bluuebunny/crossref_metadata_2025_split huggingface dataset:
Should the concomitant use of erlotinib and acid-reducing agents be avoided? The drug interaction between erlotinib and acid-reducing agents
Authors: Duong Silvia , Leung Mova 
Published: August 2010

Context. Erlotinib, an epidermal growth factor receptor tyrosine kinase inhibitor, exhibits a drug interaction with proton pump inhibitors (PPIs) and histamine-2 receptor antagonists (H2RAs). The manufacturer recommends avoidance of the combination however, the extent of the drug interaction is not clearly understood. Evidence acquisition. A literature search was performed and the pharmacokinetics and pharmacology of acid-reducing agents were reviewed. Results. Acid-reducing agents reduce the solubility, and subsequent absorption, of erlotinib by raising gastric pH. Our literature search was unable to identify any published studies or case reports that address this issue. Until more information is available, the clinical relevance of this interaction, and whether it actually leads to failure of therapy, is unknown. PPIs would all be expected to exhibit a similar effect on erlotinib. Of the H2RAs, co-administration appears to have a greater impact than administering them separately. Ranitidine, famotidine, and nizatidine should likely have similar effects on erlotinib absorption. Cimetidine has a shorter duration of action, but should be used with caution because of its effects on cytochrome P450 3A4, a pathway also utilized by erlotinib. Antacids are not expected to have a significant effect. Conclusions. The clinical relevance of this drug interaction is unknown. Until more information is available, decision making regarding this interaction should be on a patient-by-patient basis. The indication for acid-reducing therapy should be reevaluated and stopping therapy or changing therapy can be considered. However, there may be occasions where any benefit of such actions will be exceeded by its risks.
von Willebrand factor promotes leukocyte extravasation
Authors: Petri Björn , Broermann Andre , Li Hang , Khandoga Alexander G. , Zarbock Alexander , Krombach Fritz , Goerge Tobias , Schneider Stefan W. , Jones Claire , Nieswandt Bernhard , Wild Martin K. , Vestweber Dietmar 
Published: August 2010

Abstract
von Willebrand factor (VWF) is an important player in hemostasis but has also been suggested to promote inflammatory processes. Gene ablation of VWF causes a simultaneous defect in P-selectin expression making it difficult to identify VWF-specific functions. Therefore, we analyzed whether blocking antibodies against VWF would be able to interfere with neutrophil extravasation. We found that these antibodies inhibited neutrophil recruitment into thioglycollate-inflamed peritoneum and KC-stimulated cremaster by approximately 50%. Whereas platelet-VWF was not involved, the contribution of VWF to granulocyte recruitment was strictly dependent on the presence of platelets and the accessibility of their VWF-receptor glycoprotein Ib. Surprisingly, platelet P-selectin was largely dispensable for leukocyte extravasation, in agreement with our observation that anti-VWF antibodies did not affect leukocyte rolling and adhesion. Searching for possible effects downstream of leukocyte capture, we found that anti-VWF antibodies significantly inhibited thioglycollate-induced vascular permeability. The increase of permeability was independent of circulating granulocytes, showing that it was not a side effect of neutrophil diapedesis. Collectively, our results demonstrate that VWF-associated platelets strongly support neutrophil extravasation at a step downstream of leukocyte docking to the vessel wall. This step could be related to leukocyte diapedesis facilitated by destabilization of the endothelial barrier.
Zosuquidar, a novel modulator of P-glycoprotein, does not improve the outcome of older patients with newly diagnosed acute myeloid leukemia: a randomized, placebo-controlled trial of the Eastern Cooperative Oncology Group 3999
Authors: Cripe Larry D. , Uno Hajime , Paietta Elisabeth M. , Litzow Mark R. , Ketterling Rhett P. , Bennett John M. , Rowe Jacob M. , Lazarus Hillard M. , Luger Selina , Tallman Martin S. 
Published: August 2010

