bluuebunny/crossref_metadata_2025_split huggingface dataset:
Penciclovir Susceptibilities of Herpes Simplex Virus Isolates from Patients Using Penciclovir Cream for Treatment of Recurrent Herpes Labialis
Authors: Sarisky Robert T. , Bacon Teresa , Boon Ron , Locke Leslie , Nguyen Tammy T. , Leary Jeffry , Esser Klaus , Saltzman Robin 
Published: October 2002

ABSTRACT

The antiherpesvirus agent penciclovir (PCV) shares an identical activation pathway and a similar mode of action with acyclovir (ACV). However, since PCV represents a relatively recent treatment option, the clinical resistance profile to PCV is less well known. A susceptibility program was established to assess the resistance profile for serial herpes simplex virus isolates from immunocompetent patients with recurrent herpes labialis obtained throughout a 4-day period of treatment with topical PCV (1% cream) or a placebo. Two isolates (2 of 1,035 [0.19%]), representing 0.34% of the patients (2 of 585), were confirmed to be PCV-resistant (Pcv
r
) herpes simplex virus type 1 by a plaque reduction assay in MRC-5 cells. These two viruses were highly resistant to PCV (50% inhibitory concentrations [IC
50
s], >55 μg/ml) and were isolated less than 17 h after the start of patient-initiated treatment. However, subsequent isolates on days 2 and 3 from these patients were completely susceptible to PCV (IC
50
s, <2.0 μg/ml). Thus, it is not clear whether the resistance to PCV for these two early-treatment isolates was directly associated with the 17 h of PCV treatment; several possible explanations are discussed. In an analysis of the distribution of IC
50
differences between the first and last isolates, there were three patients with minor IC
50
increases in the PCV-treated population and one in the placebo-treated group, although statistically, only the latter was an outlier. No patients were found to have Pcv
r
virus at the end of acute treatment, regardless of treatment group. Overall, the prevalence of Pcv
r
was found to be similar to the 0.3% Acv
r
reported for immunocompetent, untreated populations.
Comparative Study of Mechanisms of Herpes Simplex Virus Inactivation by Sodium Lauryl Sulfate and
n
-Lauroylsarcosine
Authors: Piret Jocelyne , Roy Sylvie , Gagnon Mylène , Landry Sébastien , Désormeaux André , Omar Rabeea F. , Bergeron Michel G. 
Published: October 2002

ABSTRACT

The mechanisms of herpes simplex virus (HSV) inactivation by sodium lauryl sulfate (SLS) and
n
-lauroylsarcosine (LS), two anionic surfactants with protein denaturant potency, have been evaluated in cultured cells. Results showed that pretreatment of HSV type 1 (HSV-1) strain F and HSV-2 strain 333 with either surfactant inhibited, in a concentration- and time-dependent manner, their infectivities on Vero cells. SLS was a more potent inhibitor of HSV-2 strain 333 infectivity than LS with respect to the concentration (4.8-fold lower) and time (2.4-fold shorter) required to completely inactivate the virus. No inhibition of both herpesvirus strains infectivities was observed when Vero cells were pretreated with either surfactant. LS prevented the binding of HSV-2 strain 333 to cells without affecting the stable attachment and the rate of penetration into cells, whereas SLS exerted the opposite effect. Both SLS and LS inhibited, in a concentration-dependent manner, the HSV-2 strain 333-induced cytopathic effect, probably by affecting newly synthesized virions that come into contact with surfactant molecules present in culture medium. The pretreatment of HSV-2 strain 333 with specific combinations of SLS and LS concentrations inhibited the viral infectivity in a synergistic manner and resulted in only a small increase in their toxicities for exponentially growing Vero cells compared with that caused by each compound alone. Taken together, these results suggest that SLS and LS, alone or combined, could represent potent candidates as microbicides in topical vaginal formulations to prevent the transmission of herpes and possibly other pathogens that cause sexually transmitted diseases, including human immunodeficiency virus type 1.
Phase I Dose Escalation Trial Evaluating the Pharmacokinetics, Anti-Human Cytomegalovirus (HCMV) Activity, and Safety of 1263W94 in Human Immunodeficiency Virus-Infected Men with Asymptomatic HCMV Shedding
Authors: Lalezari Jacob P. , Aberg Judith A. , Wang Laurene H. , Wire Mary Beth , Miner Richard , Snowden Wendy , Talarico Christine L. , Shaw Shuching , Jacobson Mark A. , Drew W. Lawrence 
Published: October 2002

