bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genetic and Biochemical Characterization of the Chromosomal Class A β-Lactamases of
Raoultella
(formerly
Klebsiella
)
planticola
and
Raoultella ornithinolytica
Authors: Walckenaer Estelle , Poirel Laurent , Leflon-Guibout Véronique , Nordmann Patrice , Nicolas-Chanoine Marie-Hélène 
Published: December 2003

ABSTRACT

Enterobacterial strains of
Raoultella
spp. display a penicillinase-related β-lactam resistance pattern suggesting the presence of a chromosomal
bla
gene. From whole-cell DNA of
Raoultella planticola
strain ATCC 33531
T
and
Raoultella ornithinolytica
strain ATCC 31898
T
,
bla
genes were cloned and expressed into
Escherichia coli
. Each gene encoded an Ambler class A β-lactamase, named PLA-1 and ORN-1 for
R. planticola
and
R. ornithinolytica
, respectively. These β-lactamases (291 amino acids), with the same pI value of 7.8, had a shared amino acid identity of 94%, 37 to 47% identity with the majority of the chromosome-encoded class A β-lactamases previously described for
Enterobacteriaceae
, and 66 to 69% identity with the two β-lactamases LEN-1 and SHV-1 from
Klebsiella pneumoniae
. However, the highest identity percentage (69 to 71%) was found with the plasmid-mediated β-lactamase TEM-1. PLA-1, which displayed very strong hydrolytic activity against penicillins, also displayed significant hydrolytic activity against cefepime and, to a lesser extent, against cefotaxime and aztreonam, but there was no hydrolytic activity against ceftazidime. Such a substrate profile suggests that the
Raoultella
β-lactamases PLA-1 and ORN-1 should be classified into the group 2be of the β-lactamase classification of K. Bush, G. A. Jacoby, and A. A. Medeiros (Antimicrob. Agents Chemother.
39:
1211-1233, 1995). The highly homologous regions upstream of the
bla
PLA-1A
and
bla
ORN-1A
genes comprised a nucleotide sequence identical to the −35 region and another one very close to the −10 region of the
bla
LEN-1
gene. From now on, as the
bla
gene sequences of the most frequent
Raoultella
and
Klebsiella
species are available, the
bla
gene amplification method can be used to differentiate these species from each other, which the biochemical tests currently carried out in the clinical laboratory are unable to do.
FKS1
Mutations Responsible for Selective Resistance of
Saccharomyces cerevisiae
to the Novel 1,3-β-Glucan Synthase Inhibitor Arborcandin C
Authors: Ohyama Takao , Miyakoshi Shunichi , Isono Fujio 
Published: December 2003

ABSTRACT

Arborcandin C is a novel antibiotic with potent antifungal activity that inhibits 1,3-β-glucan synthase in fungi. We examined spontaneous
Saccharomyces cerevisiae
mutants which are selectively resistant to arborcandin C and revealed that a single amino acid replacement in Fks1p of Asn
470
with Lys or of Leu
642
with Ser confers selective resistance on Fks1p mutants.
Effect of Parenteral Fluoroquinolone Administration on Persistence of Vancomycin-Resistant
Enterococcus faecium
in the Mouse Gastrointestinal Tract
Authors: Donskey Curtis J. , Helfand Marion S. , Pultz Nicole J. , Rice Louis B. 
Published: December 2003

ABSTRACT

We examined the effect of subcutaneous fluoroquinolone antibiotic administration on persistence and density of vancomycin-resistant
Enterococcus faecium
stool colonization in mice. Levofloxacin and ciprofloxacin did not promote colonization in comparison to saline controls, whereas moxifloxacin and gatifloxacin promoted persistent overgrowth in a dose-dependent fashion.
Effect of Heat-Treated Amphotericin B on Renal and Fungal Cytotoxicity
Authors: Bartlett Karen , Yau Edwin , Hartsel Scott C. , Hamer Alison , Tsai Gina , Bizzotto Dan , Wasan Kishor M. 
Published: December 2003

ABSTRACT

The purpose of this investigation was to determine the cytotoxicity of amphotericin B (AMB; trade name Fungizone [FZ]) following the administration of FZ and a heat-treated form of FZ (HFZ) to LLC-PK
1
pig kidney cells and
Cryptococcus neoformans
var.
gattii
cells. HFZ was significantly less toxic to kidney cells than FZ at all concentrations tested. For both FZ and HFZ, the concentration range which resulted in a 50% reduction of the growth of fungal cells was 0.125 to 1 mg/ml. These findings suggest that heat treatment decreases AMB's renal cytotoxicity without modifying its antifungal activity.
In Vitro Evaluation of Nonnucleoside Reverse Transcriptase Inhibitors UC-781 and TMC120-R147681 as Human Immunodeficiency Virus Microbicides
Authors: Van Herrewege Yven , Michiels Jo , Van Roey Jens , Fransen Katrien , Kestens Luc , Balzarini Jan , Lewi Paul , Vanham Guido , Janssen Paul 
Published: December 2003

