bluuebunny/crossref_metadata_2025_split huggingface dataset:
Plasmid-Encoded Tet B Tetracycline Resistance in
Haemophilus parasuis
Authors: Lancashire John F. , Terry Tamsin D. , Blackall P. J. , Jennings Michael P. 
Published: April 2005

ABSTRACT

The complete sequence of two plasmids, pHS-Tet (5.1 kb) and pHS-Rec (9.5 kb), isolated from
Haemophilus parasuis
strain HS1543 has been obtained. Plasmid pHS-Tet contains four open reading frames including a
tet
(B) tetracycline resistance gene which unusually did not have an associated
tetR
repressor gene. From a total of 45
H. parasuis
isolates surveyed (15 international reference strains, 15 field isolates selected for their genetic diversity, and 15 recent Australian field isolates), 2 tetracycline-resistant field isolates (HS226 and HS1859) were identified. Analysis of three additional isolates from the same disease outbreak as strain HS1859 revealed a further tetracycline-resistant
H. parasuis
strain (HS1857, serovar 8) and a tetracycline-resistant
Actinobacillus pleuropneumoniae
strain (HS1861). An approximately 10.6-kb plasmid was identified in field isolate HS226 and outbreak strains HS1857, HS1859, and HS1861. Southern hybridization analysis of these plasmids showed that the Tet B determinant was present, and restriction digest comparisons suggest that these plasmids are related. This is believed to be the first report of native
H. parasuis
plasmids and Tet B-mediated tetracycline resistance in this microorganism.
Antipneumococcal Activity of Ceftobiprole, a Novel Broad-Spectrum Cephalosporin
Authors: Kosowska Klaudia , Hoellman Dianne B. , Lin Gengrong , Clark Catherine , Credito Kim , McGhee Pamela , Dewasse Bonifacio , Bozdogan Bülent , Shapiro Stuart , Appelbaum Peter C. 
Published: April 2005

ABSTRACT

Ceftobiprole
(previously known as BAL9141), an
anti-methicillin-resistant
Staphylococcus aureus
cephalosporin, was very highly active against a panel of 299
drug-susceptible and -resistant pneumococci, with MIC
50
and
MIC
90
values (μg/ml) of 0.016 and 0.016 (penicillin
susceptible), 0.06 and 0.5 (penicillin intermediate), and 0.5 and 1.0
(penicillin resistant). Ceftobiprole, imipenem, and
ertapenem had lower MICs against all pneumococcal
strains than amoxicillin, cefepime, ceftriaxone, cefotaxime,
cefuroxime, or cefdinir. Macrolide and penicillin G MICs generally
varied in parallel, whereas fluoroquinolone MICs did not correlate with
penicillin or macrolide susceptibility or resistance.
All strains were susceptible to linezolid, quinupristin-dalfopristin,
daptomycin, vancomycin, and teicoplanin. Time-kill analyses showed that
at 1× and 2× the MIC, ceftobiprole was bactericidal
against 10/12 and 11/12 strains, respectively. Levofloxacin,
moxifloxacin, vancomycin, and teicoplanin were each bactericidal
against 10 to 12 strains at 2× the MIC. Azithromycin and
clarithromycin were slowly bactericidal, and telithromycin was
bactericidal against only 5/12 strains at 2× the MIC. Linezolid
was mainly bacteriostatic, whereas quinupristin-dalfopristin and
daptomycin showed marked killing at early time periods. Prolonged
serial passage in the presence of subinhibitory concentrations of
ceftobiprole failed to yield mutants with high MICs towards this
cephalosporin, and single-passage selection showed very low frequencies
of spontaneous mutants with breakthrough MICs towards
ceftobiprole.
Geographical and Ecological Analysis of Resistance, Coresistance, and Coupled Resistance to Antimicrobials in Respiratory Pathogenic Bacteria in Spain
Authors: Pérez-Trallero Emilio , García-de-la-Fuente Celia , García-Rey César , Baquero Fernando , Aguilar Lorenzo , Dal-Ré Rafael , García-de-Lomas Juan 
Published: April 2005

