bluuebunny/crossref_metadata_2025_split huggingface dataset:
Equilibrium denaturation studies of the Escherichia coli factor for inversion stimulation: Implications for in vivo function
Authors: Hobart Sarah A. , Ilin Sergey , Moriarty Daniel F. , Osuna Robert , Colón Wilfredo 
Published: July 2002

AbstractThe Factor for Inversion Stimulation (FIS) is a dimeric DNA binding protein found in enteric bacteria that is involved in various cellular processes, including stimulation of certain specialized DNA recombination events and transcription regulation of a large number of genes. The intracellular FIS concentration, when cells are grown in rich media, varies dramatically during the early logarithmic growth phase. Its broad range of concentrations could potentially affect the nature of its quaternary structure, which in turn, could affect its ability to function in vivo. Thus, we examined the stability of FIS homodimers under a wide range of concentrations relevant to in vivo expression levels. Its urea‐induced equilibrium denaturation was monitored by far‐ and near‐UV circular dichroism (CD), tyrosine fluorescence, and tyrosine fluorescence anisotropy. The denaturation transitions obtained were concentration‐dependent and showed similar midpoints (Cm) and m values, suggesting a two‐state denaturation process involving the native dimer and unfolded monomers (N2 ↔ 2U). The ΔG for the unfolding of FIS determined from global and individual curve fitting was 14.2 kcal/mole. At concentrations <9 μM, the FIS dimer began to dissociate, as noted by the change in CD signal and size‐exclusion high‐pressure liquid chromatography retention times and peak width. The estimated dimer dissociation constant based on the CD and size‐exclusion chromatography data is in the micromolar range, resulting in a ΔG of at least 5 kcal/mole less than that calculated from the urea denaturation data. This discrepancy suggests a deviation from a two‐state denaturation model, perhaps due to a marginally stable monomeric intermediate. These observations have implications for the stability and function of FIS in vivo.
Subcritical Rossby Waves in Zonal Shear Flows with Nonlinear Critical Layers
Authors: Maslowe S. A. , Clarke S. R. 
Published: July 2002

It was shown by Benney and Bergeron [1] that singular neutral modes with nonlinear critical layers are mathematically possible in a variety of shear flows. These are usually subcritical modes; i.e., they occur at values of the flow parameters where their linear, viscous counterparts would be damped. One question raised then is how such modes might be generated.This article treats the problem of Rossby waves propagating in a mixing layer with velocity profile ū = tanh y. The beta parameter, which is a measure of the stabilizing Coriolis force, is taken to be large enough so that linear instability cannot occur. First, computed dispersion curves are presented for singular modes with nonlinear critical layers. Then, full numerical simulations are employed to illustrate how these modes can be generated by resonant interaction with conventional nonsingular Rossby waves, even when the singular mode is absent initially.
Deciphering the Cross-Talk of Implantation: Advances and Challenges
Authors: Paria B. C. , Reese Jeff , Das Sanjoy K. , Dey S. K. 
Published: July 2002

Implantation involves a series of steps leading to an effective reciprocal signaling between the blastocyst and the uterus. Except for a restricted period when ovarian hormones induce a uterine receptive phase, the uterus is an unfavorable environment for blastocyst implantation. Because species-specific variations in implantation strategies exist, these differences preclude the formulation of a unifying theme for the molecular basis of this event. However, an increased understanding of mammalian implantation has been gained through the use of the mouse model. This review summarizes recognized signaling cascades and new research in mammalian implantation, based primarily on available genetic and molecular evidence from implantation studies in the mouse. Although the identification of new molecules associated with implantation in various species provides valuable insight, important questions remain regarding the common molecular mechanisms that govern this process. Understanding the mechanisms of implantation promises to help alleviate infertility, enhance fetal health, and improve contraceptive design.
The success of any species depends on its reproductive efficiency. For sexual reproduction, an egg and sperm must overcome many obstacles to fuse and co-mingle their genetic material at fertilization. The zygote develops into a blastocyst with two cell lineages (the inner cell mass and the trophectoderm), migrates within the reproductive tract, and ultimately implants into a transiently permissive host tissue, the uterus. However, the molecular basis of the road map connecting the blastocyst with the endometrium across species is diverse (1) and not fully understood. Recent advances have identified numerous molecules involved in implantation (1–4), yet new discoveries have not yielded a unifying scheme for the mechanisms of implantation.
Diversity of β-Lactam Resistance-Conferring Amino Acid Substitutions in Penicillin-Binding Protein 3 of
Haemophilus influenzae
Authors: Dabernat Henri , Delmas Catherine , Seguy Martine , Pelissier Roseline , Faucon Genevieve , Bennamani Safia , Pasquier Christophe 
Published: July 2002

