alpha 1 antitrypsin

Summary

Summary: Plasma glycoprotein member of the serpin superfamily which inhibits TRYPSIN; NEUTROPHIL ELASTASE; and other PROTEOLYTIC ENZYMES. Commonly referred to as alpha 1-proteinase inhibitor (A1PI), it exists in over 30 different biochemical variant forms known collectively as the Pi (protease inhibitor) system. Hereditary A1PI deficiency is associated with PULMONARY EMPHYSEMA.

Top Publications

  1. ncbi Wild-type alpha 1-antitrypsin is in the canonical inhibitory conformation
    P R Elliott
    Department of Medicine, University of Cambridge, UK
    J Mol Biol 275:419-25. 1998
  2. pmc Alpha1-antitrypsin polymerization and the serpinopathies: pathobiology and prospects for therapy
    David A Lomas
    Respiratory Medicine Unit, Department of Medicine, University of Cambridge, Cambridge Institute for Medical Research, Cambridge, United Kingdom
    J Clin Invest 110:1585-90. 2002
  3. ncbi The proteasome participates in degradation of mutant alpha 1-antitrypsin Z in the endoplasmic reticulum of hepatoma-derived hepatocytes
    J H Teckman
    Department of Pediatrics, Washington University School of Medicine, St. Louis, Missouri 63110, USA
    J Biol Chem 276:44865-72. 2001
  4. ncbi Intracellular inclusions containing mutant alpha1-antitrypsin Z are propagated in the absence of autophagic activity
    Takahiro Kamimoto
    Department of Cell Genetics, National Institute of Genetics, Mishima, Japan
    J Biol Chem 281:4467-76. 2006
  5. ncbi Activation of endoplasmic reticulum-specific stress responses associated with the conformational disease Z alpha 1-antitrypsin deficiency
    Matthew W Lawless
    Respiratory Research Division, Royal College of Surgeons in Ireland, Education and Research Center, Beaumont Hospital, Dublin, Ireland
    J Immunol 172:5722-6. 2004
  6. ncbi A kinetic mechanism for the polymerization of alpha1-antitrypsin
    T R Dafforn
    Department of Haematology, Department of Medicine, University of Cambridge, Cambridge Institute for Medical Research, Wellcome Trust Medical Research Council Building, Hills Road, Cambridge CB2 2XY, United Kingdom
    J Biol Chem 274:9548-55. 1999
  7. pmc Alpha1-antitrypsin deficiency. 1: epidemiology of alpha1-antitrypsin deficiency
    M Luisetti
    Laboratorio di Biochimica e Genetica, Clinica Malattie Apparato Respiratorio, IRCCS Policlinico San Matteo, Universita di Pavia, Italy
    Thorax 59:164-9. 2004
  8. pmc Cleaved antitrypsin polymers at atomic resolution
    M A Dunstone
    The Ian Potter Foundation Protein Crystallography Laboratory, St Vincent s Institute of Medical Research, Fitzroy, Victoria, Australia
    Protein Sci 9:417-20. 2000
  9. ncbi Osmolytes as modulators of conformational changes in serpins
    M K Chow
    Department of Biochemistry and Molecular Biology, Monash University, Clayton, Victoria, Australia
    Biol Chem 382:1593-9. 2001
  10. ncbi Comprehensive glyco-proteomic analysis of human alpha1-antitrypsin and its charge isoforms
    Daniel Kolarich
    Department of Chemistry, Biochemistry Division, University of Natural Resources and Applied Life Sciences BOKU, Vienna, Austria
    Proteomics 6:3369-80. 2006

Detail Information

Publications248 found, 100 shown here

  1. ncbi Wild-type alpha 1-antitrypsin is in the canonical inhibitory conformation
    P R Elliott
    Department of Medicine, University of Cambridge, UK
    J Mol Biol 275:419-25. 1998
    ..This pocket may provide a target for rational drug design to prevent the formation of polymers and the associated plasma deficiency, liver cirrhosis and emphysema...
  2. pmc Alpha1-antitrypsin polymerization and the serpinopathies: pathobiology and prospects for therapy
    David A Lomas
    Respiratory Medicine Unit, Department of Medicine, University of Cambridge, Cambridge Institute for Medical Research, Cambridge, United Kingdom
    J Clin Invest 110:1585-90. 2002
  3. ncbi The proteasome participates in degradation of mutant alpha 1-antitrypsin Z in the endoplasmic reticulum of hepatoma-derived hepatocytes
    J H Teckman
    Department of Pediatrics, Washington University School of Medicine, St. Louis, Missouri 63110, USA
    J Biol Chem 276:44865-72. 2001
    ..Although there is substantial evidence that other mechanisms contribute to ER degradation of alpha(1)-ATZ, the data reported here indicate that the proteasome plays an important role in many cell types including hepatocytes...
  4. ncbi Intracellular inclusions containing mutant alpha1-antitrypsin Z are propagated in the absence of autophagic activity
    Takahiro Kamimoto
    Department of Cell Genetics, National Institute of Genetics, Mishima, Japan
    J Biol Chem 281:4467-76. 2006
    ....
  5. ncbi Activation of endoplasmic reticulum-specific stress responses associated with the conformational disease Z alpha 1-antitrypsin deficiency
    Matthew W Lawless
    Respiratory Research Division, Royal College of Surgeons in Ireland, Education and Research Center, Beaumont Hospital, Dublin, Ireland
    J Immunol 172:5722-6. 2004
    ..These findings have important implications for the design of future therapeutics for Z A1AT liver disease and may also impact on drug design for other conformational diseases...
  6. ncbi A kinetic mechanism for the polymerization of alpha1-antitrypsin
    T R Dafforn
    Department of Haematology, Department of Medicine, University of Cambridge, Cambridge Institute for Medical Research, Wellcome Trust Medical Research Council Building, Hills Road, Cambridge CB2 2XY, United Kingdom
    J Biol Chem 274:9548-55. 1999
    ..Taken together, these data allow us to propose a kinetic mechanism for alpha1-antitrypsin polymer formation that involves the generation of an unstable intermediate, which can form polymers or generate latent protein...
  7. pmc Alpha1-antitrypsin deficiency. 1: epidemiology of alpha1-antitrypsin deficiency
    M Luisetti
    Laboratorio di Biochimica e Genetica, Clinica Malattie Apparato Respiratorio, IRCCS Policlinico San Matteo, Universita di Pavia, Italy
    Thorax 59:164-9. 2004
    ..The protein and molecular characteristics of variants of the alpha1-antitrypsin (AAT) gene are described, and available data on the genetic epidemiology of AAT deficiency are presented...
  8. pmc Cleaved antitrypsin polymers at atomic resolution
    M A Dunstone
    The Ian Potter Foundation Protein Crystallography Laboratory, St Vincent s Institute of Medical Research, Fitzroy, Victoria, Australia
    Protein Sci 9:417-20. 2000
    ..Here, we describe the first crystallographic evidence of a beta-strand linked polymer form of alpha1-antitrypsin: the crystal structure of a cleaved alpha1-antitrypsin polymer...
  9. ncbi Osmolytes as modulators of conformational changes in serpins
    M K Chow
    Department of Biochemistry and Molecular Biology, Monash University, Clayton, Victoria, Australia
    Biol Chem 382:1593-9. 2001
    ..The implications of these results in the context of conformational changes and states adopted by alpha1-antitrypsin are discussed...
  10. ncbi Comprehensive glyco-proteomic analysis of human alpha1-antitrypsin and its charge isoforms
    Daniel Kolarich
    Department of Chemistry, Biochemistry Division, University of Natural Resources and Applied Life Sciences BOKU, Vienna, Austria
    Proteomics 6:3369-80. 2006
    ..Fucosylation of diantennary structures was marginal and of the core alpha1,6 type...
