bluuebunny/crossref_metadata_2025_split huggingface dataset:
Lack of Pharmacokinetic Interaction between Linezolid and Antacid in Healthy Volunteers
Authors: Grunder Gabriela , Zysset-Aschmann Yvonne , Vollenweider Florence , Maier Thomas , Krähenbühl Stephan , Drewe Juergen 
Published: December 2005

ABSTRACT

Several antibiotics show significant pharmacokinetic interactions when they are given orally concomitantly with antacids. The objective of this study was to evaluate the effects of antacid (containing magnesium) on the pharmacokinetics of linezolid. A single dose of 600 mg linezolid was given orally alone and 10 min after administration of the antacid Maalox 70mVal, which contains 600 mg magnesium hydroxide and 900 mg aluminum hydroxide, to nine healthy males and nine healthy females in a crossover and randomized study. Linezolid plasma concentrations were determined by high-performance liquid chromatography, and pharmacokinetic parameters were calculated for both treatments. Coadministration with antacids did not change the pharmacokinetics of linezolid. The ratios (90% confidence intervals) of the individual values of the area under the concentration-time curve and the maximum concentration in plasma (
C
max
) (linezolid plus antacid versus linezolid alone) were 1.01 (0.99 to 1.02) and 0.99 (0.96 to 1.02), respectively. Likewise, no significant difference in any of the other pharmacokinetic parameters was observed between the treatment groups (the time to
C
max
, lag time, volume of distribution [
V
/
F
], and clearance [CL/
F
]). However, a significant sex difference was observed for AUC,
C
max
,
V/F
, and CL/
F
; and these differences could be almost completely explained by the differences in body weight between males and females. No clinically relevant adverse effects were detected under either condition. The coadministration of antacids had no effect on the pharmacokinetics of linezolid. This demonstrates that the oral absorption of linezolid was not affected by the presence of antacids containing magnesium hydroxide and aluminum hydroxide. Antacids can be safely administered together with linezolid.
In Vitro and In Vivo Interactions between Miltefosine and Other Antileishmanial Drugs
Authors: Seifert Karin , Croft Simon L. 
Published: December 2005

ABSTRACT

The interaction of miltefosine with amphotericin B, sodium stibogluconate, paromomycin, and sitamaquine was assessed in vitro and additionally for the first three combinations in vivo. In vitro interactions were indifferent for miltefosine combined with amphotericin B (mean sums of fractional inhibitory concentrations [mean ∑FICs] ranging from 1.22 to 1.51 at the 50% effective concentration [EC
50
] level and 1.08 to 1.38 at the EC
90
level), sitamaquine (mean ∑FICs from 1.33 to 1.38 and 1.0 to 1.02, respectively), and paromomycin (mean ∑FICs from 0.79 to 0.93 at the EC
50
and 0.77 to 1.35 at the EC
90
level). Some synergy was observed for miltefosine combined with sodium stibogluconate (mean ∑FICs from 0.61 to 0.75 at EC
50
and 0.49 to 0.97 at EC
90
). Different interactions were found in vivo, where the highest potentiation of miltefosine activity was achieved with amphotericin B (activity enhancement index [AEI] of up to 11.3). No significant interaction was observed when miltefosine was combined with sodium stibogluconate (AEI of up to 2.38). The potentiation of miltefosine in vivo was also achieved with the combination of miltefosine and paromomycin (AEI of up to 7.22).
Resistance ofLeishmania donovanito Sodium Stibogluconate Is Related to the Expression of Host and Parasite γ-Glutamylcysteine Synthetase
Authors: Carter K. C. , Hutchison S. , Henriquez F. L. , Légaré D. , Ouellette M. , Roberts C. W. , Mullen A. B. 
Published: December 2005

