bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ulex europaeus agglutinin II (UEA‐II) is a novel, potent inhibitor of complement activation
Authors: Lekowski Robert , Collard Charles D. , Reenstra Wende R. , Stahl Gregory L. 
Published: July 2002

AbstractComplement is an important mediator of vascular injury following oxidative stress. We recently demonstrated that complement activation following endothelial oxidative stress is mediated by mannose‐binding lectin (MBL) and activation of the lectin complement pathway. Here, we investigated whether nine plant lectins which have a binding profile similar to that of MBL competitively inhibit MBL deposition and subsequent complement activation following human umbilical vein endothelial cell (HUVEC) oxidative stress. HUVEC oxidative stress (1% O2, 24 hr) significantly increased Ulex europaeus agglutinin II (UEA‐II) binding by 72 ± 9% compared to normoxic cells. UEA‐II inhibited MBL binding to HUVEC in a concentration‐dependent manner following oxidative stress. Further, MBL inhibited UEA‐II binding to HUVEC in a concentration‐dependent manner following oxidative stress, suggesting a common ligand. UEA‐II (≤ 100 μmol/L) did not attenuate the hemolytic activity, nor did it inhibit C3a des Arg formation from alternative or classical complement pathway‐specific hemolytic assays. C3 deposition (measured by ELISA) following HUVEC oxidative stress was inhibited by UEA‐II in a concentration‐dependent manner (IC50 = 10 pmol/L). UEA‐II inhibited C3 and MBL co‐localization (confocal microscopy) in a concentration‐dependent manner on HUVEC following oxidative stress (IC50 ≈ 1 pmol/L). Finally, UEA‐II significantly inhibited complement‐dependent neutrophil chemotaxis, but failed to inhibit fMLP‐mediated chemotaxis, following endothelial oxidative stress. These data demonstrate that UEA‐II is a novel, potent inhibitor of human MBL deposition and complement activation following human endothelial oxidative stress.
Folding and stability of the b subunit of the F1F0 ATP synthase
Authors: Revington Matthew , Dunn Stanley D. , Shaw Gary S. 
Published: July 2002

AbstractThe F1F0 ATP synthase is a reversible molecular motor that employs a rotary catalytic cycle to couple a chemiosmotic membrane potential to the formation/hydrolysis of ATP. The multisubunit enzyme contains two copies of the b subunit that form a homodimer as part of a narrow, peripheral stalk structure that connects the membrane (F0) and soluble (F1) sectors. The three‐dimensional structure of the b subunit is unknown making the nature of any interactions or conformational changes within the F1F0 complex difficult to interpret. We have used circular dichroism and analytical ultracentrifugation analyses of a series of N‐ and C‐terminal truncated b proteins to investigate its stability and structure. Thermal denaturation of the b constructs exhibited distinct two‐state, cooperative unfolding with Tm values between 30 and 40°C. CD spectra for the region comprising residues 53–122 (b53–122) showed θ222/θ208 = 0.99, which reduced to 0.92 in the presence of the hydrophobic solvent trifluoroethanol. Thermodynamic parameters for b53–122 (ΔG, ΔH and ΔCp) were similar to those reported for several nonideal, coiled‐coil proteins. Together these results are most consistent with a noncanonical and unstable parallel coiled‐coil at the interface of the b dimer.
Strain‐specified relative conformational stability of the scrapie prion protein
Authors: Peretz David , Scott Michael R. , Groth Darlene , Williamson R. Anthony , Burton Dennis R. , Cohen Fred E. , Prusiner Stanley B. 
Published: July 2002

AbstractStudies of prion biology and diseases have elucidated several new concepts, but none was more heretical than the proposal that the biological properties that distinguish different prion strains are enciphered in the disease‐causing prion protein (PrPSc). To explore this postulate, we examined the properties of PrPSc from eight prion isolates that propagate in Syrian hamster (SHa). Using resistance to protease digestion as a marker for the undenatured protein, we examined the conformational stabilities of these PrPSc molecules. All eight isolates showed sigmoidal patterns of transition from native to denatured PrPSc as a function of increasing guanidine hydrochloride (GdnHCl) concentration. Half‐maximal denaturation occurred at a mean value of 1.48 M GdnHCl for the Sc237, HY, SHa(Me7), and MT‐C5 isolates, all of which have ∼75‐d incubation periods; a concentration of 1.08 M was found for the DY strain with a ∼170‐d incubation period and ∼1.25 M for the SHa(RML) and 139H isolates with ∼180‐d incubation periods. A mean value of 1.39 M GdnHCl for the Me7‐H strain with a ∼320‐d incubation period was found. Based on these results, the eight prion strains segregated into four distinct groups. Our results support the unorthodox proposal that distinct PrPSc conformers encipher the biological properties of prion strains.
Performance Evaluation of a Window Room Air Conditioner With
Microchannel Condensers
Authors: Kim Man-Hoe , Bullard Clark W. 
Published: July 2002

Abstract
A performance evaluation for a residential window air conditioning system with microchannel condensers has been performed. First, a series of wind-tunnel calorimeter tests were conducted for two different prototype microchannel heat exchangers. The measured heat transfer and pressure drop characteristics for the heat exchangers were then compared to calculated value for four conventional finned round-tube designs, which were obtained using a validated simulation model for identical air and refrigerant inlet conditions. Finally, two prototype microchannel condensers are installed in the system and system performance tests were conducted. System characteristics such as capacity, energy efficiency ratio, and suction and discharge pressures and temperatures are presented, and compared with those for the conventional system. Refrigerant charge requirements for a window air conditioner with a microchannel condenser can be decreased by 35 percent compared to the conventional baseline system. The condenser core volume and weight can be reduced by 55 and 35 percent, respectively.
Role of the Neurotransmitter Reuptake-Blocking Activity of Antidepressants in Reversing Chloroquine Resistance In Vitro in
Plasmodium falciparum
Authors: Taylor Dale , Walden Jason C. , Robins Ashley H. , Smith Peter J. 
Published: July 2002

ABSTRACT

Since the discovery of the chloroquine (CQ) resistance reversal properties of several different, structurally unrelated classes of compounds, including antidepressants, the way is again open to employ the aminoquinoline drugs to combat malaria effectively. In this study, CQ sensitivity was restored to varying extents in vitro in the CQ-resistant
Plasmodium falciparum
strain RSA11 by using the antidepressants amitriptyline, citalopram, oxaprotiline, and nomifensine. The 50% inhibitory concentrations (IC
50
) of CQ were reduced from 360 to as low as 11 nM when antidepressants were present. These particular antidepressants are highly specific for blocking the ATP-binding cassette transport protein-mediated reuptake of different neurotransmitters at the synaptic level. This study was aimed at determining the extent to which the neurotransmitter reuptake-blocking properties of these antidepressants play a role in the reversal process. None of the compounds or CQ-antidepressant combinations tested had innate antimalarial activity. No chemosensitizer or combination showed an increased CQ accumulation or significant shift in the IC
50
in the CQ-sensitive clone D10. Of the compounds tested, citalopram, a highly specific serotonin reuptake blocker, produced the largest shift observed in the IC
50
for the resistant isolate RSA11. No particular class of antidepressant was found to be better than any other at restoring CQ sensitivity. We conclude that the resistance-reversing properties of these compounds do not correlate with their activities as reuptake blockers.
Cloning and Nucleotide Sequence of the DNA Gyrase (
gyrA
) Gene from
Mycoplasma hominis
and Characterization of Quinolone-Resistant Mutants Selected In Vitro with Trovafloxacin
Authors: Bébéar C. M. , Grau O. , Charron A. , Renaudin H. , Gruson D. , Bébéar C. 
Published: July 2002

ABSTRACT

We report the cloning and characterization of the
gyrA
gene of the
Mycoplasma hominis
DNA gyrase, which was previously shown to be associated with quinolone resistance in this organism. The 2,733-bp
gyrA
gene encodes a protein of 911 amino acids with a calculated molecular mass of 102.5 kDa. As expected,
M. hominis
GyrA exhibits higher homology with the GyrA subunits of the gram-positive bacteria
Clostridium acetobutylicum
,
Bacillus subtilis
,
Streptococcus pneumoniae
, and
Staphylococcus aureus
than with its
Escherichia coli
counterpart. Knowing the entire sequence of the
gyrA
gene of
M. hominis
could be very useful for confirming the role of the GyrA subunit in fluoroquinolone resistance. Twenty-nine mutants of
M. hominis
were selected stepwise for resistance to trovafloxacin, a new potent fluoroquinolone, and their
gyrA
,
gyrB
,
parC
, and
parE
quinolone resistance-determining regions were characterized. Three rounds of selection yielded 3 first-step, 12 second-step, and 14 third-step mutants. The first-step mutants harbored a single substitution, Glu460→Lys (
E. coli
coordinates), in ParE. GyrA changes, Ser83→Leu, Glu87→Lys, and Ala119→Glu or Val, were found only in the second round of selection. At the third step, additional substitutions, at ParC Ser80, Ser81, and Glu84 and ParE Leu440, associated with high-level resistance to fluoroquinolones, appeared. Thus, high-level resistance to trovafloxacin required three steps and was associated with alterations in both fluoroquinolone targets. According to these genetic data, in
M. hominis
, as in
Staphylococcus aureus
and
Streptococcus pneumoniae
, topoisomerase IV seems to be the primary target of trovafloxacin.
Pentamidine Inhibition of Group I Intron Splicing in
Candida albicans
Correlates with Growth Inhibition
Authors: Miletti Karl E. , Leibowitz Michael J. 
Published: July 2002