  11. ncbi Structure of a serpin-protease complex shows inhibition by deformation
    J A Huntington
    Department of Haematology, University of Cambridge, Wellcome Trust Centre for Molecular Mechanisms in Disease, Cambridge Institute for Medical Research, UK
    Nature 407:923-6. 2000
    ..It is this ability of the conformational mechanism to crush as well as inhibit proteases that provides the serpins with their selective advantage...
  12. ncbi What do dysfunctional serpins tell us about molecular mobility and disease?
    P E Stein
    Department of Haematology, University of Cambridge, MRC Centre, UK
    Nat Struct Biol 2:96-113. 1995
    ..In particular, comparisons of variants affecting different serpins allow us to define the domains which control this folding and show how spontaneous but inappropriate changes in conformation cause diverse diseases...
  13. ncbi Tauroursodeoxycholic acid inhibits apoptosis induced by Z alpha-1 antitrypsin via inhibition of Bad
    Stanley D W Miller
    Respiratory Research Division, Department of Medicine, Royal College of Surgeons in Ireland, Education and Research Centre, Beaumont Hospital, Dublin, Ireland
    Hepatology 46:496-503. 2007
    ..CONCLUSION: These data show that caspase-4 is not essential for ZAAT-induced apoptosis in HEK293 cells and implicates P-I-3-kinase and Bad as potential therapeutic targets for the liver disease associated with ZAAT deficiency...
  14. pmc alpha-1 antitrypsin inhibits caspase-3 activity, preventing lung endothelial cell apoptosis
    Irina Petrache
    Department of Medicine, The Johns Hopkins University School of Medicine, Baltimore, MD, USA
    Am J Pathol 169:1155-66. 2006
    ....
  15. ncbi Alpha-1-antitrypsin and a broad spectrum metalloprotease inhibitor, RS113456, have similar acute anti-inflammatory effects
    A Churg
    Department of Pathology, University of British Columbia, Vancouver, British Columbia, Canada
    Lab Invest 81:1119-31. 2001
    ..The antiproteolytic effects of these agents do not seem to be mediated by protection of endogenous alpha1AT...
  16. pmc A novel ER alpha-mannosidase-like protein accelerates ER-associated degradation
    N Hosokawa
    Department of Molecular and Cellular Biology, Institute for Frontier Medical Sciences, Kyoto University, Kyoto 606 8397, Japan
    EMBO Rep 2:415-22. 2001
    ..The results suggest that EDEM is directly involved in ERAD, and targets misfolded glycoproteins for degradation in an N-glycan dependent manner...
  17. ncbi The serpin inhibitory mechanism is critically dependent on the length of the reactive center loop
    A Zhou
    Department of Haematology, University of Cambridge, Wellcome Trust Center for Molecular Mechanisms in Disease, Cambridge Institute for Medical Research, Hills Road, Cambridge CB2 2XY, United Kingdom
    J Biol Chem 276:27541-7. 2001
    ..We conclude that the length of the serpin reactive center loop is critical for its mechanism of inhibition and is precisely regulated to balance the efficiency of inhibition and stability of the final complex...
  18. ncbi Alpha-1-antitrypsin inhibits human immunodeficiency virus type 1
    L Shapiro
    Department of Medicine, Division of Infectious Diseases, University of Colorado Health Sciences Center, Denver, Colorado 80262, USA
    FASEB J 15:115-122. 2001
    ..A novel host-pathogen interaction is suggested, and an alternative strategy to treat HIV-1-related disease may be possible...
  19. pmc Identification and DNA sequence analysis of 15 new alpha 1-antitrypsin variants, including two PI*Q0 alleles and one deficient PI*M allele
    J P Faber
    Institut für Klinische Biochemie der Universität Bonn, Germany
    Am J Hum Genet 55:1113-21. 1994
    ..The limitation of IEF compared with DNA sequence analysis, for identification of new variants, their generation by mutagenesis, and the clinical relevance of the three deficiency alleles are discussed...
  20. ncbi alpha 1-Proteinase inhibitor, alpha 1-antichymotrypsin, and alpha 2-macroglobulin are the antiapoptotic factors of vascular smooth muscle cells
    Y Ikari
    Department of Pathology, University of Washington, Seattle, Washington 98195, USA
    J Biol Chem 276:11798-803. 2001
    ..In conclusion, the plasma proteinase inhibitors prevent degradation of extracellular matrix by proteinases derived from cells. Presumably an intact cell-matrix interaction inhibits caspase activation and supports cell survival...
  21. ncbi The C-terminal 26-residue peptide of serpin A1 is an inhibitor of HIV-1
    Luis Fernando Congote
    Endocrine Laboratory, McGill University Health Centre, 687 avenue des pins, ouest, Montreal, Canada H3A 1A1
    Biochem Biophys Res Commun 343:617-22. 2006
    ..These serpin peptides represent a novel class of antiviral agents...
  22. ncbi Oncostatin M is a potent stimulator of alpha1-antitrypsin secretion in lung epithelial cells: modulation by transforming growth factor-beta and interferon-gamma
    A Boutten
    Services de Biochimie A et de Pneumologie, INSERM U408, Hopital Bichat, Paris and U F R Sciences Pharmaceutiques, Chatenay Malabry, France
    Am J Respir Cell Mol Biol 18:511-20. 1998
    ..Our results suggest that during an inflammatory process, alveolar epithelial cells may contribute to the antiprotease defense within the lung...
  23. ncbi Involvement of Sp1 elements in the promoter activity of the alpha1-proteinase inhibitor gene
    Y Li
    Department of Ophthalmology and Visual Sciences, University of Illinois at Chicago College of Medicine, Chicago, Illinois 60612, USA
    J Biol Chem 273:9959-65. 1998
    ..This information may help elucidate the molecular pathways leading to the altered alpha1-proteinase inhibitor expression in keratoconus...
  24. ncbi The selective advantage of alpha1-antitrypsin deficiency
    David A Lomas
    Department of Medicine, University of Cambridge, Cambridge Institute for Medical Research, Wellcome Trust MRC Building, Hills Road, Cambridge, CB2 2XY UK
    Am J Respir Crit Care Med 173:1072-7. 2006
    ....
  25. ncbi C-terminal fragment of alpha1-antitrypsin activates human monocytes to a pro-inflammatory state through interactions with the CD36 scavenger receptor and LDL receptor
    S Janciauskiene
    Gastroenterology Hepatology Section, Department of Medicine, University Hospital Malmo, 20502 Malmo, Sweden
    Atherosclerosis 158:41-51. 2001
    ..This also supports important roles for CD36 and LDL receptors in atherogenesis and suggests that blockade of CD36 receptor can be protective in pro-inflammatory activation of human monocytes...
  26. ncbi Protective effects of alpha 1-antitrypsin on acute lung injury in rabbits induced by endotoxin
    Zhijun Jie
    Department of Pulmonology, Zhongshan Hospital, Medical Center of Fudan University, Shanghai 200032, China
    Chin Med J (Engl) 116:1678-82. 2003
    ..To investigate whether pretreatment with alpha(1)-antitrypsin (AAT) can attenuate acute lung injury (ALI) in rabbits induced with endotoxin...
  27. pmc IL10 polymorphisms are associated with airflow obstruction in severe alpha1-antitrypsin deficiency
    Dawn L DeMeo
    Brigham and Women s Hospital, Channing Laboratory, 181 Longwood Avenue, Boston, MA 02115, USA
    Am J Respir Cell Mol Biol 38:114-20. 2008
    ..Haplotype analysis of IL10 SNPs suggested the strongest association with IL10 promoter SNPs. IL10 is likely an important modifier gene for the development of COPD in individuals with severe AAT deficiency...
  28. ncbi Matrix metalloproteinase-26 is associated with estrogen-dependent malignancies and targets alpha1-antitrypsin serpin
    Wei Li
    Cell Adhesion and Extracellular Matrix Biology Program, Cancer Research Center, The Burnham Institute, La Jolla, California 92037, USA
    Cancer Res 64:8657-65. 2004
    ..In summary, we hypothesize that MMP-26, by cleaving and inactivating the AAT serpin, operates as a unique functional link that regulates a coordinated interplay between Ser and metalloproteinases in estrogen-dependent neoplasms...
