bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of Gender, AIDS, and Acetylator Status on Intrapulmonary Concentrations of Isoniazid
Authors: Conte John E. , Golden Jeffrey A. , McQuitty Mari , Kipps Juliana , Duncan Sheila , McKenna Elaine , Zurlinden Elisabeth 
Published: July 2002

ABSTRACTThe objective of the present study was to evaluate the effects of gender, AIDS, and acetylator status on the steady-state concentrations of orally administered isoniazid in plasma and lungs. Isoniazid was administered at 300 mg once daily for 5 days to 80 adult volunteers. Subjects were assigned to eight blocks according to gender, presence or absence of AIDS, and acetylator status. Blood was obtained prior to administration of the first dose, 1 h after administration of the last dose, and at the completion of bronchoscopy and bronchoalveolar lavage (BAL), which was performed 4 h after administration of the last dose. The metabolism of caffeine was used to determine acetylator status. Standardized bronchoscopy was performed without systemic sedation. The volume of epithelial lining fluid (ELF) recovered was calculated by the urea dilution method. Isoniazid concentrations in plasma, BAL fluid, and alveolar cells (ACs) were measured by high-performance liquid chromatography. AIDS status or gender had no significant effect on the concentrations of isoniazid in plasma at 1 or 4 h. Concentrations in plasma at 4 h and concentrations in ELF were greater in slow acetylators than fast acetylators. The concentration in plasma (1.85 ± 1.60 μg/ml [mean ± standard deviation;n= 80]) at 1 h following administration of the last dose was not significantly different from that in ELF (2.25 ± 3.50 μg/ml) or ACs (2.61 ± 5.01 μg/ml). For the entire study group, concentrations in plasma at 1 h were less than 1.0, 2.0, and 3.0 μg/ml for 34.7, 60, and 82.7% of the subjects, respectively; concentrations in ELF were less than 1.0, 2.0, and 3.0 μg/ml in 30 (37.5%), 53 (66.0%), and 58 (72.5%) of the subjects, respectively; and concentrations in ACs were less than 1.0, 2.0, and 3.0 μg/ml in 43 (53.8%), 59 (73.8%), and 65 (81.3%) of the subjects, respectively. The concentrations of orally administered isoniazid in plasma were not affected by gender or the presence of AIDS. The concentrations in plasma at 4 h and the concentrations in ELF, but not the concentrations in ACs, were significantly greater in slow acetylators than fast acetylators. Concentrations in plasma and lungs were low compared to recommended therapeutic concentrations in plasma and published MICs of isoniazid forMycobacterium tuberculosis. The optimal concentrations of isoniazid in ACs and ELF are unknown, but these data suggest that the drug enters these compartments by passive diffusion and achieves concentrations similar to those found in plasma.
Characterization of a Novel Plasmid-Mediated Cephalosporinase (CMY-9) and Its Genetic Environment in anEscherichia coliClinical Isolate
Authors: Doi Yohei , Shibata Naohiro , Shibayama Keigo , Kamachi Kazunari , Kurokawa Hiroshi , Yokoyama Keiko , Yagi Tetsuya , Arakawa Yoshichika 
Published: July 2002

ABSTRACTAnEscherichia colistrain, HKYM68, which showed resistance to broad-spectrum cephalosporins was isolated from a sputum specimen in Japan. The high-level resistance of the strain to ceftazidime, cefpirome, and moxalactam was carried by a self-transferable plasmid. The β-lactamase gene responsible for the resistance was cloned and sequenced. The deduced amino acid sequence of this gene product, CMY-9, had a single amino acid substitution (E85D), the residue reported to be part of the recognition site for the R1 side chain of β-lactams, compared with the amino acid sequence of CMY-8 and also had 78% identity with the amino acid sequence of CepH, a chromosomal cephalosporinase ofAeromonas hydrophila. Asul1-type class 1 integron containing anaacA1-orfGgene cassette was identified upstream ofblaCMY-9and ended with a truncated 3′ conserved segment. The following 2.1 kb was almost identical to the common region of integrons In6 and In7 and the integron of pSAL-1, except thatorf513encoding a putative transposase was identified instead oforf341due to addition of a single nucleotide.blaCMY-9was closely located downstream of the end of the common region. These observations are indicative of the exogenous derivation ofblaCMY-9from some environmental microorganisms such as aeromonads.
Simple Fibroblast-Based Assay for Screening of New Antimicrobial Drugs against
Mycobacterium tuberculosis
Authors: Takii Takemasa , Yamamoto Yoshifumi , Chiba Taku , Abe Chiyoji , Belisle John T. , Brennan Patrick J. , Onozaki Kikuo 
Published: July 2002