ABSTRACTSequencing studies showed that the γ-glutamylcysteine synthetase (γ-GCS) heavy chain genes from sodium stibogluconate (SSG)-resistant (SSG-R) and SSG-susceptible (SSG-S)Leishmania donovanistrains were identical, indicating that SSG resistance was related to quantitative differences in γ-GCS expression rather than gene interstrain polymorphisms. In vitro infection of murine macrophages with the SSG-R strain, but not the SSG-S strain, down regulated expression of host γ-GCS, which would result in a reduction in intramacrophage glutathione (GSH) levels and promote an oxidative intramacrophage environment. This would inhibit, or minimize, the reduction of SSG pentavalent antimony to its more toxic trivalent form. Macrophage studies showed that the SSG-R strain expressed higher levels of γ-GCS compared to the SSG-S strain, which would result in higher GSH levels, giving increased protection against oxidative stress and facilitating SSG efflux. However a similar differential effect on host and parasite γ-GCS expression was not obtained when using tissues from infected mice. In this case γ-GCS expression was organ and strain dependent for both the host and the parasite, indicating that environmental conditions have a profound effect on γ-GCS expression. Consistent with the proposed mechanism from in vitro studies, increasing tissue GSH levels in the presence of SSG by cotreatment ofL. donovani-infected mice with SSG solution and GSH incorporated into nonionic surfactant vesicles was more effective in reducing liver, spleen, and bone marrow parasite burdens than monotherapy with SSG. Together, these results indicate that SSG resistance is associated with manipulation of both host and parasite GSH levels byL. donovani.
Lovastatin Has Significant Activity against Zygomycetes and Interacts Synergistically with Voriconazole
Authors: Chamilos Georgios , Lewis Russell E. , Kontoyiannis Dimitrios P. 
Published: December 2005

ABSTRACT

Zygomycetes are emerging opportunistic molds resistant to most conventional antifungals. We evaluated the in vitro activity of lovastatin (LOV), a 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitor, against seven clinical isolates of
Zygomycetes
by using standard microdilution methods in three different media, disk diffusion testing, and viability dye staining. To further study the in vivo efficacy of LOV against zygomycetes, we developed a
Drosophila melanogaster
model of zygomycosis. In different experiments, groups of Toll-deficient (
Tl
) flies fed LOV-containing food were subsequently injected with two representative
Zygomycetes
isolates (
Mucor
and
Rhizopus
spp.). Finally, we examined the effects of LOV on voriconazole (VRC) activity against zygomycetes in vitro by checkerboard dilution, Epsilometer test-based methods, and bis-(1,3-dibutylbarbituric acid) trimethine oxonol staining and in vivo in
Tl
flies fed food containing LOV plus VRC and infected with zygomycetes. LOV exhibited significant, medium, and strain-independent fungicidal activity against all
Zygomycetes
isolates in vitro by all testing methods (MIC
50
, 48.0 μg/ml; 50% minimal fungicidal concentration, 56.0 μg/ml; 50% effective concentration, 29.4 μg/ml [6.6 to 38.9 μg/ml]).
Tl
flies fed LOV-containing food and infected with
Mucor
had a significantly better 6-day survival rate than did infected
Tl
flies fed regular food (
P
= 0.0005). LOV displayed in vitro synergy with VRC against all
Zygomycetes
isolates (fractional inhibitory concentration index, 0.104 to 0.290) by all methods used. LOV also displayed synergy with VRC in the
Drosophila
model of zygomycosis (
P
< 0.01). LOV is significantly active against zygomycetes and synergizes with triazoles inherently resistant to them, such as VRC. The clinical significance of these findings needs to be further explored.
Regulation of hematopoiesis in vitro and in vivo by invariant NKT cells
Authors: Kotsianidis Ioannis , Silk Jonathan D. , Spanoudakis Emmanouil , Patterson Scott , Almeida Antonio , Schmidt Richard R. , Tsatalas Costas , Bourikas George , Cerundolo Vincenzo , Roberts Irene A. G. , Karadimitris Anastasios 
Published: December 2005

AbstractInvariant natural killer T cells (iNKT cells) are a small subset of immunoregulatory T cells highly conserved in humans and mice. On activation by glycolipids presented by the MHC-like molecule CD1d, iNKT cells promptly secrete T helper 1 and 2 (Th1/2) cytokines but also cytokines with hematopoietic potential such as GM-CSF. Here, we show that the myeloid clonogenic potential of human hematopoietic progenitors is increased in the presence of glycolipid-activated, GM-CSF–secreting NKT cells; conversely, short- and long-term progenitor activity is decreased in the absence of NKT cells, implying regulation of hematopoiesis in both the presence and the absence of immune activation. In accordance with these findings, iNKT-cell–deficient mice display impaired hematopoiesis characterized by peripheral-blood cytopenias, reduced marrow cellularity, lower frequency of hematopoietic stem cells (HSCs), and reduced early and late hematopoietic progenitors. We also show that CD1d is expressed on human HSCs. CD1d-expressing HSCs display short- and long-term clonogenic potential and can present the glycolipid α-galactosylceramide to iNKT cells. Thus, iNKT cells emerge as the first subset of regulatory T cells that are required for effective hematopoiesis in both steady-state conditions and under conditions of immune activation.
Identification of the annexin A2 heterotetramer as a receptor for the plasmin-induced signaling in human peripheral monocytes
Authors: Laumonnier Yves , Syrovets Tatiana , Burysek Ladislav , Simmet Thomas 
Published: December 2005

