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Lung fibrosis

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https://www.readbyqxmd.com/read/28651010/macrophages-but-not-neutrophils-are-critical-for-proliferation-of-burkholderia-cenocepacia-and-ensuing-host-damaging-inflammation
#1
Jennifer Mesureur, Joana R Feliciano, Nelly Wagner, Margarida C Gomes, Lili Zhang, Monica Blanco-Gonzalez, Michiel van der Vaart, David O'Callaghan, Annemarie H Meijer, Annette C Vergunst
Bacteria of the Burkholderia cepacia complex (Bcc) can cause devastating pulmonary infections in cystic fibrosis (CF) patients, yet the precise mechanisms underlying inflammation, recurrent exacerbations and transition from chronic stages to acute infection and septicemia are not known. Bcc bacteria are generally believed to have a predominant extracellular biofilm life style in infected CF lungs, similar to Pseudomonas aeruginosa, but this has been challenged by clinical observations which show Bcc bacteria predominantly in alveolar macrophages...
June 26, 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28651005/optimization-of-a-murine-and-human-tissue-model-to-recapitulate-dermal-and-pulmonary-features-of-systemic-sclerosis
#2
Tomoya Watanabe, Tetsuya Nishimoto, Logan Mlakar, Jonathan Heywood, Maya Malaab, Stanley Hoffman, Carol Feghali-Bostwick
The murine bleomycin (BLM)-induced fibrosis model is the most widely used in systemic sclerosis (SSc) studies. It has been reported that systemic delivery of BLM via continuous diffusion from subcutaneously implanted osmotic minipumps can cause fibrosis of the skin, lungs, and other internal organs. However, the mouse strain, dosage of BLM, administration period, and additional important features differ from one report to the next. In this study, by employing the pump model in C57BL/6J mice, we show a dose-dependent increase in lung fibrosis by day 28 and a transient increase in dermal thickness...
2017: PloS One
https://www.readbyqxmd.com/read/28650861/microbiome-in-interstitial-lung-disease-from-pathogenesis-to-treatment-target
#3
Margaret L Salisbury, MeiLan K Han, Robert P Dickson, Philip L Molyneaux
PURPOSE OF REVIEW: This review summarizes current knowledge of the role of the lung microbiome in interstitial lung disease and poses considerations of the microbiome as a therapeutic target. RECENT FINDINGS: Although historically considered sterile, bacterial communities have now been well documented in lungs in health and disease. Studies in idiopathic pulmonary fibrosis (IPF) suggest that increased bacterial burden and/or abundance of potentially pathogenic bacteria may drive disease progression, acute exacerbations, and mortality...
June 24, 2017: Current Opinion in Pulmonary Medicine
https://www.readbyqxmd.com/read/28649564/primary-ciliary-dyskinesia-an-update-on-clinical-aspects-genetics-diagnosis-and-future-treatment-strategies
#4
REVIEW
Virginia Mirra, Claudius Werner, Francesca Santamaria
Primary ciliary dyskinesia (PCD) is an orphan disease (MIM 244400), autosomal recessive inherited, characterized by motile ciliary dysfunction. The estimated prevalence of PCD is 1:10,000 to 1:20,000 live-born children, but true prevalence could be even higher. PCD is characterized by chronic upper and lower respiratory tract disease, infertility/ectopic pregnancy, and situs anomalies, that occur in ≈50% of PCD patients (Kartagener syndrome), and these may be associated with congenital heart abnormalities...
2017: Frontiers in Pediatrics
https://www.readbyqxmd.com/read/28649446/phenotypic-profiling-of-cftr-modulators-in-patient-derived-respiratory-epithelia
#5
Saumel Ahmadi, Zoltan Bozoky, Michelle Di Paola, Sunny Xia, Canhui Li, Amy P Wong, Leigh Wellhauser, Steven V Molinski, Wan Ip, Hong Ouyang, Julie Avolio, Julie D Forman-Kay, Felix Ratjen, Jeremy A Hirota, Johanna Rommens, Janet Rossant, Tanja Gonska, Theo J Moraes, Christine E Bear
Pulmonary disease is the major cause of morbidity and mortality in patients with cystic fibrosis, a disease caused by mutations in the Cystic Fibrosis Transmembrane conductance Regulator (CFTR) gene. Heterogeneity in CFTR genotype-phenotype relationships in affected individuals plus the escalation of drug discovery targeting specific mutations highlights the need to develop robust in vitro platforms with which to stratify therapeutic options using relevant tissue. Toward this goal, we adapted a fluorescence plate reader assay of apical CFTR-mediated chloride conductance to enable profiling of a panel of modulators on primary nasal epithelial cultures derived from patients bearing different CFTR mutations...
