bluuebunny/crossref_metadata_2025_split huggingface dataset:
Exposure to environmental pollutants is related to sore throats and increased expression of HLA‐DQ in the upper airway mucosa of man
Authors: Rees L.E.N. , Jones P. , Pinkerton K. , Cogan T. , Ayling S.M. , Belafsky P. , Birchall M.A. 
Published: December 2008

Objectives.  To determine the symptomatic and mucosal immune response to environmental pollution in UK population.Methods.  We performed a prospective, matched questionnaire and laryngeal biopsy study in normal persons (n = 63). Subjects completed a validated health questionnaire. Levels of exposure to pollutants for the year prior to the study were determined via area‐based measurements of environmental particulates and composite air quality indices (CAQI). Quantitative multiple‐colour immunofluorescence was used to measure in vivo expression of antigens in laryngeal mucosal pinch biopsies: CD45 (RO, RC: leucocytes), CD4, CD8, CD79, (lymphocytes), MHC I, II (antigen presenting molecules). Multiple linear regression, correcting for age, was used to explore the relationship between dependent variables and pollution measures.Results.  Complete data were available for 49 (questionnaire) and 54 (immunohistology) subjects. High levels of particulates and CAQI were associated with self‐reported frequent sore throats (P = 0.04 and 0.01, respectively), and with a trend towards increased asthma (P = 0.07 and 0.08). Dual HLA‐DQ (MHC II) and CD45 (leucocyte) expression by laryngeal epithelium was significantly correlated with levels of particulates (P = 0.03) and CAQI (P = 0.04). CAQI alone was significantly associated with CD4+ expression (P = 0.002).Conclusions.  Pollution is known be associated with an increased prevalence of asthma, but this is the first report of an association with throat symptoms. We hypothesise that environmental pollution may contribute to pharyngeal inflammation by selective up‐regulation of the MHC Class II molecule, HLA‐DQ in epithelium and subsequent activation of leucocytes.
In vivo real time histology examination of the upper airway mucosa using confocal endomicroscopy
Authors: Hughes O.R. , Ayling S.M. , Birchall M.A. 
Published: December 2008

Objectives.  We aim to establish whether in vivo confocal endomicroscopy (1) delivers a clear image of subcellular structures within the upper airway mucosa and (2) allows leucocytes to be identified using topical antibodies against CD45, the common leucocyte antigen.Methods.  Endoscopic confocal images were captured from the supraglottic and tracheal mucosa in anaesthetised Landrace–Large white hybrid pigs using a rigid endoscope (Optiscan, Melbourne, Auctralia). 10% fluroscein was administered intravenously as contrast; 30 min later 0.05% acriflavine was applied as a topical contrast to the mucosa immediately prior to imaging of two pigs. In a further two pigs, 10% fluorescently labelled anti‐CD45 antibody was applied topically immediately prior to imaging. Images were captured and reviewed on a computer screen at the time of examination.Results.  High‐resolution (x1000 magnification) images of the nuclei and cytoplasm of individual cells within the stratified squamous and respiratory epithelium of the supraglottis and trachea were captured using concurrent fluroscein and acriflavine staining. Intravenous fluroscein highlighted subsurface capillaries within which individual erythrocytes appeared as unstained shadows. Discrete leucocytes were clearly visible within the mucosa following topical application of anti‐CD45 antibody.Conclusion.  In vivo confocal endomicroscopy allows examination of the upper airway mucosa at cellular resolution in real time. We have, for the first time, combined in vivo confocal imaging with antibody targeting of specific cell markers in the upper airway in large animals. Combining confocal endomicroscopy with topical antibodies against tumour markers (e.g. EGFR and p53) may allow tumours to be diagnosed and characterised during endoscopic examination without taking a biopsy.
Accuracy of diffusion‐weighted magnetic resonance imaging in the diagnosis of cholesteatoma
Authors: Khan S. , Rowlands R.G. , Benjamin E. , Abramovich S. 
Published: December 2008

