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https://www.readbyqxmd.com/read/28822689/cholesterol-lowering-gene-therapy-counteracts-the-development-of-non-ischemic-cardiomyopathy-in-mice
#1
Ilayaraja Muthuramu, Ruhul Amin, Andrey Postnov, Mudit Mishra, Joseph Pierre Aboumsallem, Tom Dresselaers, Uwe Himmelreich, Paul P Van Veldhoven, Olivier Gheysens, Frank Jacobs, Bart De Geest
A causal role of hypercholesterolemia in non-ischemic heart failure has never been demonstrated. Adeno-associated viral serotype 8 (AAV8)-low-density lipoprotein receptor (AAV8-LDLr) gene transfer was performed in LDLr-deficient mice without and with pressure overload induced by transverse aortic constriction (TAC). AAV8-LDLr gene therapy resulted in an 82.8% (p < 0.0001) reduction of plasma cholesterol compared with controls. Mortality rate was lower (p < 0.05) in AAV8-LDLr TAC mice compared with control TAC mice (hazard ratio for mortality 0...
August 1, 2017: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/28821283/gene-expression-profiling-of-idiopathic-interstitial-pneumonias-iips-identification-of-potential-diagnostic-markers-and-therapeutic-targets
#2
Yasushi Horimasu, Nobuhisa Ishikawa, Masaya Taniwaki, Kakuhiro Yamaguchi, Kosuke Hamai, Hiroshi Iwamoto, Shinichiro Ohshimo, Hironobu Hamada, Noboru Hattori, Morihito Okada, Koji Arihiro, Yuji Ohtsuki, Nobuoki Kohno
BACKGROUND: Chronic fibrosing idiopathic interstitial pneumonia (IIP) is characterized by alveolar epithelial damage, activation of fibroblast proliferation, and loss of normal pulmonary architecture and function. This study aims to investigate the genetic backgrounds of IIP through gene expression profiling and pathway analysis, and to identify potential biomarkers that can aid in diagnosis and serve as novel therapeutic targets. METHODS: RNA extracted from lung specimens of 12 patients with chronic fibrosing IIP was profiled using Illumina Human WG-6 v3 BeadChips, and Ingenuity Pathway Analysis was performed to identify altered functional and canonical signaling pathways...
August 18, 2017: BMC Medical Genetics
https://www.readbyqxmd.com/read/28820502/oligonucleotides-targeting-periostin-ameliorates-pulmonary-fibrosis
#3
A Tomaru, T Kobayashi, J A Hinneh, P B Tonto, C N D' Alessandro-Gabazza, H Fujimoto, K Fujiwara, Y Takahashi, M Ohnishi, T Yasuma, K Nishihama, M Yoshino, K Takao, M Toda, T Totoki, Y Takei, K Yoshikawa, O Taguchi, E C Gabazza
Idiopathic pulmonary fibrosis (IPF) is a fatal disease with a median survival of 3 to 4 years after diagnosis. It is the most frequent form of a group of interstitial pneumonias of unknown etiology. Current available therapies prevent deterioration of lung function but no therapy has shown to improve survival. Periostin is a matricellular protein of the fasciclin 1 family. There is increased deposition of periostin in lung fibrotic tissues. Here, we evaluated whether small interfering RNA or antisense oligonucleotide against periostin inhibit lung fibrosis by direct administration into the lung by intranasal route...
August 18, 2017: Gene Therapy
https://www.readbyqxmd.com/read/28818548/severe-acute-interstitial-lung-disease-after-nivolumab-in-three-non-small-cell-lung-cancer-patients-with-imaging-findings-of-airway-obstruction-adjacent-to-lung-tumors
#4
Kenji Nakahama, Akihiro Tamiya, Yoshihiko Taniguchi, Yumiko Sasaki, Masanori Akira, Shinji Atagi
Nivolumab has been associated with unique adverse events known as immune-related adverse events. Although interstitial lung disease (ILD) is a life-threatening immune-related adverse event, the risk of ILD during nivolumab treatment is unclear. In this report, we encountered three patients with stage IV non-small cell lung cancer with signs of lung obstruction caused by tumor-mediated compression on imaging who developed acute ILD within 10 days of commencing nivolumab treatment. The first case involved a 74-year-old Japanese female never-smoker, the second a 67-year-old Japanese female never-smoker, and the third a 75-year-old Japanese female current-smoker...