ABSTRACT

The sequences of the
ftsI
gene, encoding the transpeptidase domain of penicillin binding protein (PBP) 3A and/or PBP 3B, which are involved in septal peptidoglycan synthesis, were determined for 108 clinical strains of
Haemophilus influenzae
with reduced susceptibility to β-lactam antibiotics with or without β-lactamase production and were compared to those of the ampicillin-susceptible Rd strain and ampicillin-susceptible clinical isolates. The sequences have 18 different mutation patterns and were classified into two groups on the basis of amino acid substitutions deduced from the nucleotide sequences located between bp 960 and 1618 of the
ftsI
gene. In group I strains (
n
= 7), His-517 was substituted for Arg-517. In group II strains (
n
= 101), Lys-526 was substituted for Asn-526. In subgroup IIa (
n
= 5;
H. influenzae
ATCC 49247), the only observed substitution was Lys-526 for Asn-526; in subgroup IIb (
n
= 56), Val-502 was substituted for Ala-502 (
n
= 13), along with several other substitutions: Asn-350 for Asp-350 (
n
= 15), Asn-350 for Asp-350 and Glu-490 for Gly-490 (
n
= 14), and Asn-350 for Asp-350 and Ser-437 for Ala-437 (
n
= 5). In subgroup IIc (
n
= 25), Thr-502 was substituted for Ala-502. In subgroup IId, Val-449 was substituted for Ile-449 (
n
= 15). The MICs of β-lactam antibiotics for the 108 strains were to 8 to 16 times the MICs for susceptible strains. The strains, isolated from both adults and children, were analyzed for genetic relationship by pulsed-field gel electrophoresis and by determination of
ftsI
sequence phylogeny. Both analyses revealed the lack of clonality and the heterogeneity of the strains, but some clusters suggest the spread and/or persistence of a limited number of strains of the same pulsotype and pattern of amino acid substitutions. Reduced susceptibility to β-lactam, brought about by mutations of the
ftsI
gene, is becoming a frequent phenomenon, affecting both strains that produce β-lactamase and those that do not. The level of resistance remains low but opens the way to greater resistance in the future.
Alterations in Penicillin-Binding Protein 1A Confer Resistance to β-Lactam Antibiotics in
Helicobacter pylori
Authors: Gerrits M. M. , Schuijffel D. , van Zwet A. A. , Kuipers E. J. , Vandenbroucke-Grauls C. M. J. E. , Kusters J. G. 
Published: July 2002

ABSTRACT

Most
Helicobacter pylori
strains are susceptible to amoxicillin, an important component of combination therapies for
H. pylori
eradication. The isolation and initial characterization of the first reported stable amoxicillin-resistant clinical
H. pylori
isolate (the Hardenberg strain) have been published previously, but the underlying resistance mechanism was not described. Here we present evidence that the β-lactam resistance of the Hardenberg strain results from a single amino acid substitution in HP0597, a penicillin-binding protein 1A (PBP1A) homolog of
Escherichia coli
. Replacement of the wild-type HP0597 (
pbp1A
) gene of the amoxicillin-sensitive (Amx
s
)
H. pylori
strain 1061 by the Hardenberg
pbp1A
gene resulted in a 100-fold increase in the MIC of amoxicillin. Sequence analysis of
pbp1A
of the Hardenberg strain, the Amx
s
H. pylori
strain 1061, and four amoxicillin-resistant (Amx
r
) 1061 transformants revealed a few amino acid substitutions, of which only a single Ser
414
→Arg substitution was involved in amoxicillin resistance. Although we cannot exclude that mutations in other genes are required for high-level amoxicillin resistance of the Hardenberg strain, this amino acid substitution in PBP1A resulted in an increased MIC of amoxicillin that was almost identical to that for the original Hardenberg strain.
Pressure of Zidovudine Accelerates the Reversion of Lamivudine Resistance-Conferring M184V Mutation in the Reverse Transcriptase of Human Immunodeficiency Virus Type 1
Authors: Diallo Karidia , Oliveira Maureen , Moisi Daniela , Brenner Bluma , Wainberg Mark A. , Götte Matthias 
Published: July 2002

ABSTRACTWe cultured lamivudine-resistant human immunodeficiency virus type 1 (HIV-1) variants over an extended period of time in the presence of zidovudine and observed a premature reversion of the resistance-conferring M184V mutation. These data suggest that the presence of ZDV amplifies differences in replication capacity between wild-type HIV-1 and the mutant variant.
Antibiotic Susceptibilities of 96 Isolates of
Bacillus anthracis
Isolated in France between 1994 and 2000
Authors: Cavallo Jean-Didier , Ramisse Francoise , Girardet Monique , Vaissaire Josée , Mock Michelle , Hernandez Eric 
Published: July 2002

ABSTRACT

Ninety-six isolates of
Bacillus anthracis
recovered in France between 1994 and 2000 were tested for their susceptibilities to 25 different antibiotics. Resistance to penicillin G and amoxicillin was 11.5%. All of the isolates were resistant to cotrimoxazole and susceptible to doxycycline, ciprofloxacin, pefloxacin, levofloxacin, teicoplanin, vancomycin, clindamycin, imipenem, and rifampin.
Alkoxyalkyl Esters of Cidofovir and Cyclic Cidofovir Exhibit Multiple-Log Enhancement of Antiviral Activity against Cytomegalovirus and Herpesvirus Replication In Vitro
Authors: Beadle James R. , Hartline Caroll , Aldern Kathy A. , Rodriguez Natalie , Harden Emma , Kern Earl R. , Hostetler Karl Y. 
Published: July 2002

ABSTRACT

The incidence of cytomegalovirus (CMV) retinitis is declining in AIDS patients but remains a significant clinical problem in patients with organ transplants and bone marrow transplants. Prophylaxis with ganciclovir (GCV) or valganciclovir reduces the incidence of CMV disease but may lead to the emergence of drug-resistant virus with mutations in the UL97 or UL54 gene. It would be useful to have other types of oral therapy for CMV disease. We synthesized hexadecyloxypropyl and octadecyloxyethyl derivatives of cyclic cidofovir (cCDV) and cidofovir (CDV) and found that these novel analogs had 2.5- to 4-log increases in antiviral activity against CMV compared to the activities of unmodified CDV and cCDV. Multiple-log increases in activity were noted against laboratory CMV strains and various CMV clinical isolates including GCV-resistant strains with mutations in the UL97 and UL54 genes. Preliminary cell studies suggest that the increase in antiviral activity may be partially explained by a much greater cell penetration of the novel analogs. 1-
O
-Hexadecyloxypropyl-CDV, 1-
O
-octadecyloxyethyl-CDV, and their corresponding cCDV analogs are worthy of further preclinical evaluation for treatment and prevention of CMV and herpes simplex virus infections in humans.
Methods for Data Mining from Large Multinational Surveillance Studies
Authors: Poupard James , Brown James , Gagnon Robert , Stanhope Michael J. , Stewart Chad 
Published: July 2002