Objectives.  Recent interest has focused on various MRI techniques as a way of evaluating patients with cholesteatoma both pre‐ and post‐mastoidectomy.1,2 The aim of this study is to determine the role of diffusion‐weighted MRI imaging in detecting primary and recurrent cholesteatoma, and its accuracy in differentiating cholesteatoma from granulations and inflammatory tissue.Methods.  We have designed a prospective pilot study evaluating whether diffusion‐weighted MRI imaging can accurately distinguish cholesteatoma from inflammatory tissue and fluid within the middle ear and mastoid cavity. We have established a database of consecutive patients placed on the waiting list for mastoidectomy and compared the preoperative reports with the perioperative findings during mastoidectomy. Outcomes were the presence or otherwise of cholesteatoma.Results.  Between April and December 2007, 15 patients underwent preoperative ECHO planar MRI imaging and tympanomastoidectomy. Cholesteatoma was identified in six patients at time of surgery. This had been identified preoperatively on diffusion MRI scanning in five patients. In nine patients who did not have cholesteatoma at time of surgery all had negative preoperative scans. The MRI scans had a sensitivity and specificity of 83% and 100%, respectively.Conclusions.  We have demonstrated that diffusion‐weighted MRI imaging may be useful in the diagnosis and confirmation of cholesteatoma. In particular, a negative diffusion‐weighted scan can almost certainly exclude the presence of cholesteatoma. This technique may be particularly valuable following canal‐wall up mastoid surgery thus avoiding the requirement for a second‐look procedure, on those patients whose postoperative hearing thresholds are satisfactory and do not require ossiculoplasty.References.  1 Vercruysse J.P., De Foer B., Pouillon M. et al. (2006) The value of diffusion‐weighted MR imaging in the diagnosis of primary acquired and residual cholesteatoma: a surgical verified study of 100 patients. Eur. Radiol. 16, 1461–14672 Stasolla A., Magluilo G., Parrotto D. et al. (2004) Detection of postoperative relapsing/residual cholesteatoma with diffusion‐weighted echo‐planar magnetic resonance imaging. Otol. Neurotol. 25, 879–884
Common garden comparisons of native and introduced plant populations: latitudinal clines can obscure evolutionary inferences
Authors: Colautti Robert I. , Maron John L. , Barrett Spencer C. H. 
Published: December 2008

AbstractCommon garden studies are increasingly used to identify differences in phenotypic traits between native and introduced genotypes, often ignoring sources of among‐population variation within each range. We re‐analyzed data from 32 common garden studies of 28 plant species that tested for rapid evolution associated with biological invasion. Our goals were: (i) to identify patterns of phenotypic trait variation among populations within native and introduced ranges, and (ii) to explore the consequences of this variation for how differences between the ranges are interpreted. We combined life history and physiologic traits into a single principal component (PCALL) and also compared subsets of traits related to size, reproduction, and defense (PCSIZE, PCREP, and PCDEF, respectively). On average, introduced populations exhibited increased growth and reproduction compared to native conspecifics when latitude was not included in statistical models. However, significant correlations between PC‐scores and latitude were detected in both the native and introduced ranges, indicating population differentiation along latitudinal gradients. When latitude was explicitly incorporated into statistical models as a covariate, it reduced the magnitude and reversed the direction of the effect for PCALL and PCSIZE. These results indicate that unrecognized geographic clines in phenotypic traits can confound inferences about the causes of evolutionary change in invasive plants.
PERSPECTIVE: Principles of ecological immunology
Authors: Sadd Ben M. , Schmid‐Hempel Paul 
Published: December 2008

AbstractDefending self against nonself is a major problem in a world in which individuals are under constant pressure from parasites that gain fitness benefits at a cost to their host. Defences that have evolved are diverse, and range from behavioural adaptations to physiochemical barriers. The immune defence is a final line of protection and is therefore of great importance. Given this importance, variability in immune defence would seem counterintuitive, yet that is what is observed. Ecological immunology attempts to explain this variation by invoking costs and trade‐offs, and in turn proposing that the optimal immune defence will vary over environments. Studies in this field have been highly successful in establishing an evolutionary ecology framework around immunology. However, in order enrich our understanding of this area, it is perhaps time to broaden the focus to include parasites as more than simply elicitors of immune responses. In essence, to view immunity as produced by the host, the environment, and the active involvement of parasites.
The Danish Cartoon Controversy and the Exclusivist Turn in European Civic Nationalism
Authors: Kahn Robert A. 
Published: December 2008

AbstractThe Danish cartoon controversy raises questions about the inclusiveness of Western European civic nationalism. The controversy highlighted a harsh, exclusivist brand of Danish civic nationalism that cast Muslim migrants as outsiders. The controversy also saw a broader group of cartoon supporters from across Europe fault Muslims for failing to respect liberal traditions of freedom of speech and secularism, traditions now explicitly labeled ‘European’. However, others pushed the debate in a more open direction by defending the Jyllands Posten's freedom of expression in ethnically neutral terms and explicitly challenging the contrast between an enlightened Europe and an intolerant Muslim other.
Forging the Nepali Nation through Law: A Reflection on the Use of Western Legal Tools in a Himalayan Kingdom
Authors: Malagodi Mara 
Published: December 2008

AbstractThe present article endeavours to analyse the use and scope of Western positivistic legal tools in the creation of the Nepali nation. It suggests a two‐level analysis. First, a historical analysis of Nepal's political and legal developments is presented to investigate the rationale of using law as a social engineering and homogenising tool promoting an identifiably Nepali national identity. Second, the article focuses on the current debates concerning constitutional change in Nepal. The debates about the demise of the 1990 Constitution in 2007, and the election of a Constituent Assembly need to be investigated in the light of the growing politicisation of ethnicity in the country. The overarching demand for inclusion stems from the discontent of Nepal's ethno‐linguistic, religious, and regional minorities with their historical subordination. Ultimately, the article aims to demonstrate that the Nepali experience is situated somewhere between the civic and ethnic models of nationalism Kohn enunciated.
Building a Nation in Rwanda? De‐ethnicisation and its Discontents
Authors: Purdeková Andrea 
Published: December 2008

AbstractRwanda remains in the eastern camp of ethnic ideas and projects of a ‘nation’ inasmuch as it is dominated by cultural as opposed to civic/political elements. Although the Rwandan attempt remains exclusive internally, it does not affirm the validity of an idealised Kohnian dichotomy between ‘exclusive’ ethnic nationalism and ‘inclusive’ civic nationalism. To avoid the trap of a bi‐polar and value‐ladden division, while preserving the useful insights of Kohn, the paper calls for a re‐conceptualisation of nation‐building projects along the continuum of their relative inclusiveness/exclusiveness, both internally (who shapes the ‘idea of nation’) and externally (the boundaries of nation).
The Relevance of Kohn's Dichotomy to the Russian Nineteenth‐Century Concept of Nationalism
Authors: Rabow‐Edling Susanna 
Published: December 2008

AbstractThis article challenges the common distinction between a Western and an Eastern type of nationalism with regard to Russian nationalism. Analysing the civic nationalism of the Decembrists and the cultural nationalism of the Slavophiles, it argues that the type of nationalism that appears in a specific country has more to do with timing than with place or social conditions. The article also suggests that intellectual thought should be studied in an international rather than a national context and that the world of ideas has to be granted a considerable degree of autonomy from socioeconomic conditions.
Pharmacokinetics of High-Dose Oseltamivir in Healthy Volunteers
Authors: Wattanagoon Y. , Stepniewska K. , Lindegårdh N. , Pukrittayakamee S. , Silachamroon U. , Piyaphanee W. , Singtoroj T. , Hanpithakpong W. , Davies G. , Tarning J. , Pongtavornpinyo W. , Fukuda C. , Singhasivanon P. , Day N. P. J. , White N. J. 
Published: December 2008

ABSTRACT
The effects of loading doses and probenecid coadministration on oseltamivir pharmacokinetics at four increasing dose levels in groups of eight healthy adult Thai volunteers (125 individual series) were evaluated. Doses of up to 675 mg were well-tolerated. The pharmacokinetics were dose linear. Oseltamivir phosphate (OS) was rapidly and completely absorbed and converted (median conversion level, 93%) to the active carboxylate metabolite. Median elimination half-lives (and 95% confidence intervals [CI]) were 1.0 h (0.9 to 1.1 h) for OS and 5.1 h (4.7 to 5.7 h) for oseltamivir carboxylate (OC). One subject repeatedly showed markedly reduced OS-to-OC conversion, indicating constitutionally impaired carboxylesterase activity. The coadministration of probenecid resulted in a mean contraction in the apparent volume of distribution of OC of 40% (95% CI, 37 to 44%) and a reduction in the renal elimination of OC of 61% (95% CI, 58 to 62%), thereby increasing the median area under the concentration-time curve (AUC) for OC by 154% (range, 71 to 278%). The AUC increase for OC in saliva was approximately three times less than the AUC increase for OC in plasma. A loading dose 1.25 times the maintenance dose should be given for severe influenza pneumonia. Probenecid coadministration may allow considerable dose saving for oseltamivir, but more information on OC penetration into respiratory secretions is needed to devise appropriate dose regimens.
Multiple Peptides Homologous to Herpes Simplex Virus Type 1 Glycoprotein B Inhibit Viral Infection
Authors: Akkarawongsa Radeekorn , Pocaro Nina E. , Case Gary , Kolb Aaron W. , Brandt Curtis R. 
Published: December 2008

ABSTRACT

The 773-residue ectodomain of the herpes simplex virus type 1 (HSV-1) glycoprotein B (gB) has been resistant to the use of mutagenic strategies because the majority of the induced mutations result in defective proteins. As an alternative strategy for the identification of functionally important regions and novel inhibitors of infection, we prepared a library of overlapping peptides homologous to the ectodomain of gB and screened for the ability of the peptides to block infection. Seven of 138 15-mer peptides inhibited infection by more than 50% at a concentration of 100 μM. Three peptides (gB94, gB122, and gB131) with 50% effective concentrations (EC
50
s) below 20 μM were selected for further studies. The gB131 peptide (residues 681 to 695 in HSV-1 gB [gB-1]) was a specific entry inhibitor (EC
50
, ∼12 μM). The gB122 peptide (residues 636 to 650 in gB-1) blocked viral entry (EC
50
, ∼18 μM), protected cells from infection (EC
50
, ∼72 μM), and inactivated virions in solution (EC
50
, ∼138 μM). We were unable to discern the step or steps inhibited by the gB94 peptide, which is homologous to residues 496 to 510 in gB-1. Substitution of a tyrosine in the gB122 peptide (Y640 in full-length gB-1) reduced the antiviral activity eightfold, suggesting that this residue is critical for inhibition. This peptide-based strategy could lead to the identification of functionally important regions of gB or other membrane proteins and identify novel inhibitors of HSV-1 entry.
Association between Antimicrobial Consumption and Resistance in
Escherichia coli
Authors: Bergman Miika , Nyberg Solja T. , Huovinen Pentti , Paakkari Pirkko , Hakanen Antti J. 
Published: December 2008

ABSTRACT

During a 9-year study period from 1997 through 2005, the association between antimicrobial resistance rates in
Escherichia coli
and outpatient antimicrobial consumption was investigated in 20 hospital districts in Finland. A total of 754,293
E. coli
isolates, mainly from urine samples, were tested for antimicrobial resistance in 26 clinical microbiology laboratories. The following antimicrobials were studied: ampicillin, amoxicillin-clavulanate, cephalosporins, fluoroquinolones, trimethoprim, trimethoprim-sulfamethoxazole, pivmecillinam, and nitrofurantoin. We applied a protocol used in earlier studies in which the level of antimicrobial consumption over 1 year was compared with the level of resistance in the next year. Statistically significant associations were found for nitrofurantoin use versus nitrofurantoin resistance (
P
< 0.0001), cephalosporin use versus nitrofurantoin resistance (
P
= 0.0293), amoxicillin use versus fluoroquinolone resistance (
P
= 0.0031), and fluoroquinolone use versus ampicillin resistance (
P
= 0.0046). Interestingly, we found only a few associations between resistance and antimicrobial consumption. The majority of the associations studied were not significant, including the association between fluoroquinolone use and fluoroquinolone resistance.
Population Pharmacokinetics of Emtricitabine in Human Immunodeficiency Virus Type 1-Infected Pregnant Women and Their Neonates
Authors: Hirt Déborah , Urien Saik , Rey Elisabeth , Arrivé Elise , Ekouévi Didier K. , Coffié Patrick , Leang Sim Kruy , Lalsab Sarita , Avit Divine , Nerrienet Eric , McIntyre James , Blanche Stéphane , Dabis François , Tréluyer Jean-Marc 
Published: December 2008

ABSTRACTThe objectives of this study were to evaluate emtricitabine (FTC) pharmacokinetics in pregnant women and their neonates and to determine the optimal prophylactic dose for neonates after birth to prevent mother-to-child transmission of human immunodeficiency virus (HIV). A total of 38 HIV-infected pregnant women were administered tenofovir disoproxyl fumarate (300 mg)-FTC (200 mg) tablets—two tablets at the initiation of labor and one daily for 7 days postpartum. By pair, 11 maternal, one cord blood, and two neonatal FTC concentrations were measured using a high-performance liquid chromatography-tandem mass spectrometry validated method and analyzed by a population approach. Model and mean estimates (interpatient variability) were a two-compartment model for mothers, with an absorption rate constant of 0.54 h−1(61%), apparent elimination and intercompartmental clearances of 23.2 (17%) and 6.04 liters·h−1, and apparent central and peripheral volumes of 127 and 237 liters, respectively; an effect compartment linked to maternal circulation for cord blood and a neonatal compartment disconnected, after delivery, with a 10.6-h half-life (30%). After the 400-mg FTC administration, the median population area under the concentration-time curve and the minimal and maximal plasma FTC concentrations in pregnant women were 14.3 mg·liter−1·h and 1.68 and 0.076 mg/liter, respectively. At delivery, median (range) predicted maternal and cord blood FTC concentrations were, respectively, 1.16 (0.14 to 1.99) and 0.72 (0.05 to 1.19) mg·liter−1. We concluded that the 400-mg FTC administration in pregnant women produces higher exposition than does the 200-mg administration in other adults, at steady state. FTC was shown to have good placental transfer (80%). Administering 1 mg FTC/kg as soon as possible after birth or 2 mg/kg 12 h after birth should produce neonatal concentrations comparable to the concentrations observed in adults.
Preclinical Evaluation of GS-9160, a Novel Inhibitor of Human Immunodeficiency Virus Type 1 Integrase
Authors: Jones Gregg S. , Yu Fang , Zeynalzadegan Ameneh , Hesselgesser Joseph , Chen Xiaowu , Chen James , Jin Haolun , Kim Choung U. , Wright Matthew , Geleziunas Romas , Tsiang Manuel 
Published: December 2008

