bluuebunny/crossref_metadata_2025_split huggingface dataset:
In Vitro Activities of Three Licensed Antifungal Agents against Spanish Clinical Isolates of
Aspergillus
spp
Authors: Gomez-Lopez Alicia , Garcia-Effron Guillermo , Mellado Emilia , Monzon Araceli , Rodriguez-Tudela Juan L. , Cuenca-Estrella Manuel 
Published: September 2003

ABSTRACT

The aim of the present study was to identify retrospectively trends in the species distributions and the susceptibility patterns of
Aspergillus
species causing fungal infections in Spanish medical centers from 2000 to 2002. The susceptibilities of 338 isolates to amphotericin B, itraconazole, and voriconazole were tested.
Aspergillus fumigatus
was the most common species (54.7%), followed by
Aspergillus terreus
(14.8%) and
Aspergillus flavus
(13.9%). Non-
A. fumigatus
species were encountered in 45.3% of the samples studied. The majority of
Aspergillus
isolates were obtained from respiratory tract specimens, followed by ear and skin samples. The geometric mean (GM) MIC of amphotericin B was 0.56 μg/ml, and the amphotericin B MIC was >2 μg/ml for 16 isolates (4.7%). Nine of them were
A. terreus
. The GM MIC of itraconazole was 0.37, and the itraconazole MIC was >4 μg/ml for 12 (3.5%) isolates. The voriconazole MICs were also high for 8 of the 12 strains for which itraconazole MICs were high (voriconazole MIC range, 2 to 8 μg/ml).
Penetration of Moxifloxacin into Healthy and Inflamed Subcutaneous Adipose Tissues in Humans
Authors: Joukhadar Christian , Stass Heino , Müller-Zellenberg Ulrike , Lackner Edith , Kovar Florian , Minar Erich , Müller Markus 
Published: September 2003

ABSTRACTThe present study addressed the ability of moxifloxacin to penetrate into healthy and inflamed subcutaneous adipose tissues in 12 patients with soft tissue infections (STIs). Penetration of moxifloxacin into the interstitial space fluid of healthy and inflamed subcutaneous adipose tissues was measured by use of in vivo microdialysis following administration of a single intravenous dosage of 400 mg in six diabetic and six nondiabetic patients with STIs. For the entire study population, the mean time-concentration profile of free moxifloxacin in plasma was identical to the time-concentration profile of free moxifloxacin in tissue (Pwas not significant). For healthy and inflamed adipose tissues for the diabetic subgroup, the mean moxifloxacin areas under the concentration-time curves (AUCs) from 0 to 8 h (AUC0-8s) were 8.1 ± 7.1 and 3.7 ± 1.9 mg·h/liter, respectively (Pwas not significant). The ratios of the mean AUC0-8for inflamed tissue/AUC0-8for free moxifloxacin in plasma were 0.5 ± 0.4 for diabetic patients and 1.2 ± 0.8 for nondiabetic patients (Pwas not significant). The ratios of the AUCs from 0 to 24 h for free moxifloxacin in plasma/MIC at which 90% of isolates are inhibited were >58 and 121 h forStreptococcusspecies and methicillin-sensitiveStaphylococcus aureus, respectively. Concentrations of moxifloxacin effective against clinically relevant bacterial strains are reached in plasma and in inflamed and healthy adipose tissues. Thus, the pharmacokinetics of moxifloxacin in tissue and plasma support its use for the treatment of STIs in diabetic and nondiabetic patients.
Fluoroquinolone-Containing Third-Line Regimen against
Mycobacterium tuberculosis
In Vivo
Authors: Veziris Nicolas , Truffot-Pernot Chantal , Aubry Alexandra , Jarlier Vincent , Lounis Nacer 
Published: September 2003