ABSTRACT

1263W94 [maribavir; 5,6-dichloro-2-(isopropylamino)-1,β-
l
-ribofuranosyl-1-H-benzimidazole] is a novel benzimidazole compound for treatment of human cytomegalovirus (HCMV) infection and disease, with potent in vitro activity against HCMV and good oral bioavailability. A phase I study was conducted to determine the pharmacokinetics (PK), anti-HCMV activity, and safety of 1263W94 administered as multiple oral doses to human immunodeficiency virus type 1-infected adult male subjects with asymptomatic HCMV shedding. Subjects received one of six dosage regimens (100, 200, or 400 mg three times a day, or 600, 900, or 1,200 mg twice a day) or a placebo for 28 days. 1263W94 demonstrated linear PK, with steady-state plasma 1263W94 profiles predictable based on single-dose data. 1263W94 was rapidly absorbed following oral dosing, and values for the maximum concentration of the drug in plasma and the area under the concentration-time curve increased in proportion to the dose. 1263W94 demonstrated in vivo anti-HCMV activity in semen at all of the dosage regimens tested, with mean reductions in semen HCMV titers of 2.9 to 3.7 log
10
PFU/ml among the four regimens evaluated for anti-HCMV activity. 1263W94 was generally well tolerated; taste disturbance was the most frequently reported adverse event over the 28-day dosing period.
Pharmacodynamic Assessment of Ertapenem (MK-0826) against
Streptococcus
pneumoniae
in a Murine Neutropenic Thigh Infection Model
Authors: Xuan Dawei , Banevicius Maryanne , Capitano Blair , Kim Myo-Kyoung , Nightingale Charles , Nicolau David 
Published: October 2002

ABSTRACT

The objective of this study was to determine the susceptibility breakpoint of a new carbapenem, ertapenem (MK-0826), against
Streptococcus pneumoniae
strains based on bacterial density and survival studies in a murine thigh infection model. Sixteen
S. pneumoniae
isolates for which MICs ranged from 0.015 to 4.0 mg/liter were tested with neutropenic ICR mice. Animals were infected with bacteria at 10
5
to 10
6
CFU per thigh and were treated with ertapenem starting at 2 h postinfection for 4 days. Ertapenem was given subcutaneously at 50 mg/kg of body weight every 6 h, which simulates the human pharmacodynamic profile (in particular, the duration of time that the concentration of free drug remains above the MIC of 2 mg/liter). At 0 and 24 h postinfection, thighs were harvested for bacterial density determination. Survival was assessed during 4 days of therapy and 3 days after the therapy. A protein binding study was conducted with mice by use of the ultrafiltration method. Protein binding in mice was approximately 95%, which is comparable to that in humans. The average change in bacterial density ranged from −0.22 to −4.4 log CFU per thigh over 24 h compared to 0-h controls. The extent of microbial eradication was dependent on the MIC for the
S. pneumoniae
isolate. Substantial bactericidal activities (i.e., killing of approximately 2 log CFU per thigh) were consistently observed against isolates for which MICs were ≤2 mg/liter, which also resulted in nearly 100% survival during the 4 days of drug dosing and 3 days after the therapy. Less-pronounced and highly variable bactericidal activities were detected against isolates for which the MIC was 4 mg/liter. Substantial enhancement in bactericidal activity was observed for CBA/J mice and is attributed to the contribution of the host defenses in the immunocompetent species. Assessment of the effectiveness of ertapenem by bacterial-density reduction over 24 h and by survival over 4 days of therapy in the murine thigh infection model reveals that the drug maintains maximal efficacy against
S. pneumoniae
isolates for which the MIC of this agent is ≤2 mg/liter.
Pharmacokinetic and Pharmacodynamic Profiles of Danofloxacin Administered by Two Dosing Regimens in Calves Infected withMannheimia(Pasteurella)haemolytica
Authors: Sarasola Patxi , Lees Peter , AliAbadi Fariborz Shojaee , McKellar Quintin A. , Donachie William , Marr Kate A. , Sunderland Simon J. , Rowan Tim G. 
Published: October 2002

