bluuebunny/crossref_metadata_2025_split huggingface dataset:
Two-Dimensional Simulations of Enhanced Heat Transfer in an
Intermittently Grooved Channel
Authors: Greiner M. , Fischer P. F. , Tufo H. M. 
Published: July 2002

Abstract
Two-dimensional Navier-Stokes simulations of heat and momentum transport in an intermittently grooved passage are performed using the spectral element technique for the Reynolds number range 600⩽Re⩽1800. The computational domain has seven contiguous transverse grooves cut symmetrically into opposite walls, followed by a flat section with the same length. Periodic inflow/outflow boundary conditions are employed. The development and decay of unsteady flow is observed in the grooved and flat sections, respectively. The axial variation of the unsteady component of velocity is compared to the local heat transfer, shear stress and pressure gradient. The results suggest that intermittently grooved passages may offer even higher heat transfer for a given pumping power than the levels observed in fully grooved passages.
Purification and Biochemical Characterization of the VIM-1 Metallo-β-Lactamase
Authors: Franceschini Nicola , Caravelli Berardo , Docquier Jean-Denis , Galleni Moreno , Frère Jean-Marie , Amicosante Gianfranco , Rossolini Gian Maria 
Published: July 2002

ABSTRACT

VIM-1 is a new group 3 metallo-β-lactamase recently detected in carbapenem-resistant nosocomial isolates of
Pseudomonas aeruginosa
from the Mediterranean area. In this work, VIM-1 was purified from an
Escherichia coli
strain carrying the cloned
bla
VIM-1
gene by means of an anion-exchange chromatography step followed by a gel permeation chromatography step. The purified enzyme exhibited a molecular mass of 26 kDa in sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and an acidic pI of 5.1 in analytical isoelectric focusing. Amino-terminal sequencing showed that mature VIM-1 results from the removal of a 26-amino-acid signal peptide from the precursor. VIM-1 hydrolyzes a broad array of β-lactam compounds, including penicillins, narrow- to expanded-spectrum cephalosporins, carbapenems, and mechanism-based serine-β-lactamase inactivators. Only monobactams escape hydrolysis. The highest catalytic constant/

K
m

ratios (>10
6
M
−1
· s
−1
) were observed with carbenicillin, azlocillin, some cephalosporins (cephaloridine, cephalothin, cefuroxime, cefepime, and cefpirome), imipenem, and biapenem. Kinetic parameters showed remarkable variability with different β-lactams and also within the various penam, cephem, and carbapenem compounds, resulting in no clear preference of the enzyme for any of these β-lactam subfamilies. Significant differences were observed with some substrates between the kinetic parameters of VIM-1 and those of other metallo-β-lactamases. Inactivation assays carried out with various chelating agents (EDTA, 1,10-
o
-phenanthroline, and pyridine-2,6-dicarboxylic acid) indicated that formation of a ternary enzyme-metal-chelator complex precedes metal removal from the zinc center of the protein and revealed notable differences in the inactivation parameters of VIM-1 with different agents.
Impact of Flavophospholipol and Vancomycin on Conjugational Transfer of Vancomycin Resistance Plasmids
Authors: Riedl Sabine , Ohlsen Knut , Werner Guido , Witte Wolfgang , Hacker Jörg 
Published: July 2002

ABSTRACT

The influence of vancomycin and flavophospholipol (FPL) on the transfer rate of conjugative plasmids harboring the vancomycin resistance operon
vanA
was determined in several clinical and animal isolates of
Enterococcus faecium
. FPL significantly inhibited the frequency of transfer of conjugative VanA plasmids up to 70-fold. Vancomycin had no significant effect on the transfer rate of VanA plasmids.
Broad-Spectrum Antiviral Activity of the IMP Dehydrogenase Inhibitor VX-497: a Comparison with Ribavirin and Demonstration of Antiviral Additivity with Alpha Interferon
Authors: Markland W. , McQuaid T. J. , Jain J. , Kwong A. D. 
Published: July 2002

