bluuebunny/crossref_metadata_2025_split huggingface dataset:
Current‐source density analysis of slow brain potentials during time estimation
Authors: Gibbons Henning , Rammsayer Thomas H. 
Published: November 2004

AbstractTwo event‐related potential studies were conducted to investigate differential brain correlates of temporal processing of intervals below and above 3–4 s. In the first experiment, 24 participants were presented with auditorily marked target durations of 2, 4, and 6 s that had to be reproduced. Timing accuracy was similar for all three target durations. As revealed by current‐source density analysis, slow‐wave components during both presentation and reproduction were independent of target duration. Experiment 2 examined potential modulating effects of type of interval (filled and empty) and presentation mode (randomized and blocked presentation of target durations). Behavioral and slow‐wave findings were consistent with those of Experiment 1. Thus, the present findings support the notion of a general timing mechanism irrespective of interval duration as proposed by scalar timing theory and pacemaker‐counter models of time estimation.
Posterior brain ERP patterns related to the go/no‐go task in children
Authors: Ciesielski Kristina T. , Harris Richard J. , Cofer Lynette F. 
Published: November 2004

AbstractEvent‐related potentials (ERPs) and performance correlates of inhibition of responses to no‐go stimuli were investigated in 6–12‐year‐old children and young adults. The percent of correct responses to go stimuli was high and similar in both groups; the percent of false alarm errors to no‐go was significantly higher in children. Effective inhibition of responses to no‐go stimuli was elucidated by a negative component of ERPs, the frontal‐central N2, with peak latency 230–430 ms after stimulus onset. In adults, N2 was larger to no‐go than to go stimuli, regardless of stimulus frequency. This effect was more prominent in tasks with high (25% no‐gos and 75% gos), than with low (75% no‐gos and 25% gos) inhibitory demand. In children, the parietal N2 was generally larger to rare than to frequent stimuli, and it was more specifically related to inhibition. The analysis of the relationship of no‐go N2 to the inhibitory content of stimuli, probability of stimuli, and the contextual task difficulty suggests that child/adult differences in behavioral responses and ERPs may be related to both the immaturity of the fronto‐parietal cortical‐cortical network and to different task strategies.
Magnetic resonance imaging of two suspected cases of global brain ischemia
Authors: Panarello Gregory L. , Dewey Curtis W. , Barone Georgina , Stefanacci Joseph D. 
Published: November 2004

AbstractObjective: To describe the clinical findings and magnetic resonance imaging (MRI) characteristics of two animals with suspected global brain ischemia (GBI).Series summary: Two brachycephalic animals (Persian cat and Boston terrier) presented for altered mentation, blindness, ataxia, and seizures after being anesthetized. Common to both anesthetic protocols was ketamine. Clinically, the neurological deficits developed rapidly and did not progress after the initial 24 hours. MRI findings were most consistent with GBI. MRI, including pre‐ and post‐T1 weighted, T2 weighted, and fluid‐attenuated inversion recovery (FLAIR) studies, was used to image these animals. Abnormalities were seen post‐T1, T2, and FLAIR. Both animals improved neurologically with supportive care over several weeks, but both remained blind.New information: The use of MRI for diagnosing GBI.
Amoxicillin-Clavulanate Therapy Increases Childhood Nasal Colonization by Methicillin-Susceptible
Staphylococcus aureus
Strains Producing High Levels of Penicillinase
Authors: Guillemot Didier , Bonacorsi Stephane , Blanchard John S. , Weber Philippe , Simon Sylvie , Guesnon Bruno , Bingen Edouard , Carbon Claude 
Published: November 2004

ABSTRACT

We examined factors associated with penicillinase production by nasal carriage
Staphylococcus aureus
strains in 648 children aged 3 to 6 years attending 20 randomly sampled playschools. The children were prospectively monitored for drug use and medical events for 6 months and were then screened for
S. aureus
carriage. Isolates were tested for their susceptibility to penicillin G and methicillin, and penicillinase production by methicillin-susceptible, penicillin-resistant strains was quantified.
S. aureus
was isolated from 166 children (25.6%). Exposure to amoxicillin-clavulanate during the previous 3 months was associated with higher penicillinase production by penicillin-resistant, methicillin-susceptible strains (odds ratio, 3.6;
P
= 0.03). These results suggest that use of the amoxicillin-clavulanate combination could induce a herd selection process of
S. aureus
strains producing higher levels of penicillinase.
Pharmacokinetics and Effects of Ribavirin following Intraventricular Administration for Treatment of Subacute Sclerosing Panencephalitis
Authors: Hosoya Mitsuaki , Mori Shuichi , Tomoda Akemi , Mori Kenji , Sawaishi Yukio , Kimura Hiroshi , Shigeta Shiro , Suzuki Hitoshi 
Published: November 2004