ABSTRACT

Traditionally, large surveillance studies have been analyzed by the use of the MICs at which 90% of isolates tested are inhibited (MIC
90
s), MIC
50
s, frequency distributions, and percent susceptibility. In the past, these approaches have proved satisfactory for the monitoring of resistance. From these traditional uses, one can readily detect an increase in MICs for organism and drug combinations. Now that large surveillance studies have been conducted for a number of years and databases have grown to include a large number of datum points, new approaches to the extraction of useful information from these studies are needed. The present study proposes approaches, including the use of antibiotypes, principal components analysis, phylogenetics, and population genetic analysis, to the evaluation of data from large multinational surveillance studies. Application of these types of analyses can be used to describe genetic diversity, analyze changes in susceptibility patterns over time, and possibly, shed light on the origins and evolution of antimicrobial resistance. As global surveillance studies become more common and new questions concerning the evolution of resistance are raised, innovative approaches to analysis of the data will increase in importance.
Efficacy of Intravenous Liposomal Amphotericin B (AmBisome) against Coccidioidal Meningitis in Rabbits
Authors: Clemons Karl V. , Sobel Raymond A. , Williams Paul L. , Pappagianis Demosthenes , Stevens David A. 
Published: July 2002

ABSTRACT

The efficacy of intravenously administered liposomal amphotericin B (AmBisome [AmBi]) for the treatment of experimental coccidioidal meningitis was compared with those of oral fluconazole (FLC) and intravenously administered conventional amphotericin B (AMB). Male New Zealand White rabbits were infected by intracisternal inoculation of arthroconidia of
Coccidioides immitis
. Starting 5 days postinfection, animals received one of the following: 5% dextrose water diluent; AMB given at 1 mg/kg of body weight; AmBi given at 7.5, 15, or 22.5 mg/kg intravenously three times per week for 3 weeks; or oral FLC given at 80 mg/kg for 19 days. One week after the cessation of therapy, all survivors were euthanatized, the numbers of CFU remaining in the spinal cord and brain were determined, and histological analyses were performed. All AmBi-, FLC-, or AMB-treated animals survived and had prolonged lengths of survival compared with those for the controls (
P
< 0.0001). Treated groups had significantly lower numbers of white blood cells and significantly lower protein concentrations in the cerebrospinal fluid compared with those for the controls (
P
< 0.01 to 0.0005) and had fewer clinical signs of infection (e.g., weight loss, elevated temperature, and neurological abnormalities including motor abnormalities). The mean histological scores for AmBi-treated rabbits were lower than those for FLC-treated and control rabbits (
P
< 0.016 and 0.0005, respectively); the scores for AMB-treated animals were lower than those for the controls (
P
< 0.0005) but were similar to those for FLC-treated rabbits. All regimens reduced the numbers of CFU in the brain and spinal cord compared with those for the controls (
P
≤0.0005). AmBi-treated animals had 3- to 11-fold lower numbers of CFU than FLC-treated rabbits and 6- to 35-fold lower numbers of CFU than AmB-treated rabbits. Three of eight animals given 15 mg of AmBi per kg had no detectable infection in either tissue, whereas other doses of AmBi or FLC cleared either the brain or the spinal cord of infection in fewer rabbits. In addition, clearance of the infection from both tissues was achieved in none of the rabbits, and neither tissue was cleared of infection in AMB-treated animals. Overall, these data indicate that intravenously administered AmBi is superior to oral FLC or intravenous AMB and that FLC is better than AMB against experimental coccidioidal meningitis. These data indicate that AmBi may offer an improvement in the treatment of coccidioidal meningitis. Additional studies are warranted.
Tetracycline Rapidly Reaches All the Constituent Cells of Uropathogenic
Escherichia coli
Biofilms
Authors: Stone G. , Wood P. , Dixon L. , Keyhan M. , Matin A. 
Published: July 2002

