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Lung fibrosis

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https://www.readbyqxmd.com/read/28213819/conditional-knockout-of-activin-like-kinase-1-alk-1-leads-to-heart-failure-without-maladaptive-remodeling
#1
Kevin J Morine, Xiaoying Qiao, Vikram Paruchuri, Mark J Aronovitz, Emily E Mackey, Lyanne Buiten, Jonathan Levine, Keshan Ughreja, Prerna Nepali, Robert M Blanton, Richard H Karas, S Paul Oh, Navin K Kapur
Activin like kinase-1 (AlK-1) mediates signaling via the transforming growth factor beta (TGFβ) family of ligands. AlK-1 activity promotes endothelial proliferation and migration. Reduced AlK-1 activity is associated with arteriovenous malformations. No studies have examined the effect of global AlK-1 deletion on indices of cardiac remodeling. We hypothesized that reduced levels of AlK-1 promote maladaptive cardiac remodeling. To test this hypothesis, we employed AlK-1 conditional knockout mice (cKO) harboring the ROSA26-CreER knock-in allele, whereby a single dose of intraperitoneal tamoxifen triggered ubiquitous Cre recombinase-mediated excision of floxed AlK-1 alleles...
February 17, 2017: Heart and Vessels
https://www.readbyqxmd.com/read/28213592/the-evidence-of-benefits-of-exercise-training-in-interstitial-lung-disease-a-randomised-controlled-trial
#2
Leona M Dowman, Christine F McDonald, Catherine J Hill, Annemarie L Lee, Kathryn Barker, Claire Boote, Ian Glaspole, Nicole S L Goh, Anne M Southcott, Angela T Burge, Rebecca Gillies, Alicia Martin, Anne E Holland
BACKGROUND: Uncertainty exists regarding the clinical relevance of exercise training across the range of interstitial lung diseases (ILDs). OBJECTIVE: To establish the impact of exercise training in patients with ILDs of differing aetiology and severity. METHODS: 142 participants with ILD (61 idiopathic pulmonary fibrosis (IPF), 22 asbestosis, 23 connective tissue disease-related ILD (CTD-ILD) and 36 with other aetiologies) were randomised to either 8 weeks of supervised exercise training or usual care...
February 17, 2017: Thorax
https://www.readbyqxmd.com/read/28213469/insulin-signaling-via-the-pi3k-akt-pathway-regulates-airway-glucose-uptake-and-barrier-function-in-a-cftr-dependent-manner
#3
Samuel A Molina, Hannah K Moriarty, Danny T Infield, Barry R Imhoff, Rachel J Vance, Agnes H Kim, Jason M Hansen, William R Hunt, Michael Koval, Nael A McCarty
Cystic fibrosis-related diabetes (CFRD) is the most common co-morbidity associated with cystic fibrosis (CF) and correlates with increased rates of lung function decline. Since glucose is a nutrient present in the airways of patients with bacterial airway infections and since insulin controls glucose metabolism, the effect of insulin on CF airway epithelia was investigated to determine the role of insulin receptors and glucose transport in regulating glucose availability in the airway. The response to insulin by human airway epithelial cells was characterized by qPCR, immunoblot, immunofluorescence, and glucose uptake assays...
February 17, 2017: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/28213468/microencapsulation-of-lefty-secreting-engineered-cells-for-pulmonary-fibrosis-therapy-in-mice
#4
Hongge Ma, Shupei Qiao, Zeli Wang, Shuai Geng, Yufang Zhao, Xiaolu Hou, Weiming Tian, Xiongbiao Chen, Lifen Yao
Idiopathic pulmonary fibrosis (IPF) is a progressive disease that causes unremitting deposition of extracellular matrix proteins, thus resulting in distortion of the pulmonary architecture and impaired gas exchange. Associated with high morbidity and mortality, IPF is generally refractory to current pharmacological therapies. Lefty A, a potent inhibitor of transforming growth factor (TGF)-β signaling, has been shown to have promising antifibrotic ability in vitro for the treatment of renal fibrosis and other potential organ fibroses...
