alpha 1 antitrypsin deficiency

Summary

Summary: Deficiency of the protease inhibitor ALPHA 1-ANTITRYPSIN, leading primarily to degradation of elastin of the alveolar walls, as well as other structural proteins of a variety of tissues. (From Scriver, Beaudet, Sly, & Valle, The Metabolic and Molecular Bases of Inherited Disease, 7th ed, p4125)

Top Publications

  1. 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
  2. ncbi Worldwide racial and ethnic distribution of alpha1-antitrypsin deficiency: summary of an analysis of published genetic epidemiologic surveys
    Frederick J de Serres
    Laboratory of Toxicology, Environmental Toxicology Program, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27514 6716, USA
    Chest 122:1818-29. 2002
  3. 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
  4. ncbi Alpha-1 antitrypsin Null mutations and severity of emphysema
    Laura Fregonese
    Department of Pulmonology, Leiden University Medical Centre, Leiden, The Netherlands
    Respir Med 102:876-84. 2008
  5. 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
  6. ncbi Pattern of emphysema distribution in alpha1-antitrypsin deficiency influences lung function impairment
    David G Parr
    Lung Investigation Unit, First Floor, Nuffield House, Queen Elizabeth Hospital, Birmingham, UK B15 2TH
    Am J Respir Crit Care Med 170:1172-8. 2004
  7. 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
  8. 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
  9. ncbi Rapid screening for alpha1-antitrypsin deficiency in patients with chronic obstructive pulmonary disease using dried blood specimens
    Francisco Rodriguez
    Department of Biochemistry, Hospital Universitario Vall d Hebron, Barcelona, Spain
    Am J Respir Crit Care Med 166:814-7. 2002
  10. ncbi Alpha1-antitrypsin deficiency in 26-year-old subjects: lung, liver, and protease/protease inhibitor studies
    Eeva Piitulainen
    Department of Respiratory Medicine, Lund University, University Hospital, SE 20502 Malmo, Sweden
    Chest 128:2076-81. 2005

Detail Information

Publications245 found, 100 shown here

  1. 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...
  2. ncbi Worldwide racial and ethnic distribution of alpha1-antitrypsin deficiency: summary of an analysis of published genetic epidemiologic surveys
    Frederick J de Serres
    Laboratory of Toxicology, Environmental Toxicology Program, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27514 6716, USA
    Chest 122:1818-29. 2002
    ..There is a limited database of individuals affected by this disease worldwide. It has been estimated, for example, that there are 70,000 to 100,00 individuals affected in the United States, with comparable numbers in Europe...
  3. 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...
  4. ncbi Alpha-1 antitrypsin Null mutations and severity of emphysema
    Laura Fregonese
    Department of Pulmonology, Leiden University Medical Centre, Leiden, The Netherlands
    Respir Med 102:876-84. 2008
    ..Mutations causing total absence of serum AAT (Null mutations) were suggested to be associated with very early onset emphysema but their clinical phenotype is poorly known...
  5. 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
  6. ncbi Pattern of emphysema distribution in alpha1-antitrypsin deficiency influences lung function impairment
    David G Parr
    Lung Investigation Unit, First Floor, Nuffield House, Queen Elizabeth Hospital, Birmingham, UK B15 2TH
    Am J Respir Crit Care Med 170:1172-8. 2004
    ..409, p < 0.001). The use of single physiologic parameters as a surrogate measure of emphysema severity may introduce systematic bias in the staging of subjects with emphysema...
  7. 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...
  8. 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...
  9. ncbi Rapid screening for alpha1-antitrypsin deficiency in patients with chronic obstructive pulmonary disease using dried blood specimens
    Francisco Rodriguez
    Department of Biochemistry, Hospital Universitario Vall d Hebron, Barcelona, Spain
    Am J Respir Crit Care Med 166:814-7. 2002
    ..This single-step, cost-effective technology is optimal for working with small amounts of DNA, as are present in DBS. The method is suitable for large-scale screening, in cases where PI type is important...
  10. ncbi Alpha1-antitrypsin deficiency in 26-year-old subjects: lung, liver, and protease/protease inhibitor studies
    Eeva Piitulainen
    Department of Respiratory Medicine, Lund University, University Hospital, SE 20502 Malmo, Sweden
    Chest 128:2076-81. 2005
    ..Clinical and biochemical signs of lung and liver disease have been followed prospectively in a birth cohort of individuals with alpha1-antitrypsin (AAT) deficiency...
  11. pmc Validation of computed tomographic lung densitometry for monitoring emphysema in alpha1-antitrypsin deficiency
    D G Parr
    Lung Investigation Unit, First Floor, Nuffield House, Queen Elizabeth Hospital, Birmingham B15 2TH, UK, and Department of Radiology, Leiden University Medical Centre, The Netherlands
    Thorax 61:485-90. 2006
    ..We related progression of densitometry (15th percentile point and voxel index, threshold -950 Hounsfield units) to disease stage and FEV1 decline in two studies of subjects with alpha1-antitrypsin deficiency (PiZ)...
  12. ncbi Radiologic and clinical features of COPD patients with discordant pulmonary physiology: lessons from alpha1-antitrypsin deficiency
    Jayne Holme
    University Hospital Birmingham, Birmingham, UK
    Chest 132:909-15. 2007
    ..We investigated differences in emphysema distribution and health status in alpha(1)-antitrypsin deficient subjects (PiZ) with discordant lung function...
  13. ncbi Desmosine as a biomarker of elastin degradation in COPD: current status and future directions
    M Luisetti
    Laboratory of Biochemistry and Genetics, Institute of Respiratory Disease, IRCCS San Matteo Hospital Foundation, Pavia, Italy
    Eur Respir J 32:1146-57. 2008
    ....
  14. pmc Detection of emphysema progression in alpha 1-antitrypsin deficiency using CT densitometry; methodological advances
    David G Parr
    Department of Respiratory Medicine, University Hospitals of Coventry and Warwickshire, Clifford Bridge Road, Coventry, CV2 2DX, UK
    Respir Res 9:21. 2008
    ..However, emphysema is frequently localised to sub-regions of the lung and targeted densitometric sampling may be more informative than whole lung assessment...
  15. ncbi [Guidelines for the diagnosis and management of alpha-1 antitrypsin deficiency]
    Rafael Vidal
    Servicio de Neumologia, Hospital Universitari Vall d Hebron, Barcelona, Espana
    Arch Bronconeumol 42:645-59. 2006
  16. ncbi Emphysema due to alpha-antitrypsin deficiency: familial study of the YBARCELONA variant
    Marc Miravitlles
    Department of Pneumology, Clinical Institute of Pneumology and Thoracic Surgery, Hospital Clinic IDIBAPS, Barcelona, Spain
    Chest 124:404-6. 2003
    ..The risk associated with this variant in its heterozygous form may be similar to that described for PiMZ...
  17. pmc Alpha 1 antitrypsin deficiency alleles are associated with joint dislocation and scoliosis in Williams syndrome
    Colleen A Morris
    Department of Pediatrics, University of Nevada School of Medicine, NV, USA
    Am J Med Genet C Semin Med Genet 154:299-306. 2010
    ..These findings suggest that genes important in elastin metabolism are candidates for variability in the connective tissue abnormalities in WS...
  18. pmc High dose intravenous AAT and plasma neutrophil derived fibrinogen fragments
    J Stolk
    Thorax 60:84; author reply 84. 2005
  19. 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...
  20. ncbi Lung volume reduction surgery in patients with emphysema and alpha-1 antitrypsin deficiency
    James K Stoller
    Division of Medicine, Section of Respiratory Therapy, The Cleveland Clinic Foundation, Cleveland, Ohio 44195, USA
    Ann Thorac Surg 83:241-51. 2007
    ..The role of lung volume reduction surgery (LVRS) for individuals with alpha-1 antitrypsin (AAT) deficiency is unclear...
  21. ncbi Ongoing research in Europe: Alpha One International Registry (AIR) objectives and development
    R A Stockley
    Dept of Medicine, University Hospital Birmingham, Edgbaston, Birmingham, B15 2TH, UK
    Eur Respir J 29:582-6. 2007
    ..The success related to the convergence of national registries into a common database creating a unique registry beyond geographic boundaries and encompassing alpha1-antitrypsin deficiency from various ethnic groups...
  22. ncbi [Alpha1-antitrypsin deficiency: situation in Spain and development of a screening program]
    Cristian de la Roza
    Servicio de Neumologia, Institut Clinic del Torax, Institut d Investigacions Biomediques August Pi i Sunyer IDIBAPS, Red Respira RTIC 03 11 ISCIII, Hospital Clinic, Barcelona, Espana
    Arch Bronconeumol 42:290-8. 2006
    ..This strategy is crucial in Spain, where the disease is under diagnosed, mainly due to a low index of suspicion among doctors...
  23. ncbi Change in lung function and morbidity from chronic obstructive pulmonary disease in alpha1-antitrypsin MZ heterozygotes: A longitudinal study of the general population
    Morten Dahl
    Department of Clinical Biochemistry 54M1, Herlev University Hospital, Herlev Ringvej 75, DK 2730 Herlev, Denmark
    Ann Intern Med 136:270-9. 2002
    ..A deteriorating effect of severe alpha(1)-antitrypsin deficiency (ZZ genotype) on lung function is well known, whereas the role of intermediate deficiency (MZ genotype) remains uncertain...
  24. ncbi MEKC of desmosine and isodesmosine in urine of chronic destructive lung disease patients
    S Viglio
    Dipartimento di Biochemical, Istituto di Ricovero e Cura a Carattere Scientifico IRCCS Policlinico San Matteo, Università degli nStudi di Pavia
    Eur Respir J 15:1039-45. 2000
    ..Results obtained in subjects with alphal-antitrypsin deficiency suggest that this method might be used to evaluate the putative efficacy of replacement therapy...
  25. ncbi Rate of progression of lung function impairment in alpha1-antitrypsin deficiency
    P A Dawkins
    Lung Investigation Unit, UniversityHospital Birmingham and University of Birmingham, Birmingham, UK
    Eur Respir J 33:1338-44. 2009
    ..In PiZ alpha(1)-AT-deficient patients, FEV(1) decline was greatest in moderate disease, unlike K(CO) decline, which was greatest in severe disease. The FEV(1) decline showed associations with BDR, BMI, sex and exacerbation rate...
  26. ncbi Genetic risk factors of chronic obstructive pulmonary disease
    Ladina Joos
    Departement Innere Medizin, Kantonsspital Basel, Switzerland
    Swiss Med Wkly 132:27-37. 2002
    ..Family and twin studies suggest that genetic factors also contribute to the development of COPD. We present a detailed literature review of the genes which have been investigated as potential risk factors for this disease...
  27. 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...
  28. ncbi Emphysema lung tissue gene expression profiling
    Heiko A Golpon
    Division of Pulmonary Sciences and Critical Care Medicine, 4200 East Ninth Avenue, C272, Denver, CO 80262, USA
    Am J Respir Cell Mol Biol 31:595-600. 2004
    ....