ABSTRACT

A multicenter susceptibility surveillance (the S.A.U.C.E. project) including 2,721
Streptococcus pneumoniae
, 3,174
Streptococcus pyogenes
, and 2,645
Haemophilus influenzae
consecutive isolates was carried out in 25 hospitals all over Spain from November 2001 to October 2002 to evaluate the current epidemiology of resistance of the main bacteria involved in community-acquired respiratory tract infections. Susceptibility testing was performed in a single centralized laboratory by a broth microdilution method. The prevalence of resistant
S. pneumoniae
strains was 0.4% for cefotaxime, 4.4% for amoxicillin and amoxicillin-clavulanic acid, 25.6% for cefuroxime-axetil, 34.5% for erythromycin, clarithromycin, and azithromycin, and 36.0% for cefaclor. Phenotypes of resistance to erythromycin were MLS
B
(macrolide-lincosamide-streptogramin B) in 89.9% (gene
ermB
) and M (macrolide) in 9.7% of cases (gene
mefA
). No strain harbored both genes simultaneously. Serotypes 19, 6, 23, 14, and 3 were the most prevalent, accounting for 54.6% of the total isolates. Resistance to macrolides seems to be the most alarming point, since among penicillin-susceptible isolates it reached 15.1% compared to 55.8% among penicillin-resistant strains. Geographically, a number of regions had rates of erythromycin resistance above 40% (even higher in children). Resistance to erythromycin was also high in
S. pyogenes
isolates: mean regional 33.2%, beta-lactamase-producing
H. influenzae
were 20%, whereas 4.4% had a beta-lactamase-negative, ampicillin-resistant phenotype. We highlight the importance of different geographical frequencies of coresistance (associations of resistance to different drugs within the same species) and coupled resistance (association of resistance between different species) probably resulting from different local coselective events.
Mechanism of Anti-Human Immunodeficiency Virus Activity of β-
d
-6-Cyclopropylamino-2′,3′-Didehydro-2′,3′-Dideoxyguanosine
Authors: Ray Adrian S. , Hernandez-Santiago Brenda I. , Mathew Judy S. , Murakami Eisuke , Bozeman Carey , Xie Meng-Yu , Dutschman Ginger E. , Gullen Elizabeth , Yang Zhenjun , Hurwitz Selwyn , Cheng Yung-Chi , Chu Chung K. , McClure Harold , Schinazi Raymond F. , Anderson Karen S. 
Published: April 2005

ABSTRACT
To better understand the importance of the oxygen in the ribose ring of planar unsaturated nucleoside analogs that target human immunodeficiency virus (HIV), a 6-cyclopropyl-substituted prodrug of 2′,3′-didehydro-2′,3′-dideoxyguanosine (cyclo-d4G) was synthesized, and its cellular metabolism, antiviral activity, and pharmacokinetic behavior were studied. Cyclo-d4G had selective anti-HIV activity in primary blood mononuclear cells (PBMCs), effectively inhibiting the LAI strain of HIV-1 by 50% at 1.1 ± 0.1 μM while showing 50% inhibition of cell viability at 84.5 μM. The antiviral activity in PBMCs was not markedly affected by mutations of methionine to valine at position 184 or by thymidine-associated mutations in the viral reverse transcriptase. Mutations of leucine 74 to valine and of lysine 65 to arginine had mild to moderate resistance (as high as fivefold). Studies to delineate the mechanism of cellular metabolism and activation of cyclo-d4G showed reduced potency in inhibiting viral replication in the presence of the adenosine/adenylate deaminase inhibitor 2′-deoxycoformycin, implying that the antiviral activity is due to its metabolism to the 2′-dGTP analog d4GTP. Intracellular formation of sugar catabolites illustrates the chemical and potentially enzymatic instability of the glycosidic linkage in d4G. Further studies suggest that cyclo-d4G has a novel intracellular phosphorylation pathway. Cyclo-d4G had a lower potential to cause mitochondrial toxicity than 2′,3′-dideoxycytidine and 2′,3′-didehydro-3′-deoxythymidine in neuronal cells. Also, cyclo-d4G had advantageous synergism with many currently used anti-HIV drugs. Poor oral bioavailability observed in rhesus monkeys may be due to the labile glycosidic bond, and special formulation may be necessary for oral delivery.
Inhibitory Effect of 2′-Substituted Nucleosides on Hepatitis C Virus Replication Correlates with Metabolic Properties in Replicon Cells
Authors: Tomassini Joanne E. , Getty Krista , Stahlhut Mark W. , Shim Sung , Bhat Balkrishen , Eldrup Anne B. , Prakash Thazha P. , Carroll Steven S. , Flores Osvaldo , MacCoss Malcolm , McMasters Daniel R. , Migliaccio Giovanni , Olsen David B. 
Published: April 2005

