type. Our method is a
generalization of one introduced by Myers and is based on the explicit calculation of
quantities related to the Green function on a plane, where boundary conditions
are imposed on a finite cut. It is shown that the associated partition function
is related to correlators of exponential operators in the sine–Gordon model in
agreement with a result by Delfino et al. We also compute the short and long distance
leading terms of the entanglement entropy. We find that the bosonic entropic
c-function interpolates between the asymptotic limits of the Dirac and Majorana fermion
ones given in a previous paper. Finally, we study some universal terms for the entanglement
entropy in arbitrary dimensions which, in the case of free fields, can be expressed in terms
of the two-dimensional entropy functions.
Shiga Toxin Regulates Its Entry in a Syk-dependent Manner
Authors: Lauvrak Silje Ugland , Wälchli Sébastien , Iversen Tore-Geir , Slagsvold Hege Holte , Torgersen Maria Lyngaas , Spilsberg Bjørn , Sandvig Kirsten
Published: December 2005

Shiga toxin (Stx) is composed of an A-moiety that inhibits protein synthesis after translocation into the cytosol, and a B-moiety that binds to Gb3 at the cell surface and mediates endocytosis of the toxin. After endocytosis, Stx is transported retrogradely to the endoplasmic reticulum, and then the A-fragment enters the cytosol. In this study, we have investigated whether toxin-induced signaling is involved in its entry. Stx was found to activate Syk and induce rapid tyrosine phosphorylation of several proteins, one protein being clathrin heavy chain. Toxin-induced clathrin phosphorylation required Syk activity, and in cells overexpressing Syk, a complex containing clathrin and Syk could be demonstrated. Depletion of Syk by small interfering RNA, expression of a dominant negative Syk mutant (Syk KD), or treatment with the Syk inhibitor piceatannol inhibited not only Stx-induced clathrin phosphorylation but also endocytosis of the toxin. Also, Golgi transport of Stx was inhibited under all these conditions. In conclusion, our data suggest that Stx regulates its entry into target cells.
Dynamic Nature of Cleavage Bodies and Their Spatial Relationship to DDX1 Bodies, Cajal Bodies, and Gems
Authors: Li Lei , Roy Ken , Katyal Sachin , Sun Xuejun , Bléoo Stacey , Godbout Roseline
Published: December 2005

DDX1 bodies, cleavage bodies, Cajal bodies (CBs), and gems are nuclear suborganelles that contain factors involved in RNA transcription and/or processing. Although all four nuclear bodies can exist as distinct entities, they often colocalize or overlap with each other. To better understand the relationship between these four nuclear bodies, we examined their spatial distribution as a function of the cell cycle. Here, we report that whereas DDX1 bodies, CBs and gems are present throughout interphase, CPSF-100-containing cleavage bodies are predominantly found during S and G2 phases, whereas CstF-64-containing cleavage bodies are primarily observed during S phase. All four nuclear bodies associate with each other during S phase, with cleavage bodies colocalizing with DDX1 bodies, and cleavage bodies/DDX1 bodies residing adjacent to gems and CBs. Although inhibitors of RNA transcription had no effect on DDX1 bodies or cleavage bodies, inhibitors of DNA replication resulted in loss of CstF-64-containing cleavage bodies. A striking effect on nuclear structures was observed with latrunculin B, an inhibitor of actin polymerization, resulting in the formation of needlelike nuclear spicules made up of CstF-64, CPSF-100, RNA, and RNA polymerase II. Our results suggest that cleavage body components are highly dynamic in nature.
Role of a Cdc42p Effector Pathway in Recruitment of the Yeast Septins to the Presumptive Bud Site
Authors: Iwase Masayuki , Luo Jianying , Nagaraj Satish , Longtine Mark , Kim Hyong Bai , Haarer Brian K. , Caruso Carlo , Tong Zongtian , Pringle John R. , Bi Erfei
Published: December 2005

The septins are GTP-binding, filament-forming proteins that are involved in cytokinesis and other processes. In the yeast Saccharomyces cerevisiae, the septins are recruited to the presumptive bud site at the cell cortex, where they form a ring through which the bud emerges. We report here that in wild-type cells, the septins typically become detectable in the vicinity of the bud site several minutes before ring formation, but the ring itself is the first distinct structure that forms. Septin recruitment depends on activated Cdc42p but not on the normal pathway for bud-site selection. Recruitment occurs in the absence of F-actin, but ring formation is delayed. Mutant phenotypes and suppression data suggest that the Cdc42p effectors Gic1p and Gic2p, previously implicated in polarization of the actin cytoskeleton, also function in septin recruitment. Two-hybrid, in vitro protein binding, and coimmunoprecipitation data indicate that this role involves a direct interaction of the Gic proteins with the septin Cdc12p.
AVERTING AND INSURANCE DECISIONS IN THE WILDLAND–URBAN INTERFACE: IMPLICATIONS OF SURVEY AND EXPERIMENTAL DATA FOR WILDFIRE RISK REDUCTION POLICY
Authors: TALBERTH JOHN , BERRENS ROBERT P. , MCKEE MICHAEL , JONES MICHAEL
Published: December 2005