AbstractWe have previously demonstrated that plasmin acts as a potent proinflammatory activator of human peripheral monocytes. Here we identify the annexin A2 heterotetramer, composed of annexin A2 and S100A10, as a receptor for the plasmin-induced signaling in human monocytes. Monocytes express the annexin A2 heterotetramer on the cell surface as shown by flow cytometry, fluorescence microscopy, and coimmunoprecipitation of biotinylated cell surface proteins. Binding of plasmin to annexin A2 and S100A10 on monocytes was verified by biotin transfer from plasmin labeled with a trifunctional cross-linker. Antibodies directed against annexin A2 or S100A10 inhibited the chemotaxis elicited by plasmin, but not that induced by fMLP. Further, down-regulation of annexin A2 or S100A10 in monocytes by antisense oligodeoxynucleotides impaired the chemotactic response to plasmin, but not that to fMLP. Antisense oligodeoxynucleotides similarly decreased the TNF-α release by plasmin-stimulated, but not by LPS-stimulated, monocytes. At the molecular level, stimulation with plasmin, but not with catalytically inactivated plasmin, induced cleavage of annexin A2 and dissociation of the heterotetramer complex. Substitution of lysine to alanine in position 27 abolished the cleavage of recombinant annexin A2 in vitro. Together, these data identify the annexin A2 heterotetramer as a signaling receptor activated by plasmin via proteolysis.
Lymphomas are sensitive to perforin-dependent cytotoxic pathways despite expression of PI-9 and overexpression of bcl-2
Authors: Godal Robert , Keilholz Ulrich , Uharek Lutz , Letsch Anne , Asemissen Anne Marie , Busse Antonia , Na Il-Kang , Thiel Eckhard , Scheibenbogen Carmen 
Published: December 2005

AbstractThere is considerable interest in immunotherapeutic approaches for lymphoma. The expression of proteinase inhibitor 9 (PI-9), a molecule that inactivates granzyme B, is considered an immune escape mechanism in lymphoma. Further, lymphomas frequently overexpress the antiapoptotic molecule bcl-2, which is able to inhibit perforin-dependent cytotoxic pathways. In this study, the impact of PI-9 and bcl-2 expression on the sensitivity of lymphomas to T- and natural killer (NK) cell–mediated cytotoxicity was analyzed. We found PI-9 expression in 10 of 18 lymphoma cell lines and in 9 of 14 primary lymphomas. Overexpression of bcl-2 was found in 8 of 18 cell lines and in 12 of 14 primary lymphomas. All lymphoma cells were sensitive to cytolysis by specific T cells and cytokine-activated NK cells, and no difference in sensitivity was observed with respect to PI-9 or bcl-2 expression. Cytolysis was mediated predominantly through perforin-dependent pathways despite expression of PI-9 and bcl-2. Interestingly, the majority of lymphoma cells were resistant to cytolysis by resting allogeneic NK cells. This was due to the failure of lymphomas to induce degranulation of resting NK cells. These results show that resistance to perforin-dependent pathways is not a relevant immune escape mechanism in lymphoma and therefore is unlikely to impair clinical outcome of immunotherapeutic approaches.
ADAM-9 (MDC-9/meltrin-γ), a member of the adisintegrin and metalloproteinase family, regulates myeloma-cell–induced interleukin-6 production in osteoblasts by direct interaction with the αvβ5 integrin
Authors: Karadag Abdullah , Zhou Min , Croucher Peter I. 
Published: December 2005