ABSTRACT
The nonnucleoside reverse transcriptase inhibitors UC-781 and TMC120-R147681 (Dapivirine) effectively prevented human immunodeficiency virus (HIV) infection in cocultures of monocyte-derived dendritic cells and T cells, representing primary targets in sexual transmission. Both drugs had a favorable therapeutic index. A 24-h treatment with 1,000 nM UC-781 or 100 nM TMC120-R147681 prevented cell-free HIV infection, whereas 10-fold-higher concentrations blocked cell-associated HIV.
In Vitro Postantibiotic Effects of Rifapentine, Isoniazid, and Moxifloxacin against
Mycobacterium tuberculosis
Authors: Chan Chiu-Yeung , Au-Yeang Carrie , Yew Wing-Wai , Leung Chi-Chiu , Cheng Augustine F. B. 
Published: December 2003

ABSTRACT

Postantibiotic effects (PAEs) of rifapentine, isoniazid, and moxifloxacin against
Mycobacterium tuberculosis
ATCC 27294 were studied using a radiometric culture system. Rifapentine at 20 mg/liter gave the longest PAE (104 h) among the drugs used alone. The combinations of rifapentine plus isoniazid, rifapentine plus moxifloxacin, and isoniazid plus moxifloxacin gave PAEs of 136.5, 59.0, and 8.3 h, respectively.
Sequencing of
Neisseria meningitidis penA
Gene: the Key to Success in Defining Penicillin G Breakpoints
Authors: Arreaza Luisa , Salcedo Celia , Alcalá Belén , Uría María José , Abad Raquel , Enríquez Rocío , Vázquez Julio A. 
Published: December 2003

ABSTRACT

Testing of susceptibility to penicillin G by E-test and sequencing of an internal fragment of the
penA
gene were done for 43 meningococcal strains. Those strains for which the MIC was ≥0.094 μg/ml showed mosaic alleles, so 0.094 μg/ml is suggested as the penicillin G intermediate breakpoint when E-test is used.
Modeling Antibiotic Tolerance in Biofilms by Accounting for Nutrient Limitation
Authors: Roberts Mark E. , Stewart Philip S. 
Published: December 2003

ABSTRACT
A mathematical model of biofilm dynamics was used to investigate the protection from antibiotic killing that can be afforded to microorganisms in biofilms based on a mechanism of localized nutrient limitation and slow growth. The model assumed that the rate of killing by the antibiotic was directly proportional to the local growth rate. Growth rates in the biofilm were calculated by using the local concentration of a single growth-limiting substrate with Monod kinetics. The concentration profile of this metabolic substrate was calculated by solving a reaction-diffusion problem. The model predicted the following features: stratified patterns of growth with zones of no growth in the biofilm interior, slow killing of biofilm microorganisms that was further retarded as the initial biofilm thickness increased, nonuniform spatial patterns of killing inside the biofilm, biofilm killing rates that decrease in a nonlinear way as the concentration of the growth-limiting substrate feeding the biofilm is decreased, and heightened tolerance when external mass transfer resistance is manifested. This modeling study also provides motivation for further investigation of a hypothetical cell state in which damaged cells score as nonviable but continue to consume substrate. The existence of such a cell state can further retard biofilm killing, according to the simulations. The results support the important contributions of nutrient limitation and slow growth to the antibiotic tolerance of microorganisms in biofilms.
In Vitro Activities of the Novel Cephalosporin LB 11058 against Multidrug-Resistant Staphylococci and Streptococci
Authors: Sader Helio S. , Johnson David M. , Jones Ronald N. 
Published: December 2003