When confronted by catastrophic wildfire risk, homeowners simultaneously allocate resources between insurance and averting activities. Expected utility theory suggests that complete insurance coverage precludes investment in averting activities. However, when potential losses include a significant nonmarket component, optimal choice includes both. To investigate this issue, the authors analyze a unique combination of contingent valuation and experimental data. Both settings include a split‐sample treatment to test the influence of wildfire risk zone information. The authors find that amenity values, subjective risk, averting efficacy perception, and demographic factors influence both willingness to pay and averting share and that risk information has the predicted ordering effect. (JELC9,Q51,Q54)
Effects of Caffeine, Halothane, and 4-Chloro-m -cresol on Skeletal Muscle Lactate and Pyruvate in Malignant Hyperthermia–susceptible and Normal Swine as Assessed by Microdialysis
Authors: Bina Saiid , Cowan George , Karaian John , Muldoon Sheila , Mongan Paul , Bünger Rolf
Published: December 2005

Background

Skeletal muscle fibers from malignant hyperthermia (MH)-susceptible humans and swine are markedly more sensitive to ryanodine receptor (RyR1) agonists than those from normal individuals. Reproducible shifts in the dose-response of skeletal muscle to caffeine and halothane are the basis of the current in vitro diagnostic caffeine-halothane contracture test. In an attempt to develop a less invasive MH diagnostic test, the authors determined the effects of RyR1 agonists (caffeine, 4-chloro-m-cresol [4CmC], and halothane) on the adductor muscle with respect to the lactate-pyruvate (L/P) system that was percutaneously dialyzed using a microdialysis technique in homozygous MH-susceptible compared with normal swine.

Methods

Animals were anesthetized (ketamine-propofol) and artificially ventilated. Sets of six CMA/20 microdialysis catheters were implanted; each catheter was perfused with different RyR1 agonist concentrations. After a 30-min equilibration after implantation, one of the catheters was perfused (2 microl/min) with vehicle (0.9% saline or lipid emulsion), and the other five were perfused with caffeine (1-64 mM), 4CmC (0.1-8 mM), or halothane (prepared in lipid emulsion; 10-500 mM). Outflow dialysate fractions collected at 10-min intervals and L/P parameters were measured enzymatically.

Results

Only in the MH-susceptible group did all RyR1 agonists increase dialysate L/P in a dose-dependent manner. The dose-effect relations were most prominent with 4CmC. With the halothane lipid emulsion, data scatter was high compared with that of the caffeine group and especially the 4CmC group. There were no signs of global muscle rigidity, systemic hypermetabolism, or a clinical MH episode during microdialysis RyR1 perfusion.

Conclusions

The authors data demonstrate that the in vivo muscle microdialysis of the porcine L/P system reveals distinct differences between MH-susceptible and MH-normal muscle, especially in response to highly specific RyR1 agonists such as 4CmC. The microdialysis L/P technique seems to have an MH diagnostic potential in the clinical setting.
Enthalpic and entropic contributions mediate the role of disulfide bonds on the conformational stability of Interleukin‐4
Authors: Vaz Daniela C. , Rodrigues J. Rui , Sebald Walter , Dobson Christopher M. , Brito Rui M.M.
Published: December 2005

The role of disulfide bridges in the structure, stability, and folding pathways of proteins has been the subject of wide interest in the fields of protein design and engineering. However, the relative importance of entropic and enthalpic contributions for the stabilization of proteins provided by disulfides is not always clear. Here, we perform a detailed analysis of the role of disulfides in the conformational stability of human Interleukin‐4 (IL4), a four‐helix bundle protein. In order to evaluate the contribution of two out of the three disulfides to the structure and stability of IL4, two IL4 mutants, C3T‐IL4 and C24T‐IL4, were used. NMR and ANS binding experiments were compatible with altered dynamics and an increase of the nonpolar solvent‐accessible surface area of the folded state of the mutant proteins. Chemical and thermal unfolding experiments followed by fluorescence and circular dichroism revealed that both mutant proteins have lower conformational stability than the wild‐type protein. Transition temperatures of unfolding decreased 14°C for C3T‐IL4 and 10°C for C24T‐IL4, when compared to WT‐IL4, and the conformational stability, at 25°C, decreased 4.9 kcal/mol for C3T‐IL4 and 3.2 kcal/mol for C24T‐IL4. Interestingly, both the enthalpy and the entropy of unfolding, at the transition temperature, decreased in the mutant proteins. Moreover, a smaller change in heat capacity of unfolding was also observed for the mutants. Thus, disulfide bridges in IL4 play a critical role in maintaining the thermodynamic stability and core packing of the helix bundle.
Breaking symmetry in protein dimers: Designs and functions
Authors: Brown Jerry H.
Published: December 2005

Symmetry, and in particular point group symmetry, is generally the rule for the global arrangement between subunits in homodimeric and other oligomeric proteins. The structures of fragments of tropomyosin and bovine fibrinogen are recently published examples, however, of asymmetric interactions between chemically identical chains. Their departures from strict twofold symmetry are based on simple and generalizable chemical designs, but were not anticipated prior to their structure determinations. The current review aims to improve our understanding of the structural principles and functional consequences of asymmetric interactions in proteins. Here, a survey of >100 diverse homodimers has focused on the structures immediately adjacent to the twofold axis. Five regular frameworks in α‐helical coiled coils and antiparallel β‐sheets accommodate many of the twofold symmetric axes. On the basis of these frameworks, certain sequence motifs can break symmetry in geometrically defined manners. In antiparallel β‐sheets, these asymmetries include register slips between strands of repeating residues and the adoption of different side‐chain rotamers to avoid steric clashes of bulky residues. In parallel coiled coils, an axial stagger between the α‐helices is produced by clusters of core alanines. Such simple designs lead to a basic understanding of the functions of diverse proteins. These functions include regulation of muscle contraction by tropomyosin, blood clot formation by fibrin, half‐of‐site reactivity of caspase‐9, and adaptive protein recognition in the matrix metalloproteinase MMP9. Moreover, asymmetry between chemically identical subunits, by producing multiple equally stable conformations, leads to unique dynamic and self‐assembly properties.
Chronic gingivitis in a new BTK mutation
Authors: Liu Anthony J. W. , Dao‐Ung Lan‐Phuong , McDonald David , Nanan Ralph
Published: December 2005

