7 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

"Cystic Fibrosis"

These pubmed results were generated on 2016/09/27

PubMed comprises more than 24 million citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

15 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

"Systems Biology"[Title/Abstract] AND ("2005/01/01"[PDAT] : "3000"[PDAT])

These pubmed results were generated on 2016/09/27

PubMed comprises more than 24 million citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

Modeling of Plasmodium falciparum Telomerase Reverse Transcriptase Ternary Complex: Repurposing of Nucleoside Analog Inhibitors.

Assay Drug Dev Technol. 2015 Dec;13(10):628-37

Authors: Mohanty P, Gupta A, Bhatnagar S

Abstract
The Plasmodium falciparum telomerase reverse transcriptase (PfTERT) is a ribonucleoprotein that assists the maintenance of the telomeric ends of chromosomes by reverse transcription of its own RNA subunit. It represents an attractive therapeutic target for eradication of the plasmodial parasite at the asexual liver stage. Automated modeling using MUSTER and knowledge-based techniques were used to obtain a three-dimensional model of the active site of reverse transcriptase domain of PfTERT, which is responsible for catalyzing the addition of incoming dNTPs to the growing DNA strand in presence of divalent magnesium ions. Further, the ternary complex of the active site of PfTERT bound to a DNA-RNA duplex was also modeled using Haddock server and represents the functional form of the enzyme. Initially, established nucleoside analog inhibitors of PfTERT, AZTTP, and ddGTP were docked in the modeled binding site of the PfTERT ternary complex using AutoDock v4.2. Subsequently, docking studies were carried out with 14 approved nucleoside analog inhibitors. Docking studies predicted that floxuridine, gemcitabine, stavudine, and vidarabine have high affinity for the PfTERT ternary complex. Further analysis on the basis of known side effects led us to propose repositioning of vidarabine as a suitable drug candidate for inhibition of PfTERT.

PMID: 26690766 [PubMed - indexed for MEDLINE]

Interview with Raúl Insa, MD, PhD.

Assay Drug Dev Technol. 2015 Dec;13(10):603-5

Authors: Insa R, Mucke H

PMID: 26690763 [PubMed - indexed for MEDLINE]

Regulatory exclusivities for medicinal products for human use in the EU.

Pharm Pat Anal. 2016;5(1):5-8

Authors: Schoonderbeek C, Jong B

PMID: 26674744 [PubMed - indexed for MEDLINE]

New Indications and a Sense of (Re)purpose.

EBioMedicine. 2015 Oct;2(10):1257-8

Authors:

PMID: 26629497 [PubMed - indexed for MEDLINE]

Repurposing Kinase Inhibitors as Antiviral Agents to Control Influenza A Virus Replication.

Assay Drug Dev Technol. 2015 Dec;13(10):638-49

Authors: Perwitasari O, Yan X, O'Donnell J, Johnson S, Tripp RA

Abstract
Influenza A virus (IAV) infection causes seasonal epidemics of contagious respiratory illness that causes substantial morbidity and some mortality. Regular vaccination is the principal strategy for controlling influenza virus, although vaccine efficacy is variable. IAV antiviral drugs are available; however, substantial drug resistance has developed to two of the four currently FDA-approved antiviral drugs. Thus, new therapeutic approaches are being sought to reduce the burden of influenza-related disease. A high-throughput screen using a human kinase inhibitor library was performed targeting an emerging IAV strain (H7N9) in A549 cells. The inhibitor library contained 273 structurally diverse, active cell permeable kinase inhibitors with known bioactivity and safety profiles, many of which are at advanced stages of clinical development. The current study shows that treatment of human A549 cells with kinase inhibitors dinaciclib, flavopiridol, or PIK-75 exhibits potent antiviral activity against H7N9 IAV as well as other IAV strains. Thus, targeting host kinases can provide a broad-spectrum therapeutic approach against IAV. These findings provide a path forward for repurposing existing kinase inhibitors safely as potential antivirals, particularly those that can be tested in vivo and ultimately for clinical use.

PMID: 26192013 [PubMed - indexed for MEDLINE]

DEK over-expression promotes mitotic defects and micronucleus formation.

