bluuebunny/crossref_metadata_2025_split huggingface dataset:
PMS-601, a New Platelet-Activating Factor Receptor Antagonist That Inhibits Human Immunodeficiency Virus Replication and Potentiates Zidovudine Activity in Macrophages
Authors: Martin M. , Serradji N. , Dereuddre-Bosquet N. , Le Pavec G. , Fichet G. , Lamouri A. , Heymans F. , Godfroid J. J. , Clayette P. , Dormont D. 
Published: July 2002

ABSTRACTWe assessed the anti-human immunodeficiency virus (anti-HIV) activity in vitro of new platelet-activating factor (PAF) receptor antagonists, as PAF and viral replication are thought to be involved in HIV neuropathogenesis. We found that PMS-601 inhibited proinflammatory cytokine synthesis and HIV replication in macrophages and potentiated the antiretroviral activity of zidovudine. These results suggest that PMS-601 is of potential value as an adjuvant treatment for HIV infection.
Pharmacokinetics of Ciprofloxacin in the Human Eye: a Clinical Study and Population Pharmacokinetic Analysis
Authors: Morlet Nigel , Graham Garry G. , Gatus Barrie , McLachlan Andrew J. , Salonikas Chris , Naidoo Daya , Goldberg Ivan , Lam Chi Man 
Published: July 2002

ABSTRACTCiprofloxacin, a fluoroquinolone antibiotic active against a wide variety of bacteria, is one of a few antibiotics which enters the human eye after oral administration. However, little is known about its pharmacokinetics in the human eye. One or two oral doses of 750 mg of ciprofloxacin (at a 12-h interval) were administered to 48 patients at various times prior to ocular surgery. Clotted blood, aqueous, and vitreous were collected at surgery, and the concentrations of ciprofloxacin were assayed by high-performance liquid chromatography. Our data were combined with those of others, and a population pharmacokinetic analysis was conducted. The concentrations of ciprofloxacin in both aqueous and vitreous were lower than those in serum and peaked at a later time. The pharmacokinetics of ciprofloxacin in aqueous and vitreous were fitted to a compartmental model in which the antibiotic was transferred into and out of the two compartments (aqueous and vitreous) by first-order processes. Population pharmacokinetic software, P-Pharm, was used to calculate the mean half-lives of the loss of ciprofloxacin from aqueous and vitreous, which were 3.5 and 5.3 h, respectively. At steady state, the mean ratios of then concentrations in aqueous and vitreous to the concentrations in serum were 23 and 17%, respectively. After the administration of one or two doses of 750 mg of ciprofloxacin, the concentrations in both aqueous and vitreous in a number of patients were lower than the MICs at which 90% of isolates are inhibited (0.5 mg/liter) for common intraocular bacterial pathogens. Simulations of concentrations in the eye after the administration of higher doses (1,500 mg of ciprofloxacin as a single dose, two doses of 750 mg 2 h apart, and 750 mg every 6 h) indicated that in approximately 20% of patients the concentrations would still be below 0.5 mg/liter. Although oral ciprofloxacin may be a beneficial adjunctive therapy, the use of oral ciprofloxacin alone may not be adequate for perioperative prophylaxis or for treatment of bacterial endophthalmitis.
Pharmacokinetic Profile and Tolerability of Indinavir-Ritonavir Combinations in Healthy Volunteers
Authors: Saah Alfred J. , Winchell Gregory A. , Nessly Michael L. , Seniuk Melissa A. , Rhodes Rand R. , Deutsch Paul J. 
Published: July 2002