ABSTRACT

Nucleosides have been widely used in the treatment of viral diseases, but relatively few have been identified as inhibitors of hepatitis C virus (HCV). The modified ribonucleosides, 2′-
C
-methyl-adenosine and 2′-
O
-methyl-cytidine, are potent inhibitors of HCV replication which specifically target the NS5B polymerase. Herein, a more extensive characterization of the effect of these compounds upon HCV replication in subgenomic replicons is reported. A highly selective antireplicative effect induced by the nucleosides in replicon-containing cell lines was maintained during an exponential growth period with potencies which paralleled the reduction of both positive- and negative-strand RNA replication. Moreover, the inhibitory effect closely correlated with the intrinsic metabolic properties of differing replicon clonal lines. Interestingly, while 2′-
C
-methyl-adenosine elicited similar inhibitory potencies in different cell lines, 2′-
O
-methyl-cytidine was found to be inactive in one replicon cell line tested, although the corresponding triphosphates comparably inhibited the in vitro activity of replication complexes isolated from these cells and the activity of NS5B polymerase using synthetic templates. The lack of antireplicative effect, attributed to poor intracellular conversion of the 2′-
O
-methyl-cytidine nucleoside to the active 5′-triphosphate, was reversed using a monophosphate prodrug. Thus, although replicon cells are useful for evaluating the effect of inhibitors upon HCV replication, these findings have important implications for their use in the identification and characterization of nucleosides and other chemotherapeutic agents requiring cellular metabolism.
Efficacy, Plasma Pharmacokinetics, and Safety of Icofungipen, an Inhibitor of
Candida
Isoleucyl-tRNA Synthetase, in Treatment of Experimental Disseminated Candidiasis in Persistently Neutropenic Rabbits
Authors: Petraitiene Ruta , Petraitis Vidmantas , Kelaher Amy M. , Sarafandi Alia A. , Mickiene Diana , Groll Andreas H. , Sein Tin , Bacher John , Walsh Thomas J. 
Published: April 2005

ABSTRACT

Icofungipen (formerly PLD-118) is a synthetic derivative of the naturally occurring β-amino acid cispentacin that blocks isoleucyl-tRNA synthetase, resulting in the inhibition of protein synthesis and growth of fungal cells. We investigated the efficacy, plasma pharmacokinetics, and safety of icofungipen in escalating dosages for the treatment of experimental subacute disseminated candidiasis in persistently neutropenic rabbits. Icofungipen was administered for 10 days starting 24 h after the intravenous inoculation of 10
3
Candida albicans
blastoconidia. Study groups consisted of rabbits treated with icofungipen at 4 (ICO-4), 10 (ICO-10), and 25 (ICO-25) mg/kg of body weight/day in two divided dosages, rabbits treated with fluconazole at 10 mg/kg/day, rabbits treated with amphotericin B at 1 mg/kg/day, and untreated controls. Levels of icofungipen in plasma were derivatized by phthaldialdehyde and quantified by high-performance liquid chromatography with fluorescence detection. Rabbits treated with ICO-10 (
P
< 0.01) and ICO-25 (
P
< 0.001) showed significant dosage-dependent tissue clearance of
C. albicans
from the liver, spleen, kidney, brain, vitreous, vena cava, and lung in comparison to untreated controls. ICO-25 cleared
C. albicans
from all tissues and had activity comparable to that of amphotericin B versus untreated controls (
P
< 0.001). Pharmacokinetics of icofungipen in plasma approximated a dose-dependent relationship of the maximum concentration of drug in serum and the area under the concentration-time curve. There was no significant elevation of the levels of hepatic transaminases, alkaline phosphatase, bilirubin, urea nitrogen, or creatinine in icofungipen-treated rabbits. Icofungipen followed dose-dependent pharmacokinetics and was effective in the treatment of experimental disseminated candidiasis, including central nervous system infection, in persistently neutropenic rabbits.
Evaluation of Disk Diffusion Method for Determining Eberconazole Susceptibility of Dermatophytes and Influence of Culture Medium
Authors: Fernández-Torres Belkys , Inza Isabel , Guarro Josep 
Published: April 2005

ABSTRACT
We have evaluated a disk diffusion method to determine the activity of eberconazole against 50 strains of dermatophytes by testing three culture media (RPMI, antibiotic medium 3, and high resolution). No differences were found among the results obtained with the three media. A significant correlation between disk diffusion and microdilution methods was observed with AM3.
Case Study of an Intense African Easterly Wave
Authors: Berry Gareth J. , Thorncroft Chris 
Published: April 2005

The life cycle of an intense African easterly wave (AEW) over the African continent is examined using European Centre for Medium-Range Weather Forecasts (ECMWF) operational analyses, Meteosat satellite images, and synoptic observations. This system, the strongest AEW of 2000, can be tracked from central North Africa into the eastern Atlantic Ocean, where it is associated with the genesis of Hurricane Alberto. Synoptic analysis of the kinematic and thermodynamic fields is supplemented by analysis of potential vorticity (PV), allowing exploration at the role of multiple scales in the evolution of this AEW. The authors’ analysis promotes the division of the AEW life cycle into three distinctive phases. (i) Initiation: The AEW development is preceded by a large convective event composed of several mesoscale convective systems over elevated terrain in Sudan. This convection provides a forcing on the baroclinically and barotropically unstable state that exists over tropical North Africa. (ii) Baroclinic growth: A low-level warm anomaly, generated close to the initial convection, interacts with a midtropospheric strip of high PV that exists on the cyclonic shear side of the African easterly jet, which is consistent with baroclinic growth. This interaction is reinforced by the generation of subsynoptic-scale PV anomalies by deep convection that is embedded within the baroclinic AEW structure. (iii) West coast development: Near the West African coast, the baroclinic structure weakens, but convection is maintained. The midtropospheric PV anomalies embedded within the AEW merge with one another and with PV anomalies that are generated by convection over topography ahead of the system. These mergers result in the production of a significant PV feature that leaves the West African coast and rapidly undergoes tropical cyclogenesis.
Initialization and Numerical Forecasting of a Supercell Storm Observed during STEPS
Authors: Sun Juanzhen 
Published: April 2005

The feasibility of initializing a numerical cloud model with single-Doppler observations and predicting the evolution of thunderstorms has been tested using an observed case of a supercell storm during the Severe Thunderstorm Electrification and Precipitation Study (STEPS). Single-Doppler observations from the Weather Surveillance Radar-1988 Doppler (WSR-88D) at Goodland, Kansas, are assimilated into a cloud-scale numerical model using a four-dimensional variational data assimilation (4DVAR) scheme. A number of assimilation and short-range numerical prediction experiments are conducted. Both the assimilation and prediction results are compared with those of a dual-Doppler synthesis. The prediction results are also verified with reflectivity observations. It is shown that the analysis of the wind field captures the major structure of the storm as revealed by the dual-Doppler synthesis. Thermodynamical and microphysical features retrieved through the dynamical model show consistency with expectations for a deep convective storm. The predicted storm evolution represented by the reflectivity field correlates well with the observations for a 2-h prediction period. The relative importance of the initial fields on the subsequent prediction of the storm evolution is examined by alternately removing the perturbation in each of the initial fields. It is shown that the prediction is most sensitive to the initialization of wind, water vapor, and temperature perturbations. A number of sensitivity experiments for initialization are conducted to show how the initial analysis depends on the application of a cycling procedure, the weights of the smoothness constraint, and the relative importance between the radial velocity and the reflectivity observations. It is found that the application of the cycling procedure improves the analysis and the subsequent forecast. Greater smoothness coefficients of the penalty term in the cost function result in a larger rms difference in the wind analysis, but help spread the information out and improve the forecast slightly. The radial velocity observations play a more important role than the reflectivity in terms of the wind analysis and the subsequent precipitation forecast.
Development of an Automated Classification Procedure for Rainfall Systems
Authors: Baldwin Michael E. , Kain John S. , Lakshmivarahan S. 
Published: April 2005