  29. pmc An evaluation of the prognostic significance of alpha-1-antitrypsin expression in adenocarcinomas of the lung: an immunohistochemical analysis
    M Higashiyama
    Department of Thoracic Surgery, Center for Adult Diseases, Osaka, Japan
    Br J Cancer 65:300-2. 1992
    ..Thus, AAT expression status in tumour cells of lung adenocarcinoma may be a biological marker of prognostic significance in regard to tumour growth...
  30. ncbi Role of imbalance between neutrophil elastase and alpha 1-antitrypsin in cancer development and progression
    Zhifu Sun
    Department of Health Sciences Research, Mayo Clinic Rochester, Rochester, MN 55905, USA
    Lancet Oncol 5:182-90. 2004
    ....
  31. ncbi Production of human alpha-1-antitrypsin from transgenic rice cell culture in a membrane bioreactor
    Karen A McDonald
    Department of Chemical Engineering and Materials Science, University of California at Davis, One Shields Avenue, Davis, California 95616, USA
    Biotechnol Prog 21:728-34. 2005
    ..Active rAAT reached levels of 100-247 mg/L (4-10% of the total extracellular protein) in the cell compartment at 5-6 days postinduction, and multiple inductions of the RAmy3D promoter were demonstrated...
  32. ncbi Alpha 1 antitrypsin activity is decreased in human amnion in premature rupture of the fetal membranes
    Noriko Izumi-Yoneda
    Department of Regenerative Medicine, University of Toyama Graduate School of Medicine and Pharmaceutical Sciences, Toyama, Japan
    Mol Hum Reprod 15:49-57. 2009
    ..However, the detailed mechanism is not well understood. Alpha 1 antitrypsin (AAT) was reported to decrease in concentration in amniotic fluid obtained from patients with PPROM...
  33. ncbi Aerosolized prolastin suppresses bacterial proliferation in a model of chronic Pseudomonas aeruginosa lung infection
    A M Cantin
    Unite de Recherche Pulmonaire, Universite de Sherbrooke, Sherbrooke, Quebec, Alberta, Canada
    Am J Respir Crit Care Med 160:1130-5. 1999
    ..aeruginosa lung infection. These data suggest that aerosolized alpha(1)PI may represent a useful nonantibiotic adjunct in the treatment and control of infection and inflammation associated with CF lung disease...
  34. ncbi alpha1-Antitrypsin inhalation reduces airway inflammation in cystic fibrosis patients
    M Griese
    Lung Research Group, Dr von Hauner Children s Hospital, Ludwig Maximilians University, Lindwurmstr 4, D 80337 Munich, Germany
    Eur Respir J 29:240-50. 2007
    ..The alpha(1)-antitrypsin deposition region may play a minor role for alpha(1)-antitrypsin inhalation in cystic fibrosis patients...
  35. ncbi EDEM as an acceptor of terminally misfolded glycoproteins released from calnexin
    Yukako Oda
    Department of Molecular and Cellular Biology, Institute for Frontier Medical Sciences, Kyoto University, Kyoto 606 8397, Japan
    Science 299:1394-7. 2003
    ..Overexpression of EDEM accelerated ERAD by promoting the release of terminally misfolded proteins from calnexin. Thus, EDEM appeared to function in the ERAD pathway by accepting substrates from calnexin...
  36. ncbi Alpha1-antitrypsin suppresses TNF-alpha and MMP-12 production by cigarette smoke-stimulated macrophages
    Andrew Churg
    Department of Pathology, University of British Columbia, 2211 Wesbrook Mall, Vancouver, BC, V6T 2B5 Canada
    Am J Respir Cell Mol Biol 37:144-51. 2007
    ....
  37. ncbi Estimated numbers and prevalence of PI*S and PI*Z alleles of alpha1-antitrypsin deficiency in European countries
    I Blanco
    Div of Internal Medicine, Respiratory Diseases Branch, Hospital Valle del Nalon, 33920 Langreo, Principado de Asturias, Spain
    Eur Respir J 27:77-84. 2006
    ..A remarkable lack in number of reliable epidemiological studies and marked differences among these European countries and regions within a given country was also found...
  38. pmc Chronic obstructive pulmonary disease in alpha1-antitrypsin PI MZ heterozygotes: a meta-analysis
    C P Hersh
    Channing Laboratory, Department of Medicine, Brigham and Women s Hospital and Harcard Medical School, 181 Longwood Avenue, Boston, MA 02115, USA
    Thorax 59:843-9. 2004
    ..The risk of COPD in PI MZ heterozygous individuals is controversial...
  39. ncbi Modification of gene expression and increase in alpha1-antitrypsin (alpha1-AT) secretion after homologous recombination in alpha1-AT-deficient monocytes
    Gillian L McNab
    Department of Respiratory Medicine, University of Birmingham, Birmingham B15 2TT, United Kingdom
    Hum Gene Ther 18:1171-7. 2007
    ..The development of this methodology to repair the gene defect in hepatocytes should have beneficial effects on secretion, thereby protecting both the lung and liver...
  40. ncbi Mutation of antitrypsin to antithrombin. alpha 1-antitrypsin Pittsburgh (358 Met leads to Arg), a fatal bleeding disorder
    M C Owen
    N Engl J Med 309:694-8. 1983
    ..The episodic nature of the bleeding was a consequence of the mutant protein's being an acute-phase reactant, the level of which increased several-fold after trauma...
  41. pmc Polymers of Z alpha1-antitrypsin co-localize with neutrophils in emphysematous alveoli and are chemotactic in vivo
    Ravi Mahadeva
    Department of Medicine, Box 157, Level 5, Addenbrookes NHS Trust, Hills Road, Cambridge CB2 2QQ, UK
    Am J Pathol 166:377-86. 2005
    ..These findings may also explain the progression of emphysema in some individuals despite alpha(1)-antitrypsin replacement therapy...
  42. ncbi Conditional expression of alpha1-antitrypsin delivered by recombinant SV40 vectors protects lymphocytes against HIV
    P Cordelier
    Department of Pathology, Jefferson Medical College, Philadelphia, PA 19107, USA
    Gene Ther 10:2153-6. 2003
    ..Combining the efficiency of rSV40 vectors with HIV-responsive expression of a highly effective anti-HIV therapeutic may be an effective approach to gene therapy of HIV replication...
  43. ncbi Interactions causing the kinetic trap in serpin protein folding
    Hana Im
    National Creative Research Initiatives, Protein Strain Research Center, Korea Institute of Science and Technology, 39 1 Hawolgok Dong, Sungbuk Gu, Seoul 136 791, Korea
    J Biol Chem 277:46347-54. 2002
    ..Mutational analyses suggest strongly that interactions not found in the final stable form cause the kinetic trap in serpin protein folding...
  44. ncbi Probing the role of the F-helix in serpin stability through a single tryptophan substitution
    Lisa D Cabrita
    Department of Biochemistry and Molecular Biology, Monash University, P O Box 13D, Victoria 3800, Australia
    Biochemistry 41:4575-81. 2002
    ..The implications of these data on both alpha1-antitrypsin function and misfolding are discussed...
  45. ncbi Exploring the role of CT densitometry: a randomised study of augmentation therapy in alpha1-antitrypsin deficiency
    A Dirksen
    Gentofte Hospital, Copenhagen University, Hellerup, Denmark
    Eur Respir J 33:1345-53. 2009
    ..In patients with alpha(1)-AT deficiency, CT is a more sensitive outcome measure of emphysema-modifying therapy than physiology and health status, and demonstrates a trend of treatment benefit from alpha(1)-AT augmentation...
  46. ncbi Complete sequence of the cDNA for human alpha 1-antitrypsin and the gene for the S variant
    G L Long
    Biochemistry 23:4828-37. 1984
    ....
  47. pmc Chemical chaperones mediate increased secretion of mutant alpha 1-antitrypsin (alpha 1-AT) Z: A potential pharmacological strategy for prevention of liver injury and emphysema in alpha 1-AT deficiency
    J A Burrows
    Departments of Pediatrics, Washington University School of Medicine, Division of Gastroenterology and Nutrition, Children s Hospital, St Louis, MO 63110, USA
    Proc Natl Acad Sci U S A 97:1796-801. 2000
    ....
  48. ncbi Rapid pulmonary expression of acute-phase reactants after local lipopolysaccharide exposure in mice is followed by an interleukin-6 mediated systemic acute-phase response
    Juanita H J Vernooy
    Nutrition and Toxicology Research Institute Maastricht NUTRIM, Department of Respiratory Medicine, University Hospital Maastricht, Maastricht, The Netherlands
    Exp Lung Res 31:855-71. 2005
    ..In conclusion, pulmonary LPS exposure induced rapid APR expression in lung, which precedes IL-6-mediated systemic elevation of APRs associated with hepatic APRs expression...
  49. pmc Small molecules block the polymerization of Z alpha1-antitrypsin and increase the clearance of intracellular aggregates
    Meera Mallya
    Department of Medicine, University of Cambridge, Cambridge Institute for Medical Research, Wellcome Trust MRC Building, Cambridge CB2 2XY, UK
    J Med Chem 50:5357-63. 2007
    ..Identifying small molecules provides a novel therapy for the treatment of liver disease associated with the Z allele of alpha1-antitrypsin...
  50. ncbi Detection of circulating and endothelial cell polymers of Z and wild type alpha 1-antitrypsin by a monoclonal antibody
    Sabina Janciauskiene
    Department of Internal Medicine, University Hospital, Malmo, 20502 Malmo, Sweden
    J Biol Chem 277:26540-6. 2002
    ..The antibody can be a powerful tool for the study of the molecular profile of AAT, not only in Z-deficiency cases but also in other (patho)physiological conditions...
  51. ncbi Polymers of alpha(1)-antitrypsin are chemotactic for human neutrophils: a new paradigm for the pathogenesis of emphysema
    Jasvir S Parmar
    Respiratory Medicine Division, Department of Medicine, University of Cambridge School of Clinical Medicine, Addenbrooke s and Papworth Hospitals, United Kingdom
    Am J Respir Cell Mol Biol 26:723-30. 2002
    ....
  52. ncbi Laboratory diagnosis of alpha1-antitrypsin deficiency
    Ilaria Ferrarotti
    Centro Diagnosi per il Deficit Ereditario di Alfa1 antitripsina, Clinica Malattie Apparato Respiratorio, Fondazione IRCCS Policlinico San Matteo, Universita di Pavia, Pavia, Italy
    Transl Res 150:267-74. 2007
    ..We also describe the diagnostic flowchart for AATD detection that we have developed accordingly...
  53. ncbi Inhibition of lipopolysaccharide-mediated human monocyte activation, in vitro, by alpha1-antitrypsin
    Sabina Janciauskiene
    Department of Medicine, Malmo University Hospital, 20502 Malmo, Sweden
    Biochem Biophys Res Commun 321:592-600. 2004
    ..Thus, our data demonstrate for the first time that AAT exhibits anti-inflammatory activity in vitro that is unrelated to inhibition of serine proteases...
  54. ncbi Longitudinal follow-up of patients with alpha(1)-protease inhibitor deficiency before and during therapy with IV alpha(1)-protease inhibitor
    M Wencker
    Ruhrlandklinik, Department of Pneumology, University Hospital, Essen, Germany
    Chest 119:737-44. 2001
    ..The efficacy of IV augmentation therapy with human alpha(1)-protease inhibitor (alpha(1)-Pi) in patients with severe alpha(1)-Pi deficiency is still under debate...
  55. ncbi Targeting a surface cavity of alpha 1-antitrypsin to prevent conformational disease
    Helen Parfrey
    Respiratory Medicine Unit, Department of Medicine, University of Cambridge, Cambridge Institute for Medical Research, Wellcome Trust MRC Building, Hills Road, Cambridge CB2 2XY, United Kingdom
    J Biol Chem 278:33060-6. 2003
    ..These results demonstrate the importance of this cavity as a site for drug design to ameliorate polymerization and prevent the associated conformational disease...
  56. ncbi Rapid PCR real-time genotyping of M-Malton alpha1-antitrypsin deficiency alleles by molecular beacons
    Germano Orru
    Dipartimento di Chirurgia e Scienze Odontostomatologiche Universita degli Studi di Cagliari, Cagliari Italy
    Diagn Mol Pathol 14:237-42. 2005
    ..This technique will be useful for research and molecular diagnostic laboratories involved in the study of alpha1-antitrypsin deficiency-related diseases...
  57. ncbi Therapeutic level of functional human alpha 1 antitrypsin (hAAT) secreted from murine muscle transduced by adeno-associated virus (rAAV1) vector
    Yuanqing Lu
    Department of Pharmaceutics, University of Florida College of Pharmacy, Gainesville, FL 32610, USA
    J Gene Med 8:730-5. 2006
    b>Alpha 1 antitrypsin (AAT) is a serine proteinase inhibitor (serpin)...
  58. pmc alpha1-Antitrypsin Portland, a bioengineered serpin highly selective for furin: application as an antipathogenic agent
    F Jean
    Vollum Institute, Oregon Health Sciences University, Portland, OR 97201, USA
    Proc Natl Acad Sci U S A 95:7293-8. 1998
    ..Finally, we propose a structural model of the alpha1-PDX-reactive site loop that explains the high degree of enzyme selectivity of this serpin and which can be used to generate small molecule furin inhibitors...
  59. ncbi The serpin alpha1-proteinase inhibitor is a critical substrate for gelatinase B/MMP-9 in vivo
    Z Liu
    Department of Dermatology, University of North Carolina, Chapel Hill 27599, USA
    Cell 102:647-55. 2000
    ..Excess NE produces lesions in GB -/- mice without cleaving alpha1-PI. Excess alpha1-PI phenocopies GB and NE deficiency in wild-type mice...
  60. ncbi Basic residues in the 37-loop of activated protein C modulate inhibition by protein C inhibitor but not by alpha(1)-antitrypsin
    Laura N Glasscock
    Department of Pathology, Center for Thrombosis and Hemostasis, The University of North Carolina School of Medicine, Chapel Hill, NC 27599 7035, USA
    Biochim Biophys Acta 1649:106-17. 2003
    ....
  61. ncbi Inhibition of HIV-1 gp160-dependent membrane fusion by a furin-directed alpha 1-antitrypsin variant
    E D Anderson
    Vollum Institute, Oregon Health Sciences University, Portland 97201
    J Biol Chem 268:24887-91. 1993
    ..The potential use of alpha 1-PDX in manipulating the activation of proproteins in a tissue- and time-specific manner is discussed...
  62. ncbi The effect of augmentation therapy on bronchial inflammation in alpha1-antitrypsin deficiency
    Robert A Stockley
    Department of Medicine, Queen Elizabeth Hospital, Edgbaston, Birmingham, United Kingdom
    Am J Respir Crit Care Med 165:1494-8. 2002
    ..In summary, short-term therapy with AAT increased lung secretion concentrations and was associated with a fall in leukotriene B(4), which is thought to be central to the airway inflammation of AAT deficiency...
  63. ncbi Serpin A1 and CD91 as host instruments against HIV-1 infection: are extracellular antiviral peptides acting as intracellular messengers?
    Luis Fernando Congote
    Endocrine Laboratory, McGill University Health Centre, 687 avenue des pins, ouest, Montreal, H3A 1A1, Canada
    Virus Res 125:119-34. 2007
    ....
  64. ncbi Application of vortex flow adsorption technology to intein-mediated recovery of recombinant human alpha1-antitrypsin
    Junfen Ma
    Massachusetts Institute of Technology, Department of Chemical Engineering, 77 Massachusetts Avenue, Cambridge, Massachusetts 02139, USA
    Biotechnol Prog 20:269-76. 2004
    ....