ABSTRACT

In this study, we propose a simple and reproducible host-cell-based assay for the screening of antimycobacterial drugs that is suitable for drug discovery. The method evaluates both antimycobacterial activity of the drugs and their cytotoxicity to host cells. The basis of this simple fibroblast-based assay (SFA) is that cells of human lung fibroblast cell line MRC-5, which are highly sensitive to mycobacterial cytotoxicity, are killed by virulent
Mycobacterium tuberculosis
strain H
37
Rv bacilli in response to the viability of bacilli. Clinically used antimycobacterial drugs inhibited the mycobacterial cytotoxicity to MRC-5 cells in a dose-dependent manner. MICs of isoniazid, streptomycin, rifampin, and ethambutol determined by this SFA (0.428, 1.816, 0.013, and 3.465 μg/ml, respectively) were within 1 log of MICs determined by the broth dilution test (BDT) using Middlebrook 7H9 medium. The MIC of pyrazinamide, which exhibits bactericidal activity only at a high dose by BDT (1,231 μg/ml at pH 6.6 and 492 μg/ml at pH 5.8), was 3.847 μg/ml in the modified method of SFA. On the other hand, sodium azide, a toxic agent for both mammalian cells and bacteria, exhibited cytotoxicity to fibroblasts at a dose lower than that required to inhibit mycobacterial growth. Thus, this fibroblast-based method enabled us to evaluate both antibacterial activity of drugs and their cytotoxicity to human cells within a short period of time.
Efficacy of Proton Pump Inhibitor Drugs against
Plasmodium falciparum
In Vitro and Their Probable Pharmacophores
Authors: Riel Michael A. , Kyle Dennis E. , Bhattacharjee Apurba K. , Milhous Wilbur K. 
Published: July 2002

ABSTRACT

The substituted benzimidazoles omeprazole, lansoprazole, rabeprazole, and pantoprazole were found to have in vitro activity against three different isolates of
Plasmodium falciparum
: D6 (which is chloroquine and pyrimethamine sensitive), W2 (chloroquine and pyrimethamine resistant), and TM91C235 (multidrug resistant). Lansoprazole and rabeprazole were the most effective against all three isolates, with a 50% inhibitory concentration (IC
50
) range of 7 to 11 μM. Omeprazole showed intermediate activity against D6 and W2 isolates, with IC
50
s of 27 to 28 μM, but had poor activity against TM91C235, with an IC
50
of 76 μM. Pantoprazole was the least effective, with IC
50
s of 73 μM against D6, 53 μM against W2, and 39 μM against TM91C235. A pharmacophore model describing the important features responsible for potent activity of the drugs was developed using computational techniques of semiempirical quantum chemical methods and the three-dimensional QSAR procedure of the CATALYST software. The important features of the pharmacophore, according to the findings based on the CATALYST procedures, are the hydrogen bond acceptor and donor sites at the benzimidine nitrogen atoms and the two aromatic hydrophobic sites in the molecules. AM1 quantum chemical calculations identified the electrostatic potential surface surrounding the sulfoxide atom as crucial for potent activity.
Role of Active Efflux in Association with Target Gene Mutations in Fluoroquinolone Resistance in Clinical Isolates of
Vibrio cholerae
Authors: Baranwal Somesh , Dey Keya , Ramamurthy T. , Nair G. Balakrish , Kundu Manikuntala 
Published: July 2002

