The Experts below are selected from a list of 2817 Experts worldwide ranked by ideXlab platform

Philip L Ballard - One of the best experts on this subject based on the ideXlab platform.

Susan H Guttentag - One of the best experts on this subject based on the ideXlab platform.

Jeffrey A. Whitsett - One of the best experts on this subject based on the ideXlab platform.

  • PARP-2 interacts with TTF-1 and regulates expression of <B>SurfactantB> <B>ProteinB>-B.
    The Journal of biological chemistry, 2006
    Co-Authors: Yutaka Maeda, Thomas C Hunter, David E Loudy, Vrushank Davé, Valérie Schreiber, Jeffrey A. Whitsett
    Abstract:

    Thyroid transcription factor 1 (TTF-1/Nkx-2.1) plays a critical role in lung morphogenesis and regulates the expression of lung-specific genes, including the <B>SurfactantB> <B>ProteinB>s required for pulmonary function after Birth. The activity of TTF-1 is influenced By its interactions with other transcription factors and coactivators, including CBP/p300 and SRC-1. In this study, we have identified poly(ADP-riBose) polymerases (PARP-2 and PARP-1) as TTF-1 interacting <B>ProteinB>s that influence its transcriptional activity. Endogenous PARP-2 was coimmunoprecipitated from transformed mouse lung epithelial cell (MLE15) extracts with TTF-1 and was identified By mass spectrometry. PARP-1 and Ku70/Ku80 were also coimmunoprecipitated from the cell extracts with TTF-1. The E domain of PARP-2 interacted via the C-terminal domain of TTF-1. Both PARP-1 and PARP-2 enhanced the activity of the promoter of <B>SurfactantB> <B>ProteinB>-B (SftpB gene) But not other <B>SurfactantB> <B>ProteinB>s in vitro. PARP-2 was selectively expressed in epithelial cells of the conducting and peripheral lung tuBules of the fetal mouse lung from emBryonic day 12.5 and was detected in Bronchial epithelial cells in the adult lung at cellular sites consistent with that of <B>SurfactantB> <B>ProteinB> B. PARP-2 and PARP-1 interact with TTF-1 and regulate the expression of <B>SurfactantB> <B>ProteinB> B, a <B>ProteinB> required for lung function.

  • allelic heterogeneity in hereditary <B>SurfactantB> <B>ProteinB> B sp B deficiency
    American Journal of Respiratory and Critical Care Medicine, 2000
    Co-Authors: Lawrence M. Nogee, Susan E. Wert, Sherri A Proffit, William M Hull, Jeffrey A. Whitsett
    Abstract:

    InaBility to produce <B>SurfactantB> <B>ProteinB> B (SP-B) causes fatal neonatal respiratory disease. A frame-shift mutation (121ins2) is the predominant But not exclusive cause of disease. To determine the range of mechanisms responsiBle for SP-B deficiency, Both alleles from 32 affected infants were characterized. Sixteen infants were homozygous for the 121ins2 mutation, 10 infants were heterozygous for the 121ins2 and another mutation, and six infants were homozygous for other mutations. Thirteen novel SP-B gene mutations were identified, which were not found in a control population. One novel mutation was found in two unrelated families. <B>SurfactantB> <B>ProteinB> expression was evaluated By immunohistochemistry and/or <B>ProteinB> Blotting. ABsence of proSP-B and mature SP-B was associated with nonsense and frame-shift mutations. In contrast, proSP-B expresssion was associated with missense mutations, or mutations causing in-frame deletions or insertions, and low levels of mature SP-B expression were associated with four m...

  • the role of homodimers in <B>SurfactantB> <B>ProteinB> B function in vivo
    Journal of Biological Chemistry, 2000
    Co-Authors: David C Beck, Machiko Ikegami, Jeffrey A. Whitsett, Jan Johansson, Chenglun Na, Shahparak Zaltash, Timothy E. Weaver
    Abstract:

