The Experts below are selected from a list of 4173 Experts worldwide ranked by ideXlab platform
Matthias Griese - One of the best experts on this subject based on the ideXlab platform.
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compound sftpb 1549c gaa 121ins2 and 457delc heterozygosity in severe Congenital Lung Disease and surfactant protein b sp b deficiency
Human Mutation, 1999Co-Authors: M Tredano, Ruurd M Van Elburg, Ageeth G Kaspers, Luc J I Zimmermann, Claude Houdayer, Pierre Aymard, William M Hull, Jeffrey A Whitsett, Jacques Elion, Matthias GrieseAbstract:Several human respiratory disorders have been linked to an abnormality of pulmonary surfactant synthesis or turnover. Among those conditions, hereditary deficiency in the hydrophobic surfactant protein B (SP-B) has been recognized as a rare cause of respiratory failure in term newborn infants. Homozygosity for a common mutation (1549C-->GAA, or 121ins2) of the SP-B-encoding gene (SFTPB) results in rapidly fatal respiratory failure, with complete absence of the mRNA and protein observed in Lung fluid or biopsy specimens. Hereditary SP-B deficiency is also associated with aberrant processing of proSP-C and deficiency of the active SP-C peptide. In the present study, we characterized the SFTPB gene in an infant with severe unexplained respiratory distress and identified a paternally derived 1549C-->GAA lesion, as well as a hitherto unreported mutation (457delC) inherited from the mother. Analysis of bronchoalveolar lavage fluid demonstrated the complete absence of SP-B, However, unlike previous infants with hereditary SP-B deficiency, proSP-C was processed to the active SP-C peptide, suggesting that the defect in SP-B, rather than SP-C, caused the respiratory distress in this infant. The present findings demonstrate the importance of SFTPB in pulmonary function and support the need for further genotype-phenotype correlations in patients with SP-B deficiency. Hum Mutat 14:502-509, 1999, (C) 1999 Wiley Liss, Inc
David A. Dean - One of the best experts on this subject based on the ideXlab platform.
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featured article electroporation mediated gene delivery of surfactant protein b sp b restores expression and improves survival in mouse model of sp b deficiency
Experimental Biology and Medicine, 2017Co-Authors: Rebecca C Barnett, Michael Barravecchia, Rosemary Norman, Fabeha Fazal, Karen L De Mesy Bentley, Jennifer L Young, David A. DeanAbstract:Surfactant Protein B Deficiency is a rare but lethal monogenetic, Congenital Lung Disease of the neonate that is unresponsive to any treatment except Lung transplantation. Based on the potential that gene therapy offers to treat such intractable Diseases, our objective was to test whether an electroporation-based gene delivery approach could restore surfactant protein B expression and improve survival in a compound knockout mouse model of surfactant protein B deficiency. Surfactant protein B expression can be shut off in these mice upon withdrawl of doxycycline, resulting in decreased levels of surfactant protein B within four days and death due to Lung dysfunction within four to seven days. Control or one of several different human surfactant protein B-expressing plasmids was delivered to the Lung by aspiration and electroporation at the time of doxycycline removal or four days later. Plasmids expressing human surfactant protein B from either the UbC or CMV promoter expressed surfactant protein B in thes...
M Tredano - One of the best experts on this subject based on the ideXlab platform.