ABSTRACTThe enzyme IMP dehydrogenase (IMPDH) catalyzes an essential step in the de novo biosynthesis of guanine nucleotides, namely, the conversion of IMP to XMP. The major event occurring in cells exposed to competitive IMPDH inhibitors such as ribavirin or uncompetitive inhibitors such as mycophenolic acid (MPA) is a depletion of the intracellular GTP and dGTP pools. Ribavirin is approved as an inhaled antiviral agent for treatment of respiratory syncytial virus (RSV) infection and orally, in combination with alpha interferon (IFN-α), for the treatment of chronic hepatitis C virus (HCV) infection. VX-497 is a potent, reversible uncompetitive IMPDH inhibitor which is structurally unrelated to other known IMPDH inhibitors. Studies were performed to compare VX-497 and ribavirin in terms of their cytotoxicities and their efficacies against a variety of viruses. They included DNA viruses (hepatitis B virus [HBV], human cytomegalovirus [HCMV], and herpes simplex virus type 1 [HSV-1]) and RNA viruses (respiratory syncytial virus [RSV], parainfluenza-3 virus, bovine viral diarrhea virus, Venezuelan equine encephalomyelitis virus [VEEV], dengue virus, yellow fever virus, coxsackie B3 virus, encephalomyocarditis virus [EMCV], and influenza A virus). VX-497 was 17- to 186-fold more potent than ribavirin against HBV, HCMV, RSV, HSV-1, parainfluenza-3 virus, EMCV, and VEEV infections in cultured cells. The therapeutic index of VX-497 was significantly better than that of ribavirin for HBV and HCMV (14- and 39-fold, respectively). Finally, the antiviral effect of VX-497 in combination with IFN-α was compared to that of ribavirin with IFN-α in the EMCV replication system. Both VX-497 and ribavirin demonstrated additivity when coapplied with IFN-α, with VX-497 again being the more potent in this combination. These data are supportive of the hypothesis that VX-497, like ribavirin, is a broad-spectrum antiviral agent.
In Vitro Assessment of Antifungal Therapeutic Potential of Salivary Histatin-5, Two Variants of Histatin-5, and Salivary Mucin (MUC7) Domain 1
Authors: Situ Hongsa , Bobek Libuse A. 
Published: July 2002

ABSTRACT

Human salivary histatin-5 (Hsn-5) is a 24-residue peptide that possesses potent antifungal activity in vitro. The
MUC7
gene encodes human salivary low-molecular-weight mucin (MG2). The candidacidal activity of MUC7 domain 1 (MUC7 D1, the N-terminal 51 amino acid residues of MUC7) in vitro has also been demonstrated. In this study, we have investigated the antifungal therapeutic potential of Hsn-5, its two variants, R12I/K17N and R12I/H21L, and MUC7 D1. First, these peptides were tested for activities against different clinically important fungi. We found them to possess broad-spectrum antifungal activities; specifically, most exhibited excellent in vitro activity against eight clinically important fungal strains tested, including
Candida albicans
and
Candida glabrata
and their azole-resistant counterparts and
Cryptococcus neoformans
and its amphotericin B-resistant counterpart. These findings also suggest that the mechanism of action of both Hsn-5 and MUC7 D1 for these fungi is different from that of amphotericin B or azole antifungal agents. Second, we examined the stability of these peptides in whole human saliva and human serum. In saliva, the Hsn-5 variants R12I/K17N and R12I/H21L and MUC7 D1 degraded at a lower rate than Hsn-5. In human serum, MUC7 D1 was also more stable than Hsn-5; both peptides were more stable in serum than in saliva. Third, we examined the cytotoxicity of these peptides using human erythrocytes and two human cell lines (KB and HSG). No (or very low) hemolytic activity was observed with any of the four peptides, even at the highest protein concentration tested (200 μM), while amphotericin B caused 100% hemolysis at only 12.5 μM. The toxic effects of Hsn-5 and MUC7 D1 toward KB and HSG cells were also much lower than that of amphotericin B as measured by trypan blue exclusion. Together, these findings indicate that the investigated peptides possess high antifungal therapeutic potential, in particular for the treatment of drug-resistant fungal strains associated with immunocompromised (particularly human immunodeficiency virus-infected) patients. The same peptides could also be used as components of artificial saliva for patients with salivary dysfunction.
Role of Human Immunodeficiency Virus (HIV) Type 1 Envelope in the Anti-HIV Activity of the Betulinic Acid Derivative IC9564
Authors: Holz-Smith Sonia L. , Sun I-Chen , Jin Lei , Matthews Thomas J. , Lee Kuo-Hsiung , Chen Chin Ho 
Published: July 2002