  29. ncbi Clinical course and prognosis of never-smokers with severe alpha-1-antitrypsin deficiency (PiZZ)
    H A Tanash
    Department of Respiratory Medicine, Malmo University Hospital, Entrance 35, S 205 02, Malmo, Sweden
    Thorax 63:1091-5. 2008
    ....
  30. ncbi Secondary outputs of alpha1-antitrypsin deficiency targeted detection programme
    I Ferrarotti
    Centro di Diagnosi per il Deficit Ereditario di Alfa1 Antitripsina, Laboratorio di Biochimica e Genetica, Clinica di Malattie dell Apparato Respiratorio, Fondazione IRCCS Policlinico San Matteo, Universita di Pavia, Italy
    Respir Med 102:354-8. 2008
    ..Individuals enrolled in AATD detection programmes represent an interesting cohort both for public health and research purposes...
  31. 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
  32. ncbi A randomized clinical trial of alpha(1)-antitrypsin augmentation therapy
    A Dirksen
    Department of Respiratory Medicine, The Rigshospital, Copenhagen, Denmark
    Am J Respir Crit Care Med 160:1468-72. 1999
    ..We conclude that lung density measurements by CT may facilitate future randomized clinical trials of investigational drugs for a disease in which little progress in therapy has been made in the past 30 yr...
  33. ncbi Role of human neutrophil peptides in lung inflammation associated with alpha1-antitrypsin deficiency
    L Terry Spencer
    Division of Pulmonary Diseases, Department of Pediatrics, University of Florida College of Medicine, Gainesville, FL 32610 0296, USA
    Am J Physiol Lung Cell Mol Physiol 286:L514-20. 2004
    ..Importantly, the proinflammatory effects of HNP were blocked by alpha(1)-AT. HNP likely play an important role in amplifying and maintaining neutrophil-mediated inflammation in the lungs...
  34. pmc Chronic obstructive pulmonary disease. 1: Susceptibility factors for COPD the genotype-environment interaction
    A J Sandford
    University of British Columbia McDonald Research Laboratories iCAPTURE Center, St Paul s Hospital, Vancouver, BC, Canada
    Thorax 57:736-41. 2002
    ..Candidate gene association studies in COPD are reviewed. Efforts to identify interactions between genetic factors and environmental determinants such as smoking may lead to improved understanding of the pathogenesis of the disease...
  35. ncbi Longitudinal changes in physiological, radiological, and health status measurements in alpha(1)-antitrypsin deficiency and factors associated with decline
    L J Dowson
    Lung Investigation Unit, Nuffield House, Queen Elizabeth Hospital, Birmingham, United Kingdom
    Am J Respir Crit Care Med 164:1805-9. 2001
    ..002). Progression of emphysema in alpha(1)-ATD is dependent on baseline physiology and exacerbation frequency and may be detected by several different measurements of which HRCT density mask analysis and DL(CO) appear most sensitive...
  36. pmc Predictors of mortality in alpha1-antitrypsin deficiency
    P A Dawkins
    Lung Investigation Unit, Queen Elizabeth Hospital, Birmingham, UK
    Thorax 58:1020-6. 2003
    ..The aim of this study was to investigate the predictive potential of several parameters, including CT scanning, for mortality in patients with severe alpha(1)-antitrypsin deficiency...
  37. ncbi Alpha1-antitrypsin deficiency
    James K Stoller
    Department of Pulmonary, Allergy, and Critical Care Medicine, Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, OH 44195, USA
    Lancet 365:2225-36. 2005
    ..Evidence suggests that this approach is safe, slows the decline of lung function, could reduce infection rates, and might enhance survival. However, uncertainty about the cost-effectiveness of this expensive treatment remains...
  38. 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...
  39. 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...
  40. 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...
  41. ncbi Identification of a novel alpha1-antitrypsin null variant (Q0Cairo)
    Michele Zorzetto
    Clinica Malattie Apparato Respiratorio, IRCCS Policlinico S Matteo, Pavia 27100, Italy
    Diagn Mol Pathol 14:121-4. 2005
    ..The proposed nomenclature of Q0cairo is from the birthplace of the father of first recognized subject. Serum levels and isoelectric focusing of AAT were consistent with the presence of the Null variant...
  42. ncbi PI S and PI Z alpha-1 antitrypsin deficiency worldwide. A review of existing genetic epidemiological data
    F J de Serres
    Center for the Evaluation of Risks to Human Reproduction, Environmental Toxicology Program, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709 2233, USA
    Monaldi Arch Chest Dis 67:184-208. 2007
    ....
  43. pmc Short-term variability of biomarkers of proteinase activity in patients with emphysema associated with type Z alpha-1-antitrypsin deficiency
    Jan Stolk
    Department of Pulmonology, Leiden University Medical Center, Leiden, The Netherlands
    Respir Res 6:47. 2005
    ..Cross-sectional studies have shown increased levels of biomarkers of extracellular matrix degradation in vivo. Longitudinal variability of these biomarkers is unknown but desirable for clinical studies with proteinase inhibitors...
  44. ncbi Heterozygous alpha-I antitrypsin deficiency as a co-factor in the development of chronic liver disease: a review
    K F Kok
    Department of Hepato Gastroenterology, Rijnstate Hospital, Arnhem, The Netherlands
    Neth J Med 65:160-6. 2007
    ..For the future, other interventions such as gene therapy or strategies to inhibit polymerisation are promising...
  45. ncbi Results of a case-detection programme for alpha1-antitrypsin deficiency in COPD patients
    C de la Roza
    Dept of Pneumology, Institut Clinic del Torax, Hospital Clinic, Red Respira, Barcelona 08036, Spain
    Eur Respir J 26:616-22. 2005
    ..Diagnostic yield and costs depend largely on inclusion criteria and the protocol for processing of samples...
  46. ncbi Alpha 1-antitrypsin deficiency associated with panniculitis
    S J Hendrick
    Department of Dermatology, University of Texas Medical Branch, Galveston 77550
    J Am Acad Dermatol 18:684-92. 1988
    ..The identification of the alpha 1-antitrypsin deficiency state as the cause of a distinct type of panniculitis adds additional evidence for the elimination of the term Weber-Christian disease...
  47. ncbi Distribution of alpha-1 -antitrypsin phenotypes in Serbian newborns and children with liver disease
    A Topic
    Acta Paediatr 91:726-7. 2002
  48. ncbi The relationship of chronic sputum expectoration to physiologic, radiologic, and health status characteristics in alpha(1)-antitrypsin deficiency (PiZ)
    Lee J Dowson
    Lung Investigation Unit, Nuffield House, Queen Elizabeth University Hospital, Birmingham B15 2TH, UK
    Chest 122:1247-55. 2002
    ..Second, to use multivariate analysis to determine how these factors influence health status...
  49. ncbi Validation of a rapid, simple method to measure alpha1-antitrypsin in human dried blood spots
    Marina Gorrini
    Clin Chem 52:899-901. 2006
  50. ncbi Respiratory symptoms and lung function in 30-year-old individuals with alpha-1-antitrypsin deficiency
    Elisabeth Bernspång
    Department of Respiratory Medicine, Lund University, University Hospital, Malmo, Entrance 35, SE 205 02 Malmo, Sweden
    Respir Med 101:1971-6. 2007
    ..The aim of this study was to examine the prevalence of smoking, respiratory symptoms and lung function at the age of 30 in AAT-deficient individuals (PiZ and PiSZ) identified by neonatal screening...
  51. 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...
  52. ncbi High-resolution computed tomography scanning in alpha1-antitrypsin deficiency: relationship to lung function and health status
    L J Dowson
    Lung Investigation Unit, Queen Elizabeth Hospital, Birmingham, UK
    Eur Respir J 17:1097-104. 2001
    ....
  53. pmc Sputum chemotactic activity in chronic obstructive pulmonary disease: effect of alpha(1)-antitrypsin deficiency and the role of leukotriene B(4) and interleukin 8
    I S Woolhouse
    Department of Medicine, Queen Elizabeth Hospital, Birmingham, UK
    Thorax 57:709-14. 2002
    ..However, the chemoattractant nature of secretions from these patients has yet to be clarified...
  54. ncbi Biochemical efficacy and safety of a new pooled human plasma alpha(1)-antitrypsin, Respitin
    James K Stoller
    Department of Pulmonary and Critical Care Medicine, Cleveland Clinic Foundation, Cleveland, OH 44195, USA
    Chest 122:66-74. 2002
    ..Augmentation therapy with pooled human plasma-derived alpha(1)-antitrypsin (AAT) has been shown to have biochemical efficacy in restoring serum AAT levels above the protective threshold. Also, clinical efficacy has been suggested...
  55. ncbi Delay in diagnosis of alpha1-antitrypsin deficiency: a continuing problem
    James K Stoller
    Department of Pulmonary, Allergy, and Critical Care Medicine, Cleveland Clinic Foundation, A 90, 9500 Euclid Ave, Cleveland, OH 44195, USA
    Chest 128:1989-94. 2005
    ..We also determined whether individuals living near medical centers with an expressed interest in AAT deficiency experienced shorter diagnostic delays than those living at a distance...
  56. ncbi Trends in the diagnosis of symptomatic patients with alpha1-antitrypsin deficiency between 1968 and 2003
    Michael A Campos
    Division of Pulmonary and Critical Care Medicine, University of Miami School of Medicine, PO Box 016960 R 47, Miami, FL 33101, USA
    Chest 128:1179-86. 2005
    ..To support current guidelines recommending AATD testing of all individuals with COPD, we analyzed the diagnostic experience of a large cohort of symptomatic patients with AATD...
  57. pmc Alpha 1-antitrypsin deficiency. 3: Clinical manifestations and natural history
    M Needham
    Department of Respiratory Medicine, Queen Elizabeth Hospital, Birmingham, UK
    Thorax 59:441-5. 2004
    ..A review of the clinical manifestations of alpha(1)-antitrypsin (AAT) deficiency, including lung disease and liver disease, and risk factors affecting the rate of decline in lung function in AAT deficient patients...
  58. ncbi Influence of calibration on densitometric studies of emphysema progression using computed tomography
    David G Parr
    Lung Investigation Unit, First Floor, Nuffield House, Queen Elizabeth Hospital, Birmingham B15 2TH, UK
    Am J Respir Crit Care Med 170:883-90. 2004
    ..Internal air calibration is therefore critical in longitudinal and multicenter lung densitometry studies of emphysema and incorporation of a correction factor is essential for quantitative image analysis...
  59. ncbi Volume adjustment of lung density by computed tomography scans in patients with emphysema
    S B Shaker
    Department of Respiratory Medicine, Gentofte Hospital, Hellerup, Denmark
    Acta Radiol 45:417-23. 2004
    ..To determine how to adjust lung density measurements for the volume of the lung calculated from computed tomography (CT) scans in patients with emphysema...
  60. pmc Prevalence and phenotype of subjects carrying rare variants in the Italian registry for alpha1-antitrypsin deficiency
    I Ferrarotti
    J Med Genet 42:282-7. 2005
  61. ncbi Health implications of alpha1-antitrypsin deficiency in Sub-Sahara African countries and their emigrants in Europe and the New World
    Frederick J de Serres
    National Institute of Environmental Health Sciences, Laboratory of Molecular Toxicology, Environmental Toxicology Program, Research Triangle Park, NC 27709 2233, USA
    Genet Med 7:175-84. 2005
    ..In addition, to discuss the unique susceptibility of these populations and emigrants to Europe and the New World to the adverse health effects associated with exposure to environmental microbes, chemicals, and particulates...
  62. ncbi Mortality in individuals with severe deficiency of alpha1-antitrypsin: findings from the National Heart, Lung, and Blood Institute Registry
    James K Stoller
    Department of Pulmonary, Allergy, and Critical Care Medicine, The Cleveland Clinic Foundation, 9500 Euclid Ave, A90, Cleveland, OH 44195, USA
    Chest 127:1196-204. 2005
    ..2 years)...
  63. pmc Correlation between annual change in health status and computer tomography derived lung density in subjects with alpha1-antitrypsin deficiency
    J Stolk
    Department of Pulmonology, Leiden University Medical Center, Leiden, The Netherlands corrected
    Thorax 58:1027-30. 2003
    ..A study was undertaken to investigate prospectively the correlation between annual change in health status and computer tomography (CT) derived lung density in subjects with alpha(1)-antitrypsin deficiency...
  64. ncbi The protease inhibitor PI*S allele and COPD: a meta-analysis
    M Dahl
    Dept of Clinical Biochemistry, Herlev University Hospital, Copenhagen, Denmark
    Eur Respir J 26:67-76. 2005
    ..In conclusion, the results show that the PI SZ genotype is a significant risk factor for chronic obstructive pulmonary disease. The risk of chronic obstructive pulmonary disease due to the PI MS genotype is not substantially elevated...
  65. ncbi Factors associated with advanced liver disease in adults with alpha1-antitrypsin deficiency
    Christopher L Bowlus
    Division of Gastroenterology, University of California at Davis, UC Davis Medical Center, 4150 V Street, PSSB 3500, Sacramento, CA 95817, USA
    Clin Gastroenterol Hepatol 3:390-6. 2005
    ..Our study aim was to characterize the liver disease in AAT and identify factors associated with advanced liver disease...
  66. 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...
  67. ncbi Thirteen-year experience in lung transplantation for emphysema
    Stephen D Cassivi
    Division of Cardiothoracic Surgery, Washington University Medical Center, St Louis, Missouri 63110 1013, USA
    Ann Thorac Surg 74:1663-9; discussion 1669-70. 2002
    ..We analyzed the results of our single-institution series of lung transplants for emphysema to identify outcome differences and factors predicting mortality and morbidity in these two groups...
  68. pmc Alpha1-antitrypsin deficiency. 4: Molecular pathophysiology
    D A Lomas
    Respiratory Medicine Unit, Department of Medicine, University of Cambridge, Cambridge Institute for Medical Research, Cambridge CB2 2XY, UK
    Thorax 59:529-35. 2004
    ..The current goals are to determine the cellular response to polymeric alpha(1)-antitrypsin and to develop therapeutic strategies to block polymerisation in vivo...
  69. ncbi A review of alpha-1 antitrypsin deficiency
    Justin Ranes
    Department of Pulmonary, Allergy, and Critical Care Medicine A90, The Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, OH 44195, USA
    Semin Respir Crit Care Med 26:154-66. 2005
    ....
  70. ncbi Alpha1-antitrypsin deficiency: a report from the 2nd meeting of the Alpha One International Registry, Rapallo (Genoa, Italy), 2001
    M Luisetti
    Dept of Respiratory Diseases, IRCCS San Matteo, Pavia, Italy
    Eur Respir J 20:1050-6. 2002
    ..In the framework of a rare and often under-recognised condition, this meeting is likely to be central to improving understanding and increasing awareness of alpha1-antitrypsin deficiency...
  71. ncbi Repeatability of lung density measurements with low-dose computed tomography in subjects with alpha-1-antitrypsin deficiency-associated emphysema
    J Stolk
    Department of Pulmonology C3 P, Leiden University Medical Center, Leiden, The Netherlands
    Invest Radiol 36:648-51. 2001
    ..The aim of the present study was to assess the intraindividual variation of lung densities measured by MSCT of patients with emphysema...
  72. ncbi The alpha 1-antitrypsin gene and its deficiency states
    R G Crystal
    Trends Genet 5:411-7. 1989
    ....
  73. ncbi Molecular diagnosis of intermediate and severe alpha(1)-antitrypsin deficiency: MZ individuals with chronic obstructive pulmonary disease may have lower lung function than MM individuals
    M Dahl
    Department of Clinical Biochemistry, Herlev University Hospital, DK 2730 Herlev, Denmark
    Clin Chem 47:56-62. 2001
    ..We tested whether intermediate (MZ, SZ) and severe (ZZ) alpha(1)-antitrypsin deficiency affects lung function in the population at large...
  74. 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...
  75. ncbi Inherited chronic obstructive pulmonary disease: new selective-sequencing workup for alpha1-antitrypsin deficiency identifies 2 previously unidentified null alleles
    Janke Prins
    Department of Clinical Chemistry, Meander Medical Center, Utrechtseweg 160, Amersfoort, The Netherlands
    Clin Chem 54:101-7. 2008
    ..0 g/l...