ABSTRACT

We previously demonstrated that pentamidine, which has been clinically used against
Pneumocystis carinii
, inhibits in vitro a group I intron ribozyme from that organism. Another fungal pathogen,
Candida albicans
, also harbors a group I intron ribozyme (Ca.LSU) in the essential rRNA genes in almost half of the clinical isolates analyzed. To determine whether pentamidine inhibits Ca.LSU in vitro and in cells, phylogenetically closely related intron-containing (4-1) and intronless (62-1) strains were studied. Splicing in vitro of the Ca.LSU group I intron ribozyme was completely inhibited by pentamidine at 200 μM. On rich glucose medium, the intron-containing strain was more sensitive to growth inhibition by pentamidine than was the intronless strain, as measured by disk or broth microdilution assays. On rich glycerol medium, they were equally susceptible to pentamidine. At pentamidine levels selectively inhibiting the intron-containing strain (1 μM) in glucose liquid cultures, inhibition of splicing and rRNA maturation was detected by quantitative reverse transcription-PCR within 1 min with a 10- to 15-fold accumulation of precursor rRNA. No comparable effect was seen in the intronless strain. These results correlate the cellular splicing inhibition of Ca.LSU with the growth inhibition of strain 4-1 harboring Ca.LSU. Broth microdilution assays of 13
Candida
strains showed that intron-containing strains were generally more susceptible to pentamidine than the intronless strains. Our data suggest that ribozymes found in pathogenic microorganisms but absent in mammals may be targets for antimicrobial therapy.
In Vitro Comparison of Terbinafine and Itraconazole against
Penicillium marneffei
Authors: McGinnis Michael R. , Nordoff Nicole G. , Ryder Neil S. , Nunn Gary B. 
Published: July 2002

ABSTRACT

We evaluated terbinafine and itraconazole against 30 isolates of
Penicillium marneffei
using a modification of the National Committee for Clinical Laboratory Standards broth macrodilution MIC testing protocol for yeasts. The minimal fungicidal concentration (MFC) was determined by plating 100 μl from each MIC drug dilution having no growth onto Sabouraud glucose agar incubated at 30°C. The MFC was the dilution at which growth was absent at 72 h of incubation. The MICs, in micrograms per milliliter, were as follows: terbinafine, 0.03 to 1.0 (geometric mean titer, 0.09); itraconazole, 0.03 to 0.5 (geometric mean titer, 0.04). The MFCs, in micrograms per milliliter, were as follows: terbinafine, 0.03 to 8 (geometric mean titer, 2.60); itraconazole, 0.03 to 8 (geometric mean titer, 2.45). Primary fungicidal activity (MFC within 2 dilutions of MIC) was observed with terbinafine in eight isolates and with itraconazole in four isolates. The data indicate that terbinafine is active against
P. marneffei
in vitro and may have a previously unrealized role in the management of infections caused by this fungus.
Studies of the Novel Ketolide ABT-773: Transport, Binding to Ribosomes, and Inhibition of Protein Synthesis in
Streptococcus pneumoniae
Authors: Capobianco John O. , Cao ZhenSheng , Shortridge Virginia D. , Ma ZhenKun , Flamm Robert K. , Zhong Ping 
Published: July 2002