ABSTRACT

Quinolones are among the drugs of choice in the management of cholera caused by
Vibrio cholerae
. In this study, we demonstrate that, in addition to mutations detected in the target genes
gyrA
and
parC
, proton motive force-dependent efflux is involved in quinolone resistance in clinical isolates of
V. cholerae
.
Extrusion of Penem Antibiotics by Multicomponent Efflux Systems MexAB-OprM, MexCD-OprJ, and MexXY-OprM of
Pseudomonas aeruginosa
Authors: Okamoto Kiyomi , Gotoh Naomasa , Nishino Takeshi 
Published: July 2002

ABSTRACT

The high intrinsic penem resistance of
Pseudomonas aeruginosa
is due to the interplay among the outer membrane barrier, the active efflux system MexAB-OprM, and AmpC β-lactamase. We studied the roles of two other efflux systems, MexCD-OprJ and MexXY-OprM, in penem resistance by overexpressing each system in an AmpC- and MexAB-OprM-deficient background and found that MexAB-OprM is the most important among the three efflux systems for extrusion of penems from the cell interior.
Characterization of a
Listeria monocytogenes
Scott A Isolate with High Tolerance towards High Hydrostatic Pressure
Authors: Karatzas Kimon A. G. , Bennik Marjon H. J. 
Published: July 2002

ABSTRACT

An isolate of
L. monocytogenes
Scott A that is tolerant to high hydrostatic pressure (HHP), named AK01, was isolated upon a single pressurization treatment of 400 MPa for 20 min and was further characterized. The survival of exponential- and stationary-phase cells of AK01 in ACES [
N
-(2-acetamido)-2-aminoethanesulfonic acid] buffer was at least 2 log units higher than that of the wild type over a broad range of pressures (150 to 500 MPa), while both strains showed higher HHP tolerance (piezotolerance) in the stationary than in the exponential phase of growth. In semiskim milk, exponential-phase cells of both strains showed lower reductions upon pressurization than in buffer, but again, AK01 was more piezotolerant than the wild type. The piezotolerance of AK01 was retained for at least 40 generations in rich medium, suggesting a stable phenotype. Interestingly, cells of AK01 lacked flagella, were elongated, and showed slightly lower maximum specific growth rates than the wild type at 8, 22, and 30°C. Moreover, the piezotolerant strain AK01 showed increased resistance to heat, acid, and H
2
O
2
compared with the wild type. The difference in HHP tolerance between the piezotolerant strain and the wild-type strain could not be attributed to differences in membrane fluidity, since strain AK01 and the wild type had identical in situ lipid melting curves as determined by Fourier transform infrared spectroscopy. The demonstrated occurrence of a piezotolerant isolate of
L. monocytogenes
underscores the need to further investigate the mechanisms underlying HHP resistance of food-borne microorganisms, which in turn will contribute to the appropriate design of safe, accurate, and feasible HHP treatments.
Tightly Bound Binary Toxin in the Cell Wall ofBacillus sphaericus
Authors: Klein Daniela , Uspensky Igor , Braun Sergei 
Published: July 2002