Abstract:  A 5‐yr‐old Caucasian boy with a new mutation in Bruton's tyrosine kinase (BTK) is described. Full sequencing of the BTK gene revealed a point mutation in exon 17 resulting in an amino acid change from tryptophan to serine at location 581 of the tyrosine kinase domain. Clinically the child presented with chronic gingivitis and had no prior history of bacterial infections. Whereas serum immunoglobulin M (IgM) levels were undetectable, IgG levels were in the low normal range. The gingivitis completely resolved after intravenous immunoglobulin therapy. Lymphocyte phenotyping revealed 0.05% B cells in his peripheral blood, which were IgG−, IgM+, IgD+, CD38+, CD20+, CD27−. However, 40% of the B cells also expressed CD5. This subpopulation of B cells has not previously been described in X‐linked agammaglobulinaemia (XLA) patients. We suggest that the occurrence of CD5+ B cells could correlate with a late onset and mild clinical presentations of XLA.
Delayed effusive pericarditis and recurrent pleural effusion after radiation treatment for Hodgkin's disease responsive to per os doxycycline
Authors: Fragoulis Konstantinos N. , Handrinou Eleni , Papadopoulos Vasilis , Dardoufas Konstantinos , Falagas Matthew E.
Published: December 2005

Abstract:  We present our experience with a patient with effusive pericarditis and recurrent pleural effusion that first developed 23 yr after radiation treatment for the nodular sclerosis type of Hodgkin's disease. Extensive diagnostic work up including pericardial and pleural biopsy, excluded any other cause (than radiation) of the recurrent pleural effusion. Pericarditis and pleural effusion were not controlled with regimens including steroid and non‐steroid anti‐inflammatory agents. The fluid collections improved only with per os doxycycline (100 mg twice a day). Four episodes of recurrent pleural effusions were also controlled with per os doxycycline. Although the concentration of doxycycline in the pericardial and pleural fluid when given orally is smaller compared with that achieved by direct installation of the agent, the fact that all episodes of pleural effusion improved with an agent commonly used for pleurodesis is intriguing.
Primary sclerosing cholangitis complicating plasma cell dyscrasia (PCD): remission of PCD following liver transplant
Authors: Fontana Vincenzo , Ahn Yeon S. , Horstman Lawrence H. , Tzakis Andreas G. , O'Brien Christopher B.
Published: December 2005

Abstract:  We report the first case of primary sclerosing cholangitis (PSC) complicated with plasma cell dyscrasia (PCD) in which liver transplant resulted in unexpected therapeutic benefit of PCD. A 61‐year‐old man with 12 yr history of PSC presented with a monoclonal gammopathy of undetermined significance (MGUS) with an IgG level of 3400 mg/dL. It was stable initially for 3 yr but progressed to features consistent with multiple myeloma (MM): IgG rose to 5290 mg/dL along with development of terminal stage of liver failure. Liver transplant was performed in desperation. Unexpectedly, MM underwent clinical remission following transplant. At 3 and 14 months following transplant, IgG stayed below 2080 mg/dL and he was able to return to full‐time employment. This case may suggest that chronic antigenic stimulation from cirrhotic liver contributed to MGUS and subsequent transformation to MM. Liver transplant eliminated chronic antigenic stimulation, apparently leading to remission of MM. Since PCD is often associated with other chronic liver diseases, similar benefit may accrue to a range of patients with chronic liver diseases complicating PCD.
Comparative genomic analysis of phytopathogenic fungi using expressed sequence tag (EST) collections
Authors: SOANES DARREN M. , TALBOT NICHOLAS J.
Published: December 2005

We describe the analysis of 57 727 unique expressed sequence tags (ESTs) from 15 species of phytopathogenic and three species of saprophytic fungi. This resource is held within the COGEME phytopathogen EST database (http://cogeme.ex.ac.uk/). Comparative analysis was performed to investigate the differences between pathogenic and free‐living fungi based on a substantial collection of expressed gene sequences and available, completed fungal genome sequences. We report that the expressed gene inventories of pathogenic fungi were not significantly more similar to each other than to those of free‐living filamentous fungi. As expected, however, filamentous fungi as a group share more sequences in common than with the free‐living yeast species Saccharomyces cerevisiae. Interestingly, ESTs of the obligate biotrophic fungus Blumeria graminis f. sp. hordei were more dissimilar to those of all other fungal species assessed, having a lower number of sequences in common with filamentous ascomycetes studied to date and also possessing a larger proportion of unisequences of unknown function. Our analysis of ESTs in the COGEME database enabled identification of a set of functional groups of genes that are more highly represented in the genomes of pathogenic fungi than non‐pathogenic species.
Influence of acute serotonin reuptake inhibition on colonic sensorimotor function in man
Authors: TACK J. , BROEKAERT D. , CORSETTI M. , FISCHLER B. , JANSSENS J.
Published: December 2005

Background  It is unclear whether decreased serotonin transporter function contributes to sensorimotor abnormalities in irritable bowel syndrome.

Aim  To study the influence of acute serotonin transporter inhibition on colonic sensorimotor function in man.