August 15, 2017: Journal of Infection and Chemotherapy: Official Journal of the Japan Society of Chemotherapy
https://www.readbyqxmd.com/read/28817393/increased-expiratory-computed-tomography-density-reveals-possible-abnormalities-in-radiologically-preserved-lung-parenchyma-in-idiopathic-pulmonary-fibrosis
#5
Valentina Petroulia, Manuela Funke, Pascal Zumstein, Sabina Berezowska, Lukas Ebner, Thomas Geiser, Nenad Torbica, Johannes Heverhagen, Alexander Poellinger
OBJECTIVES: Idiopathic pulmonary fibrosis (IPF) is a progressive lethal chronic lung disease with unclear pathogenesis. Radiological hallmark is the pattern of usual interstitial pneumonia accentuated in peripheral and basal areas with otherwise preserved lung structure. One hypothesis is that alveolar collapse and consequent induration lead to fibrotic transformation of lung tissue. The aim of the study was to investigate normal-appearing tissue during expiration for signs of collapsibility and differences from other diseases or controls...
August 16, 2017: Investigative Radiology
https://www.readbyqxmd.com/read/28814604/macrophage-restricted-shp2-tyrosine-phosphatase-acts-as-a-rheostat-for-mmp12-through-tgf-%C3%AE-activation-in-the-prevention-of-age-related-emphysema-in-mice
#6
Jiaqi Xu, Bo Tao, Xiaohong Guo, Shiyi Zhou, Yongda Li, Yuqin Zhang, Zanhua Zhou, Hongqiang Cheng, Xue Zhang, Yuehai Ke
Persistent activation of macrophages in lungs plays a critical role in the production of matrix metalloproteinases (MMPs) that contributes to the destruction of alveolar walls, a hallmark for pulmonary emphysema. Dysregulated TGF-β1 signaling has been an essential determinant in the elevation of MMPs during the development of emphysema. Nevertheless, the mechanism for this MMP-dependent pathogenesis has yet to be clearly investigated. Recently, we identified an important role for tyrosine phosphatase Src homology domain-containing protein tyrosine phosphatase 2 (Shp2) in regulating the activation of alveolar macrophages...
August 16, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28814429/nintedanib-macrophage-activation-and-ameliorates-vascular-and-fibrotic-manifestations-in-the-fra2-mouse-model-of-systemic-sclerosis
#7
Jingang Huang, Christiane Maier, Yun Zhang, Alina Soare, Clara Dees, Christian Beyer, Ulrike Harre, Chih-Wei Chen, Oliver Distler, Georg Schett, Lutz Wollin, Jörg H W Distler
BACKGROUND: Nintedanib is an inhibitor targeting platelet-derived growth factor receptor, fibroblast growth factor receptor and vascular endothelial growth factor receptor tyrosine kinases that has recently been approved for the treatment of idiopathic pulmonary fibrosis. The aim of this study was to analyse the effects of nintedanib in the fos-related antigen-2 (Fra2) mouse model of systemic sclerosis (SSc). METHODS: The effects of nintedanib on pulmonary arterial hypertension with proliferation of pulmonary vascular smooth muscle cells (PVSMCs) and luminal occlusion, on microvascular disease with apoptosis of microvascular endothelial cells (MVECs) and on fibroblast activation with myofibroblast differentiation and accumulation of extracellular matrix were analysed...
August 16, 2017: Annals of the Rheumatic Diseases
https://www.readbyqxmd.com/read/28814329/severe-persistent-pulmonary-hypertension-of-the-newborn-and-dysmorphic-features-in-neonate-with-a-deletion-involving-twist1-and-phf14-a-case-report
#8
Carina Schinagl, Guro Reinholt Melum, Olaug Kristin Rødningen, Kathrine Bjørgo, Jannicke Hanne Andresen
BACKGROUND: Persistent pulmonary hypertension is a well-known disease of the newborn that in most cases responds well to treatment with nitric oxide and treatment of any underlying causes. Genetic causes of persistent pulmonary hypertension of the newborn are rare. The TWIST1 gene is involved in morphogenetics, and deletions are known to cause Saethre-Chotzen syndrome. Deletions of PHF14 have never been reported in neonates, but animal studies have shown a link between severe defects in lung development and deletions of this gene...
August 17, 2017: Journal of Medical Case Reports
https://www.readbyqxmd.com/read/28812117/-extracorporeal-membrane-oxygenation-for-treatment-of-acute-respiratory-failure-outcome-of-patients-with-interstitial-lung-disease
#9
F C Trudzinski, P M Lepper
No abstract text is available yet for this article.