ABSTRACT
Ribavirin is a broad-spectrum antiviral drug with inhibitory activity against many RNA viruses, including measles virus. Five patients with subacute sclerosing panencephalitis (SSPE) were treated with ribavirin by intraventricular administration. Although there were transient side effects attributed to ribavirin, such as drowsiness, headache, lip and gingival swelling, and conjunctival hyperemia, intraventricular ribavirin therapy was generally safe and well tolerated. The cerebrospinal fluid (CSF) ribavirin concentration decreased, as described by a monoexponential function, after a single intraventricular dose. There was considerable interindividual variability, however, in the peak level and half-life. We aimed to adjust the individual dose and frequency of intraventricular administration based on the peak level and half-life of ribavirin in the CSF in order to maintain the CSF ribavirin concentration at the target level. Clinical effectiveness (significant neurologic improvement and/or a significant decrease in titers of hemagglutination inhibition antibodies against measles virus in CSF) was observed for four of five patients. For these four patients, CSF ribavirin concentrations were maintained at a level at which SSPE virus replication was almost completely inhibited in vitro and in vivo, whereas the concentration was lower in the patient without clinical improvement. These results suggest that intraventricular administration of ribavirin is effective against SSPE if the CSF ribavirin concentration is maintained at a high level. Intraventricular ribavirin therapy should be pursued further for its potential use for patients with SSPE and might be applied in the treatment of patients with encephalitis caused by other RNA viruses.
Pharmacodynamic Profiling of Piperacillin in the Presence of Tazobactam in Patients through the Use of Population Pharmacokinetic Models and Monte Carlo Simulation
Authors: Lodise Thomas P. , Lomaestro Ben , Rodvold Keith A. , Danziger Larry H. , Drusano George L. 
Published: November 2004

ABSTRACTThe primary objectives of this analysis were to determine which pharmacokinetic model most accurately describes the elimination pathways for piperacillin in the presence of tazobactam through population pharmacokinetic modeling and to characterize its pharmacodynamic profile. Once the optimal pharmacokinetic model was identified, Monte Carlo simulation of 10,000 subjects with ADAPT II was performed to estimate the probability of attaining a target free-piperacillin concentration greater than the MIC for 50% of the dosing interval for 3.375 g every 6 h or every 4 h given as a 0.5-h infusion at each MIC between 0.25 and 32 μg/ml. In the population pharmacokinetic analysis, measurements of bias and precision, observed-predicted plots, andr2values were highly acceptable for all three models and all three models were appropriate candidates for the Monte Carlo simulation evaluation. Visual comparison of the distribution of the piperacillin concentrations at the pharmacodynamic endpoint—h 3 concentrations of a 6-h dosing interval—between the simulated populations and raw data revealed that the linear model was most reflective of the raw data at the pharmacodynamic endpoint, and the linear model was therefore selected for the target attainment analysis. In the target attainment analysis, administration of 3 g of piperacillin every 6 h resulted in a robust target attainment rate that exceeded 95% for MICs of ≤8 mg/liter. The 4-h piperacillin administration interval had a superior pharmacodynamic profile and provided target attainment rates exceeding 95% for MICs of ≤16 mg/liter. This study indicates that piperacillin-tazobactam should have utility for empirical therapy of hospital-onset infections.
Oral Activity of a Methylenecyclopropane Analog, Cyclopropavir, in Animal Models for Cytomegalovirus Infections
Authors: Kern Earl R. , Bidanset Deborah J. , Hartline Caroll B. , Yan Zhaohua , Zemlicka Jiri , Quenelle Debra C. 
Published: November 2004