  65. ncbi Do native and polymeric alpha1-antitrypsin activate human neutrophils in vitro?
    Caroline Persson
    Department of Clinical Sciences, Wallenberg Laboratory, University Hospital Malmo, S 20502 Malmo, Sweden
    Chest 129:1683-92. 2006
    ..The discrepancies between these observations prompted us to re-examine the effects of AAT...
  66. ncbi Gene regulation of the serine proteinase inhibitors alpha1-antitrypsin and alpha1-antichymotrypsin
    Noor Kalsheker
    Division of Clinical Chemistry, School of Clinical Laboratory Sciences, University Hospital, Queen s Medical Centre, Nottingham NG7 2UH, U K
    Biochem Soc Trans 30:93-8. 2002
    ..100 bp upstream from the transcription initiation site, and a further interleukin-1-responsive enhancer has been identified approx. 13 kb upstream. The pathways for a humoral response are being mapped at high resolution...
  67. ncbi A novel method for rapid genotypic identification of alpha 1-antitrypsin variants
    Ilaria Ferrarotti
    Laboratorio di Biochimica e Genetica, Clinica di Malattie dell Apparato Respiratorio, IRCCS Policlinico S Matteo, Pavia, Italy
    Diagn Mol Pathol 13:160-3. 2004
    ..We found a complete agreement among our results, IEF, and genotypes obtained by standard methods. We concluded that this novel method combines efficiency, ease, swiftness, and low cost...
  68. ncbi Functional diversification during evolution of the murine alpha(1)-proteinase inhibitor family: role of the hypervariable reactive center loop
    Karen W Barbour
    Department of Biological Sciences, University of South Carolina, Columbia, SC 29208, USA
    Mol Biol Evol 19:718-27. 2002
    ..The possible physiological benefits of alpha(1)-PI diversity are discussed...
  69. ncbi HIV-1 proprotein processing as a target for gene therapy
    P Cordelier
    Department of Pathology, Jefferson Medical College, Philadelphia, PA 19107, USA
    Gene Ther 10:467-77. 2003
    ....
  70. pmc Alpha1-antitrypsin deficiency. 2: genetic aspects of alpha(1)-antitrypsin deficiency: phenotypes and genetic modifiers of emphysema risk
    D L DeMeo
    Channing Laboratory and Division of Pulmonary and Critical Care Medicine, Department of Medicine, Brigham and Women s Hospital, Boston, MA 02446, USA
    Thorax 59:259-64. 2004
    ..The role of modifying genetic factors which may interact with environmental factors (such as cigarette smoking) is discussed, and directions for future research are presented...
  71. ncbi 6-mer peptide selectively anneals to a pathogenic serpin conformation and blocks polymerization. Implications for the prevention of Z alpha(1)-antitrypsin-related cirrhosis
    Ravi Mahadeva
    Respiratory Medicine Unit, Department of Medicine, University of Cambridge, Cambridge CB2 2XY, United Kingdom
    J Biol Chem 277:6771-4. 2002
    ..Furthermore they demonstrate how a conformational disease process can be selectively inhibited with a small peptide...
  72. ncbi Indomethacin increases liver damage in a murine model of liver injury from alpha-1-antitrypsin deficiency
    David A Rudnick
    Department of Pediatrics, Washington University School of Medicine, St Louis Children s Hospital, St Louis, MO 63110, USA
    Hepatology 44:976-82. 2006
    ....
  73. ncbi Asthma features in severe alpha1-antitrypsin deficiency: experience of the National Heart, Lung, and Blood Institute Registry
    Edward Eden
    James P Mara Center for Lung Disease, St Luke s Roosevelt Hospital Center, New York, NY 10019, USA
    Chest 123:765-71. 2003
    ..To describe asthma features in a cohort with alpha(1)-antitrypsin (AAT) deficiency, and determine the impact of asthma on FEV(1) decline...
  74. ncbi Alpha1-antitrypsin deficiency--a model for conformational diseases
    Robin W Carrell
    Department of Hematology, University of Cambridge, Cambridge Institute for Medical Research, Cambridge, United Kingdom
    N Engl J Med 346:45-53. 2002
  75. ncbi Linkage analysis of alpha 1-antitrypsin deficiency: lessons for complex diseases
    E K Silverman
    Channing Laboratory, Brigham and Women s Hospital, Boston, Mass 02114, USA
    Hum Hered 52:223-32. 2001
    ..We have used the protease inhibitor (PI) type as a genetic marker rather than a disease gene, and we have performed linkage analysis between PI type and serum A1AT level and spirometry-related phenotypes...
  76. ncbi Effects of noninhibitory alpha-1-antitrypsin on primary human monocyte activation in vitro
    F Moraga
    Department of Medicine, University Hospital Malmo, Sweden
    Arch Biochem Biophys 386:221-6. 2001
    ....
  77. pmc Heteropolymerization of S, I, and Z alpha1-antitrypsin and liver cirrhosis
    R Mahadeva
    Respiratory Medicine Unit, Department of Medicine and Department of Haematology, University of Cambridge, Cambridge Institute for Medical Research, Wellcome Trust MRC Building, Hills Road, Cambridge CB2 2XY, United Kingdom
    J Clin Invest 103:999-1006. 1999
    ..Taken together, these results indicate that not only may mixed variants form heteropolymers, but that this can causally lead to the development of cirrhosis...
  78. ncbi Validation of a rapid, simple method to measure alpha1-antitrypsin in human dried blood spots
    Marina Gorrini
    Clin Chem 52:899-901. 2006
  79. pmc Prolastin, a pharmaceutical preparation of purified human alpha1-antitrypsin, blocks endotoxin-mediated cytokine release
    Izabela Nita
    Department of Medicine, Lund University, University Hospital Malmo, 20502 Malmo, Sweden
    Respir Res 6:12. 2005
    ..There is increasing evidence that AAT is able to exert effects other than protease inhibition. We investigated whether Prolastin, a preparation of purified pooled human AAT used for augmentation therapy, exhibits anti-bacterial effects...
  80. ncbi Potential role of inhibitors of neutrophil elastase in treating diseases of the airway
    Bilal Chughtai
    Division of Pulmonary Critical Care Medicine, Stony Brook University, Stony Brook, New York 11984 8172, USA
    J Aerosol Med 17:289-98. 2004
    ....
  81. pmc Screening for Alpha 1 antitrypsin deficiency in Tunisian subjects with obstructive lung disease: a feasibility report
    Sabri Denden
    Biochemistry and Molecular Biology Laboratory, Faculty of Pharmacy, AV Avicienne 1, 5019 Monastir, Tunisia
    Orphanet J Rare Dis 4:12. 2009
    ..We therefore planned a screening study for detection of AATD in patients with OLD in a cohort of patients from Kairouan in central Tunisia...
  82. ncbi Proteolytic inactivation of alpha 1-proteinase inhibitor in infected bronchial secretions from patients with cystic fibrosis
    S Suter
    Dept of Pediatrics, University of Geneva, Switzerland
    Eur Respir J 4:40-9. 1991
    ....
  83. ncbi The alpha 1-antitrypsin gene and its deficiency states
    R G Crystal
    Trends Genet 5:411-7. 1989
    ....
  84. ncbi Assessment of regional progression of pulmonary emphysema with CT densitometry
    M Els Bakker
    Division of Image Processing, Department of Radiology, Leiden University Medical Center, Albinusdreef 2, 2333 ZA Leiden, The Netherlands
    Chest 134:931-7. 2008
    ..To test this hypothesis, a method was developed to assess emphysema severity at different levels in the lungs in order to estimate regional changes...
  85. ncbi Cryptic haplotypes of SERPINA1 confer susceptibility to chronic obstructive pulmonary disease
    Sally Chappell
    Division of Clinical Chemistry, Molecular Medical Sciences, Institute of Genetics, University Hospital, Queens Medical Centre, University of Nottingham, Nottingham, United Kingdom
    Hum Mutat 27:103-9. 2006
    ..In contrast, no haplotype associations for SERPINA3 were identified...