ABSTRACTGS-9160 is a novel and potent inhibitor of human immunodeficiency virus type 1 (HIV-1) integrase (IN) that specifically targets the process of strand transfer. It is an authentic inhibitor of HIV-1 integration, since treatment of infected cells results in an elevation of two-long terminal repeat circles and a decrease of integration junctions. GS-9160 has potent and selective antiviral activity in primary human T lymphocytes producing a 50% effective concentration (EC50) of ∼2 nM, with a selectivity index (50% cytotoxic concentration/EC50) of ∼2,000. The antiviral potency of GS-9160 decreased by 6- to 10-fold in the presence of human serum. The antiviral activity of GS-9160 is synergistic in combination with representatives from three different classes of antiviral drugs, namely HIV-1 protease inhibitors, nonnucleoside reverse transcriptase inhibitors, and nucleotide reverse transcriptase inhibitors. Viral resistance selections performed with GS-9160 yielded a novel pattern of mutations within the catalytic core domain of IN; E92V emerged initially, followed by L74M. While E92V as a single mutant conferred 12-fold resistance against GS-9160, L74M had no effect as a single mutant. Together, these mutations conferred 67-fold resistance to GS-9160, indicating that L74M may potentiate the resistance caused by E92V. The pharmacokinetic profile of GS-9160 in healthy human volunteers revealed that once-daily dosing was not likely to achieve antiviral efficacy; hence, the clinical development of this compound was discontinued.
Multiple Regulatory Pathways Associated with High-Level Ciprofloxacin and Multidrug Resistance in
Salmonella enterica
Serovar Enteritidis: Involvement of
ramA
and Other Global Regulators
Authors: O'Regan Edel , Quinn Teresa , Pagès Jean-Marie , McCusker Matthew , Piddock Laura , Fanning Séamus 
Published: December 2008

ABSTRACT

Mechanisms of antibiotic resistance were examined in nalidixic acid-resistant
Salmonella enterica
serovar Enteritidis field isolates displaying decreased susceptibility to ciprofloxacin and in in vitro-derived ciprofloxacin-resistant mutants (104-cip and 5408-cip). All field isolates harbored a single
gyrA
mutation (D87Y). Deletion of
acrB
and complementation with wild-type
gyrA
increased quinolone susceptibility. Selection for ciprofloxacin resistance was associated with the development of an additional
gyrA
(S83F) mutation in 104-cip, novel
gyrB
(E466D) and
parE
(V461G) mutations in 5408-cip, overexpression of
acrB
and decreased susceptibility to nonquinolone antibiotics in both mutants, and decreased OmpF production and altered lipopolysaccharide in 104-cip. Complementation of mutated
gyrA
and
gyrB
with wild-type alleles restored susceptibility to quinolones in 104-cip and significantly decreased the ciprofloxacin MIC in 5408-cip. Complementation of
parE
had no effect on quinolone MICs. Deletion of
acrB
restored susceptibility to ciprofloxacin and other antibiotics tested. Both
soxS
and
marA
were overexpressed in 104-cip, and
ramA
was overexpressed in 5408-cip. Inactivation of each of these global regulators lowered ciprofloxacin MICs, decreased expression of
acrB
, and restored susceptibility to other antibiotics. Mutations were found in
soxR
(R20H) and in
soxS
(E52K) in 104-cip and in
ramR
(G25A) in 5408-cip. In conclusion, both efflux activity and a single
gyrA
mutation contribute to nalidixic acid resistance and reduced ciprofloxacin sensitivity. Ciprofloxacin resistance and decreased susceptibility to multiple antibiotics can result from different genetic events leading to development of target gene mutations, increased efflux activity resulting from differential expression of global regulators associated with mutations in their regulatory genes, and possible altered membrane permeability.