  76. ncbi Lung function, smoking and survival in severe alpha 1-antitrypsin deficiency, PiZZ
    M C Wu
    National Heart, Lung and Blood Institute, Bethesda, MD 20892
    J Clin Epidemiol 41:1157-65. 1988
    ..The application of these results to the planning of studies on replacement therapy, smoking intervention strategy and longitudinal follow-up is discussed...
  77. ncbi Short-term supplementation therapy does not affect elastin degradation in severe alpha(1)-antitrypsin deficiency. The American-Italian AATD Study Group
    D J Gottlieb
    Department of Medicine, Boston University School of Medicine, MA 02118 2394, USA
    Am J Respir Crit Care Med 162:2069-72. 2000
    ..These findings raise the possibilities that protective levels of AAT in the lungs are insufficient or that elastin degradation in the lungs of these subjects is not dependent upon neutrophil elastase at this time...
  78. 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...
  79. ncbi Formation and current results of a patient-organized registry for alpha(1)-antitrypsin deficiency
    J K Stoller
    Department of Pulmonary Medicine, The Cleveland Clinic Foundation, Cleveland, OH 44195, USA
    Chest 118:843-8. 2000
    ....
  80. 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...
  81. ncbi The role of chlamydia in the pathogenesis of pulmonary emphysema. Electron microscopy and immunofluorescence reveal corresponding findings as in atherosclerosis
    D Theegarten
    Department of Pathology, Ruhr University Bochum, Germany
    Virchows Arch 437:190-3. 2000
    ..Chronic infection and bacterial colonization associated with progressive disease seems to be relevant not only in atherosclerosis but also in pulmonary emphysema...
  82. ncbi Cholangiocarcinoma in two siblings with emphysema and alpha-1-antitrypsin deficiency
    D M Parham
    Department of Pathology, Ninewells Hospital and Medical School, Dundee
    Q J Med 71:359-67. 1989
    ..This lends support to the view that alpha-1-antitrypsin deficiency plays a role in the development of some primary liver tumours...
  83. ncbi Chronic liver disease in heterozygous alpha1-antitrypsin deficiency PiZ
    H P Fischer
    Department of Pathology, University of Bonn, Germany
    J Hepatol 33:883-92. 2000
    ..We analyzed whether patients with this genetic defect carrying a single PiZ gene are at increased risk for developing chronic liver disease...
  84. ncbi Matrix metalloprotease polymorphisms are associated with gas transfer in alpha 1 antitrypsin deficiency
    Christopher J McAloon
    Lung Investigation Unit, University Hospital Birmingham, Birmingham, UK
    Ther Adv Respir Dis 3:23-30. 2009
    ..Matrix metalloproteinases [MMPs] are believed to be important in the pathophysiology of COPD, and may therefore confer susceptibility to this phenotype in patients with AATD...
  85. ncbi Prevalence and impact of bronchiectasis in alpha1-antitrypsin deficiency
    David G Parr
    Department of Respiratory Medicine, University Hospitals of Coventry and Warwickshire, Coventry CV2 2DX, UK
    Am J Respir Crit Care Med 176:1215-21. 2007
    ..alpha(1)-Antitrypsin (AAT) deficiency is associated with increased risk of chronic obstructive pulmonary disease (COPD), in particular emphysema, but airway disease is less well described...
  86. ncbi SERPINA1 gene variants in individuals from the general population with reduced alpha1-antitrypsin concentrations
    Michele Zorzetto
    Center for Diagnosis of Severe Alpha1 antitrypsin Deficiency, Laboratory of Biochemistry and Genetics, Institute for Respiratory Disease and Unit of Statistics and Biometry, Fondazione IRCCS Policlinico San Matteo, University of Pavia, Italy
    Clin Chem 54:1331-8. 2008
    ..We decided to perform an exhaustive investigation of SERPINA1 gene variants in individuals from the general population with a moderately reduced serum AAT concentration, because such information is currently unavailable...
  87. 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...
  88. ncbi Outcome of bilateral lung volume reduction in patients with emphysema potentially eligible for lung transplantation
    B F Meyers
    Division of Cardiothoracic Surgery and the Division of Pulmonary and Critical Care Medicine, Washington University School of Medicine, St Louis, MO, USA
    J Thorac Cardiovasc Surg 122:10-7. 2001
    ..The outcomes of these 99 patients are reviewed to assess the consequences of proceeding with lung volume reduction surgery on patients potentially eligible for lung transplantation...
  89. 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...
  90. 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...
  91. ncbi Genetic epidemiology of severe, early-onset chronic obstructive pulmonary disease. Risk to relatives for airflow obstruction and chronic bronchitis
    E K Silverman
    Channing Laboratory, Brigham and Women s Hospital, Boston, MA 02115, USA
    Am J Respir Crit Care Med 157:1770-8. 1998
    ..The increased risk to relatives of early-onset COPD probands for reduced FEV1 and chronic bronchitis, limited to current or ex-smokers, suggests genetic risk factor(s) for COPD that are expressed in response to cigarette smoking...
  92. ncbi PI*S(iiyama), a deficiency gene of alpha 1-antitrypsin: evidence for the occurrence in western Japan
    I Yuasa
    Department of Legal Medicine, Tottori University School of Medicine, Yonago, Japan
    Jpn J Hum Genet 38:185-91. 1993
    ..Crossed immunoelectrophoresis after isoelectric focusing and agarose gel electrophoresis showed atypical banding patterns. PI*S(iiyama) is a rare deficiency gene, but it can occur sporadically all over the Japan...