  86. ncbi Deletion 14q(q24.3 to q32.1) syndrome: significance of peculiar facial appearance in its diagnosis, and deletion mapping of Pi(alpha 1-antitrypsin)
    Y Yamamoto
    Hum Genet 74:190-2. 1986
    ..3 to q32.1) syndrome. The level of alpha 1-antitrypsin in the patient was only about half of that of his parents and controls, and the Pi locus was tentatively assigned to band 14q32.1...
  87. ncbi Prevalence of common HFE and SERPINA1 mutations in patients with hepatocellular carcinoma in a Moroccan population
    Sayeh Ezzikouri
    Laboratoire de Virologie, Institut Pasteur du Maroc, Casablanca, Morocco
    Arch Med Res 39:236-41. 2008
    ..Our objective was to estimate the prevalence of HFE and SERPINA1 (formerly known as alpha1-antitrypsin, AAT) mutations and assess their influence on hepatocellular carcinoma development...
  88. ncbi Influence of alpha-1 antitrypsin heterozygosity on treatment efficacy of HCV combination therapy
    Karin F Kok
    Department of Gastroenterology and Hepatology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands
    Eur J Gastroenterol Hepatol 22:808-12. 2010
    ..There is limited evidence to suggest that there is an increased prevalence of heterozygous A1AT carriers in HCV, but it is unclear how this affects treatment success...
  89. ncbi Alpha 1 antitrypsin polymorphism in the Tunisian population with special reference to pulmonary disease
    S Denden
    Biochemistry and Molecular Biology Laboratory, Faculty of Pharmacy, Rue Avicenne, Monastir, Tunisia
    Pathol Biol (Paris) 56:106-10. 2008
    The study investigated alpha 1 antitrypsin (AAT) gene polymorphism in the Tunisian population. We aimed to analyze the correlation between Pi polymorphism and the risk of developing chronic obstructive pulmonary disease (COPD).
  90. ncbi Homozygous deficiency of heparin cofactor II: relevance of P17 glutamate residue in serpins, relationship with conformational diseases, and role in thrombosis
    Javier Corral
    University of Murcia, Centro Regional de Hemodonación de Murcia, Murcia, Spain
    Circulation 110:1303-7. 2004
    ..Recent data obtained in mice lacking HCII suggest that this serpin might inhibit thrombosis in the arterial circulation. However, the clinical relevance and molecular mechanisms associated with deficiency of HCII in humans are unclear...
  91. ncbi The conformational dynamics of a metastable serpin studied by hydrogen exchange and mass spectrometry
    Yuko Tsutsui
    Department of Physiology and Biophysics, Case Western Reserve University, Cleveland, Ohio 44106, USA
    Biochemistry 45:6561-9. 2006
    ..A surprising degree of flexibility is seen in beta-strand 6A, and it is speculated that this flexibility may deter the formation of edge-edge polymers...
  92. ncbi Alpha-1-antitrypsin stimulates fibroblast proliferation and procollagen production and activates classical MAP kinase signalling pathways
    K Dabbagh
    Centre for Cardiopulmonary Biochemistry and Respiratory Medicine, Royal Free and University College Medical School, UCL, The Rayne Institute, London, United Kingdom
    J Cell Physiol 186:73-81. 2001
    ....
  93. ncbi Augmentation therapy reduces frequency of lung infections in antitrypsin deficiency: a new hypothesis with supporting data
    J Lieberman
    Department of Medicine, UCLA School of Medicine, Los Angeles, CA, USA
    Chest 118:1480-5. 2000
    ..To propose an hypothesis that antiprotease augmentation therapy reduces the incidence of lung infections in alpha(1)-antitrypsin (AAT)-deficient patients, and to present supporting data...
  94. ncbi Human EDEM2, a novel homolog of family 47 glycosidases, is involved in ER-associated degradation of glycoproteins
    Steven W Mast
    Department of Biochemistry and Molecular Biology and Complex Carbohydrate Research Center, University of Georgia, 315 Riverbend Road, Athens, GA 30602 4712, USA
    Glycobiology 15:421-36. 2005
    ..Overexpression of EDEM2 accelerates the degradation of misfolded alpha1-antitrypsin, indicating that the protein is involved in ERAD...
  95. pmc Topography of a 2.0 A structure of alpha1-antitrypsin reveals targets for rational drug design to prevent conformational disease
    P R Elliott
    Department of Medicine, University of Cambridge, The Wellcome Trust Centre for Molecular Mechanisms in Disease, Cambridge Institute for Medical Research, United Kingdom
    Protein Sci 9:1274-81. 2000
    ..This structure allows us to define five cavities that are potential targets for rational drug design to develop agents that will prevent conformational transitions and ameliorate the associated disease...
  96. ncbi A polymorphism of the alpha1-antitrypsin gene represents a risk factor for liver disease
    Sally Chappell
    Institute of Genetics, University of Nottingham, Nottingham, United Kingdom
    Hepatology 47:127-32. 2008
    ..The SNP therefore appears to confer susceptibility to liver disease, although reporter gene assays failed to show any functional differences between alleles...
  97. ncbi Oxidation of either methionine 351 or methionine 358 in alpha 1-antitrypsin causes loss of anti-neutrophil elastase activity
    C Taggart
    Pulmonary Division, Royal College of Surgeons in Ireland, Beaumont Hospital, Dublin 9, Ireland
    J Biol Chem 275:27258-65. 2000
    ..We suggest that inactivation of alpha(1)-antitrypsin by oxidation of either methionine 351 or 358 provides a mechanism for regulation of its activity at sites of inflammation...
  98. pmc A protein-based therapeutic for human cytomegalovirus infection
    F Jean
    Vollum Institute, and Department of Molecular Microbiology and Immunology, Oregon Health Sciences University, 3181 Southwest Sam Jackson Park Road, Portland, OR 97201, USA
    Proc Natl Acad Sci U S A 97:2864-9. 2000
    ....
  99. ncbi Alpha-1-antitrypsin expression in the lung is increased by airway delivery of gene-transfected macrophages
    D Zhang
    College of Medicine, University of Cincinnati, Cincinnati, OH 45267, USA
    Gene Ther 10:2148-52. 2003
    ..5+/-0.9, 2.6+/-1.1 and 2.2+/-0.8 mg/l, respectively. These results suggest that airway delivery of macrophages overexpressing hA1AT may be an effective approach to enhance alveolar protection in A1AT deficiency...
  100. ncbi Active site distortion is sufficient for proteinase inhibition by serpins: structure of the covalent complex of alpha1-proteinase inhibitor with porcine pancreatic elastase
    Alexey Dementiev
    Department of Biochemistry and Molecular Genetics, University of Illinois at Chicago, Chicago, Illinois 60607, USA
    J Biol Chem 281:3452-7. 2006
    ..The present structure shows that active site distortion alone is sufficient for inhibition and suggests that enhanced proteolysis is not necessarily exploited in vivo...
  101. ncbi [Alpha 1-proteinase inhibitor deficiency and isolated liver cirrhosis without pulmonary emphysema in a 53-year-old female patient]
    S Stintzing
    Medizinische Klinik 1, Friedrich Alexander Universitat Erlangen Nurnberg, 91054 Erlangen
    Dtsch Med Wochenschr 130:2823-5. 2005
    ..She reported neither alcohol nor drug abuse and had no previous serious illness. She had smoked about 10 pack years of cigarettes in the past...

Research Grants65

  1. Mice Humanized with Hepatocytes and iPS Cells from Patients with Metabolic Diseas
    Stephen C Strom; Fiscal Year: 2010
    ..We propose these humanized mice will be a technology platform to better understand the human disease and it will aid in the development of gene or cellular therapy to correct these devastating diseases. ..
