Genomes and Genes
alpha 1 antitrypsin deficiency
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)
Publications234 found, 100 shown here
- Worldwide racial and ethnic distribution of alpha1-antitrypsin deficiency: summary of an analysis of published genetic epidemiologic surveysFrederick 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...
- Alpha1-antitrypsin deficiency. 2: genetic aspects of alpha(1)-antitrypsin deficiency: phenotypes and genetic modifiers of emphysema riskD 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...
- Laboratory diagnosis of alpha1-antitrypsin deficiencyIlaria 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...
- Alpha-1 antitrypsin Null mutations and severity of emphysemaLaura 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...
- MEKC of desmosine and isodesmosine in urine of chronic destructive lung disease patientsS 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...
- Alpha1-antitrypsin deficiency. 1: epidemiology of alpha1-antitrypsin deficiencyM 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...
- Alpha1-antitrypsin deficiency in 26-year-old subjects: lung, liver, and protease/protease inhibitor studiesEeva 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...
- Detection of emphysema progression in alpha 1-antitrypsin deficiency using CT densitometry; methodological advancesDavid 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...
- Desmosine as a biomarker of elastin degradation in COPD: current status and future directionsM Luisetti
Laboratory of Biochemistry and Genetics, Institute of Respiratory Disease, IRCCS San Matteo Hospital Foundation, Pavia, Italy
Eur Respir J 32:1146-57. 2008....
- Rate of progression of lung function impairment in alpha1-antitrypsin deficiencyP 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...
- Validation of computed tomographic lung densitometry for monitoring emphysema in alpha1-antitrypsin deficiencyD 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)...
- Exploring the role of CT densitometry: a randomised study of augmentation therapy in alpha1-antitrypsin deficiencyA 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...
- Chronic obstructive pulmonary disease. 1: Susceptibility factors for COPD the genotype-environment interactionA 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...
- Alpha1-antitrypsin deficiencyJames 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...
- Role of human neutrophil peptides in lung inflammation associated with alpha1-antitrypsin deficiencyL 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...
- Predictors of mortality in alpha1-antitrypsin deficiencyP 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...
- Longitudinal changes in physiological, radiological, and health status measurements in alpha(1)-antitrypsin deficiency and factors associated with declineL 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...
- Estimated numbers and prevalence of PI*S and PI*Z alleles of alpha1-antitrypsin deficiency in European countriesI 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...
- Longitudinal follow-up of patients with alpha(1)-protease inhibitor deficiency before and during therapy with IV alpha(1)-protease inhibitorM 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...
- [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
- Rapid PCR real-time genotyping of M-Malton alpha1-antitrypsin deficiency alleles by molecular beaconsGermano 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...
- 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...
- PI S and PI Z alpha-1 antitrypsin deficiency worldwide. A review of existing genetic epidemiological dataF 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....
- Results of a case-detection programme for alpha1-antitrypsin deficiency in COPD patientsC 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...
- Alpha 1-antitrypsin deficiency associated with panniculitisS 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...
- Heterozygous alpha-I antitrypsin deficiency as a co-factor in the development of chronic liver disease: a reviewK 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...
- Short-term variability of biomarkers of proteinase activity in patients with emphysema associated with type Z alpha-1-antitrypsin deficiencyJan 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...
- Sputum chemotactic activity in chronic obstructive pulmonary disease: effect of alpha(1)-antitrypsin deficiency and the role of leukotriene B(4) and interleukin 8I 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...
- Distribution of alpha-1 -antitrypsin phenotypes in Serbian newborns and children with liver diseaseA Topic
Acta Paediatr 91:726-7. 2002
- Biochemical efficacy and safety of a new pooled human plasma alpha(1)-antitrypsin, RespitinJames 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...
- High-resolution computed tomography scanning in alpha1-antitrypsin deficiency: relationship to lung function and health statusL J Dowson
Lung Investigation Unit, Queen Elizabeth Hospital, Birmingham, UK
Eur Respir J 17:1097-104. 2001....
- Lung volume reduction surgery in patients with emphysema and alpha-1 antitrypsin deficiencyJames 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...
- Repeatability of lung density measurements with low-dose computed tomography in subjects with alpha-1-antitrypsin deficiency-associated emphysemaJ 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...
- Linkage analysis of alpha 1-antitrypsin deficiency: lessons for complex diseasesE 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...
- Delay in diagnosis of alpha1-antitrypsin deficiency: a continuing problemJames 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...
- Validation of a rapid, simple method to measure alpha1-antitrypsin in human dried blood spotsMarina Gorrini
Clin Chem 52:899-901. 2006
- Alpha1-antitrypsin polymerization and the serpinopathies: pathobiology and prospects for therapyDavid 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
- The effect of augmentation therapy on bronchial inflammation in alpha1-antitrypsin deficiencyRobert 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...
- Rapid screening for alpha1-antitrypsin deficiency in patients with chