bluuebunny/crossref_metadata_2025_split huggingface dataset:
First radiation hybrid map of the river buffalo X chromosome (BBUX) and comparison with BTAX
Authors: Ianella P. , Venancio L. P. R. , Stafuzza N. B. , Miziara M. N. , Agarwala R. , Schäffer A. A. , Riggs P. K. , Womack J. E. , Amaral M. E. J. 
Published: February 2008

SummaryWe report the first radiation hybrid map of the river buffalo X chromosome generated from a recently constructed river buffalo (Bubalus bubalis) whole‐genome radiation hybrid panel (BBURH5000). This map contains a total of 33 cattle‐derived markers, including 10 genes, four ESTs and 19 microsatellites. The markers are distributed in two linkage groups: LG1 contains eight markers spanning 125.6 cR, and LG2 contains 25 markers spanning 366.3 cR. LG1 contains six markers in common with bovine sequence assembly build 3.1. With the exception of BMS2152, the order of these markers on our BBUX map is shuffled when compared to the cow X chromosome (Bos taurus; BTAX). From LG2, two markers (AMELX and BL22) map to a more distal portion of BTAX compared to BBUX. In addition, two pairs of LG2 markers exhibit inversions compared to BTAX (ILSTS017 and ATRX; XBM38 and PPEF1). Alternatively, when compared to the most recent bovine RH map (Bov‐Gen 3000rads), BL1098 and BMS2227 from LG1 as well as PLS3 and BMS1820 from LG2 showed inverted positions on the BBUX map. These discrepancies in buffalo and cattle maps may reflect evolutionary divergence of the chromosomes or mapping errors in one of the two species. Although the set of mapped markers does not cover the entire X chromosome, this map is a starting point for the construction of a high‐resolution map, which is necessary for characterization of small rearrangements that might have occurred between the Bubalus bubalis and Bos taurus X chromosomes.
Drug‐induced liver graft toxicity caused by cytochrome P450 poor metabolism
Authors: Kóbori László , Kõhalmy Krisztina , Porrogi Pálma , Sárváry Enikõ , Gerlei Zsuzsa , Fazakas János , Nagy Péter , Járay Jenõ , Monostory Katalin 
Published: February 2008

What is already known about this subject• The activity of drug‐metabolizing enzymes, primarily cytochrome P450 enzymes, can determine a patient's response to a drug.• Therapeutic failure or drug toxicity in the postoperative period after liver transplantation is influenced by the drug metabolizing capacity of the graft.• Dose adjustment or selection of an alternative drug, which is not a substrate for the polymorphic enzyme may prevent the development of side‐effects in recipients of poor metabolizer liver grafts.What this study adds• A validated analytical system with metabolomic tools has been developed to estimate the drug‐metabolizing capacity of transplanted liver, which allows the prediction of potential poor metabolizer phenotypes of donors and facilitates the improvement of individual recipient therapy.• In the test of drug‐metabolizing status, one of the liver grafts was found to be a CYP2C9 poor metabolizer, while the other was a CYP2C19 poor metabolizer.• Rationalization of the medication resulted in the recovery of both the grafts and the recipients within 1 week.AimsThe drug‐metabolizing capacity of transplanted liver highly influences drug efficacy or toxicity, particularly in the early postoperative period. The aim of our study was to predict therapeutic failures or severe adverse drug reactions by phenotyping for cytochrome P450 (P450) polymorphism resulting in reduced or no activity of the key drug‐metabolizing enzymes.MethodsA validated analytical system with metabolomic tools has been developed for estimation of the drug‐metabolizing capacity of transplanted liver, which allows the prediction of potential poor metabolizer phenotypes of donors and facilitates improvement of the individual recipient therapy.ResultsOf the 109 liver donors in Hungary, the frequency of poor metabolizers was found to be 0.92%, 5.5% and 8.3% for CYP2C9, CYP2C19 and CYP2D6, respectively. In the present study, two liver grafts transplanted in paediatric recipients were reported to be poor metabolizer phenotypes. The liver grafts presented normal function in the early postoperative days; 2 weeks after transplantation, however, increasing liver enzymes were detected. Histological investigation of a liver biopsy suggested drug toxicity. The test of drug metabolizing status showed one of the liver grafts to be a CYP2C9 poor metabolizer, and the other was found to be a CYP2C19 poor metabolizer. Rationalization of the medication resulted in the recovery of both the grafts and the recipients within 1 week.ConclusionsProspective investigation of the P450 status may lead to the optimization of drug choice and/or dose for a more effective therapy, avoid serious adverse effects, and decrease medical costs. Phenotyping donor livers and tailored medication can contribute to the improvement of graft and recipient survival.
Pyrazinamide blood concentrations in children suffering from tuberculosis: a comparative study at two doses
Authors: Gupta Pooja , Roy Vandana , Sethi Gulshan Rai , Mishra Tarun Kumar 
Published: February 2008

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT • Pyrazinamide is recommended in doses varying from 15 to 40 mg kg−1. The most commonly used average daily dose is 25 mg kg−1. Its use is associated with dose dependent hepatotoxicity.• Lower doses are not used because of lack of pharmacokinetic data especially in children. There is only one detailed study of pyrazinamide in children at a dose of 35 mg kg−1. WHAT THIS STUDY ADDS • This is the first study evaluating serum concentrations of pyrazinamide in children at a dose of 15 mg kg−1 which is on the lower side of the recommended dose. The study also compared the serum concentrations and pharmacokinetics achieved with this dose with the widely used dose of 25 mg kg−1 in children suffering from tuberculosis.• The pharmacokinetics and pharmacodynamic indices of pyrazinamide were comparable with the 25 and 15 mg kg−1 doses.AIMSTo evaluate the pharmacokinetics and pharmacodynamic indices of pyrazinamide at doses of 15 and 25 mg kg−1 in children suffering from tuberculosis.METHODSTwenty children with tuberculosis received pyrazinamide at a single dose of 25 mg kg−1 (group I) and 15 mg kg−1 (group II). Serial blood samples were collected and the drug concentrations were analyzed spectrophotometrically. The pharmacokinetic parameters were calculated and the duration of time for which pyrazinamide concentrations in serum remained above the pyrazinamide inhibitory concentrations of 20 μg ml−1 and 25 μg ml−1 was studied.RESULTSThe mean peak serum concentration was 42.4 ± 3.3 μg ml−1 (95% CI ± 6.5) and 38.6 ± 3.9 μg ml−1 (95% CI ± 7.7) in groups I and II, respectively. The elimination half‐life was 9.3 ± 1.3 h and 10.5 ± 2.3 h (P = 0.6) and clearance was 0.06 ± 0.01 l h−1 kg−1 and 0.04 ± 0.01 l h−1 kg−1 (P = 0.08) in groups I and II, respectively. Pharmacokinetic parameters and PKPD indices were comparable with both the doses.CONCLUSIONSThe study indicates that comparable serum concentrations of pyrazinamide are attained with 25 mg kg−1 and 15 mg kg−1 doses in children. The elimination half‐life was longer and volume of distribution greater in children than in the adult population.
Strategic use of an adenoviral vector for rapid and efficient ex vivo‐generation of cytomegalovirus pp65‐reactive cytolytic and helper T cells
Authors: Forsberg Ole , Carlsson Björn , Tötterman Thomas H. , Essand Magnus 
Published: February 2008

SummaryCytomegalovirus (CMV) reactivation can cause severe complications for transplant patients. Such patients can be protected against CMV‐associated diseases through reconstitution of donor‐derived CMV‐reactive cytolytic and helper T cells. We have developed a strategic protocol for efficient simultaneous generation of CMV‐reactive CD8+ and CD4+ T cells ex vivo. The protocol uses peripheral blood lymphocytes (PBLs), antigen‐modified mature dendritic cells (DCs) generated in only 3 d and an adenoviral vector encoding the CMV pp65 antigen (Adpp65) both as an endogenous and exogenous source of antigen. PBLs stimulated once with Adpp65‐transduced DCs (endogenously expressed pp65) resulted in preferential activation and expansion of pp65‐specific CD8+ T cells while PBLs stimulated with DCs pulsed with cell lysate from Adpp65‐transduced autologous monocytes (exogenously expressed pp65) yielded pp65‐specific CD4+ T cells. Stimulation with double‐modified DCs efficiently activated and expanded cytolytic and helper T cells simultaneously. The frequency of T cells producing interferon‐γ in response to pp65 increased after one stimulation on average 9·6‐fold to 4·3% for CD8+ T cells and 25·8‐fold to 6·5% for CD4+ T cells. This implies that sufficient number of pp65‐specific cytolytic and helper T cells for adoptive transfer may be obtained in only 2 weeks.
Thalidomide in advanced mastocytosis
Authors: Damaj Gandhi , Bernit Emmanuelle , Ghez David , Claisse Jean‐François , Schleinitz Nicolas , Harlé Jean‐Robert , Canioni Danielle , Hermine Olivier 
Published: February 2008

SummaryMastocytosis is an acquired orphan disease characterized by the abnormal accumulation of mast cells responsible for organ failure and systemic symptoms. Cytoreductive drugs have been shown to be effective, but have rarely resulted in complete or long‐term remission. We report two patients with advanced systemic mastocytosis (SM) who were treated successfully with thalidomide, given at the maximal tolerated dosage. B and C‐findings as well as clinical symptoms rapidly improved. After a follow‐up of more than 1 year, the patients remained in partial remission. Thalidomide seems to be an active drug in advanced SM. However, clinical trials are warranted to define its efficacy and safety profiles.
Suppression of cytokine expression by roflumilast and dexamethasone in a model of chronic asthma
Authors: Herbert C. , Hettiaratchi A. , Webb D. C. , Thomas P. S. , Foster P. S. , Kumar R. K. 
Published: February 2008

SummaryBackgroundIn a mouse model of mild chronic asthma, both inflammation and remodelling can be suppressed by dexamethasone (a glucocorticoid) and roflumilast (a selective phosphodiesterase‐4 inhibitor).ObjectiveTo better understand the underlying molecular mechanisms, we investigated the effects of treatment on airway expression of inflammation‐related cytokines, as well as on epithelial expression of growth factors.MethodsBALB/c mice systemically sensitized to ovalbumin were challenged with aerosolized antigen for 6 weeks and treated with roflumilast or dexamethasone during the final 2 weeks. Expression of mRNA, for a variety of cytokines and growth factors, was assessed in selectively dissected proximal airways or in airway epithelium obtained by laser capture microdissection.ResultsIn the airway wall of vehicle‐treated challenged animals, there was significantly elevated expression of mRNA for a variety of pro‐inflammatory and T helper type 2 cytokines, as well as for IFN‐γ. All these cytokines were suppressed by dexamethasone. Treatment with roflumilast reduced expression of IL‐17A, TNF‐α, granulocyte‐macrophage colony‐stimulating factor and IL‐6, but did not inhibit other cytokines. Both drugs suppressed the enhanced expression of mRNA for growth factors such as TGF‐β1 and FGF‐2 in airway epithelium.ConclusionsWhereas dexamethasone non‐specifically inhibits numerous mediators involved in inflammation and the immune response, roflumilast selectively inhibits a subset of pro‐inflammatory cytokines and growth factors. These mediators and/or the cells that produce them may have critical roles in the pathogenesis of the lesions of chronic asthma.
Role of epidermal growth factor receptor in maintaining airway goblet cell hyperplasia in rats sensitized to allergen
Authors: Takeyama K. , Tamaoki J. , Kondo M. , Isono K. , Nagai A. 
Published: February 2008

SummaryBackground
Stimulation of epidermal growth factor receptor (EGFR) induces airway goblet cell hyperplasia, but the role of this molecule in the maintenance of this pathologic change remains uncertain.Objective
To determine the mechanisms by which goblet cell hyperplasia is maintained in airway epithelium, we investigated EGFR‐induced signalling pathways that lead to both mucin production and antiapoptosis in vitro. We also tested whether the inhibition of EGFR tyrosine kinase speeds reversal of established goblet cell hyperplasia to normal epithelial phenotype in vivo.Methods
MUC5AC production was measured by immunoassay, and antiapoptotic responses were determined by Bcl‐2 expression and terminal deoxynucleotidyl transferase‐mediated dUTP‐biotin Nick End Labelling staining using NCI‐H292 cells. The effect of an inhibitor of EGFR tyrosine kinase (AG1478) on goblet cell hyperplasia was also determined in rats sensitized with ovalbumin (OVA).Results
MUC5AC was constitutively expressed and few apoptotic cells were observed in NCI‐H292 cells under non‐stimulated condition. TGF‐α increased MUC5AC and Bcl‐2 expression, an effect that was prevented by inhibitors of EGFR tyrosine kinase (AG1478), MEK (PD98059), and NF‐κB (CAPE). After the addition of TGF‐α, AG1478 and an inhibitor of phosphatidylinositol 3 kinase/Akt (LY294002), but not PD98059, induced a marked apoptotic response, which was prevented by the caspase inhibitor Z‐VAD fmk. Goblet cell hyperplasia and EGFR expression in airway epithelium were noted in the OVA‐sensitized rats. Intratracheal instillation of AG1478 induced apoptosis of goblet cells, reverting the airway epithelium to normal epithelial phenotype.Conclusion
These findings indicate that EGFR plays an important role in the maintenance of goblet cell hyperplasia. We speculate that inhibitors of the EGFR cascade might be an effective therapy of airway remodelling.
Assessment of the immunoglobulin E‐mediated immune response to milk‐specific proteins in allergic patients using microarrays
Authors: Gaudin J.‐C. , Rabesona H. , Choiset Y. , Yeretssian G. , Chobert J.‐M. , Sakanyan V. , Drouet M. , Haertlé T. 
Published: February 2008

SummaryBackground
Cow's milk allergy (CMA) is one of the most widespread human allergies, especially in young children. Although CMA is intensively studied, little is known about the recognition patterns of milk allergens in allergic patients, and the determination these patterns is a prerequisite for the development of efficient diagnostic and prognostic tools. Several factors present difficulties for such a determination, because (i) milk contains a large number of potential allergens; (ii) the majority of these allergens consist of complex suspensions rather than solutions; (iii) the major allergens, such as caseins, cannot be highly purified in large amounts; and (iv) most of the time, very small amount of young patients' sera are readily available.Methods
To overcome these difficulties, we developed a sensitive microarray assay that, in combination with near‐infrared fluorescence detection, was used to study the immune response to milk and purified native milk proteins.Results
This new assay allowed us to assess the binding ability of IgE to milk allergens from a large number of young patients using reduced amounts of clinical material. The data show that bovine lactoferrin can be classed as a strong milk allergen. We confirmed that bovine caseins are the main allergens in milk and that αS1‐casein is more allergenic than αS2‐, β‐ and κ‐caseins, which were recognized with almost a similar frequency by the sera of patients.Conclusion
Microarray methods, in combination with near‐infrared fluorescence detection, can be useful for the in vitro diagnosis of food allergies.
Allergic rhinitis in children with asthma: a questionnaire‐based study
Authors: Hamouda S. , Karila C. , Connault T. , Scheinmann P. , De Blic J. 
Published: February 2008

SummaryBackground
Allergic rhinitis (AR) and asthma frequently coexist but has rarely been evaluated in children.Objective
This prospective study aimed to estimate the prevalence of AR in asthmatic children, and ascertain whether AR is a risk factor for the severity of asthma.Methods
The questionnaire, modified from the adult form of the score for allergic rhinitis (SFAR), was completed by 404 asthmatic children aged 3–18 years seen in the outpatient clinic between June 2005 and July 2007. Each item was assigned a number of points with a final score ranging from 0 to 17. AR and asthma were classified according to ARIA and GINA 2004 recommendations, respectively.Results
AR was diagnosed in 237 patients (58.7%). It was intermittent in 57.8% of the patients and persistent in 42.2%. A total score 9 was discriminant for AR (sensitivity=91.1%, specificity=95.2%, positive predictive value=96.4%, negative predictive value=88.3%, Youden's Index=0.86). The proportion of children having mild or moderate‐to‐severe asthma was independent of the presence of AR, 61.6% of moderate‐to‐severe asthmatic children and 55.4% of intermittent and mild asthmatic children having AR.Conclusion
AR and asthma are frequently associated (58.7%). The SFAR adapted for children seems to be a simple and a reliable tool to detect AR in asthmatic children.
Inhibition of airway eosinophilia and pulmonary pathology in a mouse model of allergic asthma by the live vaccine strain of Francisella tularensis
Authors: KuoLee R. , Zhou H. , Harris G. , Zhao X. , Qiu H. , Patel G. B. , Chen W. 
Published: February 2008

SummaryBackground
It has been suggested that exposure to certain microbes and their products, particularly during neonatal and early childhood periods, may shift the immune response towards a T‐helper cell (Th) 1 phenotype and thereby prevent the development of and/or alleviate the clinical symptoms of allergic airway diseases.Objective
We evaluated the ability of the live vaccine strain (LVS) of Francisella tularensis to suppress airway eosinophilia and pulmonary pathology in a murine model of allergic airway disease.Methods
C57BL/6 mice were sensitized by intraperitoneal injection of ovalbumin (OVA) on days 1 and 14, and challenged intranasally (i.n.) with OVA on day 21 or thereafter. Some sensitized mice were i.n. treated with live LVS or its cell‐free sonicate extract (CFSE) before i.n. OVA challenge. Bronchoalveolar lavage fluid, regional lymph node cells, lung tissues and serum samples were collected 3–7 days after the i.n. challenge.Results
Intranasal and, to a lesser degree, intradermal immunization of OVA‐sensitized mice with LVS suppressed the development of airway eosinophilia and associated pulmonary pathology induced by i.n. OVA challenge. Moreover, CFSE prepared from LVS showed a similar inhibitory effect whereas neither LPS nor DNA purified from F. tularensis LVS had such an effect. The inhibition was associated with the reduction in mRNA expression and protein levels of Th2 cytokines IL‐5 and IL‐13 in the lungs and the enhanced production of OVA‐induced IFN‐γ by local draining lymph node cells, but not with the serum levels of OVA‐specific IgG1 or IgE.Conclusion
F. tularensis LVS is capable of suppressing allergic airway inflammation probably through a Th1‐mediated suppression of an ongoing Th2 response mechanism, and raises the possibility of exploring LVS and its components as potential therapeutic modalities for human allergic asthma.
Simulations of tip‐enhanced optical microscopy reveal atomic resolution
Authors: DOWNES ANDREW , SALTER DONALD , ELFICK ALISTAIR 
Published: February 2008