An automated procedure for classifying rainfall systems (meso-α scale and larger) was developed using an operational analysis of hourly precipitation estimates from radar and rain gauge data. The development process followed two main phases: a training phase and a testing phase. First, 48 hand-selected cases were used to create a training dataset, from which a set of attributes related to morphological aspects of rainfall systems were extracted. A hierarchy of classes for rainfall systems, in which the systems are separated into general convective (heavy rain) and nonconvective (light rain) classes, was envisioned. At the next level of classification hierarchy, convective events are divided into linear and cellular subclasses, and nonconvective events belong to the stratiform subclass. Essential attributes of precipitating systems, related to the rainfall intensity and degree of linear organization, were determined during the training phase. The attributes related to the rainfall intensity were chosen to be the parameters of the gamma probability distribution fit to observed rainfall amount frequency distributions using the generalized method of moments. Attributes related to the degree of spatial continuity of each rainfall system were acquired from correlogram analysis. Rainfall systems were categorized using hierarchical cluster analysis experiments with various combinations of these attributes. The combination of attributes that resulted in the best match between cluster analysis results and an expert classification were used as the basis for an automated classification procedure. The development process shifted into the testing phase, where automated procedures for identifying and classifying rainfall systems were used to analyze every rainfall system in the contiguous 48 states during 2002. To allow for a feasible validation, a testing dataset was extracted from the 2002 data. The testing dataset consisted of 100 randomly selected rainfall systems larger than 40 000 km2 as identified by an automated identification system. This subset was shown to be representative of the full 2002 dataset. Finally, the automated classification procedure classified the testing dataset into stratiform, linear, and cellular classes with 85% accuracy, as compared to an expert classification.
Localization of ADAMTS13 to the stellate cells of human liver
Authors: Uemura Masahito , Tatsumi Kouko , Matsumoto Masanori , Fujimoto Masao , Matsuyama Tomomi , Ishikawa Masatoshi , Iwamoto Taka-aki , Mori Toshio , Wanaka Akio , Fukui Hiroshi , Fujimura Yoshihiro 
Published: April 2005

Abstract
Although the chromosomal localization (9q34) of the gene encoding the human form of ADAMTS13 (a disintegrin-like and metalloproteinase with thrombospondin type-1 motifs 13) and its exclusive expression in the liver have been established, the cells that produce this enzyme are yet to be determined. We investigated the expression of ADAMTS13 mRNA and protein in fresh frozen specimens obtained during liver biopsies of 8 patients with liver diseases. In situ hybridizations to localize ADAMTS13 mRNA showed positive signals exclusively in perisinusoidal cells with irregularly elongated dendritic processes extending between hepatocytes. Furthermore, ADAMTS13 was detected immunohistochemically in perisinusoidal cells, whereas no staining was observed in hepatocytes. The positive cells varied in shape from unipolar to dendritic with irregularly elongated cytoplasmic processes, features common to hepatic stellate cells (HSCs). Double-labeling experiments revealed that the ADAMTS13-positive cells also expressed α-smooth muscle actin, confirming that these cells were activated HSCs. These results suggest that HSCs may be major cells producing ADAMTS13 in human liver.
Validation of a brief telephone battery for neurocognitive assessment of patients with pulmonary arterial hypertension
Authors: Taichman Darren B , Christie Jason , Biester Rosette , Mortensen Jennifer , White Joanne , Kaplan Sandra , Hansen-Flaschen John , Palevsky Harold I , Elliott C Gregory , Hopkins Ramona O 
Published: April 2005

Abstract

Background
The effects of pulmonary arterial hypertension on brain function are not understood, despite patients' frequent complaints of cognitive difficulties. Using clinical instruments normally administered during standard in-person assessment of neurocognitive function in adults, we assembled a battery of tests designed for administration over the telephone. The purpose was to improve patient participation, facilitate repeated test administration, and reduce the cost of research on the neuropsychological consequences of acute and chronic cardiorespiratory diseases. We undertook this study to validate telephone administration of the tests.

Methods
23 adults with pulmonary arterial hypertension underwent neurocognitive assessment using both standard in-person and telephone test administration, and the results of the two methods compared using interclass correlations.

Results
For most of the tests in the battery, scores from the telephone assessment correlated strongly with those obtained by in-person administration of the same tests. Interclass correlations between 0.5 and 0.8 were observed for tests that assessed attention, memory, concentration/working memory, reasoning, and language/crystallized intelligence (p ≤ 0.05 for each). Interclass correlations for the Hayling Sentence Completion test of executive function approached significance (p = 0.09). All telephone tests were completed within one hour.

Conclusion
Administration of this neurocognitive test battery by telephone should facilitate assessment of neuropsychological deficits among patients with pulmonary arterial hypertension living across broad geographical areas, and may be useful for monitoring changes in neurocognitive function in response to PAH-specific therapy or disease progression.