April 14, 2017: NPJ Genomic Medicine
https://www.readbyqxmd.com/read/28649402/evolutionary-adaptations-of-biofilms-infecting-cystic-fibrosis-lungs-promote-mechanical-toughness-by-adjusting-polysaccharide-production
#6
Kristin Kovach, Megan Davis-Fields, Yasuhiko Irie, Kanishk Jain, Shashvat Doorwar, Katherine Vuong, Numa Dhamani, Kishore Mohanty, Ahmed Touhami, Vernita D Gordon
Biofilms are communities of microbes embedded in a matrix of extracellular polymeric substances, largely polysaccharides. Multiple types of extracellular polymeric substances can be produced by a single bacterial strain. The distinct polymer components of biofilms are known to provide chemical protection, but little is known about how distinct extracellular polysaccharides may also protect biofilms against mechanical stresses such as shear or phagocytic engulfment. Decades-long infections of Pseudomonas. aeruginosa biofilms in the lungs of cystic fibrosis patients are natural models for studies of biofilm fitness under pressure from antibiotics and the immune system...
2017: NPJ Biofilms and Microbiomes
https://www.readbyqxmd.com/read/28649308/association-between-spirometry-controlled-chest-ct-scores-using-computer-animated-biofeedback-and-clinical-markers-of-lung-disease-in-children-with-cystic-fibrosis
#7
Thomas Kongstad, Kent Green, Frederik Buchvald, Marianne Skov, Tania Pressler, Kim Gjerum Nielsen
Background: Computed tomography (CT) of the lungs is the gold standard for assessing the extent of structural changes in the lungs. Spirometry-controlled chest CT (SCCCT) has improved the usefulness of CT by standardising inspiratory and expiratory lung volumes during imaging. This was a single-centre cross-sectional study in children with cystic fibrosis (CF). Using SCCCT we wished to investigate the association between the quantity and extent of structural lung changes and pulmonary function outcomes, and prevalence of known CF lung pathogens...
2017: European Clinical Respiratory Journal
https://www.readbyqxmd.com/read/28649248/a-combination-of-podophyllotoxin-and-rutin-alleviates-radiation-induced-pneumonitis-and-fibrosis-through-modulation-of-lung-inflammation-in-mice
#8
Savita Verma, Bhargab Kalita, Sania Bajaj, Hridayesh Prakash, Ajay Kumar Singh, Manju Lata Gupta
Pneumonitis and pulmonary fibrosis are predominant consequences of radiation exposure, whether planned or accidental. The present study, demonstrates radioprotective potential of a formulation, prepared by combining podophyllotoxin and rutin (G-003M), in mice exposed to 11 Gy thoracic gamma radiation (TGR). Treated mice were observed for survival and other symptomatic features. Formation of reactive oxygen species (ROS)/nitric oxide (NO) was measured in bronchoalveolar lavage cells. DNA damage and cell death were assessed in alveolar cells by terminal deoxynucleotidyl transferase dUTP nick-end labeling assay...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28648751/the-muc5b-promoter-polymorphism-and-telomere-length-in-patients-with-chronic-hypersensitivity-pneumonitis-an-observational-cohort-control-study
#9
Brett Ley, Chad A Newton, Isabel Arnould, Brett M Elicker, Travis S Henry, Eric Vittinghoff, Jeffrey A Golden, Kirk D Jones, Kiran Batra, Jose Torrealba, Christine Kim Garcia, Paul J Wolters
BACKGROUND: Patients with hypersensitivity pneumonitis are at risk of developing pulmonary fibrosis, which is associated with reduced survival. In families with multiple affected members, individuals might be diagnosed as having idiopathic pulmonary fibrosis (IPF) or chronic (fibrotic) hypersensitivity pneumonitis, which suggests these disorders share risk factors. We aimed to test whether the genomic risk factors associated with the development and progression of IPF are also associated with the development of fibrosis and reduced survival in people with chronic hypersensitivity pneumonitis...
June 22, 2017: Lancet Respiratory Medicine
https://www.readbyqxmd.com/read/28646679/hypoxia-induced-adam-17-expression-is-mediated-by-rsk1-dependent-c-ebp%C3%AE-activation-in-human-lung-fibroblasts
#10
Jing-Yun Chen, Chien-Huang Lin, Bing-Chang Chen
Hypoxia was identified as a mediator of lung fibrosis in patients with chronic obstructive asthma (COA). Overexpression of a disintegrin and metalloproteinase 17 (ADAM 17) and connective tissue growth factor (CTGF) leads to development of tissue fibrosis. However, the signaling pathway in hypoxia-induced ADAM 17 expression remains poorly defined. In this study, we investigated the roles that ribosomal S-6 kinase 1 (RSK1)/CCAAT/enhancer-binding protein β (C/EBPβ)-dependent ADAM 17 expression plays in hypoxia-induced CTGF expression in human lung fibroblasts...