SummaryWe have performed finite element electromagnetic analysis of ‘apertureless’ scanning near‐field optical microscope tips. A variety of radii was considered, from 40 nm down to 1 nm, and the enhancement of optical scattering from the region beneath the probe apex was modelled in air and water. We observed sizeable spectral shifts when the radius decreases, together with a surprising increase in the amount of scattering from small tips. The lateral resolution is considered, which is shown to be always smaller than the tip radius, and for 1‐nm‐radius tips can allow atomic resolution imaging with sufficient optical enhancement. Gold, silver, copper and aluminium were modelled as tip materials.
Single molecules probe local density of modes (LDOS) around photonic nanostructures
Authors: COLAS DES FRANCS G. , SANCHEZ‐MOSTEIRO G. , UJUE‐GONZALEZ M. , MARKEY L. , VAN HULST N. , DEREUX A. 
Published: February 2008

SummaryAccording to Fermi's golden rule, the fluorescence decay rate is directly proportional to the projected local density of photonic modes (LDOS) at the molecule location. The relevant LDOS depends on the molecule orientation. In this paper, the direct measurement of the fluorescence lifetime near gold dot photonic structures is investigated and compared to calculated LDOS. Detailed analysis of the decay channels is presented on the basis of numerical simulations.
Near‐ and far‐field verification of electro‐optic effect enhancement on a tunable lithium niobate photonic crystal
Authors: BERNAL M.‐P. , ROUSSEY M. , BAIDA F. I. 
Published: February 2008

SummaryIn this paper, we present the optical response of a tunable lithium niobate photonic crystal (PC) using the electro‐optic effect of the material. The band gap tunability is 300 times higher than what one could expect for a bulk lithium niobate device of the same characteristics. Theoretical calculations based on the finite‐difference time domain technique have allowed us to determine the physical origin of this enhanced electro‐optic coefficient. Indeed, the effective second‐order susceptibility in the LN nanostructure increases, giving rise to an ultra‐compact low‐voltage photonic crystal modulator when it operates at its band edge. In addition, the theoretical and far‐field transmission results are confirmed by near‐field optical microscopy images of the structure at different excitation voltages.
Detection in near‐field domain of biomolecules adsorbed on a single metallic nanoparticle
Authors: BARBILLON G. , BIJEON J.‐L. , BOUILLARD J.‐S. , PLAIN J. , LAMY De La CHAPELLE M. , ADAM P.‐M. , ROYER P. 
Published: February 2008

SummaryIn this paper, we study the performances of nanosensors based on Localized Surface Plasmon Resonance in the context of biological sensing. We demonstrate the sensitivity and the selectivity of our designed nanosensors by studying the influence of the concentration of Streptavidin on the shift of Localized Surface Plasmon Resonance wavelength. In addition, to study the detection of biomolecules on a single Au nanoparticle, we used a Scanning Near‐field Optical Microscope. These results represent new steps for applications in biological research and medical diagnostics.
Biomolecular sensors utilizing waveguide modes excited by evanescent fields
Authors: FUJIMAKI M. , ROCKSTUHL C. , WANG X. , AWAZU K. , TOMINAGA J. , IKEDA T. , KOGANEZAWA Y. , OHKI Y. 
Published: February 2008

SummaryProperties of evanescent‐field‐coupled waveguide‐mode sensors consisting of a multi‐layer structure made of a SiO2 waveguide, a thin metal layer (Au, Cu, W or Ti), and a high refractive index glass substrate illuminated under the Kretschmann configuration have been theoretically and experimentally investigated. In all cases, reflectivity changes attributed to streptavidin combining to biotinyl groups were observed in close spectral vicinity of the waveguide resonances. The sensors with the Au and the Cu layers show superior sensitivity as compared to those with the W and the Ti layers, whereas the W and Ti layers show better thermal and chemical stability. The results indicate that the materials of thin metal layers should be chosen in accordance with the purpose of sensors and/or environment in which the sensors are used.