ABSTRACT

We reported previously that purine 2-(hydroxymethyl)methylenecyclopropane analogs have good activity against cytomegalovirus infection. A second-generation analog, (
Z
)-9-{[2,2-bis-(hydroxymethyl)cyclopropylidene]methyl}guanine (ZSM-I-62, cyclopropavir [CPV]), has particularly good activity against murine and human cytomegaloviruses (MCMV and HCMV) in vitro. To determine the oral activity of this compound in vivo, BALB/c or severe combined immunodeficient (SCID) mice infected with MCMV and two models using SCID mice implanted with human fetal tissue and subsequently infected with HCMV were used. In MCMV-infected normal mice, CPV at 10 mg/kg of body weight was highly effective in preventing mortality when administered at 24, 48, or 72 h post-viral inoculation and reduced titers of virus in tissues of SCID mice by 2 to 5 log
10
. In one HCMV model, human fetal retinal tissue was implanted into the anterior chamber of the mouse eye and inoculated with the Toledo strain of HCMV, and in the second, human fetal thymus and liver tissues were implanted under the kidney capsule of mice and then inoculated with HCMV. In general, replication of HCMV in both types of implant tissue increased from 7 through 21 to 28 days and then gradually decreased to undetectable levels by 8 weeks postinfection. Oral treatment with 45 or 15 mg of CPV/kg initiated 24 h after infection was highly effective in reducing replication to undetectable levels in both models and was generally more effective than ganciclovir. These data indicate that the methylenecyclopropane analog, CPV, was highly efficacious in these four animal models and should be evaluated for use in HCMV infections in humans.
Antistaphylococcal Activity of WCK 771, a Tricyclic Fluoroquinolone, in Animal Infection Models
Authors: Patel Mahesh V. , De Souza Noel J. , Gupte Shrikant V. , Jafri Mohammad A. , Bhagwat Sachin S. , Chugh Yati , Khorakiwala Habil F. , Jacobs Michael R. , Appelbaum Peter C. 
Published: November 2004

ABSTRACTWCK 771, the arginine salt ofS-(−)-nadifloxacin, was evaluated in animal models of staphylococcal infection and in vitro. For 302 methicillin-susceptible strains the MIC at which 50% of isolates are inhibited (MIC50) and the MIC90of WCK 771 were 0.03 and 0.03 μg/ml, respectively, and for 198 methicillin-resistant strains the MIC50and the MIC90were 0.5 and 1.0 μg/ml, respectively. All methicillin-susceptible staphylococci were quinolone susceptible, and almost all methicillin-resistant staphylococci were quinolone resistant. WCK 771 was more potent than moxifloxacin, trovafloxacin, levofloxacin, and ciprofloxacin and had potency comparable to that of clinafloxacin. Only WCK 771 and clinafloxacin demonstrated strong potencies against vancomycin-intermediateStaphylococcus aureusstrains (MICs = 1 μg/ml). WCK 771 is not a substrate of the NorA pump, as evident from the lack of an effect of reserpine on the MICs and similar protective doses against infections caused by efflux-positive and -negative staphylococci. WCK 771 was effective by both the oral and the subcutaneous routes in mice infected intraperitoneally with quinolone-susceptible methicillin-susceptibleS. aureus(MSSA) strains. For infections caused by quinolone-resistant methicillin-resistantS. aureus(MRSA) strains, the activity of WCK 771 administered subcutaneously was superior to those of trovafloxacin and sparfloxacin, with a 50% effective dose range of 27.8 to 46.8 mg/kg of body weight. The activity of WCK 771 was superior to those of moxifloxacin, vancomycin, and linezolid in a mouse cellulitis model of infection caused by one MSSA and two MRSA strains, with effective doses of 2.5 and 5 mg/kg for the MSSA strain and 10-fold higher effective doses for MRSA strains. WCK 771, like vancomycin and linezolid, eradicated MRSA from mouse liver, spleen, kidney, and lung when it was administered subcutaneously at a dose of 50 mg/kg for four doses. These studies have demonstrated the effectiveness of WCK 771, administered orally and parenterally, for the treatment of diverse staphylococcal infections in mice, including those caused by quinolone-resistant strains.
Derivatives of a Vancomycin-ResistantStaphylococcus aureusStrain Isolated at Hershey Medical Center
Authors: Bozdogan Bülent , Ednie Lois , Credito Kim , Kosowska Klaudia , Appelbaum Peter C. 
Published: November 2004