AbstractZosuquidar, which modulates P-glycoprotein (P-gp) with minimal delay of anthracycline clearance, may reverse P-gp–mediated resistance in acute myeloid leukemia without increased toxicity. A total of 449 adults older than 60 years with acute myeloid leukemia or high-risk myelodysplastic syndrome enrolled in a randomized placebo-controlled double-blind trial (Eastern Cooperative Oncology Group 3999). Overall survival was compared between patients receiving conventional-dose cytarabine and daunorubicin and either zosuquidar (550 mg; 212 patients) or placebo (221 patients). Median and 2-year overall survival values were 7.2 months and 20% on zosuquidar and 9.4 months and 23% on placebo, respectively (P = .281). Remission rate was 51.9% on zosuquidar and 48.9% on placebo. All cause mortality to day 42 was not different (zosuquidar 22.2% vs placebo 16.3%; P = .158). In vitro modulation of P-gp activity by zosuquidar and expression of P-gp, multidrug resistance-related protein 1, lung resistance protein, and breast cancer resistance protein, were comparable in the 2 arms. Poor-risk cytogenetics were more common in P-gp+ patients. P-gp expression and cytogenetics were correlated, though independent prognostic factors. We conclude that zosuquidar did not improve outcome in older acute myeloid leukemia, in part, because of the presence P-gp independent mechanisms of resistance. This trial is registered at www.clinicaltrials.gov as #NCT00046930.
Polycomb proteins in hematologic malignancies
Authors: Martin-Perez Daniel , Piris Miguel A. , Sanchez-Beato Margarita 
Published: August 2010

AbstractThe Polycomb group (PcG) of proteins is a major mechanism of epigenetic regulation that has been broadly linked to cancer. This system can repress gene expression by chromatin modification and is essential for establishing cell identity. PcG proteins are important for stem cell function and differentiation and have a profound impact during hematopoiesis. In recent years, several published studies have deepened our knowledge of the biology of the PcG in health and disease. In this article, we review the current understanding of the mechanisms of PcG-mediated repression and their relation to DNA methylation, and we discuss the role of the PcG system in hematopoiesis and hematologic malignancies. We suggest that alteration of different PcG members is a frequent event in leukemia and lymphomas that confers the stem cell properties on tumor cells. Thus, drugs targeting Polycomb complexes could be useful for treating patients with these diseases.
Clustering of protein families into functional subtypes using Relative Complexity Measure with reduced amino acid alphabets
Authors: Albayrak Aydin , Otu Hasan H , Sezerman Ugur O 
Published: August 2010

Abstract

Background
Phylogenetic analysis can be used to divide a protein family into subfamilies in the absence of experimental information. Most phylogenetic analysis methods utilize multiple alignment of sequences and are based on an evolutionary model. However, multiple alignment is not an automated procedure and requires human intervention to maintain alignment integrity and to produce phylogenies consistent with the functional splits in underlying sequences. To address this problem, we propose to use the alignment-free Relative Complexity Measure (RCM) combined with reduced amino acid alphabets to cluster protein families into functional subtypes purely on sequence criteria. Comparison with an alignment-based approach was also carried out to test the quality of the clustering.

Results
We demonstrate the robustness of RCM with reduced alphabets in clustering of protein sequences into families in a simulated dataset and seven well-characterized protein datasets. On protein datasets, crotonases, mandelate racemases, nucleotidyl cyclases and glycoside hydrolase family 2 were clustered into subfamilies with 100% accuracy whereas acyl transferase domains, haloacid dehalogenases, and vicinal oxygen chelates could be assigned to subfamilies with 97.2%, 96.9% and 92.2% accuracies, respectively.

