bluuebunny/crossref_metadata_2025_split huggingface dataset:
Efavirenz Therapy in Rhesus Macaques Infected with a Chimera of Simian Immunodeficiency Virus Containing Reverse Transcriptase from Human Immunodeficiency Virus Type 1
Authors: Hofman Michael J. , Higgins Joanne , Matthews Timothy B. , Pedersen Niels C. , Tan Chalet , Schinazi Raymond F. , North Thomas W. 
Published: August 2004

ABSTRACT
The specificity of nonnucleoside reverse transcriptase (RT) inhibitors (NNRTIs) for the RT of human immunodeficiency virus type 1 (HIV-1) has prevented the use of simian immunodeficiency virus (SIV) in the study of NNRTIs and NNRTI-based highly active antiretroviral therapy. However, a SIV-HIV-1 chimera (RT-SHIV), in which the RT from SIVmac239 was replaced with the RT-encoding region from HIV-1, is susceptible to NNRTIs and is infectious to rhesus macaques. We have evaluated the antiviral activity of efavirenz against RT-SHIV and the emergence of efavirenz-resistant mutants in vitro and in vivo. RT-SHIV was susceptible to efavirenz with a mean effective concentration of 5.9 ± 4.5 nM, and RT-SHIV variants selected with efavirenz in cell culture displayed 600-fold-reduced susceptibility. The efavirenz-resistant mutants of RT-SHIV had mutations in RT similar to those of HIV-1 variants that were selected under similar conditions. Efavirenz monotherapy of RT-SHIV-infected macaques produced a 1.82-log-unit decrease in plasma viral-RNA levels after 1 week. The virus load rebounded within 3 weeks in one treated animal and more slowly in a second animal. Virus isolated from these two animals contained the K103N and Y188C or Y188L mutations. The RT-SHIV-rhesus macaque model may prove useful for studies of antiretroviral drug combinations that include efavirenz.
Clinical Emergence of Entecavir-Resistant Hepatitis B Virus Requires Additional Substitutions in Virus Already Resistant to Lamivudine
Authors: Tenney D. J. , Levine S. M. , Rose R. E. , Walsh A. W. , Weinheimer S. P. , Discotto L. , Plym M. , Pokornowski K. , Yu C. F. , Angus P. , Ayres A. , Bartholomeusz A. , Sievert W. , Thompson G. , Warner N. , Locarnini S. , Colonno R. J. 
Published: August 2004

ABSTRACT

Entecavir (ETV) exhibits potent antiviral activity in patients chronically infected with wild-type or lamivudine (3TC)-resistant (3TC
r
) hepatitis B virus (HBV). Among the patients treated in phase II ETV clinical trials, two patients for whom previous therapies had failed exhibited virologic breakthrough while on ETV. Isolates from these patients (arbitrarily designated patients A and B) were analyzed genotypically for emergent substitutions in HBV reverse transcriptase (RT) and phenotypically for reduced susceptibility in cultures and in HBV polymerase assays. After 54 weeks of 3TC therapy, patient A (AI463901-A) received 0.5 mg of ETV for 52 weeks followed by a combination of ETV and 100 mg of 3TC for 89 weeks. Viral rebound occurred at 133 weeks after ETV was started. The 3TC
r
RT substitutions rtV173L, rtL180M, and rtM204V were present at study entry, and the additional substitutions rtI169T and rtM250V emerged during ETV-3TC combination treatment. Reduced ETV susceptibility in vitro required the rtM250V substitution in addition to the 3TC
r
substitutions. For liver transplant patient B (AI463015-B), previous famciclovir, ganciclovir, foscarnet, and 3TC therapies had failed, and RT changes rtS78S/T, rtV173L, rtL180M, rtT184S, and rtM204V were present at study entry. Viral rebound occurred after 76 weeks of therapy with ETV at 1.0 mg, with the emergence of rtT184G, rtI169T, and rtS202I substitutions within the preexisting 3TC
r
background. Reduced susceptibility in vitro was highest when both the rtT184G and the rtS202I changes were combined with the 3TC
r
substitutions. In summary, infrequent ETV resistance can emerge during prolonged therapy, with selection of additional RT substitutions within a 3TC
r
HBV background, leading to reduced ETV susceptibility and treatment failure.
Oral Treatment of Murine Cytomegalovirus Infections with Ether Lipid Esters of Cidofovir
Authors: Kern Earl R. , Collins Deborah J. , Wan W. Brad , Beadle James R. , Hostetler Karl Y. , Quenelle Debra C. 
Published: August 2004