  93. ncbi Identification of individuals with alpha-1-antitrypsin deficiency by a targeted screening program
    Robert Bals
    Department of Internal Medicine, Division for Pulmonary Diseases, Hospital of the University of Marburg, Philipps Universtät Marburg, Baldingerstrasse 1, 35043 Marburg, Germany
    Respir Med 101:1708-14. 2007
    ..It was the aim of the study to determine whether the combination of an awareness program with the offer of a cost-free diagnostic test results in the identification of a significant number of individuals with severe AATD...
  94. ncbi Respiratory disease in aggregate quarry workers related to risk factors and Pi phenotype
    Isabel Isidro Montes
    National Institute of Silicosis, Central Hospital of Asturias, 3306 Oviedo, Spain
    J Occup Environ Med 46:1150-7. 2004
    ..To evaluate the respiratory health and its relationship with exposure to silica, smoking, alpha 1-antitrypsin, and Pi phenotype in aggregate quarries workers...
  95. ncbi Alpha-1-antitrypsin deficiency (Siiyama) as indication for lung transplantation: proper timing for surgical intervention
    G Shindo
    Cardiothoracic Department, Meditopia Numazu Medical Clinic, Numazu City, Japan
    Minerva Chir 63:241-7. 2008
    ..Lung transplantation is one of the best reliable current therapies to improve quality of life of severely impaired patients...
  96. ncbi Emphysema in alpha1-antitrypsin deficiency: does replacement therapy affect outcome?
    Raja T Abboud
    Respiratory Division, University of British Columbia, 2775 Heather Street, Vancouver, V5Z 3J5, British Columbia, Canada
    Treat Respir Med 4:1-8. 2005
    ....
  97. ncbi Does the heterozygous state of alpha-1 antitrypsin deficiency have a role in chronic liver diseases? Interim results of a large case-control study
    Arie Regev
    Division of Hepatology, Center for Liver Diseases, University of Miami, Leonard M Miller School of Medicine, FL 33136, USA
    J Pediatr Gastroenterol Nutr 43:S30-5. 2006
    ..The role of the heterozygous PiZ state of alpha-1 antitrypsin deficiency (alpha1ATD) in the pathogenesis of chronic liver disease (LD) is still a matter of controversy...
  98. pmc Hereditary alpha-1-antitrypsin deficiency and its clinical consequences
    Laura Fregonese
    Alpha1 International Registry, c o Department of Pulmology, Leiden University Medical Center, Leiden, The Netherlands
    Orphanet J Rare Dis 3:16. 2008
    ..The end-stage liver and lung disease can be treated by organ transplantation. In AATD patients with cirrhosis, prognosis is generally grave...
  99. ncbi [Emphysema due to alpha-1-antitrypsin deficiency: is it really an uncommon disease?]
    Marc Miravitlles
    Med Clin (Barc) 123:778-9. 2004
  100. ncbi Association of moderate alpha-1 antitrypsin deficiency with lung cancer in the Serbian population
    Aleksandra S Topic
    Institute of Medical Biochemistry, Faculty of Pharmacy, Belgrade, Serbia and Montenegro
    Arch Med Res 37:866-70. 2006
    ....
  101. ncbi [Alpha1-proteinase inhibitor: structure and functions]
    Takahisa Imamura
    Division of Molecular Pathology, Kumamoto University Graduate School of Medical and Pharmaceutical Sciences
    Nihon Rinsho 63:81-7. 2005

Research Grants62

  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. 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. ..
  5. Novel Protective Antiapoptotic Action of Alpha 1-Antitrypsin In Emphysema
    Rubin M Tuder; Fiscal Year: 2011
    ..activity of alpha-1 antritrypsin and may provide an opportunity improve our therapeutic approaches in alpha 1 antitrypsin deficiency- and smoking-induced emphysema...
  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. InCell 6000 High Content Instrument for Cellular Systems Biology Program
    D LANSING LANSING TAYLOR; Fiscal Year: 2013
    ....
  12. The Pathobiology of Airway Disease in Alpha-1 Antitrypsin Deficiency
    Michael A Campos; Fiscal Year: 2010
    ..abstract_text> ..
  13. 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. ..
  14. 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. ..
  15. Sarcoidosis and A1AT Genomics &Informatics Center
    Stephen R Wisniewski; Fiscal Year: 2013
    ....
  16. Characterization of human hematopoietic and endodermal progenitors derived from i
    Gustavo Mostoslavsky; Fiscal Year: 2010
    ....
  17. 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. ..
  18. 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. ..
  19. 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 ..
  20. 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. ..
  21. THERAPY FOR ALPHA-1 ANTITRYPSIN DEFECIENCY
    GORDON SNIDER; Fiscal Year: 1999
    ..abstract_text> ..
  22. 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. ..
  23. 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. ..
  24. 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. ..
  25. AAT Deficiency & Liver Diseases Caused by Proteins
    Bruce Trapnell; Fiscal Year: 2006
    ..unreadable] [unreadable]..
  26. NEWBORN SCREENING BY MULTIPLEX MOLECULAR ANALYSIS
    Edwin Naylor; Fiscal Year: 1999
    ..The screening services proposed are marketable for newborn screening and high-risk screening. ..
  27. 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. ..
  28. 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. ..
  29. Gene therapy for treatment of hemophilia A
    Hans Herweijer; Fiscal Year: 2002
    ..proposed commercial application: not available ..
  30. 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. ..
  31. Fine Mapping of a COPD Locus on Chromosome 19q
    CRAIG HERSH; Fiscal Year: 2009
    ..abstract_text> ..
  32. 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...