ABSTRACTWe have shown that urea-extracted cell wall of entomopathogenicBacillus sphaericus2297 and some other strains is a potent larvicide againstCulex pipiensmosquitoes, with 50% lethal concentrations comparable to that of the well-knownB. sphaericusbinary toxin, with which it acts synergistically. The wall toxicity develops inB. sphaericus2297 cultures during the late logarithmic stage, earlier than the appearance of the binary toxin crystal. It disappears with sporulation when the binary toxin activity reaches its peak. Disruption of the gene for the 42-kDa protein (P42) of the binary toxin abolishes both cell wall toxicity and crystal formation. However, the cell wall ofB. sphaericus2297, lacking P42, killsC. pipienslarvae when mixed withEscherichia colicells expressing P42. Thus, the cell wall toxicity in strongly toxicB. sphaericusstrains must be attributed to the presence in the cell wall of tightly bound 51-kDa (P51) and P42 binary toxin proteins. The synergism between binary toxin crystals and urea-treated cell wall preparations reflects suboptimal distribution of binary toxin subunits in both compartments. Binary toxin crystal is slightly deficient in P51, while cell wall is lacking in P42.
Molecular Characterization and Expression of Pyruvate Formate-Lyase-Activating Enzyme in a Ruminal Bacterium,
Streptococcus bovis
Authors: Asanuma Narito , Hino Tsuneo 
Published: July 2002

ABSTRACT

To clarify the significance of the activation of pyruvate formate-lyase (PFL) by PFL-activating enzyme (PFL-AE) in
Streptococcus bovis
, the molecular properties and gene expression of PFL-AE were investigated.
S. bovis
PFL-AE was deduced to consist of 261 amino acids with a molecular mass of 29.9 kDa and appeared to be a monomer protein. Similar to
Escherichia coli
PFL-AE,
S. bovis
PFL-AE required Fe
2+
for activity. The gene encoding PFL-AE (
act
) was found to be polycistronic, and the PFL gene (
pfl
) was not included. However, the
act
mRNA level changed in parallel with the
pfl
mRNA level, responding to growth conditions, and the change was contrary to the change in the lactate dehydrogenase (LDH) mRNA level. PFL-AE synthesis appeared to change in parallel with PFL synthesis. Introduction of a recombinant plasmid containing
S. bovis pfl
and the
pfl
promoter into
S. bovis
did not affect formate and lactate production, which suggests that the activity of the
pfl
promoter is low. When the
pfl
promoter was replaced by the
S. bovis ldh
promoter, PFL was overexpressed, which caused an increase in the formate-to-lactate ratio. However, when PFL-AE was overexpressed, the formate-to-lactate ratio did not change, suggesting that PFL-AE was present at a level that was high enough to activate PFL. When both PFL-AE and PFL were overexpressed, the formate-to-lactate ratio further increased. It is conceivable that LDH activity is much higher than PFL activity, which may explain why the formate-to-lactate ratio is usually low.
Binding Rather Than Metabolism May Explain the Interaction of Two Food-Grade
Lactobacillus
Strains with Zearalenone and Its Derivative ɑ́-Zearalenol
Authors: El-Nezami Hani , Polychronaki Nektaria , Salminen Seppo , Mykkänen Hannu 
Published: July 2002

ABSTRACT

The interaction between two
Fusarium
mycotoxins, zearalenone (ZEN) and its derivative ά-zearalenol (ά-ZOL), with two food-grade strains of
Lactobacillus
was investigated. The mycotoxins (2 μg ml
−1
) were incubated with either
Lactobacillus rhamnosus
strain GG or
L. rhamnosus
strain LC705. A considerable proportion (38 to 46%) of both toxins was recovered from the bacterial pellet, and no degradation products of ZEN and ά-ZOL were detected in the high-performance liquid chromatograms of the supernatant of the culturing media and the methanol extract of the pellet. Both heat-treated and acid-treated bacteria were capable of removing the toxins, indicating that binding, not metabolism, is the mechanism by which the toxins are removed from the media. Binding of ZEN or ά-ZOL by lyophilized
L. rhamnosus
GG and
L. rhamnosus
LC705 was a rapid reaction: approximately 55% of the toxins were bound instantly after mixing with the bacteria. Binding was dependent on the bacterial concentration, and coincubation of ZEN with ά-ZOL significantly affected the percentage of the toxin bound, indicating that these toxins may share the same binding site on the bacterial surface. These results can be exploited in developing a new approach for detoxification of mycotoxins from foods and feeds.
Distribution of Microbes Producing Antimicrobial ε-Poly-
l
-Lysine Polymers in Soil Microflora Determined by a Novel Method
Authors: Nishikawa Masanobu , Ogawa Ken'ichi 
Published: July 2002

ABSTRACT

We developed a simple and sensitive screening method to investigate the distribution of microbes producing an antimicrobial poly(amino acid), ε-poly-
l
-lysine (ε-PL), in microflora. An acidic dye, Poly R-478, incorporated in an agar plate detected ε-PL producers by electrostatic interaction with the secreted basic polymers. All ε-PL producers, isolated after careful and sufficient screening of soil microflora, belonged exclusively to two groups of bacteria of the family
Streptomycetaceae
and ergot fungi. They were characterized based on the density and diameter of the concentric zone formed by the secreted polymers. The density depended on each isolate. The increase in the diameter of the concentric zone per unit of time varied among isolates and was negatively correlated with the molecular weight. Although the distribution of ε-PL producers was extremely limited, their products were structurally varied. The molecular masses of the secreted polymers among the isolates ranged from 0.8 to 2.0 kDa. There were also isolates producing unknown polymers inconsistent with the correlation or producing a mixture of polymers with original and modified structures. A chemically modified polymer was an ε-PL derivative, as determined by mass spectrometry. Since the structural variations had no relation to the phylogenetic position of the isolates, it is possible that enzymes involved in the synthesis diversified after putative horizontal transfers of relevant genes.
Antigenicity of
Leishmania braziliensis
Histone H1 during Cutaneous Leishmaniasis: Localization of Antigenic Determinants
Authors: Carmelo Emma , Martínez Enrique , González Ana Cristina , Piñero José Enrique , Patarroyo Manuel E. , del Castillo Antonio , Valladares Basilio 
Published: July 2002

ABSTRACT

The humoral immune response against
Leishmania braziliensis
histone H1 by patients with cutaneous leishmaniasis is described. For this purpose, the protein was purified as a recombinant protein in a prokaryotic expression system and was assayed by enzyme-linked immunosorbent assay (ELISA) with a collection of sera from patients with cutaneous leishmaniasis and Chagas' disease. The assays showed that
L. braziliensis
histone H1 was recognized by 66% of the serum samples from patients with leishmaniasis and by 40% of the serum samples from patients with Chagas' disease, indicating that it acts as an immunogen during cutaneous leishmaniasis. In order to locate the linear antigenic determinants of this protein, a collection of synthetic peptides covering the
L. braziliensis
histone H1sequence was tested by ELISA. The experiments showed that the main antigenic determinant is located in the central region of this protein. Our results show that the recombinant
L. braziliensis
histone H1 is recognized by a significant percentage of serum samples from patients with cutaneous leishmaniasis, but use of this protein as a tool for the diagnosis of cutaneous leishmaniasis is hampered by the cross-reaction with sera from patients with Chagas' disease.
Epigallocatechin Gallate, a Potential Immunomodulatory Agent of Tea Components, Diminishes Cigarette Smoke Condensate-Induced Suppression of Anti-Legionella pneumophilaActivity and Cytokine Responses of Alveolar Macrophages
Authors: Matsunaga Kazuto , Klein Thomas W. , Friedman Herman , Yamamoto Yoshimasa 
Published: July 2002