ABSTRACT

LB 11058 is a novel parenteral cephalosporin with a C-3 pyrimidinyl-substituted vinyl sulfide group and a C-7 2-amino-5-chloro-1,3-thiazole group. This study evaluated the in vitro activity and spectrum of LB 11058 against 1,245 recent clinical isolates, including a subset of gram-positive strains with specific resistant phenotypes. LB 11058 was very active against
Streptococcus pneumoniae
. The novel cephalosporin was 8- to 16-fold more potent than ceftriaxone, cefepime, or amoxicillin-clavulanate against both penicillin-intermediate and -resistant
S. pneumoniae
. LB 11058 was also very active against both β-hemolytic streptococci (MIC at which 90% of isolates were inhibited [MIC
90
], ≤0.008 μg/ml) and viridans group streptococci (MIC
90
, 0.03 to 0.5 μg/ml), including penicillin-resistant strains. Among oxacillin-susceptible
Staphylococcus aureus
, LB 11058 MIC results varied from 0.06 to 0.25 μg/ml (MIC
50
, 0.12 μg/ml), while among oxacillin-resistant strains LB 11058 MICs varied from 0.25 to 1 μg/ml (MIC
50
, 1 μg/ml). Coagulase-negative staphylococci showed an LB 11058 susceptibility pattern similar to that of
S. aureus
, with all isolates being inhibited at ≤1 μg/ml. LB 11058 also showed reasonable in vitro activity against
Enterococcus faecalis
, including vancomycin-resistant strains (MIC
50
, 1 μg/ml), and
Bacillus
spp. (MIC
50
, 0.25 μg/ml); however, it was less active against
Enterococcus faecium
(MIC
50
, >64 μg/ml) and
Corynebacterium
spp. (MIC
50
, 32 μg/ml). Against gram-negative pathogens, LB 11058 showed activity against
Haemophilus influenzae
(MIC
90
, 0.25 to 0.5 μg/ml) and
Moraxella catarrhalis
(MIC
90
, 0.25 μg/ml), with MICs not influenced by β-lactamase production. In conclusion, LB 11058 demonstrated a broad antibacterial spectrum and was highly active against gram-positive bacteria, particularly against multidrug-resistant staphylococci and streptococci.
In Vivo Pharmacodynamic Activity of Daptomycin
Authors: Safdar Nasia , Andes David , Craig W. A. 
Published: December 2003

ABSTRACT

Daptomycin is a lipopeptide antibiotic with activity against a wide range of gram-positive bacteria. We used the neutropenic murine thigh model to characterize the pharmacodynamics of daptomycin. ICR/Swiss mice were rendered neutropenic with cyclophosphamide; and the thigh muscles of the mice were infected with strains of
Staphylococcus aureus
,
Streptococcus pneumoniae
, and
Enterococcus faecium
. Animals were treated by subcutaneous injection of daptomycin at doses of 0.20 to 400 mg/kg of body weight/day divided into one, two, four, or eight doses over 24 h. Daptomycin exhibited linear pharmacokinetics, with an area under the concentration-time curve (AUC) from time zero to infinity/dose of 9.4 and a half-life of 0.9 to 1.4 h. The level of protein binding was 90%. Free daptomycin exhibited concentration-dependent killing and produced in vivo postantibiotic effects (PAEs) of 4.8 to 10.8 h. Nonlinear regression analysis was used to determine which pharmacokinetic (PK) or pharmacodynamic (PD) parameter was important for efficacy by using free drug concentrations. The peak concentration/MIC (peak/MIC) ratio and 24-h AUC/MIC ratio were the PK and PD parameters that best correlated with in vivo efficacy (
R
2
= 83 to 87% for peak/MIC and
R
2
= 86% for the AUC/MIC ratio, whereas
R
2
= 47 to 50% for the time that the concentration was greater than the MIC) against standard strains of
S. aureus
and
S. pneumoniae
. The peak/MIC ratios required for a bacteriostatic effect ranged from 12 to 36 for
S. pneumoniae
, 59 to 94 for S.
aureus
, and 0.14 to 0.25 for
E. faecium
. The AUC/MIC ratios needed for a bacteriostatic effect ranged from 75 to 237 for
S. pneumoniae
, 388 to 537 for
S. aureus
, and 0.94 to 1.67 for
E. faecium
. The free daptomycin concentrations needed to average from one to two times the MIC over 24 h to produce a bacteriostatic effect and two to four times the MIC over 24 h to produce greater than 99% killing. The long PAE and potent bactericidal activity make daptomycin an attractive option for the treatment of infections caused by gram-positive bacteria.
Anti-
Trypanosoma cruzi
Activity of Green Tea (
Camellia sinensis
) Catechins
Authors: Paveto Cristina , Güida María C. , Esteva Mónica I. , Martino Virginia , Coussio Jorge , Flawiá Mirtha M. , Torres Héctor N. 
Published: December 2003