ABSTRACT
The betulinic acid derivative IC9564 is a potent anti-human immunodeficiency virus (anti-HIV) compound that can inhibit both HIV primary isolates and laboratory-adapted strains. However, this compound did not affect the replication of simian immunodeficiency virus and respiratory syncytial virus. Results from a syncytium formation assay indicated that IC9564 blocked HIV type 1 (HIV-1) envelope-mediated membrane fusion. Analysis of a chimeric virus derived from exchanging envelope regions between IC9564-sensitive and IC9564-resistant viruses indicated that regions within gp120 and the N-terminal 25 amino acids (fusion domain) of gp41 are key determinants for the drug sensitivity. By developing a drug-resistant mutant from the NL4-3 virus, two mutations were found within the gp120 region and one was found within the gp41 region. The mutations are G237R and R252K in gp120 and R533A in the fusion domain of gp41. The mutations were reintroduced into the NL4-3 envelope and analyzed for their role in IC9564 resistance. Both of the gp120 mutations contributed to the drug sensitivity. On the contrary, the gp41 mutation (R533A) did not appear to affect the IC9564 sensitivity. These results suggest that HIV-1 gp120 plays a key role in the anti-HIV-1 activity of IC9564.
In Vitro Susceptibility of
Coxiella burnetii
to Linezolid in Comparison with Its Susceptibilities to Quinolones, Doxycycline, and Clarithromycin
Authors: Gikas Achilleas , Spyridaki Ioanna , Scoulica Efstathia , Psaroulaki Anna , Tselentis Yannis 
Published: July 2002

ABSTRACT

The in vitro susceptibility to linezolid shown by nine Greek isolates of
Coxiella burnetii
derived from patients with acute Q fever was investigated. MICs of linezolid were compared with those of pefloxacin, ciprofloxacin, ofloxacin, trovafloxacin, doxycycline, and clarithromycin using the shell vial assay. MICs of linezolid and clarithromycin ranged from 2 to 4 μg/ml; those of doxycycline, trovafloxacin, and ofloxacin ranged from 1 to 2 μg/ml; those of pefloxacin ranged from 1 to 4 μg/ml; and those of ciprofloxacin ranged from 4 to 8 μg/ml. Linezolid was effective in controlling intracellular parasites in cultures of Vero cells infected by
C
.
burnetii
. No bactericidal activity by linezolid was obtained against
C
.
burnetii
at 8 μg/ml.
Interactions of Posaconazole and Flucytosine againstCryptococcus neoformans
Authors: Barchiesi Francesco , Schimizzi Anna Maria , Najvar Laura K. , Bocanegra Rosie , Caselli Francesca , Di Cesare Simona , Giannini Daniele , Di Francesco Luigi Falconi , Giacometti Andrea , Carle Flavia , Scalise Giorgio , Graybill John R. 
Published: July 2002