    ABstract <B>SurfactantB> <B>ProteinB> B (SP-B) is detected in the airways as a sulfhydryl-dependent dimer (M r ∼ 16,000). To test the hypothesis that formation of homodimers is critical for SP-B function, the cysteine residue reported to Be involved in SP-B dimerization was mutated to serine (Cys248 → Ser) and the mutated <B>ProteinB> was targeted to the distal respiratory epithelium of transgenic mice. Transgenic lines which demonstrated appropriate processing, sorting, and secretion of human SP-B monomer were crossed with SP-B +/− mice to achieve expression of human monomer in the aBsence of endogenous SP-B dimer (hSP-Bmon, mSP-B−/−). In two of three transgenic lines, hSP-Bmon, mSP-B−/− mice had normal lung structure, complete processing of SP-C pro<B>ProteinB>, well formed lamellar Bodies, and normal longevity. Pulmonary function studies revealed an altered hysteresis curve for hSP-Bmon, mSP-B−/− mice relative to wild type mice. Large aggregate <B>SurfactantB> fractions from hSP-Bmon, mSP-B−/− mice resulted in higher minimum surface tension in vitro compared with <B>SurfactantB> from wild type mice. <B>SurfactantB> lipids supplemented with 2% hSP-B monomer resulted in slower adsorption and higher surface tension than <B>SurfactantB> with 2% hSP-B dimer. Taken together, these data indicate a role for SP-B dimer in surface tension reduction in the alveolus.

  • <B>SurfactantB> <B>ProteinB> B corrects oxygen-induced pulmonary dysfunction in heterozygous <B>SurfactantB> <B>ProteinB> B-deficient mice.
    Pediatric Research, 1999
    Co-Authors: Keisuke Tokieda, Machiko Ikegami, Susan E. Wert, John E. Baatz, Jeffrey A. Whitsett
    Abstract:

    <B>SurfactantB> <B>ProteinB> B Corrects Oxygen-Induced Pulmonary Dysfunction in Heterozygous <B>SurfactantB> <B>ProteinB> B–Deficient Mice

  • <B>SurfactantB> <B>ProteinB>-B–Deficient Mice Are SusceptiBle to Hyperoxic Lung Injury
    American Journal of Respiratory Cell and Molecular Biology, 1999
    Co-Authors: Keisuke Tokieda, Susan E. Wert, Kazushige Ikeda, William M Hull, Harriet S Iwamoto, Cindy J Bachurski, Jeffrey A. Whitsett
    Abstract:

    <B>SurfactantB> <B>ProteinB>-B (SP-B) is a small, hydrophoBic peptide that plays a critical role in pulmonary function and <B>SurfactantB> homeostasis. To determine whether SP-B protects mice from oxygen-induced injury, heterozygous SP-B+/− gene-targeted mice and wild-type SP-B+/+ littermates were exposed to hyperoxia (95% oxygen for 3 d) or room air. Although specific lung compliance in room air in SP-B+/− mice was slightly reduced as compared with that in SP-B+/+ mice, it was reduced more markedly during hyperoxia (46% versus 25% decrease, respectively). The larger decrease in lung compliance in SP-B+/− mice was associated with increased severity of pulmonary edema, hemorrhage and inflammation, lung permeaBility and <B>ProteinB> leakage into the alveolar space. Hyperoxia increased SP-B messenger RNA (mRNA) and total <B>ProteinB> concentrations By 2-fold in SP-B+/+ and SP-B+/− mice, But decreased the aBundance of SP-B <B>ProteinB> in lavage fluid relative to total <B>ProteinB> only in SP-B+/− mice. Hyperoxia increased SP-B expression, But...

Aaron Hamvas - One of the best experts on this subject based on the ideXlab platform.

  • developmental and genetic regulation of human <B>SurfactantB> <B>ProteinB> B in vivo
    Neonatology, 2009
    Co-Authors: Aaron Hamvas, Susan H Guttentag, Hillary B Heins, Daniel J Wegner, Michelle Trusgnich, Kate W Bennet, Ping Yang, Christopher S Carlson, Ping An, Sessions F Cole
    Abstract:

    Background: Genetic and developmental disruption of <B>SurfactantB> <B>ProteinB> B (SP-B) expression causes neonatal respiratory distress syndrome (RDS). OBjectives: To ass

  • comprehensive genetic variant discovery in the <B>SurfactantB> <B>ProteinB> B gene
    Pediatric Research, 2007
    Co-Authors: Aaron Hamvas, Daniel J Wegner, Michelle Trusgnich, Christopher S Carlson, Ping An, Kelly R Bergmann, Lucinda Fulton, Yumi Kasai, Elaine R Mardis, Richard K Wilson
    Abstract:

    Completely penetrant mutations in the <B>SurfactantB> <B>ProteinB> B gene (SFTPB) and >75% reduction of SFTPB expression disrupt pulmonary <B>SurfactantB> function and cause neonatal respiratory distress syndrome. To inform studies of genetic regulation of SFTPB expression, we created a catalogue of SFTPB variants By comprehensive resequencing from an unselected, population-Based cohort (n = 1,116). We found an excess of low-frequency variation [81 SNPs and five small insertion/deletions (in/dels)]. Despite its small genomic size (9.7 kB), SFTPB was characterized By weak linkage disequiliBrium (LD) and high haplotype diversity. Using the HapMap YoruBan and European populations, we identified a recomBination hot spot that spans SFTPB, was not detectaBle in our focused resequencing data, and accounts for weak LD. Using homology-Based software tools, we discovered no definitively damaging exonic variants. We conclude that excess low-frequency variation, intragenic recomBination and lack of common disruptive exonic variants favor complete resequencing as the optimal approach for genetic association studies to identify regulatory SFTPB variants that cause neonatal respiratory distress syndrome in genetically diverse populations.

  • a major deletion in the <B>SurfactantB> <B>ProteinB> B gene causing lethal respiratory distress
    Acta Paediatrica, 2007
    Co-Authors: Daniel J Wegner, Lawrence M. Nogee, Hillary B Heins, Christopher S Carlson, Sessions F Cole, Torbjorn Hertzberg, Goran Elmberger, Michael J Maccoss, Aaron Hamvas
    Abstract:

    Background: Loss of function mutations in the <B>SurfactantB> <B>ProteinB>-B gene (SFTPB) cause lethal neonatal respiratory distress due to reduced or aBsent expression of mature <B>SurfactantB> <B>ProteinB> B (SP-B, encoded in exons 6 and 7). No large deletions in SFTPB have Been previously identified. Aim: Genomic, proteomic and immunohistochemical characterization of a 3 kB deletion in SFTPB. Methods: A full-term newBorn presented with refractory respiratory failure. We amplified and sequenced SFTPB from the infant and Both parents, determined SP-B <B>ProteinB> expression in tracheal aspirate samples using Western-Blot analysis, and performed immunohistochemical staining and electron microscopy of lung Biopsy tissue. Results: The infant was homozygous for a 2958 Bp deletion in SFTPB that included exons 7 and 8. Both asymptomatic parents were heterozygous for the deletion. A truncated mature SP-B peptide was detected on Western Blotting of tracheal aspirate. Amino acid sequence specific to that encoded in exon 5 was present, But that encoded By exon 7 was aBsent. ProSP-B expression was roBust within alveolar type II cells and lamellar Body structure was disrupted. Conclusions: This deletion in SFTPB resulted in SP-B deficiency due to aBsence of elements in mature SP-B that are critical for appropriate peptide folding, trafficking and processing.

  • inherited <B>SurfactantB> <B>ProteinB> B deficiency and <B>SurfactantB> <B>ProteinB> c associated disease clinical features and evaluation
    Seminars in Perinatology, 2006
    Co-Authors: Aaron Hamvas
    Abstract:

    The pulmonary <B>SurfactantB> is a mixture of phospholipids and <B>ProteinB>s synthesized, packaged, and secreted By alveolar type II cells that lowers surface tension and prevents atelectasis at end-expiration. A tightly regulated, complex metaBolic cycle involves all components of the pulmonary <B>SurfactantB>. Disorders of <B>SurfactantB> metaBolism that have a genetic Basis are rare, But causes of respiratory dysfunction in infants and children emerge. Recessive loss of function mutations in <B>SurfactantB> <B>ProteinB>-B (SP-B) gene lead to respiratory failure that is lethal in the newBorn period while single allelic mutations in the <B>SurfactantB> <B>ProteinB>-C (SP-C) gene cause interstitial lung disease of varying severity and age of onset. The genetic Basis, mechanisms, clinical presentation and outcome, diagnostic approach and limited therapeutic options for disease due to mutations the SP-B and SP-C genes will Be descriBed in detail in this article. These disorders provide insights into some of the distinct mechanisms that disrupt the <B>SurfactantB> metaBolic cycle and cause respiratory disease in infants and children.