ABSTRACTThe pharmacokinetics and pharmacodynamics of danofloxacin in calves with inducedMannheimia(Pasteurella)haemolyticapneumonia were evaluated. Calves received either saline as an intravenous (IV) bolus or danofloxacin (0.738 mg/kg of body weight) administered as either a single IV bolus or a 36-h continuous IV infusion. Blood samples and bronchial secretions were collected before and at predetermined times over 48 h following the start of treatment. Calves were assessed clinically throughout, and lung consolidation was assessed at necropsy. Bronchial secretions and lung tissue were cultured forM. haemolytica. Bolus administration of danofloxacin produced a high maximum drug concentration-to-MIC ratio (Cmax:MIC) of 14.5 and a time period of 9.1 h when plasma danofloxacin concentrations exceeded the MIC (T>MIC). Following danofloxacin infusion, theCmax:MIC was low (2.3), with a longT>MIC (33.3 h). The area under the curve-to-MIC ratios were 43.3 and 49.1 for the bolus and infusion administrations, respectively. The single bolus of danofloxacin was more effective than the same dose administered by continuous infusion, as indicated by a significantly lower (P< 0.05) number of animals withM. haemolyticain bronchial secretions after treatment and lower rectal temperatures in the 24 h after the start of treatment. Thus, danofloxacin exhibited concentration-dependent antimicrobial activity in cattle with respiratory disease caused byM. haemolytica.
β-Lactamases of
Kluyvera ascorbata
, Probable Progenitors of Some Plasmid-Encoded CTX-M Types
Authors: Humeniuk Christel , Arlet Guillaume , Gautier Valerie , Grimont Patrick , Labia Roger , Philippon Alain 
Published: October 2002

ABSTRACT

Kluyvera ascorbata
produces a β-lactamase that results in an atypical susceptibility pattern, including low-level resistance to penicillins, cephalothin, and cefuroxime, but this resistance is reversed by clavulanate. Ten nucleotide sequences of the corresponding gene,
bla
KLUA
, were obtained and were found to have minor variations (96 to 100%). Otherwise,
bla
KLUA
was found to be similar (95 to 100%) to some plasmid-encoded CTX-M-type β-lactamases. Finally, mobilization of
bla
KLUA
on a plasmid was found to be mediated probably by a genetic mobile element like IS
Ecp1
.
Antibiotic Susceptibilities of
Parachlamydia acanthamoeba
in Amoebae
Authors: Maurin M. , Bryskier A. , Raoult D. 
Published: October 2002

ABSTRACT

Parachlamydia acanthamoeba
are intracellular bacteria of amoebae and are considered potential etiological agents of human pneumonia. We have determined the in vitro antibiotic susceptibilities of two strains (strain Bn
9
and Hall's coccus) in
Acanthamoeba polyphaga
. The two strains were susceptible to tetracyclines, macrolides, and rifampin, but resistant to fluoroquinolones.
Evaluation of the Genetic Structure of
Xylella fastidiosa
Populations from Different
Citrus sinensis
Varieties
Authors: Della Coletta-Filho Helvécio , Machado Marcos Antonio 
Published: October 2002