February 17, 2017: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/28213277/fluorescence-and-computed-tomography-for-assessing-the-biodistribution-of-sirna-after-intratracheal-application-in-mice
#5
Antonia Geyer, Cornelia Lorenzer, Sebastian Gehrig, Manuela Simlinger, Johannes Winkler, Haider Sami, Manfred Ogris
Pulmonary delivery of nucleic acids opens the possibility for direct treatment of lung diseases, like fibrosis, cancer, and infections. Lung retention and biodistribution of nucleic acids remain important issues for the development of suitable therapeutic approaches. Moreover, monitoring the dynamic biodistribution processes of siRNA after aerosol delivery can help in identifying bottlenecks and optimising therapeutic concepts. We investigated dynamic biodistribution events after intratracheal application of chemically stabilised siRNA labeled with near infrared emitting dye AlexaFluor750 (AF750)...
February 14, 2017: International Journal of Pharmaceutics
https://www.readbyqxmd.com/read/28210941/b-lymphocytes-in-renal-interstitial-fibrosis
#6
REVIEW
Fengge Zhu, Xueyuan Bai, Xiangmei Chen
Fibrosis is defined as an excessive deposition of extracellular matrix (ECM), which leads to the destruction of organ structure and impairment of organ function. Fibrosis occurs not only in kidney but also in lung, liver, heart, and skin. Common pathways of fibrosis are thought to exist. Renal interstitial fibrosis is a complex process that involves multiple molecular signaling and multiple cellular components, in which B cells appear to be one of the emerging important players. B cells may affect fibrosis through cytokine production and through interaction with other cells including fibroblasts, macrophages and T cells...
February 16, 2017: Journal of Cell Communication and Signaling
https://www.readbyqxmd.com/read/28210319/physiology-of-respiratory-disturbances-in-muscular-dystrophies
#7
Antonella Lo Mauro, Andrea Aliverti
: Muscular dystrophy is a group of inherited myopathies characterised by progressive skeletal muscle wasting, including of the respiratory muscles. Respiratory failure, i.e. when the respiratory system fails in its gas exchange functions, is a common feature in muscular dystrophy, being the main cause of death, and it is a consequence of lung failure, pump failure or a combination of the two. The former is due to recurrent aspiration, the latter to progressive weakness of respiratory muscles and an increase in the load against which they must contract...
December 2016: Breathe
https://www.readbyqxmd.com/read/28208047/targeted-therapy-for-chronic-respiratory-disease-a-new-paradigm
#8
Peter G Gibson, Matthew J Peters, Claire E Wainwright
Targeted therapy has emerged as a highly effective treatment approach for chronic respiratory diseases. Many of these conditions have dismal outcomes; however, targeted therapy shows great results for the subgroup who respond. This represents a new way to approach these conditions and offers great promise as a future treatment direction. In severe eosinophilic asthma, therapy that targets the interleukin-5 pathway with monoclonal antibodies leads to a 50% reduction in asthma exacerbations in previously refractory disease...
February 20, 2017: Medical Journal of Australia
https://www.readbyqxmd.com/read/28208025/aeol-10150-mitigates-radiation-induced-lung-injury-in-the-nonhuman-primate-morbidity-and-mortality-are-administration-schedule-dependent
#9
Thomas J MacVittie, Allison Gibbs, Ann M Farese, Kory Barrow, Alexander Bennett, Cheryl Taylor-Howell, Abdul Kazi, Karl Prado, George Parker, William Jackson Iii
Pneumonitis and fibrosis are potentially lethal, delayed effects of acute radiation exposure. In this study, male rhesus macaques received whole-thorax lung irradiation (WTLI) with a target dose of 10.74 Gy prescribed to midplane at a dose rate of 0.80 ± 0.05 Gy/min using 6 MV linear accelerator-derived photons. The study design was comprised of four animal cohorts: one control and three treated with AEOL 10150 (n = 20 animals per cohort). AEOL 10150, a metalloporphyrin antioxidant, superoxide dismutase mimetic was administered by daily subcutaneous injection at 5 mg/kg in each of three schedules, beginning 24 ± 2 h postirradiation: from day 1 to day 28, day 1 to day 60 or a divided regimen from day 1 to day 28 plus day 60 to day 88...