Methods  Ten healthy subjects (five men, aged 20–29 years) underwent a combined manometry/barostat study of the descending colon on two occasions. Stepwise distentions by 2 mmHg increments were performed until discomfort. Subsequently, placebo or citalopram 20 mg were administered i.v. over 20 min and distentions were repeated. Afterwards, isobaric tone measurements were performed 30 min before and 90 min after ingestion of a meal. High‐amplitude propagated contractions, colonic motility index, colonic compliance, sensitivity and colonic response to a meal after placebo or citalopram were compared by t‐test and two‐way anova.

Results  Citalopram induced a significant increase in colonic motility index (5.6 ± 0.9 to 0.8 ± 1.9 mL*min, P < 0.005) and high‐amplitude propagated contractions (32 after citalopram vs. 2 after placebo, P < 0.05), which were associated with abdominal cramping. Administration of citalopram increased colonic compliance (10.3 ± 1.5 vs. 14.5 ± 2.2 mL/mmHg, P < 0.01) and inhibited colonic response to a meal (volume decrease 48 ± 12 vs. 16 ± 12 mL, P < 0.01).

Conclusions  Acute serotonin transporter inhibition in man increases colonic phasic contractility and the occurrence of high‐amplitude propagated contractions, increases colonic compliance and suppresses the colonic tonic response to a meal. These data suggest that both release and elimination of 5‐hydroxytryptamine by serotonin transporter are involved in the control of colonic motility in man.
Age threshold for endoscopy and risk of missing upper gastrointestinal malignancy – data from the Scottish audit of gastric and oesophageal cancer
Authors: PHULL P. S. , SALMON C. A. , PARK K. G. M. , RAPSON T. , THOMPSON A. M. , GILBERT F. J.
Published: December 2005

Background  Urgent endoscopy is indicated for suspected upper gastrointestinal malignancy. However, there is limited evidence on the age threshold for performing urgent endoscopy in uncomplicated dyspepsia (that is, without alarm features).

Aim  To quantify the risk of missing upper gastrointestinal malignancy within Scotland, if the age threshold for urgent endoscopy in uncomplicated dyspepsia was increased from 45 to 55 years.

Methods  Analysis of data collected prospectively by the Scottish Audit of Gastric and Oesophageal Cancer. ‘Alarm’ features at presentation were defined as dysphagia, weight loss, gastrointestinal bleeding, anaemia, vomiting, history of gastric surgery and history of peptic ulcer disease.

Results  Of the 3293 patients diagnosed with upper gastrointestinal malignancy, 290 (8.8%) patients were <55 years of age. Twenty‐one of the patients aged <55 years had no alarm features (0.64% of all patients); 12 were aged 45–55 years and nine were aged <45 years. Only two patients (one aged <45 years) underwent potentially curative surgery.

Conclusion  Upper gastrointestinal malignancy is uncommon under 55 years of age and most of the patients present with alarm features. Raising the age threshold for endoscopy for new‐onset uncomplicated dyspepsia from 45 to 55 years would not impact adversely on the diagnosis or outcome of upper gastrointestinal malignancy.
Slimline vs. glass pH electrodes: what degree of accuracy should we expect?
Authors: PANDOLFINO J. E. , GHOSH S. , ZHANG Q. , HEATH M. , BOMBECK T. , KAHRILAS P. J.
Published: December 2005

Background  Ambulatory pH monitoring is considered the gold standard for measuring oesophageal acid exposure, however, data comparing antimony and glass electrodes are limited.

Aim  To compare the accuracy of the Slimline antimony pH monitoring system and a conventional glass electrode catheter pH monitoring system during ambulatory conditions.

Methods  Eighteen subjects (13 males, 23–45 years) underwent simultaneous pH monitoring using the Slimline antimony pH electrode and MIC M3 glass pH electrode pH monitoring systems for 12 h. Acid exposure was analysed and compared by manual extraction of the data onto an excel spreadsheet.

Results  There was no statistical difference in the median per cent time the pH was <4 recorded by the two systems (Slimline, 3%, Glass MIC M3, 2%, P = 0.77) and the correlation was excellent (r = 0.84). The difference in recorded reflux events was also not significantly different between the two systems, with the absolute difference being 23 events (s.d., 26). Point‐by‐point discrepancy was 28% (s.d., 18%), however, the agreement in terms of reflex events was excellent (Kappa value, 0.89, s.d., 0.09).

Conclusion  Despite substantial point‐by‐point disagreement, the antimony Slimline pH catheter compares favourably to the Glass MIC M3 pH catheter in terms of measuring standard pH parameters.
Deficient UDP‐glucuronosyltransferase detoxification enzyme activity in the small intestinal mucosa of patients with coeliac disease
Authors: GOERRES M. , ROELOFS H. M. J. , JANSEN J. B. M. J. , PETERS W. H. M.
Published: December 2005

Background  Small intestinal malignancies in humans are rare; however, patients with coeliac disease have a relatively high risk for such tumours. Intestinal UDP‐glucuronosyltransferases are phase II drug metabolism enzymes also involved in the detoxification of ingested toxins and carcinogens. As many toxins and carcinogens are ingested via food, the human gastrointestinal tract not only has an important role in the uptake of essential nutrients, but also acts as a first barrier against such harmful constituents of the food. Therefore, the gastrointestinal mucosa contains high levels of detoxification enzymes such as cytochromes‐P450, glutathione S‐transferases and UDP‐glucuronosyltransferases.

Aim  To compare the UDP‐glucuronosyltransferase detoxification capacity in small intestinal mucosa of patients with coeliac disease vs. that in normal controls.

Methods  We assessed UDP‐glucuronosyltransferase enzyme activities towards 4‐methylumbelliferone in small intestinal biopsies of patients with coeliac disease (n = 22) and age‐ and sex‐matched controls (n = 27).

Results  Small intestinal UDP‐glucuronosyltransferase enzyme activity in controls was significantly higher than in patients with coeliac disease: 0.55 ± 0.27 vs. 0.35 ± 0.16 nmol/min mg protein, respectively (mean ± s.d., P = 0.005).

Discussion  The low small intestinal UDP‐glucuronosyltransferase detoxification activity in patients with coeliac disease may result in a deficient detoxification of potential carcinogens, and thus could explain in part the relatively high small intestinal cancer risk in these patients.
Pharmacokinetics of ruboxistaurin are significantly altered by rifampicin‐mediated CYP3A4 induction
Authors: Yeo Kwee Poo , Lowe Stephen L. , Lim Ming Tung , Voelker James R. , Burkey Jennifer L. , Wise Stephen D.
Published: December 2005

Aims

The aim of this study was to evaluate the effect of rifampicin co‐administration on the pharmacokinetics of ruboxistaurin and its active metabolite, N‐desmethyl ruboxistaurin and, in addition, to compare the changes in pharmacokinetics of ruboxistaurin and N‐desmethyl ruboxistaurin with the urinary 6β‐hydroxycortisol : cortisol ratio. Ruboxistaurin is a specific protein‐kinase‐C β inhibitor in clinical development for the treatment of diabetic microvascular complications.

Methods

This was a two‐period, one‐sequence study. Sixteen healthy male subjects completed both study periods. In period one, a single 64 mg oral dose of ruboxistaurin was administered. In period two, 600 mg rifampicin was administered daily for 9 days, during which another single 64 mg ruboxistaurin dose was administered on day 7. Blood samples were collected and assayed for ruboxistaurin and N‐desmethyl ruboxistaurin. CYP3A4 induction was assessed by ratios of urinary 6β‐hydroxycortisol : cortisol (6β‐OHC : C) obtained via 24 h and morning‐spot sampling techniques.

Results

Following repeated doses of rifampicin, both the mean Cmax and AUC(0,∞) of ruboxistaurin were significantly reduced by approximately 95% (P ≤ 0.001). For the metabolite, the mean Cmax decreased by 68% (P ≤ 0.001), and AUC(0,∞) decreased by 77% (P ≤ 0.001). The tmax values did not appear affected. The 6β‐OHC : C ratios from both 24 h and morning spot methods increased significantly, consistent with CYP3A4 induction.

Conclusions

The effect of rifampicin co‐administration on the exposure of ruboxistaurin is consistent with ruboxistaurin being a substrate of CYP3A4. Therefore, co‐administration with known CYP3A4 inducing agents (rifampicin, carbamazepine, phenobarbital, etc.) may decrease the concentrations of ruboxistaurin and N‐desmethyl‐ruboxistaurin. In this study, 6β OHC : C ratios substantially underestimated the impact of rifampicin on ruboxistaurin.
Animal models of allergen‐induced tolerance in asthma: are T‐regulatory‐1 cells (Tr‐1) the solution for T‐helper‐2 cells (Th‐2) in asthma?
Authors: Tournoy K. G. , Van Hove C. , Grooten J. , Moerloose K. , Brusselle G. G. , Joos G. F.
Published: December 2005

Non‐specific anti‐inflammatory medication is actually the treatment of choice for controlling the T‐helper type 2 (Th‐2) cell‐driven airway inflammation in asthma. The induction of counterbalancing Th‐1 cell clones, long considered a promising approach for immunotherapy, has failed to fulfil its promise because of potentially detrimental side‐effects. This is therefore probably not a valid option for the treatment of asthma.With the increasing awareness that active immune mechanisms exist to control inflammatory responses, interest rises to investigate whether these can be exploited to control allergen‐induced airway disease. The induction of antigen‐specific T cells with suppressive characteristics (regulatory T cells) is therefore a potentially interesting approach. These regulatory T cells mediate tolerance in healthy, non‐atopic individuals and have the potential of becoming an effective means of preventing allergen‐induced airway inflammation and possibly of suppressing ongoing allergic immune responses. Here we review the available knowledge about allergen‐induced suppressive immunity obtained from animal models taking into account the different developmental stages of allergic airway disease.
Exhaled breath condensate levels of eotaxin and macrophage‐derived chemokine in stable adult asthma patients
Authors: Ko F. W. S. , Lau C. Y. K. , Leung T. F. , Wong G. W. K. , Lam C. W. K. , Lai C. K. W. , Hui D. S. C.
Published: December 2005

Background
Asthma is associated with esoinophilic airway inflammation and overproduction of T‐helper type 2 (Th2) lymphocyte‐related cytokines.

Objective
This study assessed the eosinophil chemoattractant eotaxin and Th2‐specific macrophage‐derived chemokine (MDC) in the adult asthmatic airway. Eotaxin and MDC levels were determined in exhaled breath condensate (EBC) obtained from adult patients with asthma.

Methods
Fifty‐four asthmatics (20 male, mean (SD) age 40 (12) years and percentage predicted forced expiratory volume in 1 s (FEV1) 81.7 (20.8)) and 20 age‐ and sex‐matched controls were studied. EBC was collected using EcoScreen by 10 min of tidal breathing with a nose clip. Concentrations of eotaxin and MDC were measured by ELISA.