ABSTRACT

To improve the oral bioavailability of cidofovir (CDV), a series of ether lipid ester prodrugs were synthesized and evaluated for activity against murine cytomegalovirus (MCMV) infection. Four of these analogs, hexadecyloxypropyl (HDP)-CDV, octadecyloxyethyl (ODE)-CDV, oleyloxyethyl (OLE)-CDV, and oleyloxypropyl (OLP)-CDV, were found to have greater activity than CDV against human CMV and MCMV in vitro. The efficacy of oral treatment with these compounds against MCMV infections in BALB/c mice was then determined. Treatment with HDP-CDV, ODE-CDV, OLE-CDV, or OLP-CDV at 2.0 to 6.7 mg/kg of body weight provided significant protection when daily treatments were initiated 24 to 48 h after viral inoculation. Additionally, HDP-CDV or ODE-CDV administered twice weekly or as a single dose of 1.25 to 10 mg/kg was effective in reducing mortality when treatment was initiated at 24 h, 48 h, or, in some cases, 72 h after viral inoculation. In animals treated daily with HDP-CDV or ODE-CDV, virus titers in lung, liver, spleen, kidney, pancreas, salivary gland, and blood were reduced 3 to 5 log
10
-fold, which was comparable to CDV given intraperitoneally. These results indicated that HDP-CDV or ODE-CDV given orally was as effective as parenteral CDV for the treatment of experimental MCMV infection and suggest that further evaluation for use in CMV infections in humans is warranted.
Mutation in Enterovirus 71 Capsid Protein VP1 Confers Resistance to the Inhibitory Effects of Pyridyl Imidazolidinone
Authors: Shih Shin-Ru , Tsai Mun-Chung , Tseng Sung-Nien , Won Kuo-Fang , Shia Kak-Shan , Li Wen-Tai , Chern Jyh-Haur , Chen Guang-Wu , Lee Chung-Chi , Lee Yen-Chun , Peng Kuan-Chang , Chao Yu-Sheng 
Published: August 2004

ABSTRACT

Enterovirus 71 is one of the most important pathogens in the family of
Picornaviridae
that can cause severe complications in the postpoliovirus era, such as encephalitis, pulmonary edema, and even death. Pyridyl imidazolidinone is a novel class of potent and selective human enterovirus 71 inhibitor. Pyridyl imidazolidinone was identified by using computer-assisted drug design. This virologic investigation demonstrates that BPR0Z-194, one of the pyridyl imidazolidinones, targets enterovirus 71 capsid protein VP1. Time course experiments revealed that BPR0Z-194 effectively inhibited virus replication in the early stages, implying that the compound can inhibit viral adsorption and/or viral RNA uncoating. BPR0Z-194 was used to select and characterize the drug-resistant viruses. Sequence analysis of the VP1 region showed that the resistant variants differed consistently by seven amino acids in VP1 region from their parental drug-sensitive strains. Site-directed mutagenesis of enterovirus 71 infectious cDNA revealed that a single amino acid alteration at the position 192 of VP1 can confer resistance to the inhibitory effects of BPR0Z-194.
Disposition of Posaconazole following Single-Dose Oral Administration in Healthy Subjects
Authors: Krieter Philip , Flannery Brian , Musick Timothy , Gohdes Mark , Martinho Monika , Courtney Rachel 
Published: August 2004