Conclusions
The overall combination of methods in this paper is useful for clustering protein families into subtypes based on solely protein sequence information. The method is also flexible and computationally fast because it does not require multiple alignment of sequences.
Calculation of accurate small angle X-ray scattering curves from coarse-grained protein models
Authors: Stovgaard Kasper , Andreetta Christian , Ferkinghoff-Borg Jesper , Hamelryck Thomas 
Published: August 2010

Abstract

Background
Genome sequencing projects have expanded the gap between the amount of known protein sequences and structures. The limitations of current high resolution structure determination methods make it unlikely that this gap will disappear in the near future. Small angle X-ray scattering (SAXS) is an established low resolution method for routinely determining the structure of proteins in solution. The purpose of this study is to develop a method for the efficient calculation of accurate SAXS curves from coarse-grained protein models. Such a method can for example be used to construct a likelihood function, which is paramount for structure determination based on statistical inference.

Results
We present a method for the efficient calculation of accurate SAXS curves based on the Debye formula and a set of scattering form factors for dummy atom representations of amino acids. Such a method avoids the computationally costly iteration over all atoms. We estimated the form factors using generated data from a set of high quality protein structures. No ad hoc scaling or correction factors are applied in the calculation of the curves. Two coarse-grained representations of protein structure were investigated; two scattering bodies per amino acid led to significantly better results than a single scattering body.

Conclusion
We show that the obtained point estimates allow the calculation of accurate SAXS curves from coarse-grained protein models. The resulting curves are on par with the current state-of-the-art program CRYSOL, which requires full atomic detail. Our method was also comparable to CRYSOL in recognizing native structures among native-like decoys. As a proof-of-concept, we combined the coarse-grained Debye calculation with a previously described probabilistic model of protein structure, TorusDBN. This resulted in a significant improvement in the decoy recognition performance. In conclusion, the presented method shows great promise for use in statistical inference of protein structures from SAXS data.
Trichostatin A and 5-azacytidine both cause an increase in global histone H4 acetylation and a decrease in global DNA and H3K9 methylation during mitosis in maize
Authors: Yang Fei , Zhang Lu , Li Jun , Huang Jing , Wen Ruoyu , Ma Lu , Zhou Dongfeng , Li Lijia 
Published: August 2010

Abstract

Background
Modifications of DNA and histones in various combinations are correlated with many cellular processes. In this study, we investigated the possible relationship between histone H4 tetraacetylation, DNA methylation and histone H3 dimethylation at lysine 9 during mitosis in maize root meristems.

Results
Treatment with trichostatin A, which inhibits histone deacetylases, resulted in increased histone H4 acetylation accompanied by the decondensation of interphase chromatin and a decrease in both global H3K9 dimethylation and DNA methylation during mitosis in maize root tip cells. These observations suggest that histone acetylation may affect DNA and histone methylation during mitosis. Treatment with 5-azacytidine, a cytosine analog that reduces DNA methylation, caused chromatin decondensation and mediated an increase in H4 acetylation, in addition to reduced DNA methylation and H3K9 dimethylation during interphase and mitosis. These results suggest that decreased DNA methylation causes a reduction in H3K9 dimethylation and an increase in H4 acetylation.

Conclusions
The interchangeable effects of 5-azacytidine and trichostatin A on H4 acetylation, DNA methylation and H3K9 dimethylation indicate a mutually reinforcing action between histone acetylation, DNA methylation and histone methylation with respect to chromatin modification. Treatment with trichostatin A and 5-azacytidine treatment caused a decrease in the mitotic index, suggesting that H4 deacetylation and DNA and H3K9 methylation may contain the necessary information for triggering mitosis in maize root tips.
Structure and evolution of Apetala3, a sex-linked gene in Silene latifolia
Authors: Cegan Radim , Marais Gabriel AB , Kubekova Hana , Blavet Nicolas , Widmer Alex , Vyskot Boris , Doležel Jaroslav , Šafář Jan , Hobza Roman 
Published: August 2010

Abstract

Background
The evolution of sex chromosomes is often accompanied by gene or chromosome rearrangements. Recently, the gene AP3 was characterized in the dioecious plant species Silene latifolia. It was suggested that this gene had been transferred from an autosome to the Y chromosome.