February 16, 2017: Radiation Research
https://www.readbyqxmd.com/read/28207938/comparison-of-clinical-and-pathological-features-of-lung-lesions-of-systemic-igg4-related-disease-and-idiopathic-multicentric-castleman-s-disease
#10
Yasuhiro Terasaki, Shinichro Ikushima, Shoko Matsui, Akira Hebisawa, Yasunori Ichimura, Shinyu Izumi, Masuo Ujita, Machiko Arita, Keisuke Tomii, Youko Komase, Isoko Owan, Tetsuji Kawamura, Yasuo Matsuzawa, Miho Murakami, Hiroshi Ishimoto, Hiroshi Kimura, Masashi Bando, Norihiro Nishimoto, Yoshinori Kawabata, Yuh Fukuda, Takashi Ogura
AIMS: The lung lesion (IgG4-L) of IgG4-related disease (IgG4-RD) is a condition that occurs together with IgG4-RD and often mimics the lung lesion (iMCD-L) of idiopathic multicentric Castleman's disease (iMCD). Because no clinical and pathological studies had previously compared features of these diseases, we undertook this comparison with clinical and histological data. METHODS AND RESULTS: Nine patients had IgG4-L (high levels of serum IgG4 and of IgG4(+) cells in lung specimens; typical extrapulmonary manifestations)...
February 16, 2017: Histopathology
https://www.readbyqxmd.com/read/28207638/association-of-local-intrapulmonary-production-of-antibodies-specific-to-donor-major-histocompatibility-complex-class-i-with-the-progression-of-chronic-rejection-of-lung-allografts
#11
Ei Miyamoto, Hideki Motoyama, Masaaki Sato, Akihiro Aoyama, Toshi Menju, Kei Shikuma, Terumasa Sowa, Akihiko Yoshizawa, Masao Saito, Akihiro Takahagi, Satona Tanaka, Mamoru Takahashi, Keiji Ohata, Takeshi Kondo, Kyoko Hijiya, Toyofumi F Chen-Yoshikawa, Hiroshi Date
BACKGROUND: Antibody-mediated rejection may lead to chronic lung allograft dysfunction, but antibody-mediated rejection may develop in the absence of detectable donor-specific antibody (DSA) in recipient serum. This study investigated whether humoral immune responses develop not only systemically but locally within rejected lung allografts, resulting in local production of DSA. METHODS: Lewis rats received orthotopic left lung transplantation from Lewis (syngeneic control) or Brown-Norway (major histocompatibility complex-mismatched allogeneic) donor rats...
February 15, 2017: Transplantation
https://www.readbyqxmd.com/read/28203411/development-of-a-non-infectious-rat-model-of-acute-exacerbation-of-idiopathic-pulmonary-fibrosis
#12
Shan-Shan Chen, Zhao-Fang Yin, Tao Chen, Hui Qiu, Ya-Ru Wei, Shan-Shan Du, Yue-Ping Jin, Meng-Meng Zhao, Qin Wu, Dong Weng, Hui-Ping Li
BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a chronic progressive interstitial lung disease with severe pulmonary fibrosis. The main cause of IPF-associated death is acute exacerbation of IPF (AE-IPF). This study aims to develop a rat model of AE-IPF by two intratracheal perfusions with bleomycin (BLM). METHODS: Ninety male Sprague Dawley (SD) rats were randomized into three groups: an AE-IPF model group (BLM + BLM group), an IPF model group (BLM group), and a normal control group...