ABSTRACT

Posaconazole is a potent, broad-spectrum triazole antifungal agent currently in clinical development for the treatment of refractory invasive fungal infections. Eight healthy male subjects received a single 399-mg (81.7 μCi) oral dose of [
14
C]posaconazole after consuming a high-fat breakfast. Urine, feces, and blood samples were collected for up to 336 h postdose and assayed for total radioactivity; plasma and urine samples were also assayed for parent drug. Posaconazole was orally bioavailable, with a median maximum posaconazole concentration in plasma achieved by 10 h postdose. Thereafter, posaconazole was slowly eliminated, with a mean half-life of 20 h. The greatest peak in the radioactivity profile of pooled plasma extracts was due to posaconazole, with smaller peaks due to a monoglucuronide, a diglucuronide, and a smaller fragment of the molecule. The mean total amount of radioactivity recovered was 91.1%; the cumulative excretion of radioactivity in feces and in urine was 76.9 and 14.0% of the dose, respectively. Most of the fecal radioactivity was associated with posaconazole, which accounted for 66.3% of the administered dose; however, urine contained only trace amounts of unchanged posaconazole. The radioactivity profile of pooled urine extracts included two monoglucuronide conjugates and a diglucuronide conjugate of posaconazole. These observations suggest that oxidative (phase 1) metabolism by cytochrome P450 isoforms represents only a minor route of elimination for posaconazole, and therefore cytochrome P450-mediated drug interactions should have a limited potential to impact posaconazole pharmacokinetics.
SRI-286, a Thiosemicarbazole, in Combination with Mefloquine and Moxifloxacin for Treatment of Murine
Mycobacterium avium
Complex Disease
Authors: Bermudez Luiz E. , Kolonoski Peter , Seitz Lianne E. , Petrofsky Mary , Reynolds Robert , Wu Martin , Young Lowell S. 
Published: August 2004

ABSTRACT

Treatment of
Mycobacterium avium
disease remains challenging when macrolide resistance develops. We infected C57 beige mice and treated them with mefloquine, SRI-286, and moxifloxacin. SRI-286 (80 mg/kg) was bactericidal in the liver. Mefloquine plus moxifloxacin or mefloquine plus SRI-286 were better than mefloquine alone.
Emergence of Macrolide-Resistant
Streptococcus pyogenes
Strains in French Children
Authors: Bingen Edouard , Bidet Philippe , Mihaila-Amrouche Liliana , Doit Catherine , Forcet Samuel , Brahimi Naïma , Bouvet Anne , Cohen Robert 
Published: August 2004

ABSTRACT

We studied the antimicrobial susceptibility of 322
Streptococcus pyogenes
throat isolates from French children and their serotype and genomic diversity. A total of 22.4% were erythromycin resistant, and 69.4, 4.2, and 26.4% of these isolates harbored
ermB
,
ermA
, and
mefA
, respectively. Increasing resistance in France is mainly associated with a few
emm
type 28 clones.
An Internationally Spread Clone of
Streptococcus pneumoniae
Evolves from Low-Level to Higher-Level Penicillin Resistance by Uptake of Penicillin-Binding Protein Gene Fragments from Nonencapsulated Pneumococci
Authors: Hauser Christoph , Aebi Suzanne , Mühlemann Kathrin 
Published: August 2004

ABSTRACT

Low-level penicillin resistance in an international
Streptococcus pneumoniae
serotype 19F clone emerging in Switzerland was characterized by mutations in the penicillin-binding protein PBP2x. Some isolates of this clone had evolved to higher resistance levels (penicillin MICs of 0.094 and 1 μg/ml), probably by acquisition of
pbp2x
fragments from local nonencapsulated pneumococci.
T2182C Mutation in 23S rRNA Is Associated with Clarithromycin Resistance in
Helicobacter pylori
Isolates Obtained in Bangladesh
Authors: Khan Rasel , Nahar Shamsun , Sultana Jinath , Ahmad Mian Mashhud , Rahman Motiur 
Published: August 2004

ABSTRACT

Twelve clarithromycin-resistant (MIC, ≥1 μg/ml)
Helicobacter pylori
isolates were analyzed for point mutations in the 23S rRNA gene. Sequence analysis of all of the resistant isolates revealed a T-to-C transition mutation at position 2182. Transformation experiments confirmed that a single T-to-C transition mutation at position 2182 is associated with clarithromycin resistance.
Isolation of an Integron-Borne
bla
VIM-4
Type Metallo-β-Lactamase Gene from a Carbapenem-Resistant
Pseudomonas aeruginosa
Clinical Isolate in Hungary
Authors: Libisch Balázs , Gacs Mária , Csiszár Károly , Muzslay Mónika , Rókusz László , Füzi Miklós 
Published: August 2004

ABSTRACT

The first integron-borne metallo-β-lactamase gene was isolated in Hungary. The
bla
VIM-4
gene is located on a class 1 integron that also carries a novel
bla
OXA
-like gene. The integron is harbored by a serotype O12
Pseudomonas aeruginosa
strain and shows high structural similarity to integrons isolated in Greece and Poland.
Biochemical Characterization of Laboratory Mutants of Extended-Spectrum β-Lactamase TEM-60
Authors: Caporale Bibiana , Franceschini Nicola , Perilli Mariagrazia , Segatore Bernardetta , Rossolini Gian Maria , Amicosante Gianfranco 
Published: August 2004

ABSTRACT
Three mutants of the extended-spectrum β-lactamase TEM-60, the P51L, K104E, and S164R mutants, were constructed by site-directed mutagenesis. The kinetic parameters of the mutated enzymes and interactions of inhibitors were significantly different from those of TEM-60, revealing that the L51P mutation plays an important role in enzyme activity and stability in the TEM-60 background.
Clinical-Use-Associated Decrease in Susceptibility of Vancomycin-Resistant
Enterococcus faecium
to Linezolid: a Comparison with Quinupristin-Dalfopristin
Authors: Raad Issam I. , Hanna Hend A. , Hachem Ray Y. , Dvorak Tanya , Arbuckle Rebecca B. , Chaiban Gassan , Rice Louis B. 
Published: August 2004

ABSTRACT

The susceptibility of 135 vancomycin-resistant
Enterococcus faecium
bacteremic isolates to linezolid and quinupristin-dalfopristin was determined. All were susceptible to linezolid, while 88% were susceptible to quinupristin-dalfopristin prior to the clinical use of the drugs at our hospital. More than 6 months after their clinical use, a decrease in susceptibility was noted for only linezolid at 83%. This was related in part to a single G2576U gene mutation in domain V of the 23S rRNA gene.
A Fusidic Acid-Resistant Epidemic Strain of
Staphylococcus aureus
Carries the
fusB
Determinant, whereas
fusA
Mutations Are Prevalent in Other Resistant Isolates
Authors: O'Neill Alexander J. , Larsen Anders R. , Henriksen Anne S. , Chopra Ian 
Published: August 2004

ABSTRACT

Fusidic acid-resistant epidemic
Staphylococcus aureus
strains causing impetigo bullosa have been reported in Scandinavia. We show that these strains form part of a European epidemic clonotype that carries the
fusB
determinant. In contrast, resistance to fusidic acid in a collection of nonepidemic strains resulted primarily from mutations in
fusA
.
Drug Susceptibility and Genetic Evaluation of
Plasmodium falciparum
Isolates Obtained in Four Distinct Geographical Regions of Kenya
Authors: Mbaisi Abigael , Liyala Pamela , Eyase Fredrick , Achilla Rachel , Akala Hosea , Wangui Julia , Mwangi Josphat , Osuna Finnley , Alam Uzma , Smoak Bonnie L. , Davis Jon M. , Kyle Dennis E. , Coldren Rodney L. , Mason Carl , Waters Norman C. 
Published: August 2004

ABSTRACT

The drug resistance profiles of
Plasmodium falciparum
isolated from four regions in Kenya were analyzed for drug resistance profiles. We observed variability in resistance to a broad range of antimalarial drugs across Kenya as determined from in vitro drug susceptibility screening and genotyping analysis.
Distribution of Amphotericin B-Arabinogalactan Conjugate in Mouse Tissue and Its Therapeutic Efficacy against Murine Aspergillosis
Authors: Falk Rama , Grunwald Jacob , Hoffman Amnon , Domb Abraham J. , Polacheck Itzhack 
Published: August 2004

ABSTRACT
The pharmacokinetic characteristics and tissue distribution of a novel water-soluble, nontoxic amphotericin B-arabinogalactan (AMB-AG) conjugate exhibited distinct differences from those of micellar and liposomal amphotericin B formulations. These differences included extended persistence of drug in the body and its accumulation in the lungs; thus, the AMB-AG conjugate was highly effective in treating systemic murine aspergillosis.
Convenient Biological Assay for Polyethylene Glycol-Interferons in Patients with Hepatitis C
Authors: Boulestin Anne , Kamar Nassim , Legrand-Abravanel Florence , Sandres-Saune Karine , Alric Laurent , Vinel Jean-Pierre , Rostaing Lionel , Izopet Jacques 
Published: August 2004