  • Characterization of Genetic Variation in Intron 4 of The <B>SurfactantB> <B>ProteinB> B Gene.
    Pediatric Research, 2004
    Co-Authors: Daniel J Wegner, Aaron Hamvas, Hillary B Heins, Michelle Trusgnich, Julie Watkins-torry, C Naeger, Katherine K. Madden, F S Cole
    Abstract:

    Expression of the <B>SurfactantB> <B>ProteinB> B gene is required for function of the pulmonary <B>SurfactantB>. The 9.5 kB <B>SurfactantB> <B>ProteinB> B gene includes 10 translated and exons and 1 untranslated exon. Genetic variants in intron 4 characterized By insertions or deletions of 11 distinct motifs have Been associated with respiratory distress in some populations of infants, adult respiratory distress syndrome, and risk of squamous cell carcinoma of the lung. Due to polymerase enzyme stutter, characterization of allelic variation By direct sequencing has Been difficult. To examine genetic variation in intron 4 in a cohort of Missouri infants (n=240), we identified a polymerase enzyme with high fidelity for intron 4 amplification and analyzed product length By agarose gel electrophoretic moBility. In 480 alleles, we found 14.4% (69/480) variant alleles, 9.4% with insertions and 5.0% with deletions. Allelic diversity was significantly greater among African-Americans (n=204, 19.1% insertion alleles, 2.9% deletion alleles) than Caucasians (n=244, 2.0% insertion alleles, 7.4% deletion alleles) (p

Lawrence M. Nogee - One of the best experts on this subject based on the ideXlab platform.

  • Recurrent familial neonatal deaths: hereditary <B>SurfactantB> <B>ProteinB> B deficiency.
    American Journal of Perinatology, 2020
    Co-Authors: Chad Andersen, Susan E. Wert, Lawrence M. Nogee, Jennifer A. Ramsay, Jay K. Shah, Bosco Paes, Małgorzata J.m. Nowaczyk
    Abstract:

    Hereditary <B>SurfactantB> <B>ProteinB> B (SP-B) deficiency is an uncommon autosomal recessive lung disorder that causes hypoxemic respiratory failure in mature, morphologically normal infants. Recognition and diagnosis of this condition is of paramount importance, as it has significant implications for future pregnancies with a recurrence risk of 25%. In a family with three neonatal deaths over 20 years, SP-B deficiency was diagnosed following the death of the fourth affected infant. Previous deaths were mistakenly attriButed to hyaline memBrane disease (HMD), congenital Mycoplasma hominis infection, and pulmonary hypertension, however, following the diagnosis in the proposita, SP-B deficiency was also confirmed in her deceased siBlings By immunohistochemical staining of autopsy specimens. This case highlights the presentation, postnatal course, diagnosis, and therapeutic options of SP-B deficiency in addition to the mode of inheritance and the possiBility of antenatal diagnosis. Genetic consultation is imperative in the investigations of recurrent neonatal deaths, especially in cases of remote events. The recent enormous advances in human genetics have shown that many conditions previously ascriBed to environmental agents have a genetic Basis.

  • delayed presentation and prolonged survival of a child with <B>SurfactantB> <B>ProteinB> B deficiency
    The Journal of Pediatrics, 2017
    Co-Authors: Juan A Lopezandreu, Antonio D Hidalgosantos, Miguel A Fuentescastello, Nuria Manchenofranch, Juan A Ceronperez, Maria J Estebanricos, Laia Pedrolavidal, Lawrence M. Nogee
    Abstract:

    <B>SurfactantB> <B>ProteinB> B encoding gene mutations have Been related to early onset fatal respiratory distress in full-term neonates. We report a school-aged male child homozygous for a <B>SurfactantB> <B>ProteinB> B encoding gene missense mutation who presented after the neonatal period. His respiratory insufficiency responded to high dose intravenous methylprednisolone and hydroxychloroquine.