Results
In the present study we provide evidence for the existence of an X linked copy of the AP3 gene. We further show that the Y copy is probably located in a chromosomal region where recombination restriction occurred during the first steps of sex chromosome evolution. A comparison of X and Y copies did not reveal any clear signs of degenerative processes in exon regions. Instead, both X and Y copies show evidence for relaxed selection compared to the autosomal orthologues in S. vulgaris and S. conica. We further found that promoter sequences differ significantly. Comparison of the genic region of AP3 between the X and Y alleles and the corresponding autosomal copies in the gynodioecious species S. vulgaris revealed a massive accumulation of retrotransposons within one intron of the Y copy of AP3. Analysis of the genomic distribution of these repetitive elements does not indicate that these elements played an important role in the size increase characteristic of the Y chromosome. However, in silico expression analysis shows biased expression of individual domains of the identified retroelements in male plants.

Conclusions
We characterized the structure and evolution of AP3, a sex linked gene with copies on the X and Y chromosomes in the dioecious plant S. latifolia. These copies showed complementary expression patterns and relaxed evolution at protein level compared to autosomal orthologues, which suggests subfunctionalization. One intron of the Y-linked allele was invaded by retrotransposons that display sex-specific expression patterns that are similar to the expression pattern of the corresponding allele, which suggests that these transposable elements may have influenced evolution of expression patterns of the Y copy. These data could help researchers decipher the role of transposable elements in degenerative processes during sex chromosome evolution.
Interaction of silver nanoparticles with Tacaribe virus
Authors: Speshock Janice L , Murdock Richard C , Braydich-Stolle Laura K , Schrand Amanda M , Hussain Saber M 
Published: August 2010

Abstract

Background
Silver nanoparticles possess many unique properties that make them attractive for use in biological applications. Recently they received attention when it was shown that 10 nm silver nanoparticles were bactericidal, which is promising in light of the growing number of antibiotic resistant bacteria. An area that has been largely unexplored is the interaction of nanomaterials with viruses and the possible use of silver nanoparticles as an antiviral agent.

Results
This research focuses on evaluating the interaction of silver nanoparticles with a New World arenavirus, Tacaribe virus, to determine if they influence viral replication. Surprisingly exposing the virus to silver nanoparticles prior to infection actually facilitated virus uptake into the host cells, but the silver-treated virus had a significant reduction in viral RNA production and progeny virus release, which indicates that silver nanoparticles are capable of inhibiting arenavirus infection in vitro. The inhibition of viral replication must occur during early replication since although pre-infection treatment with silver nanoparticles is very effective, the post-infection addition of silver nanoparticles is only effective if administered within the first 2-4 hours of virus replication.

Conclusions
Silver nanoparticles are capable of inhibiting a prototype arenavirus at non-toxic concentrations and effectively inhibit arenavirus replication when administered prior to viral infection or early after initial virus exposure. This suggests that the mode of action of viral neutralization by silver nanoparticles occurs during the early phases of viral replication.
Profiling alumni of a Brazilian public dental school
Authors: Nunes Maria F , Silva Erica T , Santos Laura B , Queiroz Maria G , Leles Cláudio R 
Published: August 2010

Abstract

Background
Follow-up studies of former students are an efficient way to organize the entire process of professional training and curriculum evaluation. The aim of this study was to identify professional profile subgroups based on job-related variables in a sample of former students of a Brazilian public dental school.

Methods
A web-based password-protected questionnaire was sent to 633 registered dentists who graduated from the Federal University of Goias between 1988 and 2007. Job-related information was retrieved from 14 closed questions, on subjects such as gender, occupational routine, training, profits, income status, and self-perception of professional career, generating an automatic database for analysis. The two-step cluster method was used for dividing dentists into groups on the basis of minimal within-group and maximal between-group variation, using job-related variables to represent attributes upon which the clustering was based.