Cell Cycle. 2015;14(24):3939-53

Authors: Matrka MC, Hennigan RF, Kappes F, DeLay ML, Lambert PF, Aronow BJ, Wells SI

Abstract
The DEK gene encodes a nuclear protein that binds chromatin and is involved in various fundamental nuclear processes including transcription, RNA splicing, DNA replication and DNA repair. Several cancer types characteristically over-express DEK at the earliest stages of transformation. In order to explore relevant mechanisms whereby DEK supports oncogenicity, we utilized cancer databases to identify gene transcripts whose expression patterns are tightly correlated with that of DEK. We identified an enrichment of genes involved in mitosis and thus investigated the regulation and possible function of DEK in cell division. Immunofluorescence analyses revealed that DEK dissociates from DNA in early prophase and re-associates with DNA during telophase in human keratinocytes. Mitotic cell populations displayed a sharp reduction in DEK protein levels compared to the corresponding interphase population, suggesting DEK may be degraded or otherwise removed from the cell prior to mitosis. Interestingly, DEK overexpression stimulated its own aberrant association with chromatin throughout mitosis. Furthermore, DEK co-localized with anaphase bridges, chromosome fragments, and micronuclei, suggesting a specific association with mitotically defective chromosomes. We found that DEK over-expression in both non-transformed and transformed cells is sufficient to stimulate micronucleus formation. These data support a model wherein normal chromosomal clearance of DEK is required for maintenance of high fidelity cell division and chromosomal integrity. Therefore, the overexpression of DEK and its incomplete removal from mitotic chromosomes promotes genomic instability through the generation of genetically abnormal daughter cells. Consequently, DEK over-expression may be involved in the initial steps of developing oncogenic mutations in cells leading to cancer initiation.

PMID: 25945971 [PubMed - indexed for MEDLINE]

OSAnalyzer: A Bioinformatics Tool for the Analysis of Gene Polymorphisms Enriched with Clinical Outcomes.

Microarrays (Basel). 2016;5(4)

Authors: Agapito G, Botta C, Guzzi PH, Arbitrio M, Di Martino MT, Tassone P, Tagliaferri P, Cannataro M

Abstract
BACKGROUND: The identification of biomarkers for the estimation of cancer patients' survival is a crucial problem in modern oncology. Recently, the Affymetrix DMET (Drug Metabolizing Enzymes and Transporters) microarray platform has offered the possibility to determine the ADME (absorption, distribution, metabolism, and excretion) gene variants of a patient and to correlate them with drug-dependent adverse events. Therefore, the analysis of survival distribution of patients starting from their profile obtained using DMET data may reveal important information to clinicians about possible correlations among drug response, survival rate, and gene variants.
METHODS: In order to provide support to this analysis we developed OSAnalyzer, a software tool able to compute the overall survival (OS) and progression-free survival (PFS) of cancer patients and evaluate their association with ADME gene variants.
RESULTS: The tool is able to perform an automatic analysis of DMET data enriched with survival events. Moreover, results are ranked according to statistical significance obtained by comparing the area under the curves that is computed by using the log-rank test, allowing a quick and easy analysis and visualization of high-throughput data.
CONCLUSIONS: Finally, we present a case study to highlight the usefulness of OSAnalyzer when analyzing a large cohort of patients.

PMID: 27669316 [PubMed - as supplied by publisher]

Steroid-induced ocular hypertension/glaucoma: Focus on pharmacogenomics and implications for precision medicine.

Prog Retin Eye Res. 2016 Sep 22;

Authors: Elizabeth Fini M, Schwartz SG, Gao X, Jeong S, Patel N, Itakura T, Price MO, Price FW, Varma R, Daniel Stamer W

Abstract
Elevation of intraocular pressure (IOP) due to therapeutic use of glucocorticoids is called steroid-induced ocular hypertension (SIOH); this can lead to steroid-induced glaucoma (SIG). Glucocorticoids initiate signaling cascades ultimately affecting expression of hundreds of genes; this provides the potential for a highly personalized pharmacological response. Studies attempting to define genetic risk factors were undertaken early in the history of glucocorticoid use, however scientific tools available at that time were limited and progress stalled. In contrast, significant advances were made over the ensuing years in defining disease pathophysiology. As the genomics age emerged, it appeared the time was right to renew investigation into genetics. Pharmacogenomics is an unbiased discovery approach, not requiring an underlying hypothesis, and provides a way to pinpoint clinically significant genes and pathways that could not have been discovered any other way. Results of the first genome-wide association study to identify polymorphisms associated with SIOH, and follow-up on two novel genes linked to the disorder, GPR158 and HCG22, is discussed in the second half of the article. However, knowledge of genetic variants determining response to steroids in the eye also has value in its own right as a predictive and diagnostic tool. This article concludes with a discussion of how the Precision Medicine Initiative(®), announced by U.S. President Obama in his 2015 State of the Union address, is beginning to touch the practice of ophthalmology. It is argued that SIOH/SIG may provide one of the next opportunities for effective application of precision medicine.