June 21, 2017: Molecular Immunology
https://www.readbyqxmd.com/read/28646553/epithelial-mesenchymal-transition-emt-a-spectrum-of-states-role-in-lung-development-homeostasis-and-disease
#11
REVIEW
Mohit Kumar Jolly, Chris Ward, Mathew Suji Eapen, Stephen Myers, Oskar Hallgren, Herbert Levine, Sukhwinder Singh Sohal
Epithelial Mesenchymal Transition (EMT) plays key roles during lung development and many lung diseases such as Chronic Obstructive Pulmonary Disease (COPD), lung cancer and pulmonary fibrosis. Here, integrating morphological observations with underlying molecular mechanisms, we highlight the functional role of EMT in lung development and injury repair, and discuss how it can contribute to pathogenesis of chronic lung disease. We discuss the evidence of manifestation of EMT and its potential driving role in COPD, idiopathic pulmonary fibrosis (IPF), bronchiolitis obliterans syndrome (BOS), and lung cancer, while noting that all cells need not display a full EMT in any of these contexts, i...
June 24, 2017: Developmental Dynamics: An Official Publication of the American Association of Anatomists
https://www.readbyqxmd.com/read/28646530/pirfenidone-reduces-subchondral-bone-loss-and-fibrosis-after-murine-knee-cartilage-injury
#12
Deva D Chan, Jun Li, Wei Luo, Dan N Predescu, Brian J Cole, Anna Plaas
Pirfenidone is an anti-inflammatory and anti-fibrotic drug that has shown efficacy in lung and kidney fibrosis. Because inflammation and fibrosis have been linked to the progression of osteoarthritis, we investigated the effects of oral Pirfenidone in a mouse model of cartilage injury, which results in chronic inflammation and joint-wide fibrosis in mice that lack hyaluronan synthase 1 (Has1(-/-) ) in comparison to wild-type. Femoral cartilage was surgically injured in wild-type and Has1(-/-) mice, and Pirfenidone was administered in food starting after 3 days...
June 23, 2017: Journal of Orthopaedic Research: Official Publication of the Orthopaedic Research Society
https://www.readbyqxmd.com/read/28646221/aberrant-activation-of-the-human-sex-determining-gene-in-early-embryonic-development-results-in-postnatal-growth-retardation-and-lethality-in-mice
#13
Tatsuo Kido, Zhaoyu Sun, Yun-Fai Chris Lau
Sexual dimorphisms are prevalent in development, physiology and diseases in humans. Currently, the contributions of the genes on the male-specific region of the Y chromosome (MSY) in these processes are uncertain. Using a transgene activation system, the human sex-determining gene hSRY is activated in the single-cell embryos of the mouse. Pups with hSRY activated (hSRY(ON)) are born of similar sizes as those of non-activated controls. However, they retard significantly in postnatal growth and development and all die of multi-organ failure before two weeks of age...
June 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28645157/secretory-iga-response-against-pseudomonas-aeruginosa-in-the-upper-airways-and-the-link-with-chronic-lung-infection-in-cystic-fibrosis
#14
Renan Mauch, Claudio Rossi, Talita Aiello, José Ribeiro, Antonio Ribeiro, Niels Høiby, Carlos Levy
We assessed the diagnostic ability of an ELISA test for measurement of specific secretory IgA (sIgA) in saliva to identify Cystic Fibrosis (CF) patients with P. aeruginosa chronic lung infection and intermittent lung colonization. A total of 102 Brazilian CF patients and 53 healthy controls were included. Specific serum IgG response was used as a surrogate to distinguish CF patients according to their P. aeruginosa colonization/infection status. The rate of sIgA positivity was 87.1% in CF chronically infected patients (Median value = 181...
June 22, 2017: Pathogens and Disease
https://www.readbyqxmd.com/read/28645009/case-report-of-robotic-dor-fundoplication-for-scleroderma-esophagus-with-aperistalsis-on-manometry
#15
Alonso Andrade, Matthew K Folstein, Brian R Davis
Scleroderma is a systemic disease of collagen deposition resulting in fibrosis of small arteries and arterioles. It commonly affects the skin, lungs, and gastrointestinal tract. The most common site of GI tract involvement is the esophagus. We present the case report of a 44year old female with scleroderma esophagus and severe reflux which was successfully treated with robotic dor fundoplication. Because of the wide variety of symptoms with which this problem can present, a tailored approach taking into consideration the patient's symptomatology and findings during diagnostic work-up was implemented with good results...