Results
Asthma patients on inhaled corticosteroid (ICS) had a higher median interquartile range (IQR) level of eotaxin than the steroid‐naïve asthmatics (18.5 (17.7–20.1) vs. 17.9 (17.0–18.6) pg/mL, P=0.02) and controls (18.5 (17.7–20.1) pg/mL vs 17.4 (16.3–18.0) pg/mL, P=0.001). Eotaxin level in EBC had a significant negative correlation with the FEV1/forced vital capacity ratio (r=−0.43, P=0.03) in steroid‐naïve asthmatics. EBC MDC level was higher in subjects on ICS than the steroid naïve asthmatics (120 (118–125) vs. 117 (116–119) pg/mL, P=0.01) and the controls (120 (118–125) vs. 117 (116–120) pg/mL, P=0.02).

Conclusions
Eotaxin and MDC could be measured in EBC of adults with asthma. EBC eotaxin and MDC levels were higher in asthmatics on ICS than the steroid‐naïve asthmatics or controls. Exhaled chemokines may be potential non‐invasive markers for assessing airway inflammation in asthmatics.
T cell‐mediated hypersensitivity to quinolones: mechanisms and cross‐reactivity
Authors: Schmid D. A. , Depta J. P.H. , Pichler W. J.
Published: December 2005

Background
Quinolones are widely used, broad spectrum antibiotics that can induce immediate‐ and delayed‐type hypersensitivity reactions, presumably either IgE or T cell mediated, in about 2–3% of treated patients.

Objective
To better understand how T cells interact with quinolones, we analysed six patients with delayed hypersensitivity reactions to ciprofloxacin (CPFX), norfloxacin (NRFX) or moxifloxacin (MXFX).

Methods
We confirmed the involvement of T cells in vivo by patch test and in vitro by means of the lymphocyte proliferation test (LTT). The nature of the drug–T cell interaction as well as the cross‐reactivity with other quinolones were investigated through the generation and analysis (flow cytometry and proliferation assays) of quinolone‐specific T cell clones (TCC).

Results
The LTT confirmed the involvement of T cells because peripheral blood mononuclear cells (PBMC) mounted an enhanced in vitro proliferative response to CPFX and/or NRFX or MXFX in all patients. Patch tests were positive after 24 and 48 h in three out of the six patients. From two patients, CPFX‐ and MXFX‐specific CD4+/CD8+ T cell receptor (TCR) αβ+ TCC were generated to investigate the nature of the drug‐T cell interaction as well as the cross‐reactivity with other quinolones. The use of eight different quinolones as antigens (Ag) revealed three patterns of cross‐reactivity: clones exclusively reacting with the eliciting drug, clones with a limited cross‐reactivity and clones showing a broad cross‐reactivity. The TCC recognized quinolones directly without need of processing and without covalent association with the major histocompatability complex (MHC)–peptide complex, as glutaraldehyde‐fixed Ag‐presenting cells (APC) could present the drug and washing quinolone‐pulsed APC removed the drug, abrogating the reactivity of quinolone‐specific TCC.

Conclusion
Our data show that T cells are involved in delayed immune reactions to quinolones and that cross‐reactivity among the different quinolones is frequent.
Non‐haem iron transport in the rat proximal colon
Authors: Johnston K. L. , Johnson D. M. , Marks J. , Srai S. K. , Debnam E. S. , Sharp P. A.
Published: December 2005

Background  Only 10% of dietary iron is absorbed in the duodenum which implies that 90% (approximately 9 mg day−1) reaches the lower small intestine and colon. Therefore the purpose of this study was to assess the iron transport capacity of the rat proximal colon and to determine whether iron absorption is regulated by changes in dietary iron content.

Materials and methods  Rats were fed for 14 days on either iron adequate (44 mg Fe kg−1 diet) or iron‐deficient (< 0·5 mg Fe kg−1 diet) diets. The 59Fe transport across the colonic epithelium and its subsequent appearance in the blood were measured in vivo. In separate studies the colon was excised and used to measure divalent metal transporter expression.

Results  Divalent metal transporter (DMT1) was expressed at the apical membrane of the surface epithelium in rat proximal colon. In animals fed an iron‐deficient diet, DMT1 mRNA and protein expression were increased. This was accompanied by a significant increase in tissue 59Fe uptake.

Conclusions  The proximal colon can absorb non‐haem iron from the intestinal lumen. The purpose of this mechanism remains to be elucidated.
BNP and N‐terminal proBNP are both extracted in the normal kidney
Authors: Goetze J. P. , Jensen G. , Møller S. , Bendtsen F. , Rehfeld J. F. , Henriksen J. H.
Published: December 2005

Background  Increased plasma concentrations of cardiac‐derived B‐type natriuretic peptide (BNP) and N‐terminal pro‐B‐type natriuretic peptide (proBNP) are both associated with left ventricular dysfunction. Information on the regional elimination of the peptides is, however, still scarce. We therefore examined the renal and peripheral extraction of N‐terminal proBNP and BNP.

Materials and methods  The study comprised 18 patients with essential arterial hypertension, 51 with cirrhosis, and 18 control patients without kidney or liver disease. All patients underwent a haemodynamic investigation with catheterization of the femoral artery and femoral and renal veins. Blood sampling from the catheters allowed determination of the arteriovenous extraction ratio of N‐terminal proBNP and BNP.

Results  Neither the peripheral N‐terminal proBNP (13, 11, 19 pmol L−1, NS) nor the BNP plasma concentrations (4, 12, 9 pmol L−1, NS) differed between the patient groups. In addition, similar renal extractions were observed in the groups. The renal extraction of N‐terminal proBNP (0·16) was not different from that of BNP (0·16). In contrast, the N‐terminal proBNP extraction in the lower extremity was markedly lower compared with BNP (0·00 vs. 0·125, P = 0·007).