  2. Biliary Atresia, Cholestatic Liver Diseases, and Cystic Fibrosis: Indiana Univers
    Jean Pappas Molleston; Fiscal Year: 2013
    ..Because these diseases are rare, multicenter collaborations like the CHILDREN network are crucial for studying these children and improving medical management and outcnmes. ..
  3. The Pittsburgh Cholestatic Liver Disease Consortium
    Benjamin L Shneider; Fiscal Year: 2013
    ..The Pittsburgh Cholestatic Liver Disease Consortium at Children's Hospital of Pittsburgh is ideally suited to participate in these prospective investigations. ..
  4. Novel Protective Antiapoptotic Action of Alpha 1-Antitrypsin In Emphysema
    Rubin M Tuder; Fiscal Year: 2011
    ..and activity of alpha-1 antritrypsin and may provide an opportunity improve our therapeutic approaches in alpha 1 antitrypsin deficiency- and smoking-induced emphysema...
  5. Phase 2 Study of rAAV1-CB-hAAT for Treatment of Alpha-1 Antitrypsin Deficiency
    Jeffrey D Chulay; Fiscal Year: 2013
    ..Results from this Phase 2 trial will be used to develop a Phase 3 study designed to satisfy the requirements for licensure of a gene therapy treatment for this orphan disease. ..
  6. GRADS Cooperative Research Project: JHU Clinical Center
    David R Moller; Fiscal Year: 2013
    ..These studies may establish links between specific clinical phenotypes, microbial etiologies, and common pathogenic mechanisms to provide a framework for new therapeutic approaches to sarcoidosis. ..
  7. Establichment of CHLA's ChilDREN Clinical Center
    KASPER SAONUN WANG; Fiscal Year: 2013
    ..ChiLDREN will facilitate the accrual of larger cohorts of patients with these rare diseases to advance knowledge and treatment of these devastating diseases. ..
  8. Center for the Study of Pediatric Cholestasis
    Ronen Arnon; Fiscal Year: 2013
    ..The ChiLDREN program will produce new knowledge on the clinical features and causes of these diseases, and develop therapies to improve and prolong the life of these patients. ..
  9. ABCA3 and the Response to Lung Injury
    Rashmin C Savani; Fiscal Year: 2012
    ..Further, the findings emanating from these studies will be relevant to other severe conditions of the lung (e.g. cystic fibrosis) and liver (e.g. alpha-1-antitrypsin deficiency) that have similar mechanisms of disease. ..
  10. Rare Liver Disease Network
    Ronald J Sokol; Fiscal Year: 2010
    ..The RLDN will be a full partner in the Rare Diseases Clinical Research Network and will participate collaboratively with the other Clinical Research Centers and the Data and Technology Coordinating Center. ..
  11. HTS Approach to Correction of Alpha-1-Antitrypsin Misfolding Disease
    William Balch; Fiscal Year: 2009
    ..We propose to use our HTS technologies to screen large chemical libraries provided by the MLCPN to identify biologically active compounds that will prevent the disease phenotype. ..
  12. InCell 6000 High Content Instrument for Cellular Systems Biology Program
    D LANSING LANSING TAYLOR; Fiscal Year: 2013
    ....
  13. The Pathobiology of Airway Disease in Alpha-1 Antitrypsin Deficiency
    Michael A Campos; Fiscal Year: 2010
    ..abstract_text> ..
  14. Hepatocellular Carcinoma in Antitrypsin Deficiency
    David H Perlmutter; Fiscal Year: 2012
    ..This knowledge will allow us to formulate novel strategies for treatment and prevention of liver cancer. ..
  15. Optimizing vascular protective effects of antitrypsin in COPD
    Irina Petrache; Fiscal Year: 2013
    ..b>Alpha 1 antitrypsin (A1AT) is an abundant protein released by the liver, with outreaching systemic actions...
  16. The Molecular Basis of Serpin Function and Disfunction
    Patrick L Wintrode; Fiscal Year: 2011
    ..Polymerization of alpha-1 antitrypsin is the underlying cause of these symptoms. Determining the structure of the polymerization prone intermediate is an important step in developing therapeutic agents. ..
  17. Emphysema attenuation via modulation of macrophage NFKB and antiprotease activity
    Andrew A Wilson; Fiscal Year: 2013
    ..They then proceed to test whether or not life-long overexpression of AAT in resident AMs ameliorates emphysema via anti-inflammatory effects characterized by suppression of macrophages NF-:B activation in normal or AAT deficient mice. ..
  18. Regulation of Targeted Gene Correction
    Eric B Kmiec; Fiscal Year: 2012
    ..MPSVII. Hemophilia A and B and many lysosomal storage disorders among others. Our work will uncover restrictions or limitations for gene repair in hepatocvtes with the goal of treating hepatic cancer and genetic diseases of the liver. ..
  19. AAV Gene Therapy for AAT deficiency
    Richard J Samulski; Fiscal Year: 2013
    ..The long-term goal of the proposal is to design safer and more effective AAV vectors for gene therapy in patients with AAT deficiency. ..
  20. Stem Cells and Cell Therapies in Lung Biology and Diseases
    Daniel J Weiss; Fiscal Year: 2011
    ..in Lung Biology and Disease", sponsored by the NHLBI through an R13 conference grant as well as by the Alpha 1 Antitrypsin Foundation and Pulmonary Fibrosis Foundation;and July 2009 "Stem Cells and Cell Therapies in Lung Biology ..
  21. Stem Cells and Cell Therapies in Lung Biology and Diseases
    Daniel J Weiss; Fiscal Year: 2013
    ..and Disease", sponsored through the years by the NHLBI through an R13 conference grant as well as by the Alpha 1 Antitrypsin Foundation, Emory Center for Respiratory Health, LAM Treatment Alliance, Pulmonary Fibrosis Foundation, and ..
  22. Fine Mapping of COPD Susceptibility Genes
    Edwin K Silverman; Fiscal Year: 2012
    ..Genetic association studies of common variants will be undertaken in multiple populations, and functional studies of identified variants will be performed. ..
  23. Investigation of microbial hetergeneity to sarcoidosis and AAT clinical outcome
    Wonder P Drake; Fiscal Year: 2013
    ..This proposal will also enhance understanding of microbial induction of T cell anergy, for which there is a lack of appreciation in idiopathic lung diseases. ..
  24. Sarcoidosis and A1AT Genomics &Informatics Center
    Stephen R Wisniewski; Fiscal Year: 2013
    ....
  25. Characterization of human hematopoietic and endodermal progenitors derived from i
    Gustavo Mostoslavsky; Fiscal Year: 2010
    ....
  26. Dual-function vectors for in vivo gene therapy of AAT Liver disease
    Christian Mueller; Fiscal Year: 2013
    ..Finally both of these models will be utilized to assess the effect of rAAV-based RNAi mediated knockdown of the Z-AAT mRNA. ..
  27. RISK SCORE FOR CORONARY ANEURYSMS IN KAWASAKI SYNDROME
    Jane Newburger; Fiscal Year: 1992
    ....
  28. GASTROINTESTINAL PROTEINS--CELL AND MOLECULAR REGULATION
    Jeffrey Gordon; Fiscal Year: 2000
    ....
  29. Rare Liver Disease Network
    Ronald Sokol; Fiscal Year: 2005
    ..The RLDN will be a full partner in the Rare Diseases Clinical Research Network and will participate collaboratively with the other Clinical Research Centers and the Data and Technology Coordinating Center. ..
  30. Anti-inflammatory Serpin(AAT and Elafin) Gene Transfers*
    Sihong Song; Fiscal Year: 2003
    ..b>Alpha 1 antitrypsin (AAT) and elafin are serine proteinase inhibitors (serpin), and have anti-inflammatory properties...
  31. NEWBORN SCREENING BY MULTIPLEX MOLECULAR ANALYSIS
    Edwin Naylor; Fiscal Year: 2002
    ..The assay expands the number of disorders detected by newborn screening thus providing an improved public health service. PROPOSED COMMERCIAL APPLICATION: Not Available ..