January 2017: Journal of Thoracic Disease
https://www.readbyqxmd.com/read/28202251/high-incidence-of-non-tuberculous-mycobacteria-positive-cultures-among-adolescent-with-cystic-fibrosis
#13
Zoé Cavalli, Quitterie Reynaud, Romain Bricca, Raphaële Nove-Josserand, Stéphane Durupt, Philippe Reix, Marie Perceval, Michèle Pérouse de Montclos, Gérard Lina, Isabelle Durieu
BACKGROUND: We evaluated the prevalence of non-tuberculous mycobacteria (NTM)-positive cultures among our cystic fibrosis (CF) center patients, reviewed risk factors for NTM positivity, and determined its impact on lung function evolution. METHODS: From 2009 to 2014, CF adults and children attending the CF center of Lyon (France) and having at least one positive NTM isolate were included. Each case was matched by age and gender with two CF patients with no NTM isolate (controls)...
February 12, 2017: Journal of Cystic Fibrosis: Official Journal of the European Cystic Fibrosis Society
https://www.readbyqxmd.com/read/28202030/upregulation-of-interleukin-33-and-thymic-stromal-lymphopoietin-levels-in-the-lungs-of-idiopathic-pulmonary-fibrosis
#14
Jong-Uk Lee, Hun Soo Chang, Hyeon Ju Lee, Chang An Jung, Da Jeong Bae, Hyun Ji Song, Jong Sook Park, Soo-Taek Uh, Young Hoon Kim, Ki-Hyun Seo, Choon-Sik Park
BACKGROUND: Innate T helper type 2 (Th2) immune responses mediated by interleukin (IL)-33, thymic stromal lymphopoietin (TSLP), and IL-25 have been shown to play an important role in pulmonary fibrosis of animal models; however, their clinical implications remain poorly understood. METHODS: TSLP, IL-25, and IL-33 concentrations were measured in bronchoalveolar lavage fluids obtained from normal controls (NCs; n = 40) and from patients with idiopathic pulmonary fibrosis (IPF; n = 100), non-specific interstitial pneumonia (NSIP; n = 22), hypersensitivity pneumonitis (HP; n = 20), and sarcoidosis (n = 19)...
February 15, 2017: BMC Pulmonary Medicine
https://www.readbyqxmd.com/read/28199407/keratin14-mrna-expression-in-human-pneumocytes-during-quiescence-repair-and-disease
#15
Marco Confalonieri, Emanuele Buratti, Gabriele Grassi, Rossana Bussani, Marco Chilosi, Rossella Farra, Michela Abrami, Cristiana Stuani, Francesco Salton, Miriam Ficial, Paola Confalonieri, Lorenzo Zandonà, Maurizio Romano
The lung alveoli slowly self-renew pneumocytes, but their facultative regeneration capacity is rapidly efficient after an injury, so fibrosis infrequently occurs. We recently observed Keratin 14 (KRT14) expression during diffuse alveolar damage (DAD), but not in controls. We wonder if KRT14 may be a marker of pneumocyte transition from quiescence to regeneration. Quantitative PCR and Western blot analyses highlighted the presence of KRT14 (mRNA and protein) only in human lung samples with DAD or interstitial lung disease (ILD)...
2017: PloS One
https://www.readbyqxmd.com/read/28198728/personalized-medicine-in-interstitial-lung-diseases
#16
Paolo Spagnolo, Justin M Oldham, Mark G Jones, Joyce S Lee
PURPOSE OF REVIEW: A number of recent studies have explored the possibility to apply personalized medicine to interstitial lung diseases (ILDs), particularly idiopathic pulmonary fibrosis (IPF), the most common and deadly of the idiopathic interstitial pneumonias. In our review, we summarize and discuss the most recent literature on personalized medicine in IPF as well as hypersensitivity pneumonitis and sarcoidosis, with emphasis on patient subgroups for which a personalized approach to disease prognostication and management may become a reality in the near future...