June 16, 2017: International Journal of Surgery Case Reports
https://www.readbyqxmd.com/read/28644693/supplemental-oxygen-in-interstitial-lung-disease-an-art-in-need-of-science
#16
Kerri A Johannson, Sachin R Pendharkar, Kirk Mathison, Charlene D Fell, Jordan A Guenette, Meena Kalluri, Martin Kolb, Christopher J Ryerson
Interstitial lung disease (ILD) comprises a large and heterogeneous group of disorders that often lead to progressive fibrosis and premature death. Oxygen supplementation is typically used in advanced lung disease patients with resting hypoxemia; however, there is a paucity of evidence guiding the use of supplemental oxygen in ILD, and significant heterogeneity in clinical practice. It remains unclear whether supplemental oxygen improves clinically meaningful outcomes, and the role of ambulatory oxygen supplementation in isolated exertional hypoxemia is particularly controversial...
June 23, 2017: Annals of the American Thoracic Society
https://www.readbyqxmd.com/read/28643178/economic-evaluation-of-tobramycin-inhalation-powder-for-the-treatment-of-chronic-pulmonary-pseudomonas-aeruginosa-infection-in-patients-with-cystic-fibrosis
#17
Srilekha Panguluri, Praveen Gunda, Laurie Debonnett, Kamal Hamed
BACKGROUND: Chronic lung infection with Pseudomonas aeruginosa occurs in approximately 50% of patients with cystic fibrosis (CF). This infection further compromises lung function, and significantly contributes to the increased healthcare costs. OBJECTIVES: Inhaled tobramycin, used to manage P. aeruginosa infection in CF patients, is available as powder (tobramycin inhalation powder, TIP) and solution (tobramycin inhalation solution, TIS). Evidence suggests increased adherence with the use of TIP over TIS...
June 22, 2017: Clinical Drug Investigation
https://www.readbyqxmd.com/read/28642745/structure-of-o-antigen-and-hybrid-biosynthetic-locus-in-burkholderia-cenocepacia-clonal-variants-recovered-from-a-cystic-fibrosis-patient
#18
A A Hassan, Rita F Maldonado, Sandra C Dos Santos, Flaviana Di Lorenzo, Alba Silipo, Carla P Coutinho, Vaughn S Cooper, Antonio Molinaro, Miguel A Valvano, Isabel Sá-Correia
Burkholderia cenocepacia is an opportunistic pathogen associated with chronic lung infections and increased risk of death in patients with cystic fibrosis (CF). In this work, we investigated the lipopolysaccharide (LPS) of clinical variants of B. cenocepacia that were collected from a CF patient over a period of 3.5 years, from the onset of infection until death by necrotizing pneumonia (cepacia syndrome). We report the chemical structure of the LPS molecule of various sequential isolates and the identification of a novel hybrid O-antigen (OAg) biosynthetic cluster...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28642621/variants-of-the-abca3-gene-might-contribute-to-susceptibility-to-interstitial-lung-diseases-in-the-chinese-population
#19
Wei Zhou, Yi Zhuang, Jiapeng Sun, Xiaofen Wang, Qingya Zhao, Lizhi Xu, Yaping Wang
ATP-binding cassette A3 (ABCA3) is a phospholipid carrier that is mainly expressed in the alveolar epithelium. Biallelic mutations of ABCA3 has been associated with fatal respiratory distress syndrome and interstitial lung disease (ILD) in children. However, whether variations in ABCA3 have a role in the development of adult ILD, including idiopathic pulmonary fibrosis (IPF), remains to be addressed. In this study, we screened for germline variants of ABCA3 by exons-sequencing in 30 patients with sporadic IPF and in 30 matched healthy controls...
June 22, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28642129/fucoxanthin-inhibits-profibrotic-protein-expression-in-vitro-and-attenuates-bleomycin-induced-lung-fibrosis-in-vivo
#20
Sun Young Ma, Won Sun Park, Dae-Sung Lee, Grace Choi, Mi-Jin Yim, Jeong Min Lee, Won-Kyo Jung, Sae Gwang Park, Su-Kil Seo, Sung Jae Park, Il Yong Han, Yung Hyun Choi, Il-Whan Choi
Pulmonary fibrosis, a potentially fatal disease, results from acute and chronic interstitial lung diseases. Fucoxanthin (Fx), a carotenoid found in brown seaweed, shows a wide range of pharmacological activities. In this study, we investigated the antifibrotic effects of fucoxanthin and their underlying molecular mechanisms in transforming growth factor-beta1 (TGF-β1)-stimulated human pulmonary fibroblasts (HPFs). Thus, the effects of Fx on TGF-β1-induced expression of fibrotic factors, such as alpha-smooth muscle actin (α-SMA), type 1 collagen, fibronectin, and interleukin-6 (IL-6), in HPFs were investigated...
June 19, 2017: European Journal of Pharmacology
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