Conclusions  A comparable renal elimination of N‐terminal proBNP and BNP is contrasted by a selective extraction of BNP in the lower extremity. Our results suggest a different elimination mechanism in the renal and peripheral circulation, which partly may explain the higher N‐terminal proBNP compared with BNP concentrations in normal plasma.
Interleukin‐4 can induce interleukin‐4 production in dendritic cells
Authors: Maroof Asher , Penny Michelle , Kingston Rosetta , Murray Clare , Islam Sabita , Bedford Penelope A. , Knight Stella C.
Published: December 2005

The presence of interleukin‐4 (IL‐4) during the generation of dendritic cells (DC) from precursor cells results in measurable increases of IL‐12 in supernatants but IL‐4 secretion has not been reported. However, DC have IL‐4 receptors and are able to make IL‐4. We therefore sought evidence for autocrine effects of IL‐4 on DC. IL‐4 gene expression was low in DC generated from bone‐marrow stem cells in the presence of granulocyte–macrophage colony‐stimulating factor but was up‐regulated by exposure of the developing DC to IL‐4. Exposure to IL‐4 also induced intracellular IL‐4 production in DC. The intracellular IL‐4 induced in the presence of IL‐4 was increased following further DC maturation with tumour necrosis factor‐α. By contrast, in supernatants of DC, IL‐4 was rarely detected and only at late culture periods. However, after exposure of DC to IL‐4, cell‐bound IL‐4 was detected transiently, which suggested binding and internalization of the cytokine. Binding via IL‐4 receptor‐α was indicated from phosphorylation of the signal transducer and activator of transcription (STAT) protein 6, which is known to mediate IL‐4 function. Cytokine persisting within the supernatants of the cells may therefore be unrepresentative of the actual production and function of IL‐4 in the cells; IL‐4 may be produced in DC in response to exposure to IL‐4 but may then be lost from the supernatants during cell binding and activation of the cells.
Molecular cloning of several rat ABC transporters including a new ABC transporter,Abcb8, and their expression in rat testis
Authors: Melaine Nathalie , Satie Anne‐Pascale , Lassurguère Julie , Desmots Sophie , Jégou Bernard , Samson Michel
Published: December 2005

Several members of the ABC transporter superfamily play an important role in testicular physiology and defence against anticancer drugs. Using a reverse transcription‐polymerase chain reaction strategy with degenerate primers and rat testis RNA as template, we have looked for the presence of other members of this superfamily. Of the six partial cDNA found, five corresponded to ABC transporters already known –Mdr1b, Mrp1, Tapl/Abcb9, Umat/Abcb6andSur2/Abcc9– and one presented a strong homology with mouse and humanABCB8. Using a 5′ and 3′ RACE approach, we cloned the full‐length cDNA and found that the predicted protein presented 92% and 80% homology with the mouse and human proteins respectively. Strong expression of rat abcb8 was found in heart, brain and testis when compared with liver, lung and spleen. In the testis, rat abcb8 was expressed both in the somatic Sertoli cells and peritubular cells and in the germline (spermatogonia and pachytene spermatocytes). Furthermore,Umat/Abcb6was very highly expressed in the testis (high amounts in meiotic pachytene spermatocytes and low amount in post‐meiotic early spermatids). In conclusion, we confirm the presence of several ABC transporters in the testis and also provide evidence of the presence of Abcb8 in the organ.
Real‐time three‐dimensional ultrasound visualization of erection and artificial coitus
Authors: DENG JING , HALL‐CRAGGS MARGARET A. , PELLERIN D. , LINNEY ALFRED D. , LEES WILLIAM R. , RODECK CHARLES H. , TODD‐POKROPEK ANDREW
Published: December 2005

To investigate the feasibility of imaging penile erection and coitus in real time and in three dimensions, a ‘Live’ three‐dimensional (3‐D) ultrasound system was used to acquire the volume of interest at 25 Hz from five healthy men. Water baths and gel‐made artificial vaginas were devised to facilitate the 3‐D scans without the probe being in direct contact with the penis. For the first volunteer scanned with the water bath alone, the penis failed to erect within 30 min. For the other four volunteers, the ‘vagina’ successfully initiated and maintained the erection and allowed artificial intercourse. Results have shown that the ‘Live’ 3‐D ultrasound and minimally compressive imaging techniques together can offer an objective means for visualizing erection and coitus in spatial totality and temporal reality. They can be further developed to reveal more reliable details about the dynamic morphology, improving scientific understanding of sexual activities and clinical management of related problems.
Small rodent winter survival: snow conditions limit access to food resources
Authors: KORSLUND LARS , STEEN HARALD
Published: December 2005

In Fennoscandia during winter small rodents spend most of their time in the subnivean space, between the snow cover and the ground. The subnivean space is probably not a uniform habitat, but broken into accessible and inaccessible patches by ice covering the vegetation. This might reduce access to otherwise available food resources.

To test whether ice formations reduce access to food and thus limit winter survival of small rodents, we conducted an experiment where we increased subnivean space by adding corrugated aluminium sheets on the ground before onset of winter. The sheets prevented ice formation, thus mimicking natural occurring subnivean space, and providing more room for animals living in the subnivean space to forage.

During the experiment 142 Microtus oeconomus were passive induced transponder (PIT)‐tagged, and a system consisting of fixed tube‐shaped antennas and PIT‐tag readers were used to provide data to analyse winter survival and individual subnivean space use. The extent of winter grazing was measured after snow melt by examining percentage area grazed.