AbstractADAM-9, a member of the adisintegrin and metalloproteinase family, contains both metalloproteinase and disintegrin domains. Myeloma cell lines express ADAM-9; however, its function and role in the pathophysiology of multiple myeloma is unknown. The aim of this study was to establish whether primary myeloma cells express ADAM-9, whether ADAM-9 regulates IL-6 production in human osteoblasts (hOBs), whether ADAM-9 interacts with specific integrin heterodimers, and the identity of downstream signaling pathways. Primary myeloma cells demonstrated increased expression of ADAM-9 (P < .01). ADAM-9 promoted a 5-fold increase in IL-6, but not IL-1β mRNA, and a dose- and time-dependent increase in IL-6 production by hOBs (P < .01). IL-6 induction was inhibited by an antibody to the αvβ5 integrin (P < .01) but not by antibodies to other integrin heterodimers. ADAM-9 was shown to bind directly to the αvβ5 integrin on hOBs. Antibodies to ADAM-9 and αvβ5 integrin inhibited myeloma cell–induced IL-6 production by hOBs (P < .01). Furthermore, inhibitors of p38 MAPK and cPLA2, but not NF-κB and JAK2, signaling pathways inhibited ADAM-9–induced IL-6 production by hOBs (P < .01). These data demonstrate that ADAM-9, expressed by myeloma cells, stimulates IL-6 production in hOBs by binding the αvβ5 integrin. This may have important consequences for the growth and survival of myeloma cells in bone.
Tumor vascular targeting therapy with viral vectors
Authors: Liu Yanzheng , Deisseroth Albert 
Published: December 2005

AbstractTumor angiogenesis is crucial for the progression and metastasis of cancer. The vasculature of tumor tissue is different from normal vasculature. Therefore, tumor vascular targeting therapy could represent an effective therapeutic strategy with which to suppress both primary tumor growth and tumor metastasis. The use of viral vectors for tumor vascular targeting therapy is a promising strategy based on the unique properties of viral vectors. In order to circumvent the potential problems of antiviral neutralizing antibodies, poor access to extravascular tumor tissue, and toxicities to normal tissue, viral vectors need to be modified to target the tumor endothelial cells. Viral vectors that could be used for tumor vascular targeting therapy include adenoviral vectors, adeno-associated viral vectors, retroviral vectors, lentiviral vectors, measles virus, and herpes simplex viral vectors. In this review, we will summarize the strategies available for targeting viral vectors for tumor vascular targeting therapy.
A DNA-based cancer vaccine enhances lymphocyte cross talk by engaging the NKG2D receptor
Authors: Zhou He , Luo Yunping , Kaplan Charles D. , Krüger Jörg A. , Lee Sung-Hyung , Xiang Rong , Reisfeld Ralph A. 
Published: December 2005

AbstractThe NKG2D receptor is a stimulatory receptor expressed on NK cells and activated CD8 T cells. We previously demonstrated that engaging the NKG2D receptor markedly improved the efficacy of a survivin-based DNA vaccine. The combination vaccine, encoding both the NKG2D ligand H60 and survivin, activates innate and adaptive antitumor immunity and results in better protection against tumors of different origin and NKG2D expression levels. Here we demonstrate that the enhanced vaccine efficacy is in part attributable to increased cross talk between lymphocytes. Depletion of CD8 T cells during priming reduces the vaccine-induced activation of dendritic cells (DCs) and NK cell activity. Depletion of NK cells during priming leads to reduced DC activation and CTL activity. However, depletion of CD4 T cells results in the activation of DCs, NK cells, and CD8 T cells and enhances NK cell activity. The pH60/Survivin vaccine also increases DCs and NK cells but decreases CD4 T cell homing to Peyer patches, presumably as a result of changes in the homing receptor profile. Thus, by preferentially activating and attracting positive regulators and reducing negative regulators in Peyer patches, this dual-function DNA vaccine induces a microenvironment more suitable for NK cell activation and T cell priming.
Long-term air pollution exposure and living close to busy roads are associated with COPD in women
Authors: Schikowski Tamara , Sugiri Dorothea , Ranft Ulrich , Gehring Ulrike , Heinrich Joachim , Wichmann H-Erich , Krämer Ursula 
Published: December 2005

Abstract

Background
Lung function and exacerbations of chronic obstructive pulmonary disease (COPD) have been associated with short-term exposure to air pollution. However, the effect of long-term exposure to particulate matter from industry and traffic on COPD as defined by lung function has not been evaluated so far. Our study was designed to investigate the influence of long-term exposure to air pollution on respiratory symptoms and pulmonary function in 55-year-old women. We especially focused on COPD as defined by GOLD criteria and additionally compared the effects of air pollution on respiratory symptoms by questionnaire data and by lung function measurements.