PMID: 27666015 [PubMed - as supplied by publisher]

Cardiovascular Pharmacokinetics, Pharmacodynamics, and Pharmacogenomics for the Clinical Practitioner.

J Cardiovasc Pharmacol Ther. 2016 Jan;21(1):20-6

Authors: Sleder AT, Kalus J, Lanfear DE

Abstract
Current clinical cardiovascular practice requires a clinician to have a strong foundation in multiple aspects of pharmacology. Modern cardiovascular regimens are complex, and optimal management, application of evolving guidelines, and adoption of new therapies build off a more basic understanding of pharmacokinetics and pharmacodynamics. In addition, it is likely time to add a third pillar into this discussion, the expanding field of pharmacogenomics referring to the genetic influences on drug response. This field has increasing applications in medicine and clearly holds significant promise for cardiovascular disease management. Awareness of pharmacogenomic advances and the fundamentals of pharmacokinetics and pharmacodynamics can help the clinician more easily deliver great care. Here we attempt to briefly summarize and simplify key concepts of pharmacokinetics, pharmacodynamics, and pharmacogenomics relevant to the cardiovascular disease practitioner.

PMID: 26054891 [PubMed - indexed for MEDLINE]

Using Text Analytics of AJPE Article Titles to Reveal Trends In Pharmacy Education Over the Past Two Decades.

Am J Pharm Educ. 2016 Aug 25;80(6):104

Authors: Pedrami F, Asenso P, Devi S

Abstract
Objective. To identify trends in pharmacy education during last two decades using text mining. Methods. Articles published in the American Journal of Pharmaceutical Education (AJPE) in the past two decades were compiled in a database. Custom text analytics software was written using Visual Basic programming language in the Visual Basic for Applications (VBA) editor of Excel 2007. Frequency of words appearing in article titles was calculated using the custom VBA software. Data were analyzed to identify the emerging trends in pharmacy education. Results. Three educational trends emerged: active learning, interprofessional, and cultural competency. Conclusion. The text analytics program successfully identified trends in article topics and may be a useful compass to predict the future course of pharmacy education.

PMID: 27667841 [PubMed - in process]

Investigating Alternative Transport of Integral Plasma Membrane Proteins from the ER to the Golgi: Lessons from the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR).

Methods Mol Biol. 2016;1459:105-126

Authors: Amaral MD, Farinha CM, Matos P, Botelho HM

Abstract
Secretory traffic became a topical field because many important cell regulators are plasma membrane proteins (transporters, channels, receptors), being thus key targets in biomedicine and drug discovery. Cystic fibrosis (CF), caused by defects in a single gene encoding the CF transmembrane conductance regulator (CFTR), constitutes the most common of rare diseases and certainly a paradigmatic one.Here we focus on five different approaches that allow biochemical and cellular characterization of CFTR from its co-translational insertion into the ER membrane to its delivery to the plasma membrane.

PMID: 27665554 [PubMed - as supplied by publisher]

Unconventional Protein Secretion in Animal Cells.

Methods Mol Biol. 2016;1459:31-46

Authors: Ng F, Tang BL

Abstract
All eukaryotic cells secrete a range of proteins in a constitutive or regulated manner through the conventional or canonical exocytic/secretory pathway characterized by vesicular traffic from the endoplasmic reticulum, through the Golgi apparatus, and towards the plasma membrane. However, a number of proteins are secreted in an unconventional manner, which are insensitive to inhibitors of conventional exocytosis and use a route that bypasses the Golgi apparatus. These include cytosolic proteins such as fibroblast growth factor 2 (FGF2) and interleukin-1β (IL-1β), and membrane proteins that are known to also traverse to the plasma membrane by a conventional process of exocytosis, such as α integrin and the cystic fibrosis transmembrane conductor (CFTR). Mechanisms underlying unconventional protein secretion (UPS) are actively being analyzed and deciphered, and these range from an unusual form of plasma membrane translocation to vesicular processes involving the generation of exosomes and other extracellular microvesicles. In this chapter, we provide an overview on what is currently known about UPS in animal cells.