ABSTRACTA checkerboard methodology, based on standardized methods proposed by the National Committee for Clinical Laboratory Standards for broth microdilution antifungal susceptibility testing, was applied to study the in vitro interactions of flucytosine (FC) and posaconazole (SCH 56592) (FC-SCH) against 15 isolates ofCryptococcus neoformans. Synergy, defined as a fractional inhibitory concentration (FIC) index of <0.50, was observed for 33% of the isolates tested. When synergy was not achieved, there was still a decrease in the MIC of one or both drugs when they were used in combination. Antagonism, defined as a FIC of >4.0, was not observed. The in vitro efficacy of combined therapy was confirmed by quantitative determination of the CFU ofC. neoformans486, an isolate against which the FC-SCH association yielded a synergistic interaction. To investigate the potential beneficial effects of this combination therapy in vivo, we established two experimental murine models of cryptococcosis by intracranial or intravenous injection of cells ofC. neoformans486. At 1 day postinfection, the mice were randomized into different treatment groups. One group each received each drug alone, and one group received the drugs in combination. While combination therapy was not found to be significantly more effective than each single drug in terms of survival, tissue burden experiments confirmed the potentiation of antifungal activity with the combination. Our study demonstrates that SCH and FC combined are significantly more active than either drug alone againstC. neoformansin vitro as well in vivo. These findings suggest that this therapeutic approach could be useful in the treatment of cryptococcal infections.
Pharmacokinetic-Pharmacodynamic Modeling of the Electroencephalogram Effect of Imipenem in Healthy Rats
Authors: Dupuis Antoine , Couet William , Paquereau Joël , Debarre Stanley , Portron Agnès , Jamois Candice , Bouquet Serge 
Published: July 2002

ABSTRACT

A pharmacokinetic-pharmacodynamic (PK-PD) modeling approach was developed to investigate the epileptogenic activity of imipenem in rats. Initially, animals received an intravenous infusion of imipenem at a rate of 2.65 mg min
−1
for 30 min. Blood samples were collected for drug assay, and an electroencephalogram (EEG) was recorded during infusion and postinfusion. A dramatic delay was observed between concentrations of imipenem in serum and the EEG effect; this effect was accompanied by tremors and partial seizures. Indirect-effect models failed to describe these data, which were successfully fitted using an effect compartment model. The relationship between effect and concentration at the effect site was best described by a spline function. The elimination rate constant from the effect compartment was severalfold lower than that from the central compartment. The robustness of the model was then confirmed after administering the imipenem dose over 60 and 90 min. In conclusion, the successful PK-PD modeling of the imipenem EEG effect in rats constitutes a major improvement for better prediction of the epileptogenic risk associated with this antibiotic.
Effect of Famciclovir on Herpes Simplex Virus Type 1 Corneal Disease and Establishment of Latency in Rabbits
Authors: Loutsch Jeannette M. , Sainz Bruno , Marquart Mary E. , Zheng Xiaodong , Kesavan Prabakaran , Higaki Shiro , Hill James M. , Tal-Singer Ruth 
Published: July 2002

ABSTRACT
Famciclovir (FCV) is efficacious in the treatment of acute herpes zoster and recurrent genital infections but has not been used to treat ocular herpes simplex virus (HSV) infections. We evaluated the efficacy of orally administered FCV in treating HSV-1 epithelial keratitis and determined its effects on the establishment of latency and subsequent reactivation. Rabbits were inoculated with HSV-1 strain 17 syn+ and treated twice daily with increasing concentrations of FCV (60 to 500 mg/kg of body weight). This resulted in a significant, dose-dependent improvement in keratitis scores, as well as prolonged survival. Regardless of the dose of drug used, all groups exhibited the high rates of spontaneous and induced reactivation characteristic of 17syn+. The efficacy of 250 mg of FCV per kg was also compared to topical treatment with 1% trifluorothymidine (TFT). Although TFT treatment was more effective at reducing eye disease, FCV-treated rabbits had a better survival rate. Real-time quantitative PCR analysis of rabbit trigeminal ganglia (TG) demonstrated that FCV significantly reduced the HSV-1 copy number compared to that after treatment with TFT or the placebo but not in a dose-dependent manner. In summary, oral FCV treatment significantly reduces the severity of corneal lesions, reduces the number of HSV-1 genomes in the TG, improves survival, and therefore may be beneficial in reducing the morbidity of HSV keratitis in the clinic.
Molecular Cloning and Characterization of the
Salmonella enterica
Serovar Paratyphi B
rma
Gene, Which Confers Multiple Drug Resistance in
Escherichia coli
Authors: Yassien Mahmoud. A. , Ewis Hosam E. , Lu Chung-Dar , Abdelal Ahmed T. 
Published: July 2002