Methods
In consecutive cross sectional studies conducted between 1985–1994, we investigated 4757 women living in the Rhine-Ruhr Basin of Germany. NO2 and PM10 exposure was assessed by measurements done in an 8 km grid, and traffic exposure by distance from the residential address to the nearest major road using Geographic Information System data. Lung function was determined and COPD was defined by using the GOLD criteria. Chronic respiratory symptoms and possible confounders were defined by questionnaire data. Linear and logistic regressions, including random effects were used to account for confounding and clustering on city level.

Results
The prevalence of COPD (GOLD stages 1–4) was 4.5%. COPD and pulmonary function were strongest affected by PM10 and traffic related exposure. A 7 μg/m3 increase in five year means of PM10 (interquartile range) was associated with a 5.1% (95% CI 2.5%–7.7%) decrease in FEV1, a 3.7% (95% CI 1.8%–5.5%) decrease in FVC and an odds ratio (OR) of 1.33 (95% CI 1.03–1.72) for COPD. Women living less than 100 m from a busy road also had a significantly decreased lung function and COPD was 1.79 times more likely (95% CI 1.06–3.02) than for those living farther away. Chronic symptoms as based on questionnaire information showed effects in the same direction, but less pronounced.

Conclusion
Chronic exposure to PM10, NO2 and living near a major road might increase the risk of developing COPD and can have a detrimental effect on lung function.
The Gene Set Builder: collation, curation, and distribution of sets of genes
Authors: Yusuf Dimas , Lim Jonathan S , Wasserman Wyeth W 
Published: December 2005

Abstract
Background
In bioinformatics and genomics, there are many applications designed to investigate the common properties for a set of genes. Often, these multi-gene analysis tools attempt to reveal sequential, functional, and expressional ties. However, while tremendous effort has been invested in developing tools that can analyze a set of genes, minimal effort has been invested in developing tools that can help researchers compile, store, and annotate gene sets in the first place. As a result, the process of making or accessing a set often involves tedious and time consuming steps such as finding identifiers for each individual gene. These steps are often repeated extensively to shift from one identifier type to another; or to recreate a published set. In this paper, we present a simple online tool which – with the help of the gene catalogs Ensembl and GeneLynx – can help researchers build and annotate sets of genes quickly and easily.

Description
The Gene Set Builder is a database-driven, web-based tool designed to help researchers compile, store, export, and share sets of genes. This application supports the 17 eukaryotic genomes found in version 32 of the Ensembl database, which includes species from yeast to human. User-created information such as sets and customized annotations are stored to facilitate easy access. Gene sets stored in the system can be "exported" in a variety of output formats – as lists of identifiers, in tables, or as sequences. In addition, gene sets can be "shared" with specific users to facilitate collaborations or fully released to provide access to published results. The application also features a Perl API (Application Programming Interface) for direct connectivity to custom analysis tools. A downloadable Quick Reference guide and an online tutorial are available to help new users learn its functionalities.

Conclusion
The Gene Set Builder is an Ensembl-facilitated online tool designed to help researchers compile and manage sets of genes in a user-friendly environment. The application can be accessed via http://www.cisreg.ca/gsb/.
Avoiding inconsistencies over time and tracking difficulties in Applied Biosystems AB1700™/Panther™ probe-to-gene annotations
Authors: Noth Sebastian , Benecke Arndt ,   systems epigenomics group
Published: December 2005

Abstract

Background
Significant inconsistencies between probe-to-gene annotations between different releases of probe set identifiers by commercial microarray platform solutions have been reported. Such inconsistencies lead to misleading or ambiguous interpretation of published gene expression results.

Results
We report here similar inconsistencies in the probe-to-gene annotation of Applied Biosystems AB1700 data, demonstrating that this is not an isolated concern. Moreover, the online information source PANTHER does not provide information required to track such inconsistencies, hence, even correctly annotated datasets, when resubmitted after PANTHER was updated to a new probe-to-gene annotation release, will generate differing results without any feedback on the origin of the change.

Conclusion
The importance of unequivocal annotation of microarray experiments can not be underestimated. Inconsistencies greatly diminish the usefulness of the technology. Novel methods in the analysis of transcriptome profiles often rely on large disparate datasets stemming from multiple sources. The predictive and analytic power of such approaches rapidly diminishes if only least-common subsets can be used for analysis. We present here the information that needs to be provided together with the raw AB1700 data, and the information required together with the biologic interpretation of such data to avoid inconsistencies and tracking difficulties.