ABSTRACT

Xylella fastidiosa
was isolated from sweet orange plants (
Citrus sinensis
) grown in two orchards in the northwest region of the Brazilian state of São Paulo. One orchard was part of a germ plasm field plot used for studies of citrus variegated chlorosis resistance, while the other was an orchard of
C. sinensis
cv. Pêra clones. These two collections of strains were genotypically characterized by using random amplified polymorphic DNA (RAPD) and variable number of tandem repeat (VNTR) markers. The genetic diversity (

H
T

) values of
X. fastidiosa
were similar for both sets of strains; however,

H
T

RAPD
values were substantially lower than

H
T

VNTR
values. The analysis of six strains per plant allowed us to identify up to three RAPD and five VNTR multilocus haplotypes colonizing one plant. Molecular analysis of variance was used to determine the extent to which population structure explained the genetic variation observed. The genetic variation observed in the
X. fastidiosa
strains was not related to or dependent on the different sweet orange varieties from which they had been obtained. A significant amount of the observed genetic variation could be explained by the variation between strains from different plants within the orchards and by the variation between strains within each plant. It appears, therefore, that the existence of different sweet orange varieties does not play a role in the population structure of
X. fastidiosa
. The consequences of these results for the management of sweet orange breeding strategies for citrus variegate chlorosis resistance are also discussed.
Culture-Based and Non-Growth-Dependent Detection of the
Burkholderia cepacia
Complex in Soil Environments
Authors: Miller Suzanne C. M. , LiPuma John J. , Parke Jennifer L. 
Published: October 2002

ABSTRACT

Burkholderia cepacia
complex (Bcc) bacteria reside in soil, plant rhizospheres, and water, but their prevalence and distribution in outdoor environments is not clear. We sampled a variety of soil and rhizosphere environments with which people may have contact: playgrounds, athletic fields, parks, hiking trails, residential yards, and gardens. A total of 91 sites was sampled in three large U.S. cities. In the first phase of the study, putative Bcc isolates were recovered on
Burkholderia cepacia
selective agar and trypan blue tetracycline medium and subsequently examined for biochemical reactivity and growth at 32 and 22°C. Isolates were further examined by PCR assays targeting Bcc-specific ribosomal DNA and
recA
gene sequences. Among the 1,013 bacterial isolates examined, 68 were identified as Bcc; 14 (15%) of 91 sampled sites yielded Bcc isolates. In the second phase, DNA was extracted directly from soil samples and examined with PCR assays targeting Bcc 16S rRNA gene sequences. Either 82 or 93% of the soil samples were positive for at least one Bcc genomovar, depending on the PCR assay system used. Cloning and sequencing were performed to check the specificity of the PCR assays. Sequence analysis of the 463-bp 16S rRNA inserts from eight clones indicated that all were from members of the Bcc. The four soil samples from which these clones were generated did not yield isolates identified as Bcc. Based on PCR detection, Bcc appears to be prevalent in soil from urban and suburban environments. Culture-based recovery of Bcc may underestimate environmental populations.
The
pepR
Gene of
Lactobacillus sakei
Is Positively Regulated by Anaerobiosis at the Transcriptional Level
Authors: Champomier-Vergès Marie-Christine , Marceau Anika , Méra Thérèse , Zagorec Monique 
Published: October 2002