ABSTRACT
The vesicular stomatitis virus cytopathic effect reduction assay is suitable to quantify polyethylene glycol-alpha interferon 2a (PEG-IFN-α2a) and PEG-IFN-α2b. Human serum and ribavirin did not interfere with the assay. This bioassay was successfully used for assaying PEG-IFN-α2a and PEG-IFN-α2b in serum samples from patients undergoing combination therapy.
Local Genetic Patterns within a Vancomycin-Resistant
Enterococcus faecalis
Clone Isolated in Three Hospitals in Portugal
Authors: Novais Carla , Coque Teresa M. , Sousa João Carlos , Baquero Fernando , Peixe Luisa 
Published: August 2004

ABSTRACT

Eight pulsed-field gel electrophoresis subtypes and six Tn
1546
variants were identified among
Enterococcus faecalis
isolates of a single clone recovered in three geographically separate Portuguese hospitals. Some clonal subtypes were found in particular hospitals, and Tn
1546
variants were either widespread or confined to some of them. We also report on the first Tn
1546
transposon containing an IS
Ef1
insertion.
Colonization with Extraintestinal Pathogenic
Escherichia coli
among Nursing Home Residents and Its Relationship to Fluoroquinolone Resistance
Authors: Maslow Joel N. , Lautenbach Ebbing , Glaze Thomas , Bilker Warren , Johnson James R. 
Published: August 2004

ABSTRACT

In a cross-sectional fecal prevalence survey involving 49 residents of a Veterans Affairs nursing home, 59% of subjects were colonized with extraintestinal pathogenic
Escherichia coli
(ExPEC), 22% were colonized with adhesin-positive
E. coli
, and 51% were colonized with fluoroquinolone-resistant
E. coli
. Among 80 unique isolates, adhesins correlated negatively and aerobactin correlated positively with fluoroquinolone resistance.
National Surveillance of Methicillin-Resistant
Staphylococcus aureus
in Belgian Hospitals Indicates Rapid Diversification of Epidemic Clones
Authors: Denis Olivier , Deplano Ariane , Nonhoff Claire , De Ryck Raf , de Mendonça Ricardo , Rottiers Sylvianne , Vanhoof Raymond , Struelens Marc J. 
Published: August 2004

ABSTRACT

Methicillin-resistant
Staphylococcus aureus
(MRSA) strains (
n
= 455) collected in 2001 from 100 Belgian hospitals were characterized by molecular typing and by resistance gene distribution to macrolides-lincosamides-streptogramins and to aminoglycoside antibiotics. Rapid diversification of MRSA clones, compared with results of previous surveys, was evidenced by the broad geographic distribution of seven major clones belonging to the pandemic MRSA clonal complexes 5, 8, 22, 30, and 45 by multilocus sequence typing.
Designing Fluoroquinolone Breakpoints for
Streptococcus pneumoniae
by Using Genetics instead of Pharmacokinetics-Pharmacodynamics
Authors: Smith H. J. , Noreddin A. M. , Siemens C. G. , Schurek K. N. , Greisman J. , Hoban C. J. , Hoban D. J. , Zhanel G. G. 
Published: August 2004

ABSTRACT

We determined fluoroquinolone microbiological resistance breakpoints for
Streptococcus pneumoniae
by using genetic instead of pharmacokinetic-pharmacodynamic parameters. The proposed microbiological breakpoints define resistance as the MIC at which >50% of the isolates carry quinolone resistance-determining region mutations and/or, if data are available, when Monte Carlo simulations demonstrate a <90% chance of bacteriological eradication. The proposed microbiological resistant breakpoints are as follows (in micrograms per milliliter): gatifloxacin, >0.25; gemifloxacin, >0.03; levofloxacin, >1; and moxifloxacin, >0.12. Monte Carlo simulations of the once daily 400-mg doses of gatifloxacin and 750-mg doses levofloxacin demonstrated a high level of target attainment (free-drug area under the concentration-time curve from 0 to 24 h/MIC ratio of 30) by using these new genetically derived breakpoints.
Invasive
Streptococcus pneumoniae
in France: Antimicrobial Resistance, Serotype, and Molecular Epidemiology Findings from a Monthly National Study in 2000 to 2002
Authors: Decousser Jean-Winoc , Pina Patrick , Viguier Florent , Picot Franc , Courvalin Patrice , Allouch Pierre 
Published: August 2004