ABSTRACT

We have developed a method for visualizing
Escherichia coli
cells that are exposed to tetracycline in a biofilm, based on a previous report that liposomes containing the
E. coli
TetR(B) protein fluoresce when exposed to this antibiotic. By our method, cells devoid of TetR(B) also exhibited tetracycline-dependent fluorescence. At 50 μg of tetracycline ml
−1
, planktonic cells of a uropathogenic
E. coli
(UPEC) strain developed maximal fluorescence after 7.5 to 10 min of exposure. A similar behavior was exhibited by cells in a 24- or 48-h UPEC biofilm, as examined by confocal laser microscopy, regardless of whether they lined empty spaces or occupied densely packed regions. Further, a comparison of phase-contrast and fluorescent images of corresponding biofilm zones showed that all the cells fluoresced. Thus, all the biofilm cells were exposed to tetracycline and there were no pockets within the biofilm where the antibiotic failed to reach. It also appeared unlikely that niches of reduced exposure to the antibiotic existed within the biofilms.
Pharmacokinetics and Safety of Voriconazole following Intravenous- to Oral-Dose Escalation Regimens
Authors: Purkins L. , Wood N. , Ghahramani P. , Greenhalgh K. , Allen M. J. , Kleinermans D. 
Published: July 2002

ABSTRACT

In this study, the safety, tolerability, and pharmacokinetics of intravenous (i.v.)- to oral-dose regimens of voriconazole were evaluated with a group of 42 healthy men, 41 of whom completed the study. Two cohorts of subjects participated in the study. Cohort 1 (
n
= 28) took part in two study periods, each consisting of 14 days separated by a minimum 7-day washout. In one of the periods, 14 subjects received 6 mg/kg i.v. twice a day (b.i.d.) on day 1 followed by 3 mg/kg i.v. b.i.d. on days 2 to 7 and were then switched to 200 mg orally b.i.d. for days 8 to 14. In the other period, subjects received 6 mg/kg i.v. b.i.d. on day 1 followed by 5 mg/kg i.v. b.i.d. on days 2 to 7and were then switched to 400 mg orally b.i.d. for days 8 to 14. The remaining 14 subjects in cohort 1 received a matching placebo throughout the study. In cohort 2 (
n
= 14), 7 subjects received 6 mg/kg i.v. b.i.d. on day 1 followed by 4 mg/kg i.v. b.i.d. on days 2 to 7 and were then switched to 300 mg orally b.i.d. for days 8 to 14. The remaining seven subjects in cohort 2 received a matching placebo. Blood samples were taken prior to dosing on days 1 to 6 and on days 8 to 13. Blood samples were drawn prior to dosing and at frequent intervals up to 12 h following the morning dose on days 7 and 14 of each study period. The samples were assayed for voriconazole by a high-performance liquid chromatography method. The maximum concentration in plasma (
C
max
) occurred at the end of the 1-h i.v. infusion and between 1.4 and 1.8 h after oral administration. Voriconazole exhibited nonlinear pharmacokinetics, possibly due to saturable metabolism. For cohort 1, both
C
max
and the area under the concentration-time curve within a dosage interval (AUC
τ
) increased disproportionately with dose for both i.v. and oral dosing. For i.v. dosing, a 1.7-fold increase in dose resulted in 2.4- and 3.1-fold increases in
C
max
and AUC
τ
, respectively. Similarly, a 2-fold increase in oral dosing resulted in 2.8- and 3.9-fold increases in
C
max
and AUC
τ
, respectively. The mean values for
C
max
observed following oral dosing were lower than those obtained after i.v. administration, ranging from 62.7 to 89.6% of the i.v. value. After the switch from i.v. to oral dosing, most subjects achieved steady state by day 4, and mean minimum concentrations in plasma remained above clinically important MICs. The pharmacokinetic profiles for saliva followed a pattern similar to those observed for plasma; there was a highly significant correlation between plasma and saliva voriconazole concentrations (
P
< 0.0001). Voriconazole was well tolerated; the most commonly reported adverse events in voriconazole-treated subjects were mild to moderate headache, rash, and abnormal vision. Visual function tests detected no further abnormalities during voriconazole treatment.
Transport of an Antifungal Trypsin Inhibitor Isolated from Corn across the Blood-Brain Barrier
Authors: Banks William A. , Niehoff Michael L. , Brown Robert L. , Chen Zhi-Yuan , Cleveland Thomas E. 
Published: July 2002