ABSTRACT

This was a randomized, double-blind, placebo-controlled parallel study in human immunodeficiency virus type 1 (HIV-1)-uninfected healthy subjects to investigate the pharmacokinetic interaction between indinavir (IDV) and ritonavir (RTV). Subjects were allocated to treatment groups of IDV given with RTV in the following milligram doses twice daily: 800 mg of IDV-100 mg of RTV (800-100 mg), 800-200, 800-400, and 400-400 mg, placebo of IDV with RTV doses of 100, 200, and 400 mg, and placebo of both IDV and RTV. Doses of both drugs were administered for 14 days with a low-fat meal and one dose on day 15 with a high-fat meal. Blood was obtained for drug concentration measurements on days 14 and 15. Seventy-three volunteers enrolled in the study: 29 men and 44 women. Fifty-three volunteers completed the study. When compared to standard historical data for 800 mg of IDV every 8 h (q8h), the IDV area under the concentration-time curve for 24 h (AUC
24
) of IDV-RTV regimens 400-400, 800-100, and 800-200 mg were at least 1.4, 2.3, and 3.3 times higher, respectively, regardless of meal. The concentrations at the end of the dosing interval were 10 to 25 times higher than that observed in the standard regimen of 800 mg of IDV q8h for IDV-RTV 800-100 and 800-200 mg regimens, respectively. RTV at 200 mg maximally enhanced the IDV profile. Improved tolerability was associated with IDV-RTV 800-100 mg versus IDV-RTV 800-200, 800-400, and 400-400 mg q12h. The advantages of IDV-RTV twice daily over 800 mg of IDV q8h include no food restrictions and twice-daily dosing. Also, the regimens achieve levels of IDV that may be helpful in suppressing strains of HIV-1 that have reduced susceptibility to IDV or other protease inhibitors.
Effects of Miltefosine and Other Alkylphosphocholines on Human Intestinal Parasite
Entamoeba histolytica
Authors: Seifert Karin , Duchêne Michael , Wernsdorfer Walther H. , Kollaritsch Herwig , Scheiner Otto , Wiedermann Gerhard , Hottkowitz Thomas , Eibl Hansjörg 
Published: July 2002

ABSTRACT

The protozoan parasite
Entamoeba histolytica
is the cause of amoebic dysentery and liver abscess. It is therefore responsible for significant morbidity and mortality in a number of countries. Infections with
E. histolytica
are treated with nitroimidazoles, primarily with metronidazole. At this time, there is a lack of useful alternative classes of substances for the treatment of invasive amoebiasis. Alkylphosphocholines (alkyl-PCs) such as hexadecyl-PC (miltefosine) were originally developed as antitumor agents, but recently they have been successfully used for the treatment of visceral leishmaniasis in humans. We examined hexadecyl-PC and several other alkyl-PCs with longer alkyl chains, with and without double bond(s), for their activity against two strains of
E. histolytica
. The compounds with the highest activity were oleyl-PC, octadecyl-PC, and nonadecenyl-PC, with 50% effective concentrations for 48 h of treatment between 15 and 21 μM for strain SFL-3 and between 73 and 98 μM for strain HM-1:IMSS. We also tested liposomal formulations of these alkyl-PCs and miltefosine. The alkyl-PC liposomes showed slightly lower activity, but are expected to be well tolerated. Liposomal formulations of oleyl-PC or closely related alkyl-PCs could be promising candidates for testing as broad-spectrum antiprotozoal and antitumor agents in humans.
Inhibitory Activities of Lansoprazole against Respiration in
Helicobacter pylori
Authors: Nagata Kumiko , Sone Nobuhito , Tamura Toshihide 
Published: July 2002

ABSTRACT

Lansoprazole and its derivative AG-1789 dose-dependently inhibited cellular respiration by an endogenous substrate and decreased the ATP level in
Helicobacter pylori
cells. The inhibitory action of lansoprazole and AG-1789 against respiration was specific to substrates such as pyruvate and α-ketoglutarate and similar to the inhibitory action of rotenone, which is an inhibitor for the mitochondrial respiratory chain. Growth inhibition by lansoprazole and AG-1789 as well as by rotenone was augmented at high oxygen concentrations under atmospheric conditions. Since the 50% inhibitory concentrations of these compounds for the respiration were close to their MICs for
H. pylori
growth, the growth inhibition might be due to respiratory inhibition by these compounds.
Activities of Polymyxin B and Cecropin A-Melittin Peptide CA(1-8)M(1-18) against a Multiresistant Strain of
Acinetobacter baumannii
Authors: Saugar José María , Alarcón Teresa , López-Hernández Susana , López-Brea Manuel , Andreu David , Rivas Luis 
Published: July 2002