PMID: 27665549 [PubMed - as supplied by publisher]

Combination antimicrobial susceptibility testing of Burkholderia cepacia complex: significance of species.

Int J Antimicrob Agents. 2016 Sep 12;

Authors: Abbott FK, Milne KE, Stead DA, Gould IM

Abstract
The Burkholderia cepacia complex (Bcc) is notorious for the life-threatening pulmonary infections it causes in patients with cystic fibrosis. The multidrug-resistant nature of Bcc and differing infective Bcc species make the design of appropriate treatment regimens challenging. Previous synergy studies have failed to take account of the species of Bcc isolates. Etest methodology was used to facilitate minimum inhibitory concentration (MIC) and antimicrobial combination testing on 258 isolates of Bcc, identified to species level by matrix-assisted laser desorption/ionisation time-of-flight mass spectrometry (MALDI-TOF/MS). The most active antimicrobials were trimethoprim/sulphamethoxazole, doxycycline and minocycline (52.5%, 46.4% and 45.9% of isolates susceptible, respectively). Synergy was observed in 9.2% of the 1799 combinations tested; the most common synergistic combinations were tobramycin + ceftazidime, meropenem + tobramycin and levofloxacin + piperacillin/tazobactam (35.4%, 32.3% and 22.2% synergy, respectively). Antimicrobial susceptibility analysis revealed differences between Burkholderia cenocepacia and Burkholderia multivorans. Disparity in clinical outcome during infection with these two micro-organisms necessitates further investigation into the clinical outcomes of treatment regimens in light of species identification and in vitro antimicrobial susceptibility studies.

PMID: 27665523 [PubMed - as supplied by publisher]

Air pollution during pregnancy and lung development in the child.

Paediatr Respir Rev. 2016 Aug 19;

Authors: Korten I, Ramsey K, Latzin P

Abstract
Air pollution exposure has increased extensively in recent years and there is considerable evidence that exposure to particulate matter can lead to adverse respiratory outcomes. The health impacts of exposure to air pollution during the prenatal period is especially concerning as it can impair organogenesis and organ development, which can lead to long-term complications. Exposure to air pollution during pregnancy affects respiratory health in different ways. Lung development might be impaired by air pollution indirectly by causing lower birth weight, premature birth or disturbed development of the immune system. Exposure to air pollution during pregnancy has also been linked to decreased lung function in infancy and childhood, increased respiratory symptoms, and the development of childhood asthma. In addition, impaired lung development contributes to infant mortality. The mechanisms of how prenatal air pollution affects the lungs are not fully understood, but likely involve interplay of environmental and epigenetic effects. The current epidemiological evidence on the effect of air pollution during pregnancy on lung function and children's respiratory health is summarized in this review. While evidence for the adverse effects of prenatal air pollution on lung development and health continue to mount, rigorous actions must be taken to reduce air pollution exposure and thus long-term respiratory morbidity and mortality.

PMID: 27665510 [PubMed - as supplied by publisher]

Systemic Corticosteroid Responses in Children with Severe Asthma: Phenotypic and Endotypic Features.

J Allergy Clin Immunol Pract. 2016 Sep 21;

Authors: Fitzpatrick AM, Stephenson ST, Brown MR, Nguyen K, Douglas S, Brown LA

Abstract
BACKGROUND: Severe asthma in children is a heterogeneous disorder associated with variable responses to corticosteroid treatment. Criterion standards for corticosteroid responsiveness assessment in children are lacking.
OBJECTIVE: This study sought to characterize systemic corticosteroid responses in children with severe asthma after treatment with intramuscular triamcinolone and to identify phenotypic and molecular predictors of an intramuscular triamcinolone response.
METHODS: Asthma-related quality of life, exhaled nitric oxide, blood eosinophils, lung function, and inflammatory cytokine and chemokine mRNA gene expression in peripheral blood mononuclear cells were assessed in 56 children with severe asthma at baseline and 14 days after intramuscular triamcinolone injection. The Asthma Control Questionnaire was used to classify children with severe asthma into corticosteroid response groups.
RESULTS: Three groups of children with severe asthma were identified: controlled severe asthma, children who achieved control after triamcinolone, and children who did not achieve control. At baseline, these groups were phenotypically similar. After triamcinolone, discordance between symptoms, lung function, exhaled nitric oxide, and blood eosinophils was noted. Clinical phenotypic predictors were of limited utility in predicting the triamcinolone response, whereas systemic mRNA expression of inflammatory cytokines and chemokines related to IL-2, IL-10, and TNF signaling pathways, namely, AIMP1, CCR2, IL10RB, and IL5, strongly differentiated children who failed to achieve control with triamcinolone administration.
CONCLUSIONS: Systemic corticosteroid responsiveness in children with severe asthma is heterogeneous. Alternative prediction models that include molecular endotypic as well as clinical phenotypic features are needed to identify which children derive the most clinical benefit from systemic corticosteroid step-up therapy given the potential side effects.