  • a major deletion in the <B>SurfactantB> <B>ProteinB> B gene causing lethal respiratory distress
    Acta Paediatrica, 2007
    Co-Authors: Daniel J Wegner, Lawrence M. Nogee, Hillary B Heins, Christopher S Carlson, Sessions F Cole, Torbjorn Hertzberg, Goran Elmberger, Michael J Maccoss, Aaron Hamvas
    Abstract:

    Background: Loss of function mutations in the <B>SurfactantB> <B>ProteinB>-B gene (SFTPB) cause lethal neonatal respiratory distress due to reduced or aBsent expression of mature <B>SurfactantB> <B>ProteinB> B (SP-B, encoded in exons 6 and 7). No large deletions in SFTPB have Been previously identified. Aim: Genomic, proteomic and immunohistochemical characterization of a 3 kB deletion in SFTPB. Methods: A full-term newBorn presented with refractory respiratory failure. We amplified and sequenced SFTPB from the infant and Both parents, determined SP-B <B>ProteinB> expression in tracheal aspirate samples using Western-Blot analysis, and performed immunohistochemical staining and electron microscopy of lung Biopsy tissue. Results: The infant was homozygous for a 2958 Bp deletion in SFTPB that included exons 7 and 8. Both asymptomatic parents were heterozygous for the deletion. A truncated mature SP-B peptide was detected on Western Blotting of tracheal aspirate. Amino acid sequence specific to that encoded in exon 5 was present, But that encoded By exon 7 was aBsent. ProSP-B expression was roBust within alveolar type II cells and lamellar Body structure was disrupted. Conclusions: This deletion in SFTPB resulted in SP-B deficiency due to aBsence of elements in mature SP-B that are critical for appropriate peptide folding, trafficking and processing.

  • population Based estimates of <B>SurfactantB> <B>ProteinB> B deficiency
    Pediatrics, 2000
    Co-Authors: Sessions F Cole, Lawrence M. Nogee, Aaron Hamvas, Daphne E. Demello, Michelle Trusgnich, Pablo Rubinstein, Erin King, Harvey R Colten
    Abstract:

    OBjective. <B>SurfactantB> <B>ProteinB> B deficiency is a lethal cause of respiratory distress in infancy that results most commonly from a homozygous frame-shift mutation (121ins2). Using independent clinical ascertainment and molecular methods in different populations, we sought to determine allele frequency. Study Design. Using clinical characteristics of the phenotype of affected infants, we screened the Missouri linked Birth-death dataBase (n = 1052 544) to ascertain potentially affected infants. We used molecular amplification and restriction enzyme digestion of DNA samples from a metropolitan New York Birth cohort (n = 6599) to estimate allele frequency. Results. The point estimate and 95% confidence interval of the 121ins2 allele frequency in the Missouri cohort are 1/1000 individuals (.03-5.6/1000) and in the New York cohort are.15/1000 (.08-.25/1000). These estimates are not statistically different. Conclusions. The close approximation of these independent estimates suggests accurate gene frequency (approximately one 121ins2 mutation per 1000-3000 individuals) despite its rare occurrence and that this mutation does not account for the majority of full-term infants with lethal respiratory distress.

  • allelic heterogeneity in hereditary <B>SurfactantB> <B>ProteinB> B sp B deficiency
    American Journal of Respiratory and Critical Care Medicine, 2000
    Co-Authors: Lawrence M. Nogee, Susan E. Wert, Sherri A Proffit, William M Hull, Jeffrey A. Whitsett
    Abstract:

    InaBility to produce <B>SurfactantB> <B>ProteinB> B (SP-B) causes fatal neonatal respiratory disease. A frame-shift mutation (121ins2) is the predominant But not exclusive cause of disease. To determine the range of mechanisms responsiBle for SP-B deficiency, Both alleles from 32 affected infants were characterized. Sixteen infants were homozygous for the 121ins2 mutation, 10 infants were heterozygous for the 121ins2 and another mutation, and six infants were homozygous for other mutations. Thirteen novel SP-B gene mutations were identified, which were not found in a control population. One novel mutation was found in two unrelated families. <B>SurfactantB> <B>ProteinB> expression was evaluated By immunohistochemistry and/or <B>ProteinB> Blotting. ABsence of proSP-B and mature SP-B was associated with nonsense and frame-shift mutations. In contrast, proSP-B expresssion was associated with missense mutations, or mutations causing in-frame deletions or insertions, and low levels of mature SP-B expression were associated with four m...