ABSTRACTAntimicrobial susceptibilities and genetic relatedness of the vancomycin-resistantStaphylococcus aureusstrain (VRSA) isolated at Hershey, Pa. (VRSA Hershey), and its vancomycin-susceptible and high-level-resistant derivatives were studied and compared to 32 methicillin-resistantS. aureusstrains (MRSA) isolated from patients and medical staff in contact with the VRSA patient. Derivatives of VRSA were obtained by subculturing six VRSA colonies from the original culture with or without vancomycin. Ten days of drug-free subculture caused the loss ofvanAin two vancomycin-susceptible derivatives for which vancomycin MICs were 1 to 4 μg/ml. Multistep selection of three VRSA clones with vancomycin for 10 days increased vancomycin MICs from 32 to 1,024 to 2,048 μg/ml. MICs of teicoplanin, dalbavancin, and oritavancin were also increased from 4, 0.5, and 0.12 to 64, 1, and 32 μg/ml, respectively. Pulsed-field gel electrophoresis (PFGE) and multilocus sequence typing analysis indicated that VRSA Hershey was thevanA-acquired variety of a common MRSA clone in our hospital with sequence type 5 (ST5). Three of five vancomycin-intermediateS. aureusstrains tested from geographically different areas were also ST5, and the Michigan VRSA was ST371, a one-allele variant of ST5. Derivatives of VRSA Hershey had differences in PFGE profiles and the size of SmaI fragment that carries thevanAgene cluster, indicating instability of this cluster in VRSA Hershey. However induction with vancomycin increased glycopeptide MICs and stabilized the resistance.
Pharmacokinetics in Animals and Humans of a First-in-Class Peptide Deformylase Inhibitor
Authors: Ramanathan-Girish Sandhya , McColm Juliet , Clements John M. , Taupin Phil , Barrowcliffe Sue , Hevizi John , Safrin Sharon , Moore Clive , Patou Gary , Moser Heinz , Gadd Alison , Hoch Ute , Jiang Vernon , Lofland Denene , Johnson Kirk W. 
Published: November 2004

ABSTRACT

BB-83698, a potent and selective inhibitor of peptide deformylase, was the first compound of this novel antibacterial class to progress to clinical trials. Single- and/or multiple-dose studies with doses ranging from 10 to 50 mg of BB-83698/kg of body weight were done with mice, rats, and dogs. Intravenous pharmacokinetics were characterized by low to moderate clearances and moderate volumes of distribution for all species. In dogs, but not in rodents, central nervous system (CNS) effects were dose limiting for intravenously administered BB-83698 and were suspected to be related to a high maximum concentration of the agent in plasma (
C
max
) rather than to total systemic exposure. Controlled infusion studies with dogs demonstrated that CNS effects could be avoided without compromising systemic exposure by reducing the
C
max
. A randomized, double-blind, placebo-controlled, five-way-crossover, single-dose-escalation, phase I study to explore the safety, tolerability, and pharmacokinetics of intravenous BB-83698 at doses ranging from 10 to 475 mg was performed with healthy male volunteers. Systemic exposures were generally in linear relationships with administered doses in animals and humans. Pharmacokinetics were consistent, predictable, and exhibited good allometric scaling among all species (
r
2
>0.98). Moreover, BB-83698 dosing in humans proceeded to a predicted efficacious exposure (the area under the concentration-time curve/MIC ratio, up to 184) without any clinically significant adverse effects.
Antimycoplasmal Activity of Hydroxytyrosol
Authors: Furneri Pio Maria , Piperno Anna , Sajia Antonella , Bisignano Giuseppe 
Published: November 2004

ABSTRACTThe aim of this study was to investigate the in vitro antimycoplasmal activity of hydroxytyrosol. Twenty strains ofMycoplasma hominis, three strains ofMycoplasma fermentans, and one strain ofMycoplasma pneumoniaewere used. ForM. pneumoniae,M. hominis, andM. fermentans, the MICs were 0.5, 0.03 (for 90% of the strains tested), and 0.25 μg/ml, respectively.
Emergence in Asian Countries of
Staphylococcus aureus
with Reduced Susceptibility to Vancomycin
Authors: Song Jae-Hoon , Hiramatsu Keiichi , Suh Ji Yoeun , Ko Kwan Soo , Ito Teruyo , Kapi Maria , Kiem Sungmin , Kim Yeon-Sook , Oh Won Sup , Peck Kyong Ran , Lee Nam Yong 
Published: November 2004

ABSTRACT

To investigate the prevalence of
Staphylococcus aureus
with reduced susceptibility to vancomycin among methicillin-resistant
S. aureus
(MRSA) strains in Asian countries, a total of 1,357 clinical isolates of MRSA collected from 12 Asian countries were screened by using brain heart infusion agar plates containing 4 mg of vancomycin per liter. The presence of strains that were heterointermediately resistant to vancomycin (hVISA) was confirmed by population analysis. Of 347 (25.6%) MRSA isolates that grew on the screening agar plates, 58 isolates (4.3%) were hVISA. hVISA strains were found in India, South Korea, Japan, the Philippines, Singapore, Thailand, and Vietnam. However, neither vancomycin-intermediate
S. aureus
nor vancomycin-resistant
S. aureus
isolates were found among MRSA isolates from Asian countries in this survey.
Replicase-Binding Sites on Plus- and Minus-Strand Brome Mosaic Virus RNAs and Their Roles in RNA Replication in Plant Cells
Authors: Choi S.-K. , Hema M. , Gopinath K. , Santos J. , Kao C. 
Published: November 2004