ABSTRACT
A study of 257 French invasive pneumococci isolated between 2000 and 2002 showed high rates of nonsusceptibility to penicillin and macrolides (50%), contrasting with a low frequency of resistance to amoxicillin or levofloxacin (<1%) and tolerance to vancomycin (0%). The genetic homogeneity of some serogroups, including serogroup 1, enhanced the risk of epidemiological changes.
COLLECTIVE AND RELATIVE VARIABLES FOR MASSLESS FIELDS
Authors: ASSENZA L. , LONGHI G. 
Published: August 2004

In this paper, a set of canonical collective and relative variables for a classical relativistic massless field are defined and discussed. The discussion is based on a harmonic analysis on the light-cone in momentum space. It is shown how to avoid a set of consistency constraints which are necessary in the massive case. As a result a canonical separation of the angular momentum in collective and relative parts and a canonical realization of an extended BMS algebra are obtained.
STUDY OF THE LOCAL TRANSPORT AND STRUCTURAL PROPERTIES OF MULTIFILAMENTARY Ag-SHEATHED Bi(2223) TAPES
Authors: STRANO G. , GUASCONI P. , MALAGOLI A. , BELLINGERI E. , SIRI A. S. , GRASSO G. 
Published: August 2004

It is known that the current flow in high quality Ag-heathed (Bi,Pb) 2 Sr 2 CaCu 3 O 10+x tapes shows a clear inhomogeneous behavior, as demonstrated by earlier magneto-optical experiments. In order to study this effect in detail we have extracted single filaments from a multifilamentary Ag-sheathed Bi(2223) tape, prepared by the Oxide-Powder-In-Tube technique. The filaments have been isolated by chemical etching of the silver matrix, and individually characterised according to their position inside the conductor. Different series of measurements have been performed on each filament: magnetisation hysteresis loops and zero field cooled DC susceptibility by SQUID magnetometry, electrical resistivity by the four-probe method, Bi(2223) phase purity and texture by XRD analysis, and local stoichiometry by SEM/EDX analysis. The microstructure analysis, in particular the study of the c-axis parameter and the microprobe analysis have revealed a higher Pb content (matching the starting stoichiometry) in the innermost filament. In addition to this result. It has been found by magnetisation measurements that the innermost filament carries a critical current density of 53 kA/cm 2 (at 77 K), i.e. a factor of two larger than for all the filaments of the outer shell (with j c ranging between 25 and 40 kA/cm 2). This result is in quantitative agreement with the room temperature electrical resistivity measurements performed on the same samples.
Synthesis of Li/Al layered double hydroxide-guest composites under mild acid conditions
Authors: Yang Deng-Shiu , Wang Ming-Kuang , Wang Shan-Li 
Published: August 2004

AbstractLayered double hydroxides (LDHs) are known as ‘anionic clays’. They comprise a class of material with positively charged octahedral double hydroxyl layers and exchangeable anions. The Li/Al LDH term includes a group of LDHs with Li/Al octahedral double hydroxyl layers. We have demonstrated a modifed method, using Li/Al LDH-OH (OH− as interlayer anions) as the starting material, for preparing Li/Al LDH-X (X represents interlayer anions, including dioctyl sulphosuccinate (DOSS), dodecyl sulphate (DDS), mercaptoacetate (MA), EDTA, Tiron and dichromate) under mild acid conditions (pH in the range 4 to 5). However, in the case of acidsensitive anions, Fe(CN)64−, Li/Al LDH-Fe(CN)64− can be prepared by a two-step procedure using Li/Al LDH-DOSS or similar compounds as intermediates to react with acid-sensitive anions under mild alkaline conditions (pH ≈ 9).