ABSTRACTWe determined whether an antifungal 14-kDa protein trypsin inhibitor isolated from corn is able to cross the blood-brain barrier. We found that it completely crossed the blood-brain barrier by means of a saturable mechanism at a rate of 0.153 μl/g · min, with about 0.082% of the intravenously injected dose being taken up per gram of brain.
Induction of Apoptosis by a Nonnucleoside Human Immunodeficiency Virus Type 1 Reverse Transcriptase Inhibitor
Authors: Pilon A. A. , Lum J. J. , Sanchez-Dardon J. , Phenix B. N. , Douglas R. , Badley A. D. 
Published: July 2002

ABSTRACT
Inhibition of human immunodeficiency virus type 1 reverse transcriptase (RT) by both nucleoside and nonnucleoside RT inhibitors profoundly inhibits virus replication. Nucleoside RT inhibitors are known to be toxic, but there is little information regarding the toxicities of nonnucleoside RT inhibitors (NNRTI). We demonstrate that efavirenz (an NNRTI) induces caspase- and mitochondrion-dependent apoptosis of Jurkat T cells and human peripheral blood mononuclear cells. The clinical relevance of these observations is not yet clear.
Two Novel Vaginal Microbicides (Polystyrene Sulfonate and Cellulose Sulfate) InhibitGardnerella vaginalisand Anaerobes Commonly Associated with Bacterial Vaginosis
Authors: Simoes Jose A. , Citron Diane M. , Aroutcheva Alla , Anderson Robert A. , Chany Calvin J. , Waller Donald P. , Faro Sebastian , Zaneveld Lourens J. D. 
Published: July 2002

ABSTRACTThis is the first report demonstrating the in vitro inhibitory activity of two novel microbicides (cellulose sulfate and polystyrene sulfonate) against bacterial vaginosis (BV)-associated bacteria. Vaginal application of these microbicides not only may reduce the risk of acquisition of human immunodeficiency virus and other sexually transmitted infection-causing organisms but may also decrease the incidence of BV.
In Vitro Susceptibilities of Zygomycetes to Combinations of Antimicrobial Agents
Authors: Dannaoui Eric , Afeltra Javier , Meis Jacques F. G. M. , Verweij Paul E. 
Published: July 2002

ABSTRACT
Combinations of antimicrobial agents were tested against 35 strains of zygomycetes. The interaction between amphotericin B and rifampin was synergistic or additive. Flucytosine alone was inactive and, upon combination with amphotericin B, synergy was not achieved. The combination of amphotericin B with terbinafine was synergistic for 20% of strains, and the interaction between terbinafine and voriconazole was synergistic for 44% of strains. Antagonism was not observed.
Hematologic Effects of Linezolid: Summary of Clinical Experience
Authors: Gerson Stanton L. , Kaplan Sheldon L. , Bruss Jon B. , Le Vu , Arellano Felix M. , Hafkin Barry , Kuter David J. 
Published: July 2002

ABSTRACT
Linezolid has been associated with reversible myelosuppression. Clinical trial data were evaluated for anemia, thrombocytopenia, and neutropenia. Thrombocytopenia and a slight increased risk for anemia were evident at ≥2 weeks of linezolid treatment. Hematologic abnormalities were consistent with mild, reversible, duration-dependent myelosuppression. Appropriate monitoring is warranted with linezolid use.