A5103273195- Cystic Fibrosis Research Advances
- Neonatal Respiratory Health Research
- Tracheal and airway disorders
- Asthma and respiratory diseases
- Inhalation and Respiratory Drug Delivery
- Respiratory viral infections research
- Congenital Ear and Nasal Anomalies
- Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis
- Atomic and Subatomic Physics Research
- Anxiety, Depression, Psychometrics, Treatment, Cognitive Processes
- Advanced biosensing and bioanalysis techniques
- Child Nutrition and Feeding Issues
- Pediatric health and respiratory diseases
- Ion channel regulation and function
- Congenital Diaphragmatic Hernia Studies
- Respiratory Support and Mechanisms
- Ion Transport and Channel Regulation
- Adenosine and Purinergic Signaling
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Nematode management and characterization studies
- Protease and Inhibitor Mechanisms
- Cardiac, Anesthesia and Surgical Outcomes
- Psychosomatic Disorders and Their Treatments
- Pain Management and Opioid Use
- Human Health and Disease
University of Iowa
1965-2023
Cystic Fibrosis Foundation
2013-2023
Cincinnati Children's Hospital Medical Center
2012-2021
University of Cincinnati Medical Center
2018-2021
Pulmonary Associates
2016-2020
University of Cincinnati
2012-2016
Weatherford College
2014
Children's Medical Center
2013
University of East Anglia
1996-2013
University of Alabama at Birmingham
2002-2011
A new approach in the treatment of cystic fibrosis involves improving function mutant transmembrane conductance regulator (CFTR). VX-770, a CFTR potentiator, has been shown to increase activity wild-type and defective cell-surface vitro.We randomly assigned 39 adults with at least one G551D-CFTR allele receive oral VX-770 every 12 hours dose 25, 75, or 150 mg placebo for 14 days (in part 1 study) 250 28 2 study).At day 28, group subjects who received median change nasal potential difference...
<h3>Background</h3> VX-809, a cystic fibrosis transmembrane conductance regulator (CFTR) modulator, has been shown to increase the cell surface density of functional <i>F508del-CFTR</i> in vitro. <h3>Methods</h3> A randomised, double-blind, placebo-controlled study evaluated safety, tolerability and pharmacodynamics VX-809 adult patients with (n=89) who were homozygous for mutation. Subjects randomised one four 28 day dose groups (25, 50, 100 200 mg) or matching placebo. <h3>Results</h3> The...
Abstract Chronic neutrophilic inflammation is a manifestation of variety lung diseases including cystic fibrosis (CF). There increasing evidence that fragments extracellular matrix proteins, such as collagen and elastin, play an important role in inflammatory cell recruitment to the animal models airway inflammation. Unfortunately, association these peptides with human disease identification therapeutic targets directed toward pathways have remained elusive. In this study, we demonstrate...
<h3>Rationale</h3> Arikace is a liposomal amikacin preparation for aerosol delivery with potent <i>Pseudomonas aeruginosa</i> killing and prolonged lung deposition. <h3>Objectives</h3> To examine the safety efficacy of 28 days once-daily in cystic fibrosis (CF) patients chronically infected <i>P aeruginosa</i>. <h3>Methods</h3> 105 subjects were evaluated double-blind, placebo-controlled studies. Subjects randomised to (70, 140, 280 560 mg; n=7, 5, 21 36 subjects) or placebo (n=36) days....
Our objectives were to characterise the microbiota in cystic fibrosis (CF) bronchoalveolar lavage fluid (BALF), and determine its relationship inflammation disease status. BALF from paediatric adult CF patients controls undergoing clinically indicated bronchoscopy was analysed for total bacterial load by 16S rDNA sequencing. We examined 191 samples (146 45 controls) 13 centres. In aged <2 years, nontraditional taxa ( e.g . Streptococcus , Prevotella Veillonella ) constituted ∼50% of...