ABSTRACT

Polymyxin B (PXB) and the cecropin A-melittin hybrid CA(1-8)M(1-18) (KWKLFKKIGIGAVLKVLTTGLPALIS-NH
2
) were compared for antibiotic activity on reference and multiresistant
Acinetobacter baumannii
strains. Significant differences for both peptides were observed on their inner membrane interaction and inhibition by environmental factors, supporting the use of CA(1-8)M(1-18) as a potential alternative to PXB against
Acinetobacter
.
Application of 5′-Nuclease PCR for Quantitative Detection of
Listeria monocytogenes
in Pure Cultures, Water, Skim Milk, and Unpasteurized Whole Milk
Authors: Nogva Hege Karin , Rudi Knut , Naterstad Kristine , Holck Askild , Lillehaug Dag 
Published: July 2002

ABSTRACT

PCR techniques have significantly improved the detection and identification of bacterial pathogens. Countless adaptations and applications have been described, including quantitative PCR and the latest innovation, real-time PCR. In real-time PCR, e.g., the 5′-nuclease chemistry renders the automated and direct detection and quantification of PCR products possible (P. M. Holland et al., Proc. Natl. Acad. Sci. USA 88:7276–7280, 1991). We present an assay for the quantitative detection of
Listeria monocytogenes
based on the 5′-nuclease PCR using a 113-bp amplicon from the listeriolysin O gene (
hlyA
) as the target. The assay was positive for all isolates of
L. monocytogenes
tested (65 isolates including the type strain) and negative for all other
Listeria
strains (16 isolates from five species tested) and several other bacteria (18 species tested). The application of 5′-nuclease PCR in diagnostics requires a quantitative sample preparation step. Several magnetic bead-based strategies were evaluated, since these systems are simple and relatively easy to automate. The combination of nonspecific binding of bacteria to paramagnetic beads, with subsequent DNA purification by use of the same beads, gave the most satisfactory result. The detection limit was approximately 6 to 60 CFU, quantification was linear over at least 7 log units, and the method could be completed within 3 h. In conclusion, a complete quantitative method for
L. monocytogenes
in water and in skimmed and raw milk was developed.
Simultaneous Enhancement of Thermostability and Catalytic Activity of Phospholipase A
1
by Evolutionary Molecular Engineering
Authors: Song Jae Kwang , Rhee Joon Shick 
Published: July 2002

ABSTRACT

The thermal stability and catalytic activity of phospholipase A
1
from
Serratia
sp. strain MK1 were improved by evolutionary molecular engineering. Two thermostable mutants were isolated after sequential rounds of error-prone PCR performed to introduce random mutations and filter-based screening of the resultant mutant library; we determined that these mutants had six (mutant TA3) and seven (mutant TA13) amino acid substitutions. Different types of substitutions were found in the two mutants, and these substitutions resulted in an increase in nonploar residues (mutant TA3) or in differences between side chains for polar or charged residues (mutant TA13). The wild-type and mutant enzymes were purified, and the effect of temperature on the stability and catalytic activity of the enzymes was investigated. The melting temperatures of the TA3 and TA13 enzymes were increased by 7 and 11°C, respectively, compared with the melting temperature of the wild-type enzyme. Thus, we found that evolutionary molecular engineering was an effective and efficient approach for increasing thermostability without compromising enzyme activity.
Inactivation of Isocitrate Lyase Leads to Increased Production of Medium-Chain-Length Poly(3-Hydroxyalkanoates) in
Pseudomonas putida
Authors: Klinke Stefan , Dauner Michael , Scott George , Kessler Birgit , Witholt Bernard 
Published: July 2002