ABSTRACT

Lactobacillus sakei
is a lactic acid bacterium belonging to the natural flora of meat products. It constitutes the main flora of vacuum-packed meat and is largely used in western Europe as a starter for the manufacturing of fermented sausages. This species is able to grow both under aerobiosis and anaerobiosis. In many technological processes involving it, oxygen is scarce. The aim of this study was to identify the major proteins affected by growth under anaerobiosis. Using two-dimensional electrophoresis, we showed that one spot was 10-fold overexpressed when cells were grown under anaerobiosis. By N-terminal sequencing it was identified as a peptidase (PepR), and the
pepR
gene was cloned. Northern analysis revealed that
pepR
was expressed as a single 1.27-kb transcript induced under anaerobiosis. A mutant was constructed by single crossover in the
pepR
gene, and its growth and survival were not affected by anaerobiosis.
Genes Encoding the
N
-Acyl Homoserine Lactone-Degrading Enzyme Are Widespread in Many Subspecies of
Bacillus thuringiensis
Authors: Lee Sang Jun , Park Sun-Yang , Lee Jung-Ju , Yum Do-Young , Koo Bon-Tag , Lee Jung-Kee 
Published: October 2002

ABSTRACT

Gram-negative bacteria can communicate with each other by
N
-acyl homoserine lactones (AHLs), which are quorum-sensing autoinducers. Recently, the
aiiA
gene (encoding an enzyme catalyzing the degradation of AHL) has been cloned from
Bacillus
sp. strain 240B1. During investigations in the course of the ongoing
Bacillus thuringiensis
subsp.
morrisoni
genome project, an
aiiA
homologue gene in the genome sequence was found. These results led to consideration of the possibility of the widespread existence of the gene in
B. thuringiensis. aiiA
homologue genes were found in 16 subspecies of
B. thuringiensis
, and their sequences were determined. Comparison of the
Bacillus
sp. strain 240B1
aiiA
gene with the
B. thuringiensis aiiA
homologue genes showed high homologies of 89 to 95% and 90 to 96% in the nucleotide sequence and deduced amino acid sequence, respectively. Among the subspecies of
B. thuringiensis
having an
aiiA
gene, the subspecies
aizawai
,
galleriae
,
kurstaki
,
kyushuensis
,
ostriniae
, and
subtoxicus
were shown to degrade AHL. It was observed that recombinant
Escherichia coli
producing AiiA proteins also had AHL-degrading activity and could also attenuate the plant pathogenicity of
Erwinia carotovora
. These results indicate that insecticidal
B. thuringiensis
strains might have potential to compete with gram-negative bacteria in natural ecosystems by autoinducer-degrading activity.
Characterization of Virus Adsorption by Using DEAE-Sepharose and Octyl-Sepharose
Authors: Shields Patricia A. , Farrah Samuel R. 
Published: October 2002

ABSTRACT
Viruses were characterized by their adsorption to DEAE-Sepharose or by their elution from octyl-Sepharose by using buffered solutions of sodium chloride with different ionic strengths. Viruses whose adsorption to DEAE-Sepharose was reduced most rapidly by an increase in the sodium chloride concentration were considered to have the weakest electrostatic interactions with the solids; these viruses included MS2, E1, and φX174. Viruses whose adsorption to DEAE-Sepharose was reduced least rapidly were considered to have the strongest electrostatic interactions with the column; these viruses included P1, T4, T2, and E5. All of the viruses studied adsorbed to octyl-Sepharose in the presence of 4 M NaCl. Viruses that were eluted most rapidly following a decrease in the concentration of NaCl were considered to have the weakest hydrophobic interactions with the column; these viruses included φX174, CB4, and E1. Viruses that were eluted least rapidly from the columns after the NaCl concentration was decreased were considered to have the strongest hydrophobic interactions with the column; these viruses included f2, MS2, and E5.
The Diversity of
Phaseolus
-Nodulating Rhizobial Populations Is Altered by Liming of Acid Soils Planted with
Phaseolus vulgaris
L. in Brazil
Authors: Andrade D. S. , Murphy P. J. , Giller K. E. 
Published: October 2002

