Read by QxMD icon Read


Nadia Nathan, Keren Borensztajn, Annick Clement
PURPOSE OF REVIEW: Interstitial lung disease (ILD) in children (chILD) is an umbrella term for a heterogeneous group of rare respiratory disorders that are mostly chronic and associated with high morbidity and mortality. The pathogenesis of the various chILD is complex and implicates genetic contributors. The purpose of this review is to provide updated information on the molecular defects associated with the development of chILD. RECENT FINDINGS: Currently, the main mutations are identified in the surfactant genes SFTPA1, SFTPA2, SFTPB, SFTPC, ABCA3, and NKX2-1...
March 6, 2018: Current Opinion in Pulmonary Medicine
Ulrike Schindlbeck, Thomas Wittmann, Stefanie Höppner, Susanna Kinting, Gerhard Liebisch, Jan Hegermann, Matthias Griese
Mutations in the ATP-binding cassette subfamily A member 3 (ABCA3) gene are the most common monogenetic cause of surfactant dysfunction disorders in newborns and interstitial lung diseases in children and young adults. Whereas the effect of mutations resulting in truncated or incomplete proteins can be predicted, the consequences of missense variants cannot be as easily. Our aim was to investigate the intracellular handling and disturbance of the cellular surfactant system in a stable cell model with several different clinically relevant ABCA3 missense mutations...
March 5, 2018: Human Mutation
Kelli Monteiro da Costa, Raphael C Valente, Eduardo J Salustiano, Luciana B Gentile, Leonardo Freire-de-Lima, Lucia Mendonça-Previato, José O Previato
Chagas disease is a neglected disease caused by the protozoan Trypanosoma cruzi and affects 8 million people worldwide. The main chemotherapy is based on benznidazole. The efficacy in the treatment depends on factors such as the parasite strain, which may present different sensitivity to treatment. In this context, the expression of ABC transporters has been related to chemotherapy failure. ABC transporters share a well-conserved ABC domain, responsible for ATP binding and hydrolysis, whose the energy released is coupled to transport of molecules through membranes...
2018: Frontiers in Microbiology
Kazutoshi Cho, Masafumi Yamada, Kazunaga Agematsu, Hirokazu Kanegane, Noriko Miyake, Masahiro Ueki, Takuma Akimoto, Norimoto Kobayashi, Satoru Ikemoto, Mishie Tanino, Atsushi Fujita, Itaru Hayasaka, Satoshi Miyamoto, Mari Tanaka-Kubota, Koh Nakata, Masaaki Shiina, Kazuhiro Ogata, Hisanori Minakami, Naomichi Matsumoto, Tadashi Ariga
Pulmonary alveolar proteinosis (PAP) is characterized by accumulation of a surfactant-like substance in alveolar spaces and hypoxemic respiratory failure. Genetic PAP (GPAP) is caused by mutations in genes encoding surfactant proteins or genes encoding a surfactant phospholipid transporter in alveolar type II epithelial cells. GPAP is also caused by mutations in genes whose products are implicated in surfactant catabolism in alveolar macrophages (AMs). We performed whole-exome sequence analysis in a family affected by infantile-onset PAP with hypogammaglobulinemia without causative mutations in genes associated with PAP: SFTPB, SFTPC, ABCA3, CSF2RA, CSF2RB, and GATA2...
February 12, 2018: American Journal of Human Genetics
Matthias Griese
Children's interstitial lung diseases (chILD) are increasingly recognised and contain many lung developmental and genetic disorders not yet identified in adult pneumology. Worldwide, several registers have been established. The Australasian Registry Network for Orphan Lung Disease (ARNOLD) has identified problems in estimating rare disease prevalence; focusing on chILD in immunocompetent patients, a period prevalence of 1.5 cases per million children and a mortality rate of 7% were determined. The chILD-EU register highlighted the workload to be covered per patient included and provided protocols for diagnosis and initial treatment, similar to the United States chILD network...
March 31, 2018: European Respiratory Review: An Official Journal of the European Respiratory Society
Susanna Kinting, Stefanie Höppner, Ulrike Schindlbeck, Maria E Forstner, Jacqueline Harfst, Thomas Wittmann, Matthias Griese
ABCA3, a phospholipid transporter in lung lamellar bodies (LB), is essential for the assembly of pulmonary surfactant and LB biogenesis. Mutations in the ABCA3 gene are an important genetic cause for respiratory distress syndrome in neonates and interstitial lung disease in children and adults, for which there is currently no cure.The aim of this study was to prove that disease causing misfolding ABCA3 mutations can be corrected in vitro and to investigate available options for correction.We stably expressed HA-tagged wild type ABCA3 or variants p...
January 9, 2018: Human Molecular Genetics
Y M Bao, X L Liu, X L Liu, J H Chen, Y J Zheng
Objective: To summarize the clinical characteristics of the diffuse parenchymal lung diseases in a child caused by a novel compound heterozygous ABCA3 mutation and explore the association between the phenotype and ABCA3 mutation. Method: The clinical material of a patient diagnosed with diffuse parenchymal lung disease with ABCA3 mutation in December 2016 in Shenzhen Children's Hospital was analyzed. The information about ABCA3 gene mutation updated before April, 2017 was searched and collected from the gene databases (including 1000Genomes, HGMD, EXAC) and the literatures (including Wanfang Chinese database and Pubmed)...
November 2, 2017: Zhonghua Er Ke za Zhi. Chinese Journal of Pediatrics
Augusto F Schmidt, Matthew W Kemp, Judith Rittenschober-Böhm, Paranthaman S Kannan, Haruo Usuda, Masatoshi Saito, Lucy Furfaro, Shimpei Watanabe, Sarah Stock, Boris W Kramer, John P Newnham, Suhas G Kallapur, Alan H Jobe
BACKGROUND: Antenatal steroids (ANS) are standard of care for women at risk of preterm delivery; however ANS dosing and formulation have not been adequately evaluated. The standard clinical 2-dose treatment with betamethasone-acetate+betamethasone-phosphate (Beta-P+Beta-Ac) is more effective than 2 doses of Beta-P for inducing lung maturation in preterm fetal sheep. We hypothesized that the slowly-released Beta-Ac component induces similar lung maturation to Beta-P+Beta-Ac with decreased dose and fetal exposure...
November 11, 2017: American Journal of Obstetrics and Gynecology
Xiaofang Tang, John M Snowball, Yan Xu, Cheng-Lun Na, Timothy E Weaver, Geremy Clair, Jennifer E Kyle, Erika M Zink, Charles Ansong, Wei Wei, Meina Huang, Xinhua Lin, Jeffrey A Whitsett
Adaptation to respiration at birth depends upon the synthesis of pulmonary surfactant, a lipid-protein complex that reduces surface tension at the air-liquid interface in the alveoli and prevents lung collapse during the ventilatory cycle. Herein, we demonstrated that the gene encoding a subunit of the endoplasmic reticulum membrane complex, EMC3, also known as TMEM111 (Emc3/Tmem111), was required for murine pulmonary surfactant synthesis and lung function at birth. Conditional deletion of Emc3 in murine embryonic lung epithelial cells disrupted the synthesis and packaging of surfactant lipids and proteins, impaired the formation of lamellar bodies, and induced the unfolded protein response in alveolar type 2 (AT2) cells...
October 30, 2017: Journal of Clinical Investigation
Stefanie Höppner, Susanna Kinting, Adriano A Torrano, Ulrike Schindlbeck, Christoph Bräuchle, Ralf Zarbock, Thomas Wittmann, Matthias Griese
The ABCA3 lipid transporter is located in the limiting membrane of lamellar bodies (LBs) in type-II-pneumocytes. Mutations within the ABCA3 gene may functionally impair the transporter, causing lung diseases in newborns, children and adults. Assays to quantify volume and lipid filling of the LBs on the level of the vesicular structures and thereby assess the function of ABCA3 are still lacking. In the present study human influenza haemagglutinin- (HA-) tagged wild type and mutant ABCA3 proteins were stably expressed in lung A549 cells...
December 2017: Biochimica et Biophysica Acta
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
Narges Aberuyi, Soheila Rahgozar, Zohreh Khosravi Dehaghi, Alireza Moafi, Andrea Masotti, Alessandro Paolini
PURPOSE: The aim of this work was to study the correlation between the expressions of the ABCA2 and ABCA3 genes at the mRNA and protein levels in children with acute lymphoblastic leukemia (ALL) and the effects of this association on multidrug resistance (MDR). MATERIALS AND METHODS: Sixty-nine children with de novo ALL and 25 controls were enrolled in the study. Mononuclear cells were isolated from the bone marrow. The mRNA levels of ABCA2 and ABCA3 were measured by real-time polymerase chain reaction (PCR)...
2017: OncoTargets and Therapy
Angela Lemke, José Carlos Castillo-Sánchez, Florian Prodinger, Asja Ceranic, Simone Hennerbichler-Lugscheider, Jesús Pérez-Gil, Heinz Redl, Susanne Wolbank
Pulmonary surfactant (PS) reduces surface tension at the air-liquid interface in the alveolar epithelium of the lung, which is required for breathing and for the pulmonary maturity of the developing foetus. However, the origin of PS had never been thoroughly investigated, although it was assumed to be secreted from the foetal developing lung. Human amniotic membrane (hAM), particularly its epithelial cell layer, composes the amniotic sac enclosing the amniotic fluid. In this study, we therefore aimed to investigate a potential contribution of the cellular components of the hAM to pulmonary surfactant found in amniotic fluid...
July 25, 2017: Scientific Reports
Masashi Kawami, Junya Deguchi, Ryoko Yumoto, Norikazu Sakakibara, Ikuko Tsukamoto, Ryoji Konishi, Mikihisa Takano
Transforming growth factor (TGF)-β1 has received much attention as a major inducer of epithelial-mesenchymal transition (EMT) in pathological conditions such as cancer and organ fibrosis. In this study, we examined the effect of a novel nucleic acid analog, COA-Cl, on TGF-β1-induced EMT using RLE/Abca3, a cell line having alveolar type II cell-like phenotype. Changes in the cell morphology consistent with EMT were induced by TGF-β1, whereas, this response was suppressed by co-treatment of the cells with COA-Cl...
May 17, 2017: Drug Metabolism and Pharmacokinetics
Tobias R Overbeck, Johanna Arnemann, Regina Waldmann-Beushausen, Lorenz Trümper, Friedrich A Schöndube, Kirsten Reuter-Jessen, Bernhard C Danner
BACKGROUND: ATP-binding cassette transport protein A3 (ABCA3) is expressed in non-small cell lung cancer (NSCLC). We hypothesize that high-level ABCA3 expression may have a negative prognostic impact in patients with NSCLC. METHODS: In 89 patients with NSCLC and curative intended surgery, we analyzed postoperative immunohistochemistry staining of primary tumors (anti-ABCA3) and clinicopathological parameters. We used a unidimensional four point score (FPS) system for intensity assessment and, furthermore, a combined bidimensional scoring of intensity and quantity resulting in the positive index (PI)...
2017: Oncology
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
Mikihisa Takano, Chinami Nekomoto, Masashi Kawami, Ryoko Yumoto
Epithelial-mesenchymal transition (EMT) of alveolar type II epithelial cells may play an important role in the pulmonary fibrosis induced by drugs such as bleomycin (BLM) and methotrexate (MTX). In this study, we examined the role of microRNAs (miRNAs) in drug-induced EMT using RLE/Abca3, a cell line having alveolar type II cell-like phenotype. Based on the screening using miRNA microarray analysis, it was found that the expression of some miRNAs, such as miR-34a, was increased by transforming growth factor (TGF)-β1 and BLM...
April 10, 2017: Journal of Pharmaceutical Sciences
Erin V McGillick, Sandra Orgeig, Beth J Allison, Kirsty L Brain, Youguo Niu, Nozomi Itani, Katie L Skeffington, Andrew D Kane, Emilio A Herrera, Dino A Giussani, Janna L Morrison
KEY POINTS: Chronic fetal hypoxaemia is a common pregnancy complication associated with intrauterine growth restriction that may influence respiratory outcome at birth. We investigated the effect of maternal chronic hypoxia for a month in late gestation on signalling pathways regulating fetal lung maturation and the transition to air-breathing at birth using isobaric hypoxic chambers without alterations to maternal food intake. Maternal chronic hypoxia in late gestation increases fetal lung expression of genes regulating hypoxia signalling, lung liquid reabsorption and surfactant maturation, which may be an adaptive response in preparation for the successful transition to air-breathing at birth...
July 1, 2017: Journal of Physiology
Amanda B Chai, Alaina J Ammit, Ingrid C Gelissen
Respiratory diseases including asthma and chronic obstructive pulmonary disease (COPD) are characterised by excessive and persistent inflammation. Current treatments are often inadequate for symptom and disease control, and hence new therapies are warranted. Recent emerging research has implicated dyslipidaemia in pulmonary inflammation. Three ATP-binding cassette (ABC) transporters are found in the mammalian lung - ABCA1, ABCG1 and ABCA3 - that are involved in movement of cholesterol and phospholipids from lung cells...
February 28, 2017: Respiratory Research
Whitney B Eldridge, Qunyuan Zhang, Albert Faro, Stuart C Sweet, Pirooz Eghtesady, Aaron Hamvas, F Sessions Cole, Jennifer A Wambach
OBJECTIVE: To compare outcomes of infants and children who underwent lung transplantation for genetic disorders of surfactant metabolism (SFTPB, SFTPC, ABCA3, and NKX2-1) over 2 epochs (1993-2003 and 2004-2015) at St Louis Children's Hospital. STUDY DESIGN: We retrospectively reviewed clinical characteristics, mortality, and short- and long-term morbidities of infants (transplanted at <1 year; n = 28) and children (transplanted >1 year; n = 16) and compared outcomes by age at transplantation (infants vs children) and by epoch of transplantation...
May 2017: Journal of Pediatrics
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"