ABSTRACT

Medium-chain-length (mcl) poly(3-hydroxyalkanoates) (PHAs) are storage polymers that are produced from various substrates and accumulate in
Pseudomonas
strains belonging to rRNA homology group I. In experiments aimed at increasing PHA production in
Pseudomonas
strains, we generated an mcl PHA-overproducing mutant of
Pseudomonas putida
KT2442 by transposon mutagenesis, in which the
aceA
gene was knocked out. This mutation inactivated the glyoxylate shunt and reduced the in vitro activity of isocitrate dehydrogenase, a rate-limiting enzyme of the citric acid cycle. The genotype of the mutant was confirmed by DNA sequencing, and the phenotype was confirmed by biochemical experiments. The
aceA
mutant was not able to grow on acetate as a sole carbon source due to disruption of the glyoxylate bypass and exhibited two- to fivefold lower isocitrate dehydrogenase activity than the wild type. During growth on gluconate, the difference between the mean PHA accumulation in the mutant and the mean PHA accumulation in the wild-type strain was 52%, which resulted in a significant increase in the amount of mcl PHA at the end of the exponential phase in the mutant
P. putida
KT217. On the basis of a stoichiometric flux analysis we predicted that knockout of the glyoxylate pathway in addition to reduced flux through isocitrate dehydrogenase should lead to increased flux into the fatty acid synthesis pathway. Therefore, enhanced carbon flow towards the fatty acid synthesis pathway increased the amount of mcl PHA that could be accumulated by the mutant.
A Spore Counting Method and Cell Culture Model for Chlorine Disinfection Studies of
Encephalitozoon
syn.
Septata intestinalis
Authors: Wolk D. M. , Johnson C. H. , Rice E. W. , Marshall M. M. , Grahn K. F. , Plummer C. B. , Sterling C. R. 
Published: July 2002

ABSTRACT

The microsporidia have recently been recognized as a group of pathogens that have potential for waterborne transmission; however, little is known about the effects of routine disinfection on microsporidian spore viability. In this study, in vitro growth of
Encephalitozoon
syn.
Septata intestinalis
, a microsporidium found in the human gut, was used as a model to assess the effect of chlorine on the infectivity and viability of microsporidian spores. Spore inoculum concentrations were determined by using spectrophotometric measurements (percent transmittance at 625 nm) and by traditional hemacytometer counting. To determine quantitative dose-response data for spore infectivity, we optimized a rabbit kidney cell culture system in 24-well plates, which facilitated calculation of a 50% tissue culture infective dose (TCID
50
) and a minimal infective dose (MID) for
E. intestinalis
. The TCID
50
is a quantitative measure of infectivity and growth and is the number of organisms that must be present to infect 50% of the cell culture wells tested. The MID is as a measure of a system's permissiveness to infection and a measure of spore infectivity. A standardized MID and a standardized TCID
50
have not been reported previously for any microsporidian species. Both types of doses are reported in this paper, and the values were used to evaluate the effects of chlorine disinfection on the in vitro growth of microsporidia. Spores were treated with chlorine at concentrations of 0, 1, 2, 5, and 10 mg/liter. The exposure times ranged from 0 to 80 min at 25°C and pH 7. MID data for
E. intestinalis
were compared before and after chlorine disinfection. A 3-log reduction (99.9% inhibition) in the
E. intestinalis
MID was observed at a chlorine concentration of 2 mg/liter after a minimum exposure time of 16 min. The log
10
reduction results based on percent transmittance-derived spore counts were equivalent to the results based on hemacytometer-derived spore counts. Our data suggest that chlorine treatment may be an effective water treatment for
E. intestinalis
and that spectrophotometric methods may be substituted for labor-intensive hemacytometer methods when spores are counted in laboratory-based chlorine disinfection studies.
Mutagenesis of Asp-569 of Glucosyltransferase I Glucansucrase Modulates Glucan and Oligosaccharide Synthesis
Authors: Monchois Vincent , Vignon Michel , Russell Roy R. B. 
Published: July 2002