BACKGROUND. Lung infections are among the most consequential manifestations of cystic fibrosis (CF) and associated with reduced lung function shortened survival. Drugs called CFTR modulators improve activity dysfunctional transmembrane conductance regulator (CFTR) channels, which is physiological defect causing CF. However, it unclear how improved affects CF infections.
Previous studies have demonstrated that delivery of a recombinant adeno-associated virus (AAV) vector encoding the complete human cystic fibrosis transmembrane regulator (CFTR) cDNA (tgAAVCF) to nose, sinus, and lungs subjects with (CF) was safe well tolerated. In small randomized, double-blind study three doses aerosolized tgAAVCF or placebo at 30-day intervals, encouraging but non-significant trends in pulmonary function induced sputum interleukin 8 (IL-8) levels were seen early time...
Here we report the effects of gentamicin treatment on cystic fibrosis transmembrane regulator (CFTR) production and function in CF airway cells patients with premature stop mutations. Using immunocytochemical functional [6-methoxy-N- (3-sulfopropyl) quinolinium (SPQ)-based] techniques, ex vivo exposure from mutation led to identification surface-localized CFTR a dose-dependent fashion. Next, five mutations control subjects were treated parenteral for 1 wk, underwent repeated measures (nasal...
Apical membrane chloride channels control secretion by airway epithelial cells. Defective regulation of these is a prominent characteristic cystic fibrosis. In normal intact cells, activation protein kinase C (PKC) phorbol ester either stimulated or inhibited secretion, depending on the physiological status cell. cell-free patches, PKC also had dual effect: at high calcium concentration, inactivated channels; low activated channels. fibrosis PKC-dependent channel inactivation was normal, but...
It has been demonstrated previously that both the cystic fibrosis transmembrane conductance regulator (CFTR) and β 2 adrenergic receptor (β AR) can bind ezrin/radixin/moesin-binding phosphoprotein 50 (EBP50, also referred to as NHERF) through their PDZ motifs. Here, we show is major isoform expressed in airway epithelia it colocalizes with CFTR at apical membrane. AR stimulation increases activity, epithelial cells, glybenclamide sensitive. Deletion of motif from uncouples channel physically...
Recent advances in the management of cystic fibrosis (CF) target underlying defects CF transmembrane conductance regulator (CFTR) protein, but efficacy analyses remain limited to specific genotype-based subgroups. Patient-derived model systems may therefore aid expanding access these drugs. Brushed human nasal epithelial cells (HNEs) are an attractive tissue source, it remains unclear how faithfully they recapitulate bronchial cell (HBE) CFTR activity. We examined this gap using paired,...
Immunologic reactivity to lipid-DNA conjugates has traditionally been viewed as less of an issue than with viral vectors. We performed a dose escalation safety trial aerosolized cystic fibrosis transmembrane conductance regulator (CFTR) cDNA the lower airways eight adult patients, and monitored expression by RT-PCR. The was complexed cationic lipid amphiphile (GL-67) consisting cholesterol anchor linked spermine head group. CFTR transgene detected in three patients at 2-7 days after gene...
Matrix metalloproteases (MMPs) are proteolytic enzymes that regulate extracellular matrix turnover and aid in restoring tissue architecture following injury. There is an emerging role for destruction the pathogenesis of chronic neutrophilic lung diseases. In this study, we examined expression activity profiles MMPs lower airway secretions from cystic fibrosis (CF) patients, patients with acute respiratory failure (ARF), normal controls. A discrete repertoire MMP isoforms was found CF...
High-mobility group box 1 (HMGB1) is a potent inflammatory mediator elevated in sepsis and rheumatoid arthritis, although its role cystic fibrosis (CF) lung disease unknown.
Cystic fibrosis (CF) is a lethal genetic disorder characterized by airway remodeling and inflammation, leading to premature death. Recent evidence suggests the importance of protease activity in CF pathogenesis. One prominent protease, matrix metalloprotease (MMP)-9, demonstrates increased individuals undergoing acute pulmonary exacerbation. This thought be mediated both direct MMP-9 activation degradation its natural inhibitor, tissue inhibitor metalloprotease-1 (TIMP-1). To examine if this...