ABSTRACT

The objective of the present study was to compare the activities of a third-line regimen recommended by the World Health Organization (WHO) and two derivatives of that regimen with the activity of the standard combination of isoniazid, rifampin, and pyrazinamide as a positive control against
Mycobacterium tuberculosis
in a murine model. The WHO regimen combines ofloxacin (OFX), ethionamide, amikacin, and pyrazinamide; in the two derivatives of this regimen, OFX was replaced by levofloxacin (LVX) or moxifloxacin (MXF). The four drugs, a fluoroquinolone (either OFX, LVX, or MXF), ethionamide, pyrazinamide, and amikacin, were administered for the first 2 months (initial phase); and two drugs, a fluoroquinolone (either OFX, LVX, or MXF) and ethionamide, were administered for the following 10 months (continuation phase). After 6 months of treatment, only the spleens and lungs of mice treated with the standard regimen became culture negative. From 9 months onward, all of the organs of mice treated with the MXF-containing third-line regimen were culture negative. The majority of organs from mice treated with the OFX-containing regimen continued to be culture positive, and the mean CFU counts remained unchanged for as long as 12 months. The results for mice treated with the LVX-containing regimen fell between those for the groups receiving the MXF- and OFX-containing regimens. In conclusion, the activity of the OFX-containing third-line regimen against
M. tuberculosis
was rather weak in vivo, whereas when OFX was replaced by MXF, 9 months of treatment with a modified third-line regimen displayed bactericidal activity comparable to that of 6 months of treatment with the standard regimen in mice. The MXF-containing third-line regimen seems to be a powerful alternative for the treatment of tuberculosis (TB) when isoniazid and rifampin cannot be used, which is the main feature of multidrug-resistant TB.
Population Pharmacokinetics of Ciprofloxacin in Pediatric and Adolescent Patients with Acute Infections
Authors: Payen S. , Serreau R. , Munck A. , Aujard Y. , Aigrain Y. , Bressolle F. , Jacqz-Aigrain E. 
Published: September 2003

ABSTRACTThe aim of the present study was to characterize the population pharmacokinetics of ciprofloxacin in patients with and without cystic fibrosis ranging in age from 1 day to 24 years and to propose a limited sampling strategy to estimate individual pharmacokinetic parameters. Patients were divided into four groups according to the treatment schedule. They received ciprofloxacin by intravenous infusion (30 min) or by the oral route. The number of samples collected from each patient ranged from 1 to 12. The population parameters were computed for an initial group of 37 patients. The data were analyzed by nonlinear mixed-effect modeling by use of a two-compartment structural model. The interindividual variability in clearance (CL) was partially explained by a dependence on age and the patient's clinical status. In addition, a significant relationship was found between weight and the initial volume of distribution. Eighteen additional patients were used for model validation and evaluation of limited sampling strategies. When ciprofloxacin was administered intravenously, sampling at a single point (12 h after the start of infusion) allowed the precise and accurate estimation of CL and the elimination half-life, as well as the ciprofloxacin concentration at the end of the infusion. It should be noted that to take into account the presence of a lag time after oral administration, a schedule based on two sampling times of 1 and 12 h is needed. The results of this study combine relationships between ciprofloxacin pharmacokinetic parameters and patient covariates that may be useful for dose adjustment and a convenient sampling procedure that can be used for further studies.
Contribution of the MexXY Multidrug Transporter to Aminoglycoside Resistance in
Pseudomonas aeruginosa
Clinical Isolates
Authors: Sobel Mara L. , McKay Geoffrey A. , Poole Keith 
Published: September 2003

ABSTRACT

MexXY is an aminoglycoside-inducible multidrug transporter shown to contribute to intrinsic and acquired aminoglycoside resistance in laboratory isolates of
Pseudomonas aeruginosa
. To assess its contribution to aminoglycoside resistance in 14 clinical isolates demonstrating a panaminoglycoside resistance phenotype unlikely to be explained solely by aminoglycoside modification, expression of
mexXY
by these isolates was examined by reverse transcription-PCR. Elevated levels of
mexXY
expression were evident for most strains compared with those detected for an aminoglycoside-susceptible control strain, although there was no correlation between
mexXY
levels and the aminoglycoside MICs for the resistant strains, indicating that if MexXY was playing a role, other factors were also contributing. Deletion of
mexXY
from 9 of the 14 isolates resulted in enhanced susceptibilities to multiple aminoglycosides, confirming the contribution of this efflux system to the aminoglycoside resistance of these clinical isolates. Still, the impact of MexXY loss varied, with some strains clearly more or less dependent on MexXY for aminoglycoside resistance. Expression of
mexXY
also varied in these strains, with some showing high-level expression of the efflux genes independent of aminoglycoside exposure (aminoglycoside-independent hyperexpression) and others showing hyperexpression of the efflux genes that was to a greater or lesser degree aminoglycoside dependent. None of these strains carried mutations in
mexZ
, which encodes a negative regulator of
mexXY
expression, or in the
mexZ-mexXY
intergenic region. Thus,
mexXY
hyperexpression in aminoglycoside-resistant clinical isolates occurs via mutation in one or more as yet unidentified genes.
Mortality of employees of a perfluorooctanesulphonyl fluoride manufacturing facility
Authors: Alexander B H , Olsen G W , Burris J M , Mandel J H , Mandel J S 
Published: September 2003

Aim:To evaluate the mortality experience of a cohort of employees of a perfluorooctanesulphonyl fluoride (POSF) based fluorochemical production facility.Methods:A retrospective cohort mortality study followed all workers with at least one year of cumulative employment at the facility. The jobs held by cohort members were assigned to one of three exposure subgroups; high exposed, low exposed, and non-exposed, based on biological monitoring data for perfluorooctane sulphonate (PFOS).Results:A total of 145 deaths were identified in the 2083 cohort members. Sixty five deaths occurred among workers ever employed in high exposed jobs. The overall mortality rates for the cohort and the exposure subcohorts were lower than expected in the general population. Two deaths from liver cancer were observed in the workers with at least one year of high or low exposure (standardised mortality ratio (SMR) 3.08, 95% CI 0.37 to 11.10). The risk of death from bladder cancer was increased for the entire cohort (three observed, SMR 4.81, 95% CI 0.99 to 14.06). All three bladder cancers occurred among workers who held a high exposure job (SMR 12.77, 95% CI 2.63 to 37.35). The bladder cancer cases primarily worked in non-production jobs, including maintenance and incinerator and wastewater treatment plant operations.Conclusion:Workers employed in high exposure jobs had an increased number of deaths from bladder cancer; however it is not clear whether these three cases can be attributed to fluorochemical exposure, an unknown bladder carcinogen encountered during the course of maintenance work, and/or non-occupational exposures. With only three observed cases the possibility of a chance finding cannot be ruled out.
Biological monitoring of occupational exposure to N,N-dimethylacetamide with identification of a new metabolite
Authors: Perbellini L , Princivalle A , Caivano M , Montagnani R 
Published: September 2003

Aims:To study the concentration of N,N-dimethylacetamide (DMA) and its metabolite, N-methylacetamide (NMA), in urine of workers occupationally exposed to DMA in a factory producing synthetic acrylic fibres.Methods:During the first phase, 223 workers exposed to low environmental concentrations of DMA provided urine samples at the end of a work shift. High concentrations of the unmodified solvent and its metabolite were found in a group of workers whose job was to start up machinery. The second and third phases focused on conditions favouring high uptake of DMA.Results:The highest concentrations of unmodified solvent and NMA were found in the urine of workers recently engaged in starting up machinery. NMA in urine was 1.5–173.6 mg/g creatinine (median 20.5). In spite of the low environmental concentration, about 20% of the urine concentration of NMA was higher than 30 mg/g creatinine. Dermal absorption of DMA was high. A shower and a change of clothing at the end of the work shift, and washing away any solvent left on the skin, ensured that dermal absorption of DMA did not continue. This significantly reduced the NMA urinary concentration at values lower than 30 mg/g creatinine. In some urine samples, S-acetamidomethyl-mercapturic acid was identified by NMR analysis; this is probably a metabolite of N,N-dimethylacetamide—it has never before been identified in humans or animals.Conclusions:Even at low environmental concentrations of DMA, dermal absorption can be considerable. Unmodified DMA and NMA concentrations in urine are good biomarkers for monitoring occupational exposure to the solvent.
Religion, Spirituality, and Ethnicity
Authors: Nightingale Marcie C. 
Published: September 2003

Caregivers of persons with Alzheimer's disease (AD) provide an inordinate and escalating level of care. It has been postulated that: (1) religious beliefs and/or spirituality may assist individuals in their caregiving efforts; and (2) coping strategies may vary depending on ethnicity. The intent of this pilot study was to examine these theories by interviewing five African-American and five white caregivers of persons with AD using demographic and open-ended questions regarding spirituality, religious practices, and ethnicity. Five themes were identified regarding the development of the caregivers' beliefs and practices: 1. later life development of beliefs; 2. religious training and practices; 3. family influences; 4. impact of ethnicity on caregiving; and 5. impact of spirituality and religion on caregiving. All caregivers felt their spirituality and/or religious practices shaped how they approached providing care and all reported that they were influenced by their ethnic background. Most stated that religious practices and spirituality affected how they felt about providing care and that religion and spirituality helped them deal with difficult challenges. Through a better understanding of the importance of different coping mechanisms among caregivers, professionals are able to provide more sensitive care to persons of diverse groups.
Interleukin-18 attracts plasmacytoid dendritic cells (DC2s) and promotes Th1 induction by DC2s through IL-18 receptor expression
Authors: Kaser Arthur , Kaser Susanne , Kaneider Nicole C. , Enrich Barbara , Wiedermann Christian J. , Tilg Herbert 
Published: September 2003

AbstractIn vivo evidence suggests that interleukin-18 (IL-18) shapes the development of adaptive immunity toward T-helper cell type 1 (Th1) responses. Monocyte-derived dendritic cells 1 (DC1s) preferentially induce a Th1 response, while plasmacytoid DC-derived DC2s have been linked to a Th2 response. We analyzed the role of IL-18 during the initiation phase of a Th response in vitro to elucidate the basis of these in vivo observations. IL-18 was constitutively released from DC1s, but not DC2s. Neutralization of IL-18 in coculture experiments of DC1s with allogeneic naive T lymphocytes did not alter the Th1/Th2 phenotype, while anti–IL-12 efficiently down-regulated the Th1 response. Unexpectedly, IL-18 receptor (IL-18R) α and β chains were expressed on DC2 lineage. IL-18R expression was functional, as IL-18 induced chemotaxis in plasmacytoid DCs (pre-DC2s) and enhanced the allostimulatory capacity of IL-3–differentiated DC2s. Pre-DC2s exposed to IL-18 skewed the development of Th cells toward Th1 in coculture experiments of DC2s and allogeneic naive T cells, which was inhibited by IL-12 p70 neutralization. IL-18 might have a profound role during the initiation phase of an immune response by recruiting pre-DC2s and modulating the function of DC2s.
Identification of the primary collagen-binding surface on human glycoprotein VI by site-directed mutagenesis and by a blocking phage antibody
Authors: Smethurst Peter A. , Joutsi-Korhonen Lotta , O'Connor Marie N. , Wilson Erica , Jennings Nicola S. , Garner Stephen F. , Zhang Yanjun , Knight C. Graham , Dafforn Timothy R. , Buckle Ashley , IJsseldijk Martin J. W. , de Groot Philip G. , Watkins Nicholas A. , Farndale Richard W. , Ouwehand Willem H. 
Published: September 2003

AbstractGlycoprotein (GP) VI is the major receptor responsible for platelet activation by collagen, but the collagen-binding surface of GPVI is unknown. To address this issue we expressed, from insect cells, the immunoglobulin (Ig)–like ectodomains (residues 1-185) of human and murine GPVI, called hD1D2 and mD1D2, respectively. Both proteins bound specifically to collagen-related peptide (CRP), a GPVI-specific ligand, but hD1D2 bound CRP more strongly than did mD1D2. Molecular modeling and sequence comparison identified key differences between hD1D2 and mD1D2. Ten mutant hD1D2s were expressed, of which 4 had human residues replaced by their murine counterpart, and 6 had replacements by alanine. CRP binding studies with these mutants demonstrated that the exchange of lysine at position 59 for the corresponding murine glutamate substantially reduced binding to CRP. The position of lysine59 on the apical surface of GPVI suggests a mode of CRP binding analogous to that used by the related killer cell Ig-like receptors to bind HLA. This surface was confirmed as critical for collagen binding by epitope mapping of an inhibitory phage antibody against GPVI. This anti-GPVI, clone 10B12, gave dose-dependent inhibition of the hD1D2-collagen interaction. Clone 10B12 inhibited activation of platelets by CRP and collagen in aggregometry and thrombus formation by the latter in whole blood perfusion. Antibody 10B12 showed significantly reduced binding to the hD1D2-E59, and, on that basis, the GPVI:10B12 interface was modeled.
Lentivector-mediated clonal tracking reveals intrinsic heterogeneity in the human hematopoietic stem cell compartment and culture-induced stem cell impairment
Authors: Mazurier Frédéric , Gan Olga I. , McKenzie Joby L. , Doedens Monica , Dick John E. 
Published: September 2003

AbstractKnowledge of the composition and interrelationship of the various hematopoietic stem cells (HSCs) that comprise the human HSC pool and the consequence of culture on each class is required for effective therapies based on stem cells. Clonal tracking of retrovirally transduced HSCs in nonobese diabetic/severe combined immunodeficient (NOD/SCID) mice revealed heterogeneity in the repopulation capacity of SCID-repopulating cells (SRCs). However, it is impossible to establish whether HSC heterogeneity is intrinsic or whether the culture conditions required for retroviral transduction induce qualitative and quantitative alterations to SRCs. Here, we report establishment of a clonal tracking method that uses lentivectors to transduce HSCs with minimal manipulation during overnight culture without cytokine stimulation. By serial bone marrow (BM) sampling of mice receiving transplants, short-term SRCs (ST-SRCs) and long-term SRCs (LT-SRCs) were identified on the basis of repopulation dynamics demonstrating that their existence is not an experimental artifact but reflects the state of the HSC pool. However, 4 days of culture in conditions previously used for SRC retroviral transduction significantly reduced SRC number as assessed by clonal analysis. These studies provide a foundation to understand the molecular and cellular determinants of human HSC development and to develop therapies targeted to specific HSC classes.
The mechanisms controlling the recognition of tumor- and virus-infected cells by NKp46
Authors: Arnon Tal I. , Achdout Hagit , Lieberman Niva , Gazit Roi , Gonen-Gross Tsufit , Katz Gil , Bar-Ilan Ahuva , Bloushtain Noga , Lev Marianna , Joseph Aviva , Kedar Eli , Porgador Angel , Mandelboim Ofer 
Published: September 2003

AbstractThe destruction of viral-infected and tumor cells is mediated in part via the lysis receptor of natural killer (NK) cells, NKp46. The nature, however, of its lysis ligands expressed on target cells is poorly defined. Recently, we have identified a novel functional interaction between the lysis receptors NKp46 and NKp44 and the hemagglutinin of influenza and hemgglutininneuroaminidase of Sendai viruses. This recognition depends on the sialylation of NKp46 and NKp44 receptors. In this study, we expand the significance of these observations by demonstrating a conserved pattern of NKp46 and NKp44 recognition by various hemagglutinins derived from different viral strains. We further establish that this recognition is direct and mainly mediated via α2,6-linked sialic acid carried by NKp46. In addition, we demonstrate that the ability of NKp46 to recognize target cells is confined to the membrane proximal domain, and largely relies on the highly conserved sugar-carrying residue, Thr 225. This residue plays a critical dual role in NKp46 interactions with both viral hemagglutinins and the unknown tumor ligands via different mechanisms. These results may explain the ability of NK cells to kill such a broad spectrum of viral-infected and tumor cells.
Trypsin-modulating oostatic factor: a potential new larvicide for mosquito control
Authors: Borovsky D. 
Published: September 2003

SUMMARY
Trypsin-modulating oostatic factor (TMOF), a mosquito decapeptide,terminates trypsin biosynthesis in the mosquito gut. The hormone is secreted from the ovary, starting 18 h after the blood meal, circulates in the hemolymph, binds to a gut receptor and stops trypsin biosynthesis by exerting a translational control on trypsin mRNA. Because of the unique primary amino acid sequence of the hormone (YDPAPPPPPP) and its stable three-dimensional conformation, TMOF is not degraded by gut proteolytic enzymes and can traverse the gut epithelial cells into the hemolymph of adults and larvae. Using this unique property, hormone fed to different species of mosquito larvae stops food digestion and causes larval mortality. To determine the shortest amino acid sequence that can bind to the gut receptor and still cause high larval mortality, 25 analogues of TMOF were synthesized and tested. The tetrapeptide(YDPA) was as effective as the decapeptide, indicating that the binding to the gut receptor is at the N-terminus of the molecule. Cloning and expressing the hormone on the coat protein of tobacco mosaic virus (TMV) in Chlorella sp. and Saccharomyces cerevisiae cells and feeding the recombinant cells to mosquito larvae caused larval mortality. These results indicate that TMOF can be used as a new biorational insecticide against mosquito larvae.
Towards genetic manipulation of wild mosquito populations to combat malaria: advances and challenges
Authors: Riehle Michael A. , Srinivasan Prakash , Moreira Cristina K. , Jacobs-Lorena Marcelo 
Published: September 2003

SUMMARYMalaria kills millions of people every year, yet there has been little progress in controlling this disease. For transmission to occur, the malaria parasite has to complete a complex developmental cycle in the mosquito. The mosquito is therefore a potential weak link in malaria transmission, and generating mosquito populations that are refractory to the parasite is a potential means of controlling the disease. There has been considerable progress over the last decade towards developing the tools for creating a refractory mosquito. Accomplishments include germline transformation of several important mosquito vectors, the completed genomes of the mosquito Anopheles gambiae and the malaria parasite Plasmodium falciparum, and the identification of promoters and effector genes that confer resistance in the mosquito. These tools have provided researchers with the ability to engineer a refractory mosquito vector, but there are fundamental gaps in our knowledge of how to transfer this technology safely and effectively into field populations. This review considers strategies for interfering with Plasmodium development in the mosquito, together with issues related to the transfer of laboratory-acquired knowledge to the field, such as minimization of transgene fitness load to the mosquito, driving genes through populations, avoiding the selection of resistant strains, and how to produce and release populations of males only.