PMID: 27665382 [PubMed - as supplied by publisher]

Investigating Alternative Transport of Integral Plasma Membrane Proteins from the ER to the Golgi: Lessons from the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR).

Methods Mol Biol. 2016;1459:105-126

Authors: Amaral MD, Farinha CM, Matos P, Botelho HM

Abstract
Secretory traffic became a topical field because many important cell regulators are plasma membrane proteins (transporters, channels, receptors), being thus key targets in biomedicine and drug discovery. Cystic fibrosis (CF), caused by defects in a single gene encoding the CF transmembrane conductance regulator (CFTR), constitutes the most common of rare diseases and certainly a paradigmatic one.Here we focus on five different approaches that allow biochemical and cellular characterization of CFTR from its co-translational insertion into the ER membrane to its delivery to the plasma membrane.

PMID: 27665554 [PubMed - as supplied by publisher]

Hypertrophic cardiomyopathy with Jeune syndrome: The first reported case.

Turk Kardiyol Dern Ars. 2016 Sep;44(6):503-506

Authors: Güvenç O, Sündüs Uygun S, Çimen D, Aslan E, Annagür A

Abstract
Jeune syndrome (Asphyxiating thoracic dysplasia) is a rare dystrophy of the skeleton, inherited as an autosomal recessive condition. Patients develop a narrowed thorax, rhizomelic dwarfism, and hepatic, renal, and pancreatic abnormalities. High rates of pulmonary hypoplasia and pulmonary hypertension have been reported. Some patients die in early stages of life due to respiratory failure. The case of a patient referred with a history of severe asphyxiating birth, who had been diagnosed with Jeune syndrome and later hypertrophic cardiomyopathy (HCM) upon echocardiographic examination is described in the present report. This rare disease is discussed with respect to the current literature, as the present is the first reported case to be accompanied by HCM.

PMID: 27665332 [PubMed - as supplied by publisher]

Unravelling the myotonic dystrophy type 1 clinical spectrum: A systematic registry-based study with implications for disease classification.

Rev Neurol (Paris). 2016 Sep 21;

Authors: De Antonio M, Dogan C, Hamroun D, Mati M, Zerrouki S, Eymard B, Katsahian S, Bassez G, French Myotonic Dystrophy Clinical Network

Abstract
The broad clinical spectrum of myotonic dystrophy type 1 (DM1) creates particular challenges for both medical care and design of clinical trials. Clinical onset spans a continuum from birth to late adulthood, with symptoms that are highly variable in both severity and nature of the affected organ systems. In the literature, this complex phenotype is divided into three grades (mild, classic, and severe) and four or five main clinical categories (congenital, infantile/juvenile, adult-onset and late-onset forms), according to symptom severity and age of onset, respectively. However, these classifications are still under discussion with no consensus thus far. While some specific clinical features have been primarily reported in some forms of the disease, there are no clear distinctions. As a consequence, no modifications in the management of healthcare or the design of clinical studies have been proposed based on the clinical form of DM1. The present study has used the DM-Scope registry to assess, in a large cohort of DM1 patients, the robustness of a classification divided into five clinical forms. Our main aim was to describe the disease spectrum and investigate features of each clinical form. The five subtypes were compared by distribution of CTG expansion size, and the occurrence and onset of the main symptoms of DM1. Analyses validated the relevance of a five-grade model for DM1 classification. Patients were classified as: congenital (n=93, 4.5%); infantile (n=303, 14.8%); juvenile (n=628, 30.7%); adult (n=694, 34.0%); and late-onset (n=326, 15.9%). Our data show that the assumption of a continuum from congenital to the late-onset form is valid, and also highlights disease features specific to individual clinical forms of DM1 in terms of symptom occurrence and chronology throughout the disease course. These results support the use of the five-grade model for disease classification, and the distinct clinical profiles suggest that age of onset and clinical form may be key criteria in the design of clinical trials when considering DM1 health management and research.

PMID: 27665240 [PubMed - as supplied by publisher]