ABSTRACT

The trypanocidal action of green tea catechins against two different developmental stages of
Trypanosoma cruzi
is reported for the first time. This activity was assayed with the nonproliferative bloodstream trypomastigote and with the intracellular replicative amastigote parasite forms. An ethyl acetate fraction from
Camellia sinensis
green tea leaves, which contains most of the polyphenolic compounds and the maximal trypanocidal activity, was obtained by fractionation of the aqueous extract with organic solvents. The active compounds present in this extract were further purified by LH-20 column chromatography and were identified by high-performance liquid chromatography analysis with a photo diode array detector and gas chromatography coupled to mass spectroscopy. The following flavan-3-ols derivatives, known as catechins, were identified: catechin, epicatechin, gallocatechin, epigallocatechin, catechin gallate, epicatechin gallate, gallocatechin gallate, and epigallocatechin gallate. The purified compounds lysed more than 50% of the parasites present in the blood of infected BALB/c mice at concentrations as low as 0.12 to 85 pM. The most active compounds were gallocatechin gallate and epigallocatechin gallate, with minimal bactericidal concentrations that inhibited 50% of isolates tested of 0.12 and 0.53 pM, respectively. The number of amastigotes in infected Vero cells decreased by 50% in the presence of each of these compounds at 100 nM. The effects of the catechins on the recombinant
T. cruzi
arginine kinase, a key enzyme in the energy metabolism of the parasite, were assayed. The activity of this enzyme was inhibited by about 50% by nanomolar concentrations of catechin gallate or gallocatechin gallate, whereas the other members of the group were less effective. On the basis of these results, we suggest that these compounds could be used to sterilize blood and, eventually, as therapeutic agents for Chagas' disease.
Orally Administered Targeted Recombinant Beta-Lactamase Prevents Ampicillin-Induced Selective Pressure on the Gut Microbiota: a Novel Approach to Reducing Antimicrobial Resistance
Authors: Harmoinen Jaana , Mentula Silja , Heikkilä Matti , van der Rest Michel , Rajala-Schultz Päivi J. , Donskey Curtis J. , Frias Rafael , Koski Pertti , Wickstrand Nina , Jousimies-Somer Hannele , Westermarck Elias , Lindevall Kai 
Published: December 2003

ABSTRACT

Antibiotics that are excreted into the intestinal tract promote antibiotic resistance by exerting selective pressure on the gut microbiota. Using a beagle dog model, we show that an orally administered targeted recombinant β-lactamase enzyme eliminates the portion of parenteral ampicillin that is excreted into the small intestine, preventing ampicillin-induced changes to the fecal microbiota without affecting ampicillin levels in serum. In dogs receiving ampicillin, significant disruption of the fecal microbiota and the emergence of ampicillin-resistant
Escherichia coli
and TEM genes were observed, whereas in dogs treated with ampicillin in combination with an oral β-lactamase, these did not occur. These results suggest a new strategy for reducing antimicrobial resistance in humans.
Efficacy of Garenoxacin in Treatment of Experimental Endocarditis Due to
Staphylococcus aureus
or Viridans Group Streptococci
Authors: Entenza José M. , Vouillamoz Jacques , Glauser Michel P. , Moreillon Philippe 
Published: December 2003