ABSTRACT

Macrolide resistance in
Streptococcus pneumoniae
has been associated with two main mechanisms: target modification by Erm methyltransferases and efflux by macrolide pumps. The ketolide ABT-773, which has a 3-keto group and no
l
-cladinose sugar, represents a new class of drugs with in vitro activity against a variety of resistant bacteria. Several approaches were undertaken to understand how ABT-773 was able to defeat resistance mechanisms. We demonstrated tighter ribosome binding of ABT-773 than erythromycin. We also showed that ABT-773 (i) accumulated in macrolide-sensitive
S. pneumoniae
at a higher rate than erythromycin, (ii) was able to bind with methylated ribosomes, though at lower affinities than with wild-type ribosomes, and (iii) accumulated in
S. pneumoniae
strains with the efflux-resistant phenotype.
Mutations at Four Distinct Regions of the
rpoB
Gene Can Reduce the Susceptibility of
Helicobacter pylori
to Rifamycins
Authors: Heep Markus , Odenbreit Stefan , Beck Daniela , Decker Jochen , Prohaska Elke , Rieger Ulrich , Lehn Norbert 
Published: July 2002

ABSTRACT

The transformation of a panel of
rpoB
mutations (codons 525 to 586) from rifampin-resistant donor strains into
Helicobacter pylori
2802A confirmed the MICs associated with the respective mutations.
RpoB
V149X random mutations were generated and induced different levels of resistance, depending on the replacement amino acid. Mutagenesis of the
rpoB
gene at codon position 701 (R701H) induced low-level resistance.
Effect of Oral Administration of Emtricitabine on Woodchuck Hepatitis Virus Replication in Chronically Infected Woodchucks
Authors: Korba Brent E. , Schinazi R. F. , Cote Paul , Tennant Bud C. , Gerin John L. 
Published: July 2002

ABSTRACT
Emtricitabine [(−)FTC] [(−)-β-2′,3′-dideoxy-5-fluoro-3′-thiacytidine] has been shown to be an effective inhibitor of hepatitis B virus (HBV) in cell culture, with a potency and selectivity that are essentially identical to those of lamivudine. The antiviral activity of oral administration of (−)FTC against WHV replication in chronically infected woodchucks, an established and predictive model for antiviral therapy against HBV, was examined in a placebo-controlled study. (−)FTC significantly reduced viremia and intrahepatic WHV replication in a dose-dependent manner that was comparable to the antiviral activity of lamivudine observed in previous studies conducted by our laboratories. No effect on the levels of hepatic WHV RNA or the levels of woodchuck hepatitis surface antigen or anti-woodchuck hepatitis surface and core antibodies in the serum of the treated animals was observed. No evidence of drug-related toxicity was observed in any of the animals treated.
In Vitro Reversion of Amphotericin B Resistance in
Leishmania donovani
by Poloxamer 188
Authors: Espuelas S. , Legrand P. , Loiseau P. M. , Bories C. , Barratt G. , Irache J. M. 
Published: July 2002

ABSTRACT

A micellar formulation of amphotericin B (AmB) solubilized with poloxamer 188 was evaluated against an AmB
Leishmania donovani
-resistant line. A concave isobologram showed a synergistic effect of this association against promastigotes. This result was confirmed with amastigotes since the 50% effective concentration of the new formulation was 100 times less than that of the control AmB formulation.
In Vitro Activities of the Glycylcycline GAR-936 against Gram-Positive Bacteria
Authors: Boucher Helen W. , Wennersten Christine B. , Eliopoulos George M. 
Published: July 2002

ABSTRACT

The in vitro activities of GAR-936, the 9-
t
-butylglycylamido derivative of minocycline, were compared with those of doxycycline, minocycline, and tetracycline against 527 gram-positive clinical isolates. GAR-936 inhibited all strains, including those resistant to other tetracyclines, at concentrations of ≤2 μg/ml, except two strains of JK diphtheroids for which the MIC was 4 μg/ml.
Prophylactic Effect of FK463, a Novel Antifungal Lipopeptide, against
Pneumocystis carinii
Infection in Mice
Authors: Ito Mamoru , Nozu Ryoko , Kuramochi Takashi , Eguchi Natsuko , Suzuki Shuzo , Hioki Kyoji , Itoh Toshio , Ikeda Fumiaki 
Published: July 2002