The treatment resulted in increased survival which corresponded well with significantly higher space use and more grazing under the sheets.

Females showed a positive correlation between probability of survival and body mass while no such effect was observed in males.

The results suggest that the snow cover reduces survival in winter by physically enclosing the vegetation in ice and thus reducing access to otherwise available food resources. The amount of ice and its configuration might vary between years due to changing weather patterns. Our results offer a mechanistic explanation for variations in winter survival and suggest incorporating climate variables in future small rodent models.

Directional and long‐term changes in climate might result in increased ice formation in the subnivean system. Such deterioration may lead to reduced winter survival and act by stabilizing population dynamics and dampening vole cyclicity.
Syndrome specificity and behavioural disorders in young adults with intellectual disability: cultural differences in family impact
Authors: Blacher J. , McIntyre L. L.
Published: December 2005

Background  This study examined whether behaviour problems and adaptive behaviour of low functioning young adults, and well‐being of their families, varied by diagnostic syndrome [intellectual disability (ID) only, cerebral palsy, Down syndrome, autism], as well as by cultural group.

Methods  Behaviour disorders in young adults with moderate to severe ID were assessed from information provided by 282 caregivers during in‐home interviews. The sample consisted of 150 Anglo participants, and 132 Latino, primarily Spanish‐speaking, participants drawn from Southern California.

Results  Behaviour disorders and maternal well‐being showed the same pattern across disability syndromes. Autism was associated with the highest scores in multiple behaviour problem areas as well as maternal reports of lower well‐being. Down syndrome was associated with the lowest behaviour problem scores and the highest maternal well‐being. When behaviour problems were controlled for, diagnostic groups accounted for no additional variance in maternal stress or depression. The pattern of behaviour problems and well‐being did not differ by sample (Anglo vs. Latino), although level on well‐being measures did. Latina mothers reported significantly higher depression symptoms and lower morale, but also higher positive impact from their child than did Anglo mothers.

Conclusions  Caregivers of young adults with autism report more maladaptive behaviour problems and lower personal well‐being, or stress, relative to other diagnostic groups, regardless of cultural group. However, cultural differences exist in caregiver reports of depression, morale, and positive perceptions. Implications for service provision aimed at families of children with challenging behaviour problems are discussed in the context of culture.
Comparative phylogeography across two trophic levels: the oak gall wasp Andricus kollari and its chalcid parasitoid Megastigmus stigmatizans
Authors: HAYWARD ALEXANDER , STONE GRAHAM N.
Published: December 2005

Insect parasitoids are important components of many terrestrial ecosystems. However, relatively little is known about the mechanisms responsible for structuring their populations. Here we investigate the ability of Megastigmus stigmatizans, an oak gall wasp parasitoid, to track its host Andricus kollari over two different timescales, and examine its current population structure across a divide in host population structure. The divide represents a transition in gall wasp host‐plant species and offers the opportunity to examine whether the split, which divides gall wasp populations, manifests itself in the next trophic level. Analysis of mitochondrial haplotype data for parasitoid and host reveals: (i) A similar phylogeographic population structure for both, with Iberian populations more derived with respect to more eastern populations. (ii) It is likely that the host colonized the Iberian refuge earlier than the parasitoid, probably by at least one glacial cycle. (iii) Recent range expansion of central European host populations northwards has resulted in pursuit by parasitoids from the same geographic origin. (iv) In addition, Iberian parasitoid populations have crossed a major divide in host population structure to invade northern Europe. Such human‐facilitated escape from natural refugial distributions may have important implications for the composition and structure of northern European gall wasp communities.
Core of the partner switching signalling mechanism is conserved in the obligate intracellular pathogen Chlamydia trachomatis
Authors: Hua Lei , Hefty P. Scott , Lee Young Jin , Lee Young Moo , Stephens Richard S. , Price Chester W.
Published: December 2005

Chlamydia trachomatis is an obligate intracellular bacterial pathogen that can cause sexually transmitted and ocular diseases in humans. Its biphasic developmental cycle and ability to evade host‐cell defences suggest that the organism responds to external signals, but its genome encodes few recognized signalling pathways. One such pathway is predicted to function by a partner switching mechanism, in which key protein interactions are controlled by serine phosphorylation. From genome analysis this mechanism is both ancient and widespread among eubacteria, but it has been experimentally characterized in only a few. C. trachomatis has no system of genetic exchange, so here an in vitro approach was used to establish the activities and interactions of the inferred partner switching components: the RsbW switch protein/kinase and its RsbV antagonists. The C. trachomatis genome encodes two RsbV paralogs, RsbV1 and RsbV2. We found that each RsbV protein was specifically phosphorylated by RsbW, and tandem mass spectrometry located the phosphoryl group on a conserved serine residue. Mutant RsbV1 and RsbV2 proteins in which this conserved serine was changed to alanine could activate the yeast two‐hybrid system when paired with RsbW, whereas mutant proteins bearing a charged aspartate failed to activate. From this we infer that the phosphorylation state of RsbV1 and RsbV2 controls their interaction with RsbW in vivo. This experimental demonstration that the core of the partner switching mechanism is conserved in C. trachomatis indicates that its basic features are maintained over a large evolutionary span. Although the molecular target of the C. tra‐chomatis switch remains to be identified, based on the predicted properties of its input phosphatases we propose that the pathway controls an important aspect of the developmental cycle within the host, in response to signals external to the C. trachomatis cytoplasmic membrane.