  33. Bone Marrow Progenitor Cells in Lung Injury and Repair
    Erica Herzog; Fiscal Year: 2009
    ....
  34. STRATEGIC TARGETING OF VIRAL GENOMES IN BILIARY ATRESIA
    Ross Shepherd; Fiscal Year: 2009
    ..For example, during the recent SARS outbreak, hybridization patterns observed using the pan-viral microarray helped identify SARS as a novel coronavirus, demonstrating the power and utility of this approach. ..
  35. 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. ..
  36. Characterizing the Cpx stress response in E. coli
    DANIEL ISAAC; Fiscal Year: 2005
    ..Such aggregates appear to be central to the pathogenesis of several human diseases including alpha-1 antitrypsin deficiency and Huntington's disease. ..
  37. Liver Injury in Alpha-1-Antitrypsin Deficiency
    David Perlmutter; Fiscal Year: 2007
    ..Thus, the studies proposed in this competitive renewal application will address the novel concept that oxidative stress causes, or contributes to, liver cell injury in alpha-1-ATZ deficiency. ..
  38. Screening for Genetic Mechanisms for Biliary Atresia
    David Perlmutter; Fiscal Year: 2006
    ..These studies will provide new information about and a basis for many additional studies of the pathogenesis, natural history, early diagnosis and treatment of BA, a rare and severe liver disease of infants ..
  39. LOCAL EXPRESSION OF ALPHA-1-ANTITRYPSIN IN EMPHYSEMA
    David Perlmutter; Fiscal Year: 2008
    ....
  40. The Clinical Interface of Molecular and Cellular Biology
    David Perlmutter; Fiscal Year: 2006
    ....
  41. APPROACHES TO THE GENETICS OF COPD
    Edwin Silverman; Fiscal Year: 2003
    ..abstract_text> ..
  42. Views of Privacy of Genetic Information
    Robert Klitzman; Fiscal Year: 2005
    ..with 160 individuals -40 each who confront Huntington's Disease, genetically-linked breast cancer, alpha 1 antitrypsin deficiency, and, as a comparison group, coronary artery disease...
  43. Genetic Modifiers of Alpha 1-Antitrypsin Deficiency
    Edwin Silverman; Fiscal Year: 2005
    ....
  44. Alpha-1 AD Carriers and Lung Cancer Risk
    Ping Yang; Fiscal Year: 2009
    ..abstract_text> ..
  45. Asthma Candidate Genes in Alpha 1-Antitrypsin Deficiency
    Dawn DeMeo; Fiscal Year: 2007
    ..The identification of modifying factors of COPD in AAT deficiency may have significant public health relevance to COPD patients without AAT deficiency. ..
  46. Views and Approaches Toward Research Integrity Among IRBs
    Robert Klitzman; Fiscal Year: 2007
    ..We anticipate that the data from this study will serve as a significant foundation in assisting future research and the improvement of Rl through guidelines, education and other capacity building. [unreadable] [unreadable] [unreadable]..
  47. Genetics of COPD in NETT
    Edwin Silverman; Fiscal Year: 2005
    ..abstract_text> ..
  48. Health and QOL among Long-Term Lung Cancer Survivors
    Ping Yang; Fiscal Year: 2010
    ....
  49. Genetic Determinants of COPD in Diverse Ethnic Groups
    Edwin K Silverman; Fiscal Year: 2010
    ..The overall goal of this proposal is to test the hypothesis that shared genetic determinants influence the development of COPD in diverse ethnic groups. ..
  50. Therapy for Alpha-1AT Deficiency Liver Disease
    Jeffrey Teckman; Fiscal Year: 2009
    ..of these therapeutic strategies for future human trials, examine the mechanisms involved in inhibiting liver cell injury, and add to the understanding of the basic mechanisms of cellular injury in liver disease ..
  51. Hepatobiliary Pathophysiology of Liver Regeneration
    DAVID RUDNICK; Fiscal Year: 2009
    ..abstract_text> ..
  52. LIVER REGENERATION IN PEDIATRIC LIVER DISEASE
    DAVID RUDNICK; Fiscal Year: 2004
    ..In this grant we propose to determine the effects of prostaglandins on ROS synthesis, expression of genes regulating ROS metabolism, and expression and activity of negative regulators of cytokine signaling during liver regeneration. ..
  53. LIVER REGENERATION IN PEDIATRIC LIVER DISEASE
    DAVID RUDNICK; Fiscal Year: 2004
    ..abstract_text> ..
  54. CYTOSKELETAL REGULATION OF ENDOTHELIAL CELL APOPTOSIS
    Irina Petrache; Fiscal Year: 2004
    ..abstract_text> ..
  55. THE ROLE OF ALPHA-DEFENSINS IN CYSTIC FIBROSIS LUNG DISE
    L Spencer; Fiscal Year: 2004
    ..Following completion of this training and research, my long-term career interest will remain in the area of pathogenesis and applied clinical intervention of neutrophil-mediated pulmonary disease in pediatric patients. ..
  56. PECAM AND CALCIUM SIGNALING AND TRANSMIGRATION
    Steven Albelda; Fiscal Year: 2002
    ....
  57. Structure Function of the Mammalian Stress Proteins
    William Welch; Fiscal Year: 2004
    ....
  58. GENE SPECIFIC MUTATIONS IN SKIN INDUCED BY PEROXYNITRITE
    Fredika Robertson; Fiscal Year: 2001
    ..The hypothesis driving this research is that NO and peroxynitrite are mutagenic, and could be important contributors to oxidative DNA damage and mutation in human epidermal keratinocytes at sites of inflammation. ..