ABSTRACT

A genomic library from a strain of
Salmonella enterica
serovar Paratyphi B that exhibits multiple drug resistance (MDR) was constructed in
Escherichia coli
. Two of the recombinant plasmids, pNOR5 and pNOR5, conferred resistance only to fluoroquinolones in
E. coli
, whereas the third, pNCTR4, conferred the MDR phenotype. Sequence and subcloning analysis showed that it is the presence of RecA on the first two plasmids which confers resistance to fluoroquinolones in
E. coli
. A similar analysis established that the MDR phenotype conferred by pNCTR4 is due to a gene,
rma
(resistance to multiple antibiotics), which encodes a 13.5-kDa polypeptide. The derived sequence for Rma exhibits a high degree of similarity to those of a group of MarA-like activators that confer MDR in
E. coli
. A MalE-Rma fusion protein was purified to near homogeneity and was shown to interact with a DNA fragment carrying a MarA operator sequence. Furthermore, overexpression of
rma
in
E. coli
caused changes in the outer membrane protein profile that were similar to those reported for MarA. These results suggest that Rma might act as a transcriptional activator of the
marA
regulon.
In Vivo Activities of Farnesyl Pyrophosphate Synthase Inhibitors against
Leishmania donovani
and
Toxoplasma gondii
Authors: Yardley Vanessa , Khan Anis A. , Martin Michael B. , Slifer Teri R. , Araujo Fausto G. , Moreno Silvia N. J. , Docampo Roberto , Croft Simon L. , Oldfield Eric 
Published: July 2002

ABSTRACT

The in vivo activities of three bisphosphonates were determined against
Leishmania donovani
and
Toxoplasma gondii
. Alendronate was essentially inactive against both parasites. Pamidronate was active against
L. donovani
by intravenous administration. Risedronate had a 50% effective dosage of five 2.6-mg/kg of body weight intraperitoneal doses against
L. donovani-
infected mice but was less effective against
T. gondii
-infected mice.
Potency of Nonnucleoside Reverse Transcriptase Inhibitors (NNRTIs) Used in Combination with Other Human Immunodeficiency Virus NNRTIs, NRTIs, or Protease Inhibitors
Authors: King Robert W. , Klabe Ronald M. , Reid Carol D. , Erickson-Viitanen Susan K. 
Published: July 2002

ABSTRACTEfavirenz and a series of related quinazolinone nonnucleoside inhibitors of the human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) were evaluated in a series of two-drug combinations with several nucleoside RT inhibitors (NRTIs), nonnucleoside RT inhibitors (NNRTIs), and protease inhibitors (PIs). These combinations were tested in an established HIV-1 RT enzyme assay and a cell-based yield reduction assay with HIV-1 (replicative form [RF])-infected MT-2 cells. Synergy, additivity, and antagonism were determined in the two different assay systems by the method of Chou and Talalay (T.-C. Chou and P. Talalay, Adv. Enzyme Reg. 22:27-55, 1984). Efavirenz, DPC082, DPC083, DPC961, and DPC963 used in combination with the NRTIs zidovudine and lamivudine acted synergistically to inhibit RT activity in the HIV-1 RT enzyme assay and additively to slightly synergistically to inhibit HIV-1 (RF) replication in the yield reduction assay. The five NNRTIs in combination with the PI nelfinavir acted additively in the yield reduction assay to inhibit HIV-1 replication. Interestingly, efavirenz in combination with a second NNRTI acted additively to inhibit HIV-1 RT function in the enzyme assay, while it acted antagonistically to inhibit HIV-1 (RF) replication in the yield reduction assay. These data suggest that antiretroviral combination regimens containing multiple NNTRIs should be given thorough consideration before being used.
Transcriptional Analysis of the
tutE tutFDGH
Gene Cluster from
Thauera aromatica
Strain T1
Authors: Coschigano Peter W. 
Published: July 2002