ABSTRACTEven though cigarette smoking has been shown to suppress immune responses in the lungs, little is known about the effect of cigarette smoke components on respiratory infections. In the present study, the effects of cigarette smoke condensate (CSC) on bacterial replication in alveolar macrophages and the immune responses of macrophages to infection were examined. Furthermore, a possible immunotherapeutic effect of epigallocatechin gallate (EGCg), a major form of tea catechins, on the CSC-induced suppression of antimicrobial activity and immune responses of alveolar macrophages was also determined. The treatment of murine alveolar macrophage cell line (MH-S) cells with CSC significantly enhanced the replication ofLegionella pneumophilain macrophages and selectively down-regulated the production of interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-α) induced by bacterial infection. The treatment of macrophages with EGCg not only overcame the CSC-induced suppression of antimicrobial activity but also strengthened the resistance of macrophages to infection. EGCg also markedly up-regulated the CSC-suppressed IL-6 and TNF-α production by macrophages in response to infection. The results of exogenous TNF-α treatment and neutralization treatment with anti-TNF-α and anti-gamma-interferon (IFN-γ) antibodies and the determination of IFN-γ mRNA levels indicate that CSC-suppressed macrophages can be activated by EGCg to inhibitL. pneumophilagrowth by up-regulation of TNF-α and IFN-γ production. Thus, this study revealed that CSC selectively alters the immune responses of macrophages toL. pneumophilainfection and leads to an enhancement of bacterial replication in macrophages. In addition, the tea catechin EGCg can diminish such suppressive effects of CSC on alveolar macrophages.
Screening of Neonatal Calves for Persistent Infection with Bovine Viral Diarrhea Virus by Immunohistochemistry on Skin Biopsy Samples
Authors: Grooms Daniel L. , Keilen Eric D. 
Published: July 2002

ABSTRACT
Detection and elimination of cattle that are persistently infected with bovine viral diarrhea virus (BVDV) is important for controlling the transmission of this virus. Colostrum-derived antibodies make the detection of persistently BVDV-infected neonatal calves cumbersome and expensive. The objective of this study was to evaluate the use of immunohistochemical staining of skin biopsy samples from neonatal calves as a method for the early detection of persistent BVDV infection. Three hundred thirty-two 1- to 4-week-old dairy calves were screened for BVDV as part of a routine control program. Formalin-fixed skin biopsy samples were stained for BVDV antigen by immunohistochemistry (IHC), and the results were compared to those of virus isolation (VI) from white blood cell preparations. Six calves were positive by both IHC and VI and remained positive for BVDV upon subsequent follow-up testing; thus, they were classified as persistently infected with BVDV. One calf was positive by VI but negative by IHC. On subsequent testing, the calf was negative by VI, suggesting that the initial VI result was due to an acute BVDV infection. One calf was positive by IHC but negative by VI. This calf remained negative by VI on follow-up testing. Immunohistochemical staining of skin biopsy samples is a reliable method for screening neonatal calves for persistent BVDV infection and would be a useful management tool as an aid for controlling and preventing BVDV infection.
In Vitro Assessment of Antiborrelial Activity of OspA Vaccine Sera
Authors: Fawcett Paul T. , Rose Carlos D. , Gibney Kathleen M. 
Published: July 2002

ABSTRACT
Prevention of Lyme disease by the recombinant OspA-based vaccine reportedly works by preventing transmission of spirochetes from ticks to humans. We report on an in vitro microculture assay, which can be used to provide an indicator of the need for booster doses of vaccine.
QuickVue Influenza Test for Rapid Detection of Influenza A and B Viruses in a Pediatric Population
Authors: Quach Caroline , Newby Diane , Daoust Ghislaine , Rubin Earl , McDonald Jane 
Published: July 2002

ABSTRACT
The performance of a lateral-flow immunoassay, the QuickVue Influenza Test, for detection of influenza A and B viruses in comparison with that of cell culture was evaluated by using nasopharyngeal aspirates, in viral transport medium, from children with respiratory tract infections. The sensitivity and specificity were 79.2 and 82.6%, respectively.
Microimmunoassay Using a Protein Chip: Optimizing Conditions for Protein Immobilization
Authors: Seong Seung-Yong 
Published: July 2002

ABSTRACTOptimizing conditions for the microarraying of protein antigens onto glass slides were studied. Various vendors, surface functional groups, buffers, and fixatives were evaluated to enhance protein binding. A total of 125 pg of human immunoglobulin was detectable with this assay system, suggesting that protein microarray can be applied for routine immunodiagnosis.