  32. ALPHA-1-PROTEASE INHIBITOR DEFICIENCY--GENE THERAPY
    Jerry Brown; Fiscal Year: 1991
    ..This virus will then be used to infect nice undergoing liver regeneration in an effort to demonstrate stable hepatic integration and expression of A1Pi cDNA...
  33. Intrapulmonary Gene Transfer Using Compacted DNA
    Mark Cooper; Fiscal Year: 2001
    ..Delivered as an aerosol via a hand-held inhaler, PLASmin complexes may provide an effective and simple therapy for genetic deficiency states, including hemophilia and alpha(1)-antitrypsin deficiency. ..
  34. Genetic Modifiers of Alpha 1-Antitrypsin Deficiency
    Edwin Silverman; Fiscal Year: 2005
    ....
  35. STRUCTURAL DETERMINANTS OF HCG FOLDING AND ASSEMBLY
    Elliott Bedows; Fiscal Year: 1999
    ..Thus, what we learn about protein folding in our system may be applicable to our understanding of a number of disease processes. ..
  36. ALPHA-1-PROTEINASE INHIBITOR DEFICIENCY AND EMPHYSEMA
    Savio Woo; Fiscal Year: 1990
    ....
  37. THERAPY FOR ALPHA-1 ANTITRYPSIN DEFECIENCY
    GORDON SNIDER; Fiscal Year: 1999
    ..abstract_text> ..
  38. NGVL TOXICOLOGY LABORATORY
    Barry Byrne; Fiscal Year: 2006
    ..These services will be offered in an open flexible, collaborative, and interactive manner, and in compliance with the Terms of Cooperation of the NGVL. ..
  39. Environmental factors in alpha 1-antitrypsin deficiency
    Lee Newman; Fiscal Year: 2002
    ..Such research offers an opportunity to investigate environmental and genetic interactions in which the gene trait that confers susceptibility is known but in which the environmental triggers are not. ..
  40. Pulmonary Alveolar Proteinosis Research Conference
    Bruce Trapnell; Fiscal Year: 2005
    ..This conference will provide a forum where thought leaders focused on the molecular and cellular basis or clinical management of PAP will present cutting edge research, integrate concepts, and chart innovative research directions. ..
  41. RIBOZYMES AND RNA GENE THERAPIES FOR LIVER DISEASES
    Andrea Branch; Fiscal Year: 2003
    ..Northern analysis of RNAs extracted from serum samples of patients will establish the size distribution of HCV RNAs containing the terminal sequence. These studies will lead to new treatments for liver diseases. ..
  42. LIVER SPECIFIC NONVIRAL VECTORS
    Leaf Huang; Fiscal Year: 2000
    ..These studies will hopefully lead to the development of a safe and effective gene therapy vector for treating human diseases such as alpha-1-antitrypsin deficiency, factor IX deficiency and other liver- related metabolic disorders. ..
  43. Alpha-1 Antitrypsin Gene Therapy for Cystic Fibrosis
    Kenneth Brigham; Fiscal Year: 2001
    ..proposed commercial application: not available ..
  44. AAT Deficiency & Liver Diseases Caused by Proteins
    Bruce Trapnell; Fiscal Year: 2006
    ..unreadable] [unreadable]..
  45. NEWBORN SCREENING BY MULTIPLEX MOLECULAR ANALYSIS
    Edwin Naylor; Fiscal Year: 1999
    ..The screening services proposed are marketable for newborn screening and high-risk screening. ..
  46. Generation of interfering RNA molecules by trans-splicing
    COLETTE COTE; Fiscal Year: 2006
    ..Thus the regulation provided by SMaRT RNAi establishes the groundwork for a new generation of conditional knockdown model systems and potential therapeutic modalities with global applications in human disease. [unreadable] [unreadable]..
  47. MAJOR GENES FOR CARDIOVASCULAR DISEASE RISK FACTORS
    Robert Elston; Fiscal Year: 1992
    ..The sample has a size that should be approximately adequate to replicate the major earlier findings, if they are in fact replicable...
  48. Development of Alpha-1 Antitrypsin Gene Therapeutic as Treatment for COPD
    Jonathan Sanders; Fiscal Year: 2005
    ..abstract_text> ..
  49. STRUCTURAL STUDIES OF MYELOPEROXIDASE
    ROGER FENNA; Fiscal Year: 1999
    ..It is hoped that comparison of the conformations of the heme environments of these two enzymes will lead to an understanding of their structural and functional differences. ..
  50. Treatment Decisions in Advanced Genetic Lung Disease
    SUSAN MCINNES; Fiscal Year: 2003
    ..abstract_text> ..
  51. GENETIC CONSTITUTIONS AND CANCER PREDISPOSITION
    HOPE PUNNETT; Fiscal Year: 1980
    ..In addition to defining the frequency of hepatocarcinomia in this population we will look for other factors which may influence the development of malignancy in Pi deficient individuals. ..
  52. Alpha-1 Antitrypsin for Hereditary Deficiency
    Carol Ziomek; Fiscal Year: 2005
    ..Further, it will offer a safe, abundant source of AAT that will be available to explore other modes of delivery of the drug, such as aerosolization, and to engage in clinical studies in cystic fibrosis, asthma, and ARDS. ..
  53. Genetic and Environmental Factors Affecting COPD Exacerbations
    Steven Shapiro; Fiscal Year: 2009
    ....
  54. EVALUATION OF ALPHA-1-ANTITRYPSIN REPLACEMENT
    FRED KUEPPERS; Fiscal Year: 1991
    ..3. Demonstrate the therapeutic efficacy of human A-1-AT. If these experiments support our hypothesis, other elastase and protease inhibitors, some existing now, and others to be developed, may be tested in our mouse system...
  55. Small molecules to treat alpha-1 antitrypsin deficiency
    Chen Liu; Fiscal Year: 2006
    ..Moreover, success in this study will validate this methodology for prospective identification of molecular therapies for deranged protein: protein interactions. ..
  56. Bone Marrow Progenitor Cells in Lung Injury and Repair
    Erica Herzog; Fiscal Year: 2009
    ....
  57. Fine Mapping of a COPD Locus on Chromosome 19q
    CRAIG HERSH; Fiscal Year: 2009
    ..abstract_text> ..
  58. Replication of the Human Secretory Pathway in Yeast
    Stefan Wildt; Fiscal Year: 2005
    ..abstract_text> ..
  59. ALPHA-1-ANTITRYPSIN DEFICIENCY
    C Caskey; Fiscal Year: 1980
    ..Both are under development. A second focus of the application is development of methods which will predict the fetal genetic status with respect to Pi type...
  60. A GENE BASED THERAPEUTIC FOR ACUTE LUNG INJURY
    Kenneth Brigham; Fiscal Year: 1999
    ..proposed commercial application: not available ..
  61. RAPID ASSAY FOR HUMAN 1-PROTEINASE INHIBITOR DEFICIENCY
    CYNTHIA LLOYD; Fiscal Year: 1990
    ..The ultimate goal is to develop an assay that will be inexpensive and convenient to use in a variety of laboratory settings (newborn screening, reference, hospital laboratories and/or physicians's office) and for alternate site testing...
  62. GENE THERAPY USING VIRAL VECTOR FOR LU AND CARDIOVA
    Nicholas Muzyczka; Fiscal Year: 2001
    ..Finally, an Administrative Core (Core A) will insure centralized fiscal management and oversight for the subprojects and pilot/feasibility projects. ..
  63. MECHANISMS OF LIVER INJURY IN A-1-ANTITRYPSIN DEFIENCY
    Jeffrey Teckman; Fiscal Year: 1999
    ..abstract_text> ..
  64. Iminosugars for treatment of antitrypsin deficiency
    David Perlmutter; Fiscal Year: 2001
    ..proposed commercial application: not available ..
  65. Function of a-1-Antitrypsin Receptor in Lung Disease
    William Balch; Fiscal Year: 2006
    ..unreadable] [unreadable]..