ABSTRACT

The prophylactic effect of FK463, a new water-soluble echinocandin-like lipopeptide with inhibitory activity against 1,3-β-
d
-glucan synthase, against
Pneumocystis carinii
infection was investigated with the severe combined immunodeficient (SCID) mouse model. Treatment with FK463, pentamidine, and saline only was performed for 6 weeks from the day after the SCID mice were inoculated intranasally with infected lung homogenates. FK463 at 0.2 or 1.0 mg/kg of body weight, pentamidine at 4 mg/kg, or saline was subcutaneously administered daily into the backs of the SCID mice. The effects of the drugs were evaluated by detection of
P. carinii
cysts in mouse lung homogenates by toluidine blue O staining, lung histology, and PCR amplification of a
P. carinii
-specific DNA fragment from the lungs.
P. carinii
cysts were detected in the lungs of all mice administered saline. In contrast, no cysts were detected in mice administered both doses of FK463 and pentamidine. A specific DNA fragment was amplified from all mice administered saline and at least half or more of the mice administered FK463 and pentamidine. These results indicate that FK463 acts on cyst wall formation but not on trophozoite proliferation and is extremely effective in preventing
P. carinii
-associated pneumonia. These results suggest that FK463 is potentially useful as a prophylactic agent against
P. carinii
infection.
Chloramphenicol-Sensitive
Escherichia coli
Strain Expressing the Chloramphenicol Acetyltransferase (
cat
) Gene
Authors: Potrykus Joanna , Wegrzyn Grzegorz 
Published: July 2002

ABSTRACT

An
Escherichia coli
strain (strain CM2555) bearing the chloramphenicol acetyltransferase (
cat
) gene was found to be sensitive to chloramphenicol. We demonstrate that the
cat
gene is efficiently expressed in strain CM2555. Our results suggest that decreased levels of acetyl coenzyme A in
cat
-expressing CM2555 cells in the presence of chloramphenicol may cause the bacterium to be sensitive to this antibiotic.
Bacteriocin Production in Vancomycin-Resistant and Vancomycin-Susceptible
Enterococcus
Isolates of Different Origins
Authors: Del Campo Rosa , Tenorio Carmen , Jiménez-Dı́az Rufino , Rubio Carmen , Gómez-Lus Rafael , Baquero Fernando , Torres Carmen 
Published: July 2002

ABSTRACT

Bacteriocin production was determined for 218
Enterococcus
isolates (
Enterococcus faecalis
[93] and
E. faecium
[125]) obtained from different origins (human clinical samples [87], human fecal samples [78], sewage [28], and chicken samples [25]) and showing different vancomycin susceptibility patterns (vancomycin resistant, all of them
vanA
positive [56], and vancomycin susceptible [162]). All enterococcal isolates were randomly selected except for the vancomycin-resistant ones. A total of 33 isolates of eight different bacterial genera were used as indicators for bacteriocin production. Forty-seven percent of the analyzed enterococcal isolates were bacteriocin producers (80.6% of
E. faecalis
and 21.6% of
E. faecium
isolates). The percentage of bacteriocin producers was higher among human clinical isolates (63.2%, 81.8% of vancomycin-resistant isolates and 60.5% of vancomycin-susceptible ones) than among isolates from the other origins (28 to 39.3%). Only one out of the 15 vancomycin-resistant isolates from human fecal samples was a bacteriocin producer, while 44.4% of fecal vancomycin-susceptible isolates were. The bacteriocin produced by the
vanA
-containing
E. faecium
strain RC714, named bacteriocin RC714, was further characterized. This bacteriocin activity was cotransferred together with the
vanA
genetic determinant to
E. faecalis
strain JH2-2. Bacteriocin RC714 was purified to homogeneity and its primary structure was determined by amino acid sequencing, showing an identity of 88% and a similarity of 92% with the previously described bacteriocin 31 from
E. faecalis
YI717. The presence of five different amino acids in bacteriocin RC714 suggest that this could be a new bacteriocin. The results obtained suggest that the epidemiology of vancomycin resistance may be influenced by different factors, including bacteriocin production.
Combination Effect of Vancomycin and β-Lactams against a
Staphylococcus
aureus
Strain, Mu3, with Heterogeneous Resistance to Vancomycin
Authors: Aritaka Nanae , Hanaki Hideaki , Cui Longzhu , Hiramatsu Keiichi 
Published: July 2002

ABSTRACT

We tested the combined activity of vancomycin and seven β-lactam antibiotics against
Staphylococcus aureus
clinical strain Mu3, which displays heterogeneous resistance to vancomycin. When combined with vancomycin, four of the seven tested β-lactams exhibited an additive effect at or near their MICs, while all showed an antagonistic effect at lower, sub-MIC levels. This study implicated the unpredictable nature of combination therapy of β-lactams and vancomycin against
S. aureus
with reduced susceptibility to vancomycin.