ABSTRACT

PCR-mediated restriction fragment length polymorphism (RFLP) analysis of the 16S-23S rRNA internally transcribed spacer (ITS) region and the 16S rRNA gene indicated that the rhizobial populations isolated from common bean (
Phaseolus vulgaris
L.) nodules in the unlimed soil from a series of five lime rates applied 6 years previously to plots of an acidic oxisol had less diversity than those from plots with higher rates of liming. Isolates affiliated with
Rhizobium tropici
IIB and
Rhizobium leguminosarum
bv. phaseoli were predominant independent of lime application. An index of richness based on the number of ITS groups increased from 2.2 to 5.7 along the soil liming gradient, and the richness index based on “species” types determined by RFLP analysis of the 16S rRNA gene varied from 0.5 to 1.4. The Shannon index of diversity, based on the number of ITS groups, increased from 1.8 in unlimed soil to 2.8 in limed soil, and, based on RFLP analysis of the 16S rRNA gene, ranged from 0.9 to 1.4. In the limed soil, the subpopulation of
R. tropici
IIB pattern types contained the largest number of ITS groups. In contrast, there were more
R. leguminosarum
bv. phaseoli types in the unlimed soil with the lowest pH than in soils with the highest pH. The number of ITS (“strain”) groups within
R. leguminosarum
bv. phaseoli did not change with increased abundance of rhizobia in the soil, while with
R. tropici
IIB, the number of strain groups increased significantly. Some cultural and biochemical characteristics of
Phaseolus
-nodulating isolates were significantly related to changes in soil properties caused by liming, largely due to changes in the predominance of the rhizobial species groups.
Different Responses of Pyoverdine Genes to Autoinduction in
Pseudomonas aeruginosa
and the Group
Pseudomonas fluorescens-Pseudomonas putida
Authors: Ambrosi Cecilia , Leoni Livia , Visca Paolo 
Published: October 2002

ABSTRACT

We investigated the regulation of the
psbA
and
pvdA
pyoverdine biosynthesis genes, which encode the
l
-ornithine
N
5
-oxygenase homologues in
Pseudomonas
strain B10 and
Pseudomonas aeruginosa
PAO1, respectively. We demonstrate that pyoverdine
B10
, as the end product of its biosynthetic pathway, is a key participant of the control circuit regulating its own production in
Pseudomonas
strain B10. In
P. aeruginosa
PAO1, however, pyoverdine
PAO1
has no apparent role in the positive regulation of the
pvdA
gene.
Susceptibility of Interleukin-2-Deficient Mice toToxoplasma gondiiIs Associated with a Defect in the Production of Gamma Interferon
Authors: Villegas Eric N. , Lieberman Linda A. , Carding Simon R. , Hunter Christopher A. 
Published: October 2002

ABSTRACTCostimulation through the B7-CD28 interaction is an important second signal for T-cell activation, and previous studies have shown that CD28−/−mice infected withToxoplasma gondiigenerate suboptimal CD4+T-cell responses, associated with a defect in production of the T-cell growth factor interleukin-2 (IL-2). To address the role of IL-2 in the expansion of T cells during toxoplasmosis, IL-2−/−mice were infected withT. gondiiand their ability to generate a protective T-cell response was assessed. Although IL-2−/−mice produced normal levels of IL-12p40, they had reduced levels of gamma interferon (IFN-γ) in serum, had an increased parasite burden, and succumbed to infection withT. gondiiwithin 20 days. Fluorescence-activated cell sorter analysis revealed that, although uninfected IL-2−/−mice had an increased number of activated T cells compared with uninfected IL-2+/+mice, following infection they were unable to further upregulate this population. Examination of the ability of splenocytes from uninfected and infected mice to produce IFN-γ revealed that IL-2−/−mice were hyporesponsive to stimulation with anti-CD3 or parasite antigen compared with wild-type mice, and the addition of IL-2 alone or in combination with IL-12 or stimulation with phorbol myristate acetate and ionomycin did not restore the production of IFN-γ. Together, these studies reveal that IL-2−/−mice are unable to generate a protective IFN-γ response following infection withT. gondiiand suggest that IL-2−/−mice have an intrinsic defect in their ability to activate and expand IFN-γ-producing T cells required for resistance toT. gondii.