Results
There were 322 respondents (50.9%), predominantly female (64.9%) and the mean age was 34 years (SD = 6.0). The automatic selection of an optimal number of clusters included 289 cases (89.8%) in 3 natural clusters. Clusters 1, 2 and 3 included 52.2%, 30.8% and 17.0% of the sample respectively. Interpretation of within-group rank of variable importance for cluster segmentation resulted in the following characterization of clusters: Cluster 1 - specialist dentists with higher profits and positive views of the profession; Cluster 2 - general dental practitioners in small cities; Cluster 3 - underpaid and less motivated dentists with negative views of the profession. Male dentists were predominant in cluster 1 and females in cluster 3. One-way Anova showed that age and time since graduation were significantly lower in Cluster 2 (P < 0.001). Alternative solutions with 4 and 5 clusters revealed specific discrimination of Cluster 1 by gender and dental education professionals.

Conclusions
Cluster analysis was a valuable method for identifying natural grouping with relatively homogeneous cases, providing potentially meaningful information for professional orientation in dentistry in a variety of professional situations and environments.
Does pleural fluid appearance really matter? The relationship between fluid appearance and cytology, cell counts, and chemical laboratory measurements in pleural effusions of patients with cancer
Authors: Ozcakar Bulent , Martinez Carlos H , Morice Rodolfo C , Eapen Georgie A , Ost David , Sarkiss Mona G , Chiu Hsienchang T , Jimenez Carlos A 
Published: August 2010

AbstractBackgroundPrevious reports have suggested that the appearance of pleural effusions (i.e., the presence or absence of blood) might help to establish the etiology of the effusions. This study explores the relationship between pleural fluid appearance and the results of chemical and cytological analyses in a group of patients with recurrent symptomatic pleural effusions and a diagnosis of cancer.MethodsMedical records were reviewed from all 390 patients who were diagnosed with cancer, who underwent thoracentesis before placement of an intrapleural catheter (IPC) between April 2000 and January 2006. Adequate information for data analysis was available in 365 patients. The appearance of their pleural fluid was obtained from procedure notes dictated by the pulmonologists who had performed the thoracenteses. The patients were separated into 2 groups based on fluid appearance: non-bloody and bloody. Group differences in cytology interpretation were compared by using the chi square test. Cellular counts, chemical laboratory results, and survival after index procedure were compared by using the student's t test.ResultsPleural fluid cytology was positive on 82.5% of the non-bloody effusions and on 82.4% of the bloody ones. The number of red blood cells (220.5 × 103/μL vs. 12.3 × 103/μL) and LDH values (1914 IU/dl vs. 863 IU/dl) were statistically higher in bloody pleural effusions.ConclusionThe presence or absence of blood in pleural effusions cannot predict their etiology in patients with cancer and recurrent symptomatic pleural effusions.
Atypical presentation of acute pancreatitis in a man with pancreatic insufficiency and cystic fibrosis: a case report
Authors: Turner Malcolm , Jackson Hugh , Harle Robin , Bohmer Rob , Reid David W 
Published: August 2010

Abstract

Introduction
Whether acute pancreatitis can occur in pancreatically insufficient individuals with cystic fibrosis remains a matter of debate.

Case presentation
We describe a case of acute pancreatitis occurring in a 52-year-old Caucasian Australian man with moderately severe cystic fibrosis lung disease and pancreatic insufficiency. An inflammatory mass within the head of his pancreas was confirmed using computed tomography, magnetic resonance imaging and pancreatic biopsy, but serum amylase and lipase remained normal throughout the acute phase of his illness. His symptoms and the pancreatic mass resolved following the insertion of a biliary stent and the introduction of ursodeoxycholic acid.

Conclusion
Our case report highlights the potential for acute pancreatitis to occur in patients with pancreatic insufficiency and cystic fibrosis. We further demonstrate that conventional biochemical markers that are normally assessed to confirm the diagnosis may not be of particular use. As patients with cystic fibrosis survive into their fourth and fifth decades of life, atypical presentations of acute pancreatitis may become more common.