ABSTRACT

Glucansucrases of oral streptococci and
Leuconostoc mesenteroides
are enzymes of medical and biotechnological interest that synthesize α-glucans. They can also synthesize oligosaccharides in the presence of a sugar acceptor. Previous reports have identified an amino acid residue that may affect the structure of the glucan product; therefore, random mutagenesis of the corresponding Asp-569 of
Streptococcus downei
glucosyltransferase I (GTF-I) was used to further understanding of its involvement in the catalytic mechanism and to evaluate how different amino acids can modulate glucan and oligosaccharide synthesis. GTF-I variants were obtained where Asp-569 was replaced by each of the different possible classes of amino acids. These were expressed in
Escherichia coli
and purified by means of a His
6
tag. The results showed that the amino acid in position 569 influences the structure of the glucan and the size of the oligosaccharides produced by GTF-I. The results suggest that the amino acid occupying this position is more likely to interact with the acceptor molecules (oligosaccharides or elongating glucan chain) than to be directly involved in glucosyl transfer from sucrose. Engineering of the equivalent position in glucansucrases thus appears to be a good target to expand the range of oligosaccharides synthesized.
Characterization of an Atrazine-DegradingPseudaminobactersp. Isolated from Canadian and French Agricultural Soils
Authors: Topp Edward , Zhu Hong , Nour Sarah M. , Houot Sabine , Lewis Melanie , Cuppels Diane 
Published: July 2002

ABSTRACTAtrazine, a herbicide widely used in corn production, is a frequently detected groundwater contaminant. Fourteen bacterial strains able to use this herbicide as a sole source of nitrogen were isolated from soils obtained from two farms in Canada and two farms in France. These strains were indistinguishable from each other based on repetitive extragenic palindromic PCR genomic fingerprinting performed with primers ERIC1R, ERIC2, and BOXA1R. Based on 16S rRNA sequence analysis of one representative isolate, strain C147, the isolates belong to the genusPseudaminobacterin the familyRhizobiaceae. Strain C147 did not form nodules on the legumes alfalfa (Medicago sativaL.), birdsfoot trefoil (Lotus corniculatusL.), red clover (Trifolium pratenseL.), chickpea (Cicer arietinumL.), and soybean (Glycine maxL.). A number of chloro-substituteds-triazine herbicides were degraded, but methylthio-substituteds-triazine herbicides were not degraded. Based on metabolite identification data, the fact that oxygen was not required, and hybridization of genomic DNA to theatzABCgenes, atrazine degradation occurred via a series of hydrolytic reactions initiated by dechlorination and followed by dealkylation. Most strains could mineralize [ring-U-14C]atrazine, and those that could not mineralize atrazine lackedatzBoratzBC. TheatzABCgenes, which were plasmid borne in every atrazine-degrading isolate examined, were unstable and were not always clustered together on the same plasmid. Loss ofatzBwas accompanied by loss of a copy of IS1071. Our results indicate that an atrazine-degradingPseudaminobactersp. with remarkably little diversity is widely distributed in agricultural soils and that genes of the atrazine degradation pathway carried by independent isolates of this organism are not clustered, can be independently lost, and may be associated with a catabolic transposon. We propose that the widespread distribution of the atrazine-degradingPseudaminobactersp. in agricultural soils exposed to atrazine is due to the characteristic ability of this organism to utilize alkylamines, and therefore atrazine, as sole sources of carbon when theatzABCgenes are acquired.
Correlation of Activities of the Enzymes α-Phosphoglucomutase, UDP-Galactose 4-Epimerase, and UDP-Glucose Pyrophosphorylase with Exopolysaccharide Biosynthesis by
Streptococcus thermophilus
LY03
Authors: Degeest Bart , De Vuyst Luc 
Published: July 2002