ABSTRACT

The activity of garenoxacin was investigated in rats with experimental endocarditis due to staphylococci and viridans group streptococci (VGS). The staphylococci tested comprised one ciprofloxacin-susceptible and methicillin-susceptible
Staphylococcus aureus
(MSSA) isolate (isolate 1112), one ciprofloxacin-susceptible but methicillin-resistant
S. aureus
(MRSA) isolate (isolate P8), and one ciprofloxacin-resistant mutant (
grlA
) of P8 (isolate P8-4). The VGS tested comprised one penicillin-susceptible isolate and one penicillin-resistant isolate (
Streptococcus oralis
226 and
Streptococcus mitis
531, respectively). To simulate the kinetics of drugs in humans, rats were infused intravenously with garenoxacin every 24 h (peak and trough levels in serum, 6.1 and 1.0 mg/liter, respectively; area under the concentration-time curve [AUC], 63.4 mg · h/liter) or levofloxacin every 12 h (peak and trough levels in serum, 7.3 and 1.5 mg/liter, respectively; AUC, 55.6 mg · h/liter) for 3 or 5 days. Flucloxacillin, vancomycin, and ceftriaxone were used as control drugs. Garenoxacin, levofloxacin, flucloxacillin, and vancomycin sterilized ≥70% of the vegetations infected with both ciprofloxacin-susceptible staphylococcal isolates (
P
< 0.05 versus the results for the controls). Garenoxacin and vancomycin also sterilized 70% of the vegetations infected with ciprofloxacin-resistant MRSA isolate P8-4, whereas treatment with levofloxacin failed against this organism (cure rate, 0%;
P
< 0.05 versus the results obtained with the comparator drugs). Garenoxacin did not select for resistant derivatives in vivo. In contrast, levofloxacin selected for resistant variants in four of six rats infected with MRSA isolate P8-4. Garenoxacin sterilized 90% of the vegetations infected with both penicillin-susceptible and penicillin-resistant isolates of VGS. Levofloxacin sterilized only 22 and 40% of the vegetations infected with penicillin-susceptible
S. oralis
226 and penicillin-resistant
S. mitis
531, respectively. Ceftriaxone sterilized only 40% of those infected with penicillin-resistant
S. mitis
531 (
P
< 0.05 versus the results obtained with garenoxacin). No quinolone-resistant VGS were detected. In all the experiments successful quinolone treatment was predicted by specific pharmacodynamic criteria (D. R. Andes and W. A. Craig, Clin. Infect. Dis. 27:47-50, 1998). The fact that the activity of garenoxacin was equal or superior to those of the standard comparators against staphylococci and VGS indicates that it is a potential alternative for the treatment of infections caused by such bacteria.
A PROCEDURE TO TRANSLATE PARADIGM SPECIFICATIONS TO PROPOSITIONAL LINEAR TEMPORAL LOGIC AND ITS APPLICATION TO VERIFICATION
Authors: AUGUSTO JUAN CARLOS , GOMEZ RODOLFO SABAS 
Published: December 2003

Software systems have evolved from monolithic programs to systems constructed from parallel, cooperative components, as can be currently found in object-oriented applications. Although powerful, these cooperative systems are also more difficult to verify. We show that it is possible to automatically translate a PARADIGM specification to a Propositional Linear Temporal Logic based program. This has several interesting consequences: a) on one hand we allow a more declarative view of PARADIGM specifications, b) the resulting translation is an executable specification and c) as we show in this work it can also be used to verify correctness properties by automatic means. We think this will contribute to enhance the understanding, usability and further development of PARADIGM, and related methods like SOCCA, within both the Software Engineering and the Knowledge Engineering communities.
Mangalore Chemicals and Fertilizers Limited: Strategic Renewal
Authors: Maheshwari Sunil Kumar , Ravichandran N. 
Published: December 2003

This case provides a comprehensive account of the origin, foundation, growth, managerial and operational problems, labor relationship, decline in performance, change of ownership, and the initiatives taken by the new management team to revive the company. Mangalore was an initiative by Karnataka State Government in India. Originally, MCFL was conceived as a private sector organization. Eventually it was converted to a state-owned public sector undertaking. There was no accountability for the senior managers in managing the plant. Often, they had to make a trade off between their loyalty to the elected representatives and the prosperity of MCFL. Invariably, the operating officers who were usually drawn from Indian Administrative Services chose to neglect the commercial prospects of MCFL. Erratic power supply and hostile labor situation (as a consequence of inappropriate labor policies) led to frequent shut down of the plant. Consequently, the financial health of the plant deteriorated. The precarious financial position made MCFL a candidate for either closure or for sale. The Indian Government, in an attempt to revive the plant, put MCFL through two rehabilitation packages supported by its Board and its financial institutions. Eventually, MCFL was sold to UB Group in 1990. The Chairman Mr. Mallya nominated a team from UB group to manage and revive MCFL. As of 2002, MCFL is a profit-generating organization. The management has to decide, how MCFL should grow from now onwards.
Gentran Machinery, Inc. (A)
Authors: Carl Pegels C. 
Published: December 2003

The two cases describe the problems associated with the implementation of an international manufacturing joint venture in China between an American construction machinery firm and its Chinese counterpart. Case (A) presents the major hurdles the partners had to deal with: cultural, language and management problems. The conflicts between the two sides were exasperated by the lack of Western exposure to Chinese managers and the strict hierarchical management system in the Chinese side of the joint venture. Case (A) does not propose solutions but certainly raises many issues that need resolution. Case (B) proposes solutions to the problems extensively described in the "A" case. General recommendations were proposed to address the following issues: (a) the general manager's position, power and authority in the joint venture, (b) the organizational design of the joint venture, (c) clarification of the responsibility of both parties, (d) reward system and appraisal system, (e) how to deal with both the Chinese and American incompetent managers, (f) how to deal with the communication problems, both language and cultural, and (g) final comprehensive and position outline of the potential of the joint venture.