February 13, 2017: Current Opinion in Pulmonary Medicine
https://www.readbyqxmd.com/read/28198072/ager-gene-polymorphisms-and-soluble-receptor-for-advanced-glycation-end-product-in-patients-with-idiopathic-pulmonary-fibrosis
#17
Kakuhiro Yamaguchi, Hiroshi Iwamoto, Yasushi Horimasu, Shinichiro Ohshimo, Kazunori Fujitaka, Hironobu Hamada, Witold Mazur, Nobuoki Kohno, Noboru Hattori
BACKGROUND AND OBJECTIVE: The receptor for advanced glycation end product (RAGE) is a multiligand cell-surface receptor abundantly expressed in the lung. RAGE/ligand interaction has been postulated to participate in the pathogenesis of inflammatory diseases, while soluble RAGE (sRAGE) might act as a decoy receptor. A functional polymorphism rs2070600 in the gene coding RAGE (AGER) might modulate its receptor function. The aim of this study was to investigate the association of AGER polymorphisms and circulatory sRAGE with the development and progression of idiopathic pulmonary fibrosis (IPF)...
February 14, 2017: Respirology: Official Journal of the Asian Pacific Society of Respirology
https://www.readbyqxmd.com/read/28196856/vardenafil-reduces-macrophage-pro-inflammatory-overresponses-in-cystic-fibrosis-through-pde5-and-cftr-dependent-mechanisms
#18
Sabrina Noel, Nadtha Panin, Mathilde Beka, Barbara Dhooghe, Francois Huaux, Teresinha Leal
Chronic inflammation that progressively disrupts the lung tissue is a hallmark of Cystic Fibrosis (CF). In mice, vardenafil, an inhibitor of phosphodiesterase type 5 (PDE5), restores transepithelial ion transport and corrects mislocalization of the most common CF mutation, F508del-CFTR. It also reduces lung pro-inflammatory responses in mice and in patients with CF. To test the hypothesis that macrophages are target effector cells of the immunomodulatory effect of vardenafil, we isolated lung macrophages from mice homozygous for the F508del mutation or invalidated for the cftr gene and from their corresponding wild-type littermates...
February 14, 2017: Clinical Science (1979-)
https://www.readbyqxmd.com/read/28195168/taz-contributes-to-pulmonary-fibrosis-by-activating-profibrotic-functions-of-lung-fibroblasts
#19
Satoshi Noguchi, Akira Saito, Yu Mikami, Hirokazu Urushiyama, Masafumi Horie, Hirotaka Matsuzaki, Hideyuki Takeshima, Kosuke Makita, Naoya Miyashita, Akihisa Mitani, Taisuke Jo, Yasuhiro Yamauchi, Yasuhiro Terasaki, Takahide Nagase
Transcriptional coactivator with PDZ-binding motif (TAZ) regulates a variety of biological processes. Nuclear translocation and activation of TAZ are regulated by multiple mechanisms, including actin cytoskeleton and mechanical forces. TAZ is involved in lung alveolarization during lung development and Taz-heterozygous mice are resistant to bleomycin-induced lung fibrosis. In this study, we explored the roles of TAZ in the pathogenesis of idiopathic pulmonary fibrosis (IPF) through histological analyses of human lung tissues and cell culture experiments...
February 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28194086/silicosis-in-the-form-of-progressive-massive-fibrosis-a-diagnostic-challenge
#20
Somnath Bhattacharya, Atin Dey, Amitava Pal, Saurav Kar, Sayantan Saha
Silicosis is a major occupational lung disease with a relatively fatal and irreversible outcome. Early diagnosis for shifting the potential candidates to safe modes of workplace as well as for prevention of further progression is the cornerstone of management. Here, we present a complicated case of silicosis in the form of progressive massive fibrosis, which was initially interpreted as tuberculosis; radiological images had resemblance with tuberculosis and cryptogenic organizing pneumonia. Radiology-guided trucut biopsy was imperative to confirm the diagnosis...
May 2016: Indian Journal of Occupational and Environmental Medicine
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