ABSTRACT

The effects of different carbohydrates or mixtures of carbohydrates as substrates on bacterial growth and exopolysaccharide (EPS) production were studied for the yoghurt starter culture
Streptococcus thermophilus
LY03. This strain produces two heteropolysaccharides with the same monomeric composition (galactose and glucose in the ratio 4:1) but with different molecular masses. Lactose and glucose were fermented by
S. thermophilus
LY03 only when they were used as sole energy and carbohydrate sources. Fructose was also fermented when it was applied in combination with lactose or glucose. Both the amount of EPS produced and the carbohydrate source consumption rates were clearly influenced by the type of energy and carbohydrate source used, while the EPS monomeric composition remained constant (galactose-glucose, 4:1) under all circumstances. A combination of lactose and glucose resulted in the largest amounts of EPS. Measurements of the activities of enzymes involved in EPS biosynthesis, and of those involved in sugar nucleotide biosynthesis and the Embden-Meyerhof-Parnas pathway, demonstrated that the levels of activity of α-phosphoglucomutase, UDP-galactose 4-epimerase, and UDP-glucose pyrophosphorylase are highly correlated with the amount of EPS produced. Furthermore, a weaker relationship or no relationship between the amounts of EPS and the enzymes involved in either the rhamnose nucleotide synthetic branch of the EPS biosynthesis or the pathway leading to glycolysis was observed for
S. thermophilus
LY03.
Quantitative Approach in the Study of Adhesion of Lactic Acid Bacteria to Intestinal Cells and Their Competition with Enterobacteria
Authors: Lee Y. K. , Lim C. Y. , Teng W. L. , Ouwehand A. C. , Tuomola E. M. , Salminen S. 
Published: July 2002

ABSTRACT

To describe the phenomena of bacterial adhesion to intestinal cells and the competition for adhesion between bacteria, mathematical equations based on a simple dissociation process involving a finite number of bacterial receptors on intestinal cell surface were developed. The equations allow the estimation of the maximum number of
Lactobacillus
sp. and
Escherichia coli
cells that can adhere to Caco-2 cells and intestinal mucus; they also characterize the affinity of the bacteria to Caco-2 cells and intestinal and fecal mucus and the theoretical adhesion ratio of two bacteria present in a mixed suspension. The competition for adhesion between
Lactobacillus rhamnosus
GG and
E. coli
TG1 appeared to follow the proposed kinetics, whereas the competition between
Lactobacillus casei
Shirota and
E. coli
TG1 may involve multiple adhesion sites or a soluble factor in the culture medium of the former. The displacement of the adhered
Lactobacillus
by
E. coli
TG1 seemed to be a rapid process, whereas the displacement of
E. coli
TG1 by the
Lactobacillus
took more than an hour.
First Evidence of Lysogeny in
Propionibacterium freudenreichii
subsp.
shermanii
Authors: Hervé C. , Coste A. , Rouault A. , Fraslin J. M. , Gautier M. 
Published: July 2002

ABSTRACT

Dairy propionic acid bacteria, particularly the species
Propionibacterium freudenreichii
, play a major role in the ripening of Swiss type cheese. Isometric and filamentous bacteriophages infecting
P. freudenreichii
have previously been isolated from cheese. In order to determine the origin of these bacteriophages, lysogeny of
P. freudenreichii
was determined by isometric bacteriophage type analysis. The genomic DNA of 76 strains were hybridized with the DNA of nine bacteriophages isolated from Swiss type cheeses, and the DNA of 25 strains exhibited strong hybridization. Three of these strains released bacteriophage particules following UV irradiation (254 nm) or treatment with low concentrations of mitomycin C. A prophage-cured derivative of
P. freudenreichii
was readily isolated and subsequently relysogenized. Lysogeny was therefore formally demonstrated in
P. freudenreichii
.