August 15, 2017: Medizinische Klinik, Intensivmedizin und Notfallmedizin
https://www.readbyqxmd.com/read/28811904/concurrence-of-nivolumab-induced-interstitial-lung-disease-and-cancer-invasion
#10
Osamu Kanai, Koichi Nakatani, Kohei Fujita, Misato Okamura, Tadashi Mio
Nivolumab improves overall survival rates of patients with advanced or recurrent non-small-cell lung cancer (NSCLC). Among immune-related adverse events caused by nivolumab, interstitial lung disease (ILD) is a clinically serious and potentially life-threatening toxicity, for which appropriate treatment is needed immediately. However, ILD is sometimes difficult to distinguish from invasive lung adenocarcinoma using only computed tomography (CT) findings. A 71-year-old man was diagnosed with advanced lung adenocarcinoma...
November 2017: Respirology Case Reports
https://www.readbyqxmd.com/read/28810589/phenotypic-switch-in-lung-interstitial-macrophage-polarization-in-an-ovalbumin-induced-mouse-model-of-asthma
#11
Hanxiang Nie, Ailing Wang, Qing He, Qiaoyu Yang, Linlin Liu, Guqin Zhang, Yi Huang, Xuhong Ding, Hongying Yu, Suping Hu
Macrophage phenotype and function varies according to their polarized state, which in turn is dependent on microenvironmental stimuli. Under normal physiological conditions, lung interstitial macrophages that express interleukin (IL)-10 are considered to serve regulatory roles in the prevention of allergic reactions in the airways. However, the phenotypic profile of lung interstitial macrophages during the pathophysiology of asthma remains unknown. In the current study, the phenotypic characteristics of lung interstitial macrophages were investigated in an ovalbumin (OVA)-induced mouse model of asthma...
August 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28810319/-update-of-idiopathic-inflammatory-myopathy-associated-interstitial-lung-disease
#12
H Huang, C Shao, S Li
No abstract text is available yet for this article.
August 12, 2017: Chinese Journal of Tuberculosis and Respiratory Diseases
https://www.readbyqxmd.com/read/28810314/-clinical-and-pathological-characteristics-of-erdheim-chester-disease-involving-the-lungs
#13
T Lu, S Wang, H Huang, T Wang, M Wang, D R Zhong, R E Feng
Objective: To explore the clinical manifestations, pathological features, differential diagnosis and gene mutation status in patients with pulmonary involvement of Erdheim-Chester disease (ECD). Methods: The clinical data of 4 cases of Erdheim-Chester disease admitted to Peking Union Medical College Hospital from October 2014 to August 2016 were examined for imaging, microscopic and immunohistochemitry findings, and BRAFV600E mutation. The related literatures were reviewed. Results: Among the 4 cases, there were 3 males and 1 female, aging from 7 to 47 years, and the average age was 34...
August 12, 2017: Chinese Journal of Tuberculosis and Respiratory Diseases
https://www.readbyqxmd.com/read/28808949/practical-management-of-respiratory-comorbidities-in-patients-with-rheumatoid-arthritis
#14
REVIEW
James Bluett, Meghna Jani, Deborah P M Symmons
Lung disease is one of the most common causes of extra-articular morbidity and mortality in patients with rheumatoid arthritis (RA). Development of pulmonary manifestations may be due to the systemic disease itself; to serious respiratory adverse events such as pneumonitis and infections secondary to therapy; or to lifestyle habits such as smoking. Rheumatologists often need to make important treatment decisions and plan future care in RA patients with respiratory comorbidities, despite the absence of clear evidence or consensus...
August 14, 2017: Rheumatology and Therapy
https://www.readbyqxmd.com/read/28808573/osimertinib-induced-interstitial-lung-disease-in-a-patient-with-non-small-cell-lung-cancer-pretreated-with-nivolumab-a-case-report
#15
Osamu Takakuwa, Tetsuya Oguri, Takehiro Uemura, Kazuki Sone, Satoshi Fukuda, Minami Okayama, Yoshihiro Kanemitsu, Hirotsugu Ohkubo, Masaya Takemura, Yutaka Ito, Ken Maeno, Akio Niimi
Osimertinib (AZD9291) is a third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor approved for EGFR-T790M-positive non-small cell lung cancer. A high incidence of interstitial lung disease (ILD) during combination treatment with osimertinib and anti-programmed cell death-ligand 1 (PD-L1) inhibitor has been reported. The current study presents a case of ILD development during osimertinib treatment following nivolumab (an anti-PD-1 antibody) treatment. The 59-year-old female was diagnosed with stage IV lung adenocarcinoma harboring a deletion in exon 19 of the EGFR gene...