ABSTRACT

The
cis
-acting elements for
Brome mosaic virus
(BMV) RNA synthesis have been characterized primarily for RNA3. To identify additional replicase-binding elements, nested fragments of all three of the BMV RNAs, both plus- and minus-sense fragments, were constructed and tested for binding enriched BMV replicase in a template competition assay. Ten RNA fragments containing replicase-binding sites were identified; eight were characterized further because they were more effective competitors. All eight mapped to noncoding regions of BMV RNAs, and the positions of seven localized to sequences containing previously characterized core promoter elements (C. C. Kao, Mol. Plant Pathol. 3:55-62, 2001), thus suggesting the identities of the replicase-binding sites. Three contained the tRNA-like structures that direct minus-strand RNA synthesis, three were within the 3′ region of each minus-strand RNA that contained the core promoter for genomic plus-strand initiation, and one was in the core subgenomic promoter. Single-nucleotide mutations known previously to abolish RNA synthesis in vitro prevented replicase binding. When tested in the context of the respective full-length RNAs, the same mutations abolished BMV RNA synthesis in transfected barley protoplasts. The eighth site was within the intercistronic region (ICR) of plus-strand RNA3. Further mapping showed that a sequence of 22 consecutive adenylates was responsible for binding the replicase, with 16 being the minimal required length. Deletion of the poly(A) sequence was previously shown to severely debilitate BMV RNA replication in plants (E. Smirnyagina, Y. H. Hsu, N. Chua, and P. Ahlquist, Virology 198:427-436, 1994). Interestingly, the B box motif in the ICR of RNA3, which has previously been determined to bind the 1a protein, does not bind the replicase. These results identify the replicase-binding sites in all of the BMV RNAs and suggest that the recognition of RNA3 is different from that of RNA1 and RNA2.
Heptad Repeat 2-Based Peptides Inhibit Avian Sarcoma and Leukosis Virus Subgroup A Infection and Identify a Fusion Intermediate
Authors: Netter Robert C. , Amberg Sean M. , Balliet John W. , Biscone Mark J. , Vermeulen Arwen , Earp Laurie J. , White Judith M. , Bates Paul 
Published: November 2004

ABSTRACT
Fusion proteins of enveloped viruses categorized as class I are typified by two distinct heptad repeat domains within the transmembrane subunit. These repeats are important structural elements that assemble into the six-helix bundles characteristic of the fusion-activated envelope trimer. Peptides derived from these domains can be potent and specific inhibitors of membrane fusion and virus infection. To facilitate our understanding of retroviral entry, peptides corresponding to the two heptad repeat domains of the avian sarcoma and leukosis virus subgroup A (ASLV-A) TM subunit of the envelope protein were characterized. Two peptides corresponding to the C-terminal heptad repeat (HR2), offset from one another by three residues, were effective inhibitors of infection, while two overlapping peptides derived from the N-terminal heptad repeat (HR1) were not. Analysis of envelope mutants containing substitutions within the HR1 domain revealed that a single amino acid change, L62A, significantly reduced sensitivity to peptide inhibition. Virus bound to cells at 4°C became sensitive to peptide within the first 5 min of elevating the temperature to 37°C and lost sensitivity to peptide after 15 to 30 min, consistent with a transient intermediate in which the peptide binding site is exposed. In cell-cell fusion experiments, peptide inhibitor sensitivity occurred prior to a fusion-enhancing low-pH pulse. Soluble receptor for ASLV-A induces a lipophilic character in the envelope which can be measured by stable liposome binding, and this activation was found to be unaffected by inhibitory HR2 peptide. Finally, receptor-triggered conformational changes in the TM subunit were also found to be unaffected by inhibitory peptide. These changes are marked by a dramatic shift in mobility on sodium dodecyl sulfate-polyacrylamide gel electrophoresis, from a subunit of 37 kDa to a complex of about 80 kDa. Biotinylated HR2 peptide bound specifically to the 80-kDa complex, demonstrating a surprisingly stable envelope conformation in which the HR2 binding site is exposed. These experiments support a model in which receptor interaction promotes formation of an envelope conformation in which the TM subunit is stably associated with its target membrane and is able to bind a C-terminal peptide.