ABSTRACT

The denitrifying strain T1, identified as
Thauera aromatica
, is able to grow with toluene serving as its sole carbon source. Previous work identified two genes,
tutD
and
tutE
, that are involved in toluene metabolism. Two small open reading frames,
tutF
and
tutG
, which may also play a role in toluene metabolism, were also identified. The present work examines the transcriptional organization and regulation of these toluene utilization genes. Northern analysis indicates that the four genes are organized into two operons,
tutE
and
tutFDG
, and that both operons are regulated in response to toluene. Primer extension analysis has identified major transcriptional start sites located 177 bp upstream of the
tutE
translational start and 76 bp upstream of the
tutF
translational start. Furthermore, a fifth gene,
tutH
, has been identified immediately downstream of
tutG
. It is transcribed from the same start site as
tutFDG
and is predicted to code for a 286-amino-acid protein with a calculated molecular mass of about 31,800 Da. The TutH protein is predicted to have an ATP/GTP binding domain and is similar to the NorQ/NirQ family of proteins.
Transformation of Amoxapine by
Cunninghamella elegans
Authors: Moody Joanna D. , Zhang Donglu , Heinze Thomas M. , Cerniglia Carl E. 
Published: July 2002

ABSTRACT

We examined
Cunninghamella elegans
to determine its ability to transform amoxapine, a tricyclic antidepressant belonging to the dibenzoxazepine class of drugs. Approximately 57% of the exogenous amoxapine was metabolized to three metabolites that were isolated by high-performance liquid chromatography and were identified by nuclear magnetic resonance and mass spectrometry as 7-hydroxyamoxapine (48%),
N
-formyl-7-hydroxyamoxapine (31%), and
N
-formylamoxapine (21%). 7-Hydroxyamoxapine, a mammalian metabolite with biological activity, now can be produced in milligram quantities for toxicological evaluation.
Changes in Glycolytic Activity of
Lactococcus lactis
Induced by Low Temperature
Authors: Wouters Jeroen A. , Kamphuis Henrike H. , Hugenholtz Jeroen , Kuipers Oscar P. , de Vos Willem M. , Abee Tjakko 
Published: July 2002

ABSTRACT

The effects of low-temperature stress on the glycolytic activity of the lactic acid bacterium
Lactococcus lactis
were studied. The maximal glycolytic activity measured at 30°C increased approximately 2.5-fold following a shift from 30 to 10°C for 4 h in a process that required protein synthesis. Analysis of cold adaptation of strains with genes involved in sugar metabolism disrupted showed that both the phosphoenolpyruvate-dependent sugar phosphotransferase system (PTS) subunit HPr and catabolite control protein A (CcpA) are involved in the increased acidification at low temperatures. In contrast, a strain with the PTS subunit enzyme I disrupted showed increased acidification similar to that in the wild-type strain. This indicates that the PTS is not involved in this response whereas the regulatory function of 46-seryl phosphorylated HPr [HPr(Ser-P)] probably is involved. Protein analysis showed that the production of both HPr and CcpA was induced severalfold (up to two- to threefold) upon exposure to low temperatures. The
las
operon, which is subject to catabolite activation by the CcpA-HPr(Ser-P) complex, was not induced upon cold shock, and no increased lactate dehydrogenase (LDH) activity was observed. Similarly, the rate-limiting enzyme of the glycolytic pathway under starvation conditions, glyceraldehyde-3-phosphate dehydrogenase (GAPDH), was not induced upon cold shock. This indicates that a factor other than LDH or GAPDH is rate determining for the increased glycolytic activity upon exposure to low temperatures. Based on their cold induction and involvement in cold adaptation of glycolysis, it is proposed that the CcpA-HPr(Ser-P) control circuit regulates this factor(s) and hence couples catabolite repression and cold shock response in a functional and mechanistic way.