September 2017: Molecular and Clinical Oncology
https://www.readbyqxmd.com/read/28808495/the-most-frequent-abca3-nonsense-mutation-p-tyr1515-y1515x-causing-lethal-neonatal-respiratory-failure-in-a-term-neonate
#16
AlNashmi AlAnazi, Ralph Epaud, Humariya Heena, Alix de Becdelievre, Abeer Mohammad Miqdad, Pascale Fanen
Defects in the surfactant biosynthesis are associated with respiratory distress syndrome, commonly occurring in premature infants due to lung immaturity. However, interstitial lung diseases have also been observed in full-term infants with mutations in the SFTPC, SFTPB, NKX2-1, or ABCA3 genes, involved in the surfactant metabolism. Herein, we report a newborn baby with neonatal respiratory distress and diffuse lung disease caused by ABCA3 mutation. The baby died at 5 weeks of age after developing pulmonary hypertension...
July 2017: Annals of Thoracic Medicine
https://www.readbyqxmd.com/read/28805019/cd11b-gr1-dim-tolerogenic-dendritic-cell-like-cells-are-expanded-in-interstitial-lung-disease-in-skg-mice
#17
Sho Sendo, Jun Saegusa, Takaichi Okano, Soshi Takahashi, Kengo Akashi, Akio Morinobu
OBJECTIVE: SKG mice develop interstitial lung disease (ILD) resembling rheumatoid arthritis-associated ILD (RA-ILD) in human. The aim of this study is to clarify the mechanism behind the lung pathology by analyzing the lung-infiltrating cells in ILD of SKG mice. METHODS: We assessed the severity of zymosan A (ZyA)-induced ILD in SKG mice histologically, and examined lung-infiltrating cells by flow cytometry. Total lung cells and isolated monocytic myeloid-derived suppressor cells (M-MDSCs) were cultured in vitro with GM-CSF (and IL-4)...
August 13, 2017: Arthritis & Rheumatology
https://www.readbyqxmd.com/read/28804709/exploring-animal-models-that-resemble-idiopathic-pulmonary-fibrosis
#18
REVIEW
Jun Tashiro, Gustavo A Rubio, Andrew H Limper, Kurt Williams, Sharon J Elliot, Ioanna Ninou, Vassilis Aidinis, Argyrios Tzouvelekis, Marilyn K Glassberg
Large multicenter clinical trials have led to two recently approved drugs for patients with idiopathic pulmonary fibrosis (IPF); yet, both of these therapies only slow disease progression and do not provide a definitive cure. Traditionally, preclinical trials have utilized mouse models of bleomycin (BLM)-induced pulmonary fibrosis-though several limitations prevent direct translation to human IPF. Spontaneous pulmonary fibrosis occurs in other animal species, including dogs, horses, donkeys, and cats. While the fibrotic lungs of these animals share many characteristics with lungs of patients with IPF, current veterinary classifications of fibrotic lung disease are not entirely equivalent...
2017: Frontiers in Medicine
https://www.readbyqxmd.com/read/28801922/prophylaxis-with-enoxaparin-for-prevention-of-venous-thromboembolism-after-lung-transplantation-a-retrospective-study
#19
Berta Sáez-Giménez, Cristina Berastegui, Helena Sintes, Javier Perez, Ana Figueredo, Manuel López Meseguer, Víctor Monforte, Carlos Bravo, Amparo Santamaría, Maria Antonia Ramon, Susana Gómez, Antonio Roman
BACKGROUND: Venous thromboembolism (VTE) is a frequent complication after solid organ transplantation (SOT) and, specifically, after lung transplantation (LT). The objectives of this study were to evaluate prophylaxis with enoxaparin and to describe risk factors for VTE after LT. METHODS: We retrospectively reviewed the clinical records of 333 patients who underwent LT in our institution between 2009 and 2014. We compared 2 consecutive cohorts, one that received enoxaparin only during post-transplant hospital admissions and a second cohort that received 90-day extended prophylaxis with enoxaparin...
August 12, 2017: Transplant International: Official Journal of the European Society for Organ Transplantation
https://www.readbyqxmd.com/read/28801346/pan-ppar-agonist-iva337-is-effective-in-experimental-lung-fibrosis-and-pulmonary-hypertension
#20
Jerome Avouac, Irena Konstantinova, Christophe Guignabert, Sonia Pezet, Jeremy Sadoine, Thomas Guilbert, Anne Cauvet, Ly Tu, Jean-Michel Luccarini, Jean-Louis Junien, Pierre Broqua, Yannick Allanore
OBJECTIVE: To evaluate the antifibrotic effects of the pan-peroxisome proliferator-activated receptor (PPAR) agonist IVA337 in preclinical mouse models of pulmonary fibrosis and related pulmonary hypertension (PH). METHODS: IVA337 has been evaluated in the mouse model of bleomycin-induced pulmonary fibrosis and in Fra-2 transgenic mice, this latter being characterised by non-specific interstitial pneumonia and severe vascular remodelling of pulmonary arteries leading to PH...
August 11, 2017: Annals of the Rheumatic Diseases
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