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compound sftpb 1549c gaa 121ins2 and 457delc heterozygosity in severe Congenital Lung Disease and surfactant protein b sp b deficiency
Human Mutation, 1999Co-Authors: M Tredano, Ruurd M Van Elburg, Ageeth G Kaspers, Luc J I Zimmermann, Claude Houdayer, Pierre Aymard, William M Hull, Jeffrey A Whitsett, Jacques Elion, Matthias GrieseAbstract:Several human respiratory disorders have been linked to an abnormality of pulmonary surfactant synthesis or turnover. Among those conditions, hereditary deficiency in the hydrophobic surfactant protein B (SP-B) has been recognized as a rare cause of respiratory failure in term newborn infants. Homozygosity for a common mutation (1549C-->GAA, or 121ins2) of the SP-B-encoding gene (SFTPB) results in rapidly fatal respiratory failure, with complete absence of the mRNA and protein observed in Lung fluid or biopsy specimens. Hereditary SP-B deficiency is also associated with aberrant processing of proSP-C and deficiency of the active SP-C peptide. In the present study, we characterized the SFTPB gene in an infant with severe unexplained respiratory distress and identified a paternally derived 1549C-->GAA lesion, as well as a hitherto unreported mutation (457delC) inherited from the mother. Analysis of bronchoalveolar lavage fluid demonstrated the complete absence of SP-B, However, unlike previous infants with hereditary SP-B deficiency, proSP-C was processed to the active SP-C peptide, suggesting that the defect in SP-B, rather than SP-C, caused the respiratory distress in this infant. The present findings demonstrate the importance of SFTPB in pulmonary function and support the need for further genotype-phenotype correlations in patients with SP-B deficiency. Hum Mutat 14:502-509, 1999, (C) 1999 Wiley Liss, Inc
Rebecca C Barnett - One of the best experts on this subject based on the ideXlab platform.
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featured article electroporation mediated gene delivery of surfactant protein b sp b restores expression and improves survival in mouse model of sp b deficiency
Experimental Biology and Medicine, 2017Co-Authors: Rebecca C Barnett, Michael Barravecchia, Rosemary Norman, Fabeha Fazal, Karen L De Mesy Bentley, Jennifer L Young, David A. DeanAbstract:Surfactant Protein B Deficiency is a rare but lethal monogenetic, Congenital Lung Disease of the neonate that is unresponsive to any treatment except Lung transplantation. Based on the potential that gene therapy offers to treat such intractable Diseases, our objective was to test whether an electroporation-based gene delivery approach could restore surfactant protein B expression and improve survival in a compound knockout mouse model of surfactant protein B deficiency. Surfactant protein B expression can be shut off in these mice upon withdrawl of doxycycline, resulting in decreased levels of surfactant protein B within four days and death due to Lung dysfunction within four to seven days. Control or one of several different human surfactant protein B-expressing plasmids was delivered to the Lung by aspiration and electroporation at the time of doxycycline removal or four days later. Plasmids expressing human surfactant protein B from either the UbC or CMV promoter expressed surfactant protein B in thes...
Andrew Bush - One of the best experts on this subject based on the ideXlab platform.
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Congenital Lung Disease
2019Co-Authors: Andrew Bush, Lyn S Chitty, Jonny Harcourt, Richard Hewitt, Andrew G NicholsonAbstract:Abstract This chapter discusses the spectrum of Congenital Lung Disease from the upper airway down to the Lung parenchyma and microvasculature, and associated relevant malformations in the chest wall and mediastinum, and systemically. A systematic way of describing an individual malformation is proposed, using clear words to delineate the components of the malformation before planning treatment. Congenital Lung Disease may present in utero right up to old age. Many large malformations diagnosed antenatally largely regress in the third trimester of pregnancy, and are only detectable postnatally on computed tomography (CT) scanning. Management of asymptomatic Congenital cystic malformations is controversial; many remain symptom free for a long time, whereas others become the seat of infection or malignancy, or result in other complications, such as air embolism. Histological overlap between what were once thought of as discrete entities, such as Congenital cystic adenomatoid malformation and sequestration, are common, and attempting to determine histology from clinical images is fraught with difficulty. Newer imaging techniques, such as magnetic resonance and CT angiography, are increasingly used to image Congenital Lung malformations, with conventional angiography reserved for situations when therapeutic embolization of the malformation is being considered. Advances in surgical techniques, in particular for Congenital diaphragmatic hernia, mean that there are more survivors into childhood and adult life. The optimal follow-up for patients with Congenital Lung malformations, whether surgically treated or not, remains to be determined.
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editorial old problems and new solutions in pediatric pulmonology
Indian Journal of Pediatrics, 2015Co-Authors: Sushil K Kabra, Andrew BushAbstract:The series on pediatric pulmonology continues in this issue of the Journal, with four manuscripts that illustrate the new problems of our burgeoning speciality [1–4]. These are how the management of old problems (in this case TB) is being transformed by cutting edge science [1]; how the application of new technologies are creating challenging problems (Congenital Lung Disease) [2]; and how new technologies are transforming the lives of children (neuromuscular Disease and NIV) and taking mechanical ventilation, what used to be the prerogative of intensive care into the home, transforming the prognosis of children [3, 4]. However, as we shall see, the more the speciality advances, the more the basic truths we learned as students remain the bedrock of our practice. Old Disease, new technology: TB, the captain of the men of death, used to be simple – the tuberculin skin test, sputum (or other biological sample) microscopy and culture, and evidence based treatment with quadruple therapy for 2 mo, and rifampicin and isoniazid for a further 4 mo. Problem solved, even though diagnostics and determining sensitivities might take weeks – treatment could confidently be started while waiting. In children, admittedly diagnosis often had to be on clinical suspicion, because it was difficult to obtain samples. Enter the Dragon! Or rather, multidrug-resistant TB, extremely drug-resistant TB and totally drug resistant TB [5]. Perspectives have had to change rapidly; now we need rapid diagnosis and rapid sensitivity testing, for fear of starting drugs to which the organism is resistant, effectively but inadvertently proposing a single agent regime which will lead to worse problems of drug resistance. The problem has been made worse with the advent of HIVand the consequent worsening of the manifestations of TB. The modern approach is firstly to use novel tests to obtain specimens, such as sputum induction which can be taken in very young babies, and the string test. The second approach is newer microscopy and culture techniques, and specific molecular diagnostics, which are reviewed [1]. Molecular tests not merely detect MTB rapidly in sputum or gastric aspirates, but also allow drug sensitivities to be determined, a major management advance. The future will undoubtedly include molecular handprints on blood samples, as sophisticated techniques become cheaper and more accessible. New technology, new problems: Increased monitoring of pregnant women with ultrasound scanning, and increasingly MRI, has identified abnormalities which previously passed us by. Congenital Lung malformations come into just this category. In this issue, a simple clinical classification of Congenital thoracic malformations (CTM), which is applicable preand post-natally, is described. However, description is one thing, evidence based management is another. How should you counsel a woman with a fetus with a large CTM at 20 wk of the pregnancy? If the baby is born well, what further imaging should be done and when? What is the risk of complications, and should well babies be submitted to surgery to reduce the risk? And when should surgery be performed? Finally, the biggest elephant in the room, what is the risk of primary Lung malignancy in a baby with a CTM? High risk groups can be delineated, but most babies with CTMs are low risk. * Andrew Bush A.Bush@rbht.nhs.uk
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Congenital Lung Disease a plea for clear thinking and clear nomenclature
Pediatric Pulmonology, 2001Co-Authors: Andrew BushAbstract:Antenatal ultrasound has allowed the discovery of abnormalities which in the past often escaped detection. It may be unclear what advice to offer. Many large Lung malformations seen at the routine 20-weeks gestation scan have largely disappeared at term. There is now even more confusion in terms of how these malformations should be described. The nomenclature of Congenital Lung Disease was never very clear, with terms such as sequestrated segment, cystic adenomatoid malformation, hypoplastic Lung, and malinosculation being used to describe often overlapping abnormalities. However, today these terms are used inconsistently in the ante- and postnatal periods. For example, Congenital cystic adenomatoid malformation (CCAM) is used prenatally to describe a lesion which may well disappear before birth, but is used postnatally to describe an abnormality which may require lobectomy. CCAM may have a pulmonary arterial supply, or be supplied like a sequestration from the aorta, and histological features of both lesions may coexist. Thus, a complete reappraisal of the nomenclature of Congenital Lung Disease is timely; this review does not discuss treatment options.