bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Novel Action of the Proton Pump Inhibitor Rabeprazole and Its Thioether Derivative against the Motility of
Helicobacter pylori
Authors: Tsutsui Nanako , Taneike Ikue , Ohara Tatsuki , Goshi Satoshi , Kojio Seiichi , Iwakura Nobuhiro , Matsumaru Hiroyuki , Wakisaka-Saito Noriko , Zhang Hui-Min , Yamamoto Tatsuo 
Published: July 2002

ABSTRACT

The motility of
Helicobacter pylori
was maximum at 37°C and at pH 6. A newly developed proton pump inhibitor, rabeprazole (RPZ), and its thioether derivative (RPZ-TH) markedly inhibited the motility of
H. pylori
. The concentrations of the drug necessary to inhibit 50% of the motility were 0.25, 16, 16, and >64 μg/ml for RPZ-TH, RPZ, lansoprazole, and omeprazole, respectively. No such inhibitory effects were observed with H
2
blockers or anti-
H. pylori
agents. The motilities of
Campylobacter jejuni
and
C. coli
—but not those of
Vibrio cholerae
O1 and O139,
Vibrio parahaemolyticus
,
Salmonella enterica
serovar Typhimurium, and
Proteus mirabilis
—were also inhibited. Prolonged incubation with RPZ or RPZ-TH inhibited bacterial growth of only
H. pylori
, except for a turbid colony mutant. The results indicate that RPZ and RPZ-TH have a characteristic inhibitory effect against the motility of
H. pylori
(spiral-shaped bacteria), which is distinguished from that against bacterial growth.
Combinations of Artemisinin and Quinine for Uncomplicated Falciparum Malaria: Efficacy and Pharmacodynamics
Authors: de Vries Peter J. , Bich Nguyen Ngoc , Van Thien Huynh , Hung Le Ngoc , Anh Trinh Kim , Kager Piet A. , Heisterkamp Siem H. 
Published: July 2002

ABSTRACT

Combinations of artemisinin and quinine for uncomplicated falciparum malaria were studied. A total of 268 patients were randomized to 7 days of quinine at 10 mg/kg of body weight three times a day (Q) or to artemisinin at 20 mg/kg of body weight followed by 3 (AQ3) or 5 (AQ5) days of quinine. Recrudescence rates were 16, 38, and 15% for the Q, AQ3, and AQ5 groups, respectively (
P
< 0.001). Recrudescence was associated with shorter parasite clearance time (PCT) and longer treatment after the blood smear had become negative (eradication time). However, classification of patients to outcome—recrudescence or radical cure—was correct in only 77% of patients. The population kinetics of the parasitemia was estimated with nonlinear mixed-effect models. Several models were tested, but the best model was a monoexponential decline of the parasitemia in which the mean parasite elimination half-life was shorter after artemisinin (5.1 h; 95% confidence interval [CI], 4.9 to 5.2 h) than after quinine (8.0 h [95% CI, 7.5 to 8.3 h]). Attempts to simulate the initial increase of the parasitemia did not result in better models with a biologically plausible interpretation. Recrudescence was associated with slower parasite clearance and a higher simulated terminal parasitemia (
P
term
). The classification of patients to outcome groups based on
P
term
was correct in 78% of patients. The data suggest that parasite strains with reduced sensitivity to quinine are prevalent in Vietnam, with slower parasite clearance and consequent recrudescence. A single dose of artemisinin induces rapid parasite reduction and lowers the value of
P
term
, but to prevent recrudescence, this should be followed by quinine for at least 3 days after parasite clearance, or 5 days in total.
Pharmacokinetics and Pharmacodynamics of Levofloxacin againstStreptococcus pneumoniaeandStaphylococcus aureusin Human Skin Blister Fluid
Authors: Trampuz Andrej , Wenk Markus , Rajacic Zarko , Zimmerli Werner 
Published: July 2002

ABSTRACTThe pharmacokinetics of levofloxacin in serum and in skin blister fluid (SBF) was determined for 20 volunteers after a single 500-mg oral dose of levofloxacin. In addition, ex vivo bactericidal activity of SBF againstStreptococcus pneumoniaeandStaphylococcus aureuswas studied. SBF containing levofloxacin and granulocytes killed 5.2 log ofStreptococcus pneumoniaebacteria and 2.0 log ofStaphylococcus aureusbacteria during a 6-h incubation.
Nitrofurantoin Is Active against Vancomycin-Resistant Enterococci
Authors: Zhanel George G. , Hoban Daryl J. , Karlowsky James A. 
Published: July 2002

ABSTRACT

The activity of nitrofurantoin was tested against 300 isolates of
Enterococcus faecium
,
Enterococcus faecalis
, and
Enterococcus gallinarum
. No isolates tested were resistant to nitrofurantoin (MIC, ≥128 μg/ml), including vancomycin-resistant
E. faecium
isolates with
vanA
- and
vanB
-positive genotypes and vancomycin-resistant
E. gallinarum
isolates. We conclude that nitrofurantoin may provide effective treatment of urinary tract infections caused by vancomycin-resistant enterococci.
Xenograft Model for Identifying Chemotherapeutic Agents against Papillomaviruses
Authors: Pawellek A. , Hewlett G. , Kreuter J. , Rübsamen-Waigmann H. , Weber O. 
Published: July 2002

ABSTRACT
The report describes the establishment and characterization of a mouse xenograft transplantation model for the study of papillomavirus infection of bovine skin. Calf scrotal skin was inoculated with bovine papillomavirus type 2 before grafting it to the dorsum of severe combined immunodeficient mice. The grafted skin contained epidermis, dermis, and a thin layer of fat. After 5 months the induced warts not only showed histological features of papillomavirus infections but also tested positive for viral DNA and papillomavirus capsid antigen. The formation of infectious virions was demonstrated by inoculation of new transplants with crude extract from the induced warts as well as in a cell culture focus assay. Topical application of bromovinyl-2′-deoxyuridine led to a reduction in viral DNA content in the developing wart. This small-animal xenograft model should be useful for characterizing antiviral compounds and providing an understanding of the regulation of papillomavirus infections.
In Vitro Activity of a Novel Antimycobacterial Compound,
N
-Octanesulfonylacetamide, and Its Effects on Lipid and Mycolic Acid Synthesis
Authors: Parrish Nikki M. , Houston Todd , Jones Paul B. , Townsend Craig , Dick James D. 
Published: July 2002

ABSTRACT

β-Sulfonyl carboxamides have been proposed to serve as transition-state analogues of the β-ketoacyl synthase reaction involved in fatty acid elongation. We tested the efficacy of
N
-octanesulfonylacetamide (OSA) as an inhibitor of fatty acid and mycolic acid biosynthesis in mycobacteria. Using the BACTEC radiometric growth system, we observed that OSA inhibits the growth of several species of slow-growing mycobacteria, including
Mycobacterium tuberculosis
(H37Rv and clinical isolates), the
Mycobacterium avium
complex (MAC),
Mycobacterium bovis
BCG,
Mycobacterium kansasii
, and others. Nearly all species and strains tested, including isoniazid and multidrug resistant isolates of
M. tuberculosis
, were susceptible to OSA, with MICs ranging from 6.25 to 12.5 μg/ml. Only three clinical isolates of
M. tuberculosis
(CSU93, OT2724, and 401296), MAC, and
Mycobacterium paratuberculosis
required an OSA MIC higher than 25.0 μg/ml. Rapid-growing mycobacterial species, such as
Mycobacterium smegmatis, Mycobacterium fortuitum
, and others, were not susceptible at concentrations of up to 100 μg/ml. A 2-dimensional thin-layer chromatography system showed that OSA treatment resulted in a significant decrease in all species of mycolic acids present in BCG. In contrast, mycolic acids in
M. smegmatis
were relatively unaffected following exposure to OSA. Other lipids, including polar and nonpolar extractable classes, were unchanged following exposure to OSA in both BCG and
M. smegmatis
. Transmission electron microscopy of OSA-treated BCG cells revealed a disruption in cell wall synthesis and incomplete septum formation. Our results indicate that OSA inhibits the growth of several species of mycobacteria, including both isoniazid-resistant and multidrug resistant strains of
M. tuberculosis
. This inhibition may be the result of OSA-mediated effects on mycolic acid synthesis in slow-growing mycobacteria or inhibition via an undescribed mechanism. Our results indicate that OSA may serve as a promising lead compound for future antituberculous drug development.
Pharmacodynamic Evaluation of RWJ-270201, a Novel Neuraminidase Inhibitor, in a Lethal Murine Model of Influenza Predicts Efficacy for Once-Daily Dosing
Authors: Drusano G. L. , Preston S. L. , Smee D. , Bush K. , Bailey K. , Sidwell R. W. 
Published: July 2002

ABSTRACT
We examined RWJ-270201 in a lethal model of influenza in BALB/c mice. The aim was to delineate the pharmacodynamically linked variable for the drug. Challenge was performed with influenza virus A/Shongdong/09/93 (H3N2). Treatment was administered by gavage. Five doses (1 to 10 mg/kg of body weight) and three schedules (every 24, 12, and 8 h) were evaluated with 10 mice per group. There were 39 placebo-treated mice. Drug exposure was evaluated for infected mice. Exposures were calculated after population modeling of all the plasma concentration-time data simulataneously using the NPEM3 program. Evaluation of dose and schedule with Kaplan-Meier analysis and Cox proportional hazards modeling demonstrated that schedule offered no explanatory power relative to dose alone. Evaluation of peak concentration, trough concentration, and area under the concentration-time curve (AUC) by the same methods revealed that AUC was the dynamically linked variable. Again, schedule offered no further explanatory power when included in the model with AUC. This indicates that AUC is the linked variable and that the anti-influenza effect of RWJ-270201 is independent of schedule. We conclude that once-daily dosing of RWJ-270201 should be evaluated in clinical trials of influenza therapy.
In Vitro and In Vivo Activities of CS-758 (R-120758), a New Triazole Antifungal Agent
Authors: Kamai Yasuki , Harasaki Tamako , Fukuoka Takashi , Ohya Satoshi , Uchida Katsuhisa , Yamaguchi Hideyo , Kuwahara Shogo 
Published: July 2002

ABSTRACT

The activity of CS-758 (R-120758), a new triazole antifungal agent, was evaluated and compared with those of fluconazole, itraconazole, and amphotericin B in vitro and with those of fluconazole and itraconazole in vivo. CS-758 exhibited potent in vitro activity against clinically important fungi. The activity of CS-758 against
Candida
spp. was superior to that of fluconazole and comparable or superior to those of itraconazole and amphotericin B. CS-758 retained potent activity against
Candida albicans
strains with low levels of susceptibility to fluconazole (fluconazole MIC, 4 to 32 μg/ml). Against
Aspergillus
spp. and
Cryptococcus neoformans
, the activity of CS-758 was at least fourfold superior to those of the other drugs tested. CS-758 also exhibited potent in vivo activity against murine systemic infections caused by
C. albicans
,
C. neoformans
,
Aspergillus fumigatus
, and
Aspergillus flavus
. The 50% effective doses against these infections were 0.41 to 5.0 mg/kg of body weight. These results suggest that CS-758 may be useful in the treatment of candidiasis, cryptococcosis, and aspergillosis.
NB2001, a Novel Antibacterial Agent with Broad-Spectrum Activity and Enhanced Potency against β-Lactamase-Producing Strains
Authors: Li Qing , Lee Jean Y. , Castillo Rosario , Hixon Mark S. , Pujol Catherine , Doppalapudi Venkata Ramana , Shepard H. Michael , Wahl Geoffrey M. , Lobl Thomas J. , Chan Ming Fai 
Published: July 2002

ABSTRACT

Enzyme-catalyzed therapeutic activation (ECTA) is a novel prodrug strategy to overcome drug resistance resulting from enzyme overexpression. β-Lactamase overexpression is a common mechanism of bacterial resistance to β-lactam antibiotics. We present here the results for one of the β-lactamase ECTA compounds, NB2001, which consists of the antibacterial agent triclosan in a prodrug form with a cephalosporin scaffold. Unlike conventional β-lactam antibiotics, where hydrolysis of the β-lactam ring inactivates the antibiotic, hydrolysis of NB2001 by β-lactamase releases triclosan. Evidence supporting the proposed mechanism is as follows. (i) NB2001 is a substrate for TEM-1 β-lactamase, forming triclosan with a second-order rate constant (
k
cat
/

K
m

) of greater than 77,000 M
−1
s
−1
. (ii) Triclosan is detected in NB2001-treated, β-lactamase-producing
Escherichia coli
but not in
E. coli
that does not express β-lactamase. (iii) NB2001 activity against β-lactamase-producing
E. coli
is decreased in the presence of the β-lactamase inhibitor clavulanic acid. NB2001 was similar to or more potent than reference antibiotics against clinical isolates of
Staphylococcus aureus
(including MRSA),
Staphylococcus epidermidis
,
Streptococcus pneumoniae
, vancomycin-resistant
Enterococcus faecalis
,
Moraxella catarrhalis
and
Haemophilus influenza
e. NB2001 is also active against
Klebsiella pneumoniae
,
Enterobacter aerogenes
, and
Enterobacter cloacae
. The results indicate that NB2001 is a potent, broad-spectrum antibacterial agent and demonstrate the potential of ECTA in overcoming β-lactamase-mediated resistance.
Characterization of a Laboratory-Derived, High-Level Ampicillin-ResistantSalmonella entericaSerovar Typhimurium Strain That Caused Meningitis in an Infant
Authors: Chiu Cheng-Hsun , Chu Chishih , Su Lin-Hui , Wu Wan-Yu , Wu Tsu-Lan 
Published: July 2002

ABSTRACTASalmonella entericaserovar Typhimurium strain that harbored a plasmid carrying a TEM-1-type β-lactamase gene was isolated from the blood and cerebrospinal fluid of an infant with meningitis. This 3.2-kb plasmid was further characterized to be a nonconjugative pGEM series cloning vector containing a foreign insert. The strain was likely laboratory derived and contaminated the environment before it caused the infection.
Identification of Collagen-Binding Proteins in
Lactobacillus
spp. with Surface-Enhanced Laser Desorption/Ionization–Time of Flight ProteinChip Technology
Authors: Howard Jeffrey C. , Heinemann Christine , Thatcher Bradley J. , Martin Brian , Gan Bing Siang , Reid Gregor 
Published: July 2002

ABSTRACT

Biosurfactants produced by
Lactobacillus fermentum
RC-14,
L. rhamnosus
GR-1 and 36, and
L. casei
Shirota were found to contain proteins that bind to both collagen types III and VI, as determined by surface-enhanced laser desorption/ionization (SELDI)–time of flight mass spectrometry. Both collagen types III and VI immobilized on SELDI preactivated ProteinChip arrays detected several different sizes (2 to 48 kDa) of collagen-binding proteins. Overall, the RC-14-produced biosurfactant contained the greatest number of collagen-binding proteins (RC-14 > GR-1 > 36 > Shirota), including the mature form of a previously cloned 29-kDa collagen-binding protein (referred to in its mature 26-kDa form). Although biosurfactants isolated from
L. casei
Shirota and
L. rhamnosus
36 and GR-1 also contain several collagen-binding proteins, they do not contain the 26-kDa collagen-binding protein. Together, these results demonstrate the utility of the SELDI system as a means of rapidly characterizing clinically important but complex biosurfactant solutions.
Whole-Cell versus Total RNA Extraction for Analysis of Microbial Community Structure with 16S rRNA-Targeted Oligonucleotide Probes in Salt Marsh Sediments
Authors: Frischer Marc E. , Danforth Jean M. , Healy Michele A. Newton , Saunders F. Michael 
Published: July 2002

ABSTRACT

rRNA-targeted oligonucleotide probes have become powerful tools for describing microbial communities, but their use in sediments remains difficult. Here we describe a simple technique involving homogenization, detergents, and dispersants that allows the quantitative extraction of cells from formalin-preserved salt marsh sediments. Resulting cell extracts are amenable to membrane blotting and hybridization protocols. Using this procedure, the efficiency of cell extraction was high (95.7% ± 3.7% [mean ± standard deviation]) relative to direct DAPI (4′,6′-diamidino-2-phenylindole) epifluorescence cell counts for a variety of salt marsh sediments. To test the hypothesis that cells were extracted without phylogenetic bias, the relative abundance (depth distribution) of five major divisions of the gram-negative mesophilic sulfate-reducing delta proteobacteria were determined in sediments maintained in a tidal mesocosm system. A suite of six 16S rRNA-targeted oligonucleotide probes were utilized. The apparent structure of sulfate-reducing bacteria communities determined from whole-cell and RNA extracts were consistent with each other (
r
2
= 0.60), indicating that the whole-cell extraction and RNA extraction hybridization approaches for describing sediment microbial communities are equally robust. However, the variability associated with both methods was high and appeared to be a result of the natural heterogeneity of sediment microbial communities and methodological artifacts. The relative distribution of sulfate-reducing bacteria was similar to that observed in natural marsh systems, providing preliminary evidence that the mesocosm systems accurately simulate native marsh systems.
Anaerobic Xylose Fermentation by Recombinant
Saccharomyces cerevisiae
Carrying
XYL1
,
XYL2
, and
XKS1
in Mineral Medium Chemostat Cultures
Authors: Eliasson Anna , Christensson Camilla , Wahlbom C. Fredrik , Hahn-Hägerdal Bärbel 
Published: July 2002

ABSTRACT

For ethanol production from lignocellulose, the fermentation of xylose is an economic necessity.
Saccharomyces cerevisiae
has been metabolically engineered with a xylose-utilizing pathway. However, the high ethanol yield and productivity seen with glucose have not yet been achieved. To quantitatively analyze metabolic fluxes in recombinant
S. cerevisiae
during metabolism of xylose-glucose mixtures, we constructed a stable xylose-utilizing recombinant strain, TMB 3001. The
XYL1
and
XYL2
genes from
Pichia stipitis
, encoding xylose reductase (XR) and xylitol dehydrogenase (XDH), respectively, and the endogenous
XKS1
gene, encoding xylulokinase (XK), under control of the
PGK1
promoter were integrated into the chromosomal
HIS3
locus of
S. cerevisiae
CEN.PK 113-7A. The strain expressed XR, XDH, and XK activities of 0.4 to 0.5, 2.7 to 3.4, and 1.5 to 1.7 U/mg, respectively, and was stable for more than 40 generations in continuous fermentations. Anaerobic ethanol formation from xylose by recombinant
S. cerevisiae
was demonstrated for the first time. However, the strain grew on xylose only in the presence of oxygen. Ethanol yields of 0.45 to 0.50 mmol of C/mmol of C (0.35 to 0.38 g/g) and productivities of 9.7 to 13.2 mmol of C h
−1
g (dry weight) of cells
−1
(0.24 to 0.30 g h
−1
g [dry weight] of cells
−1
) were obtained from xylose-glucose mixtures in anaerobic chemostat cultures, with a dilution rate of 0.06 h
−1
. The anaerobic ethanol yield on xylose was estimated at 0.27 mol of C/(mol of C of xylose) (0.21 g/g), assuming a constant ethanol yield on glucose. The xylose uptake rate increased with increasing xylose concentration in the feed, from 3.3 mmol of C h
−1
g (dry weight) of cells
−1
when the xylose-to-glucose ratio in the feed was 1:3 to 6.8 mmol of C h
−1
g (dry weight) of cells
−1
when the feed ratio was 3:1. With a feed content of 15 g of xylose/liter and 5 g of glucose/liter, the xylose flux was 2.2 times lower than the glucose flux, indicating that transport limits the xylose flux.
Regulation of Polyglutamic Acid Synthesis by Glutamate in
Bacillus licheniformis
and
Bacillus subtilis
Authors: Kambourova Margarita , Tangney Martin , Priest Fergus G. 
Published: July 2002

ABSTRACT

The synthesis of polyglutamic acid (PGA) was repressed by exogenous glutamate in strains of
Bacillus licheniformis
but not in strains of
Bacillus subtilis
, indicating a clear difference in the regulation of synthesis of capsular slime in these two species. Although extracellular γ-glutamyltranspeptidase (GGT) activity was always present in PGA-producing cultures of
B. licheniformis
under various growth conditions, there was no correlation between the quantity of PGA and enzyme activity. Moreover, the synthesis of PGA in the absence of detectable GGT activity in
B. subtilis
S317 indicated that this enzyme was not involved in PGA biosynthesis in this bacterium. Glutamate repression of PGA biosynthesis may offer a simple means of preventing unwanted slime production in industrial fermentations using
B. licheniformis.
Development of a
Saccharomyces cerevisiae
Strain with Enhanced Resistance to Phenolic Fermentation Inhibitors in Lignocellulose Hydrolysates by Heterologous Expression of Laccase
Authors: Larsson Simona , Cassland Pierre , Jönsson Leif J. 
Published: July 2002

ABSTRACT

To improve production of fuel ethanol from renewable raw materials, laccase from the white rot fungus
Trametes versicolor
was expressed under control of the
PGK1
promoter in
Saccharomyces cerevisiae
to increase its resistance to phenolic inhibitors in lignocellulose hydrolysates. It was found that the laccase activity could be enhanced twofold by simultaneous overexpression of the homologous
t
-SNARE Sso2p. The factors affecting the level of active laccase obtained, besides the cultivation temperature, included pH and aeration. Laccase-expressing and Sso2p-overexpressing
S. cerevisiae
was cultivated in the presence of coniferyl aldehyde to examine resistance to lignocellulose-derived phenolic fermentation inhibitors. The laccase-producing transformant had the ability to convert coniferyl aldehyde at a faster rate than a control transformant not expressing laccase, which enabled faster growth and ethanol formation. The laccase-producing transformant was also able to ferment a dilute acid spruce hydrolysate at a faster rate than the control transformant. A decrease in the content of low-molecular-mass aromatic compounds, accompanied by an increase in the content of high-molecular-mass compounds, was observed during fermentation with the laccase-expressing strain, illustrating that laccase was active even at the very low levels of oxygen supplied. Our results demonstrate the importance of phenolic compounds as fermentation inhibitors and the advantage of using laccase-expressing yeast strains for producing ethanol from lignocellulose.
Distribution and Diversity of Symbiotic Thermophiles,
Symbiobacterium thermophilum
and Related Bacteria, in Natural Environments
Authors: Ueda Kenji , Ohno Michiyo , Yamamoto Kaori , Nara Hanae , Mori Yujiro , Shimada Masafumi , Hayashi Masahiko , Oida Hanako , Terashima Yuko , Nagata Mitsuyo , Beppu Teruhiko 
Published: July 2002

ABSTRACT

Symbiobacterium thermophilum
is a tryptophanase-positive thermophile which shows normal growth only in coculture with its supporting bacteria. Analysis of the 16S rRNA gene (rDNA) indicated that the bacterium belongs to a novel phylogenetic branch at the outermost position of the gram-positive bacterial group without clustering to any other known genus. Here we describe the distribution and diversity of
S. thermophilum
and related bacteria in the environment. Thermostable tryptophanase activity and amplification of the specific 16S rDNA fragment were effectively employed to detect the presence of
Symbiobacterium
. Enrichment with kanamycin raised detection sensitivity. Mixed cultures of thermophiles containing
Symbiobacterium
species were frequently obtained from compost, soil, animal feces, and contents in the intestinal tracts, as well as feeds. Phylogenetic analysis and denaturing gradient gel electrophoresis of the specific 16S rDNA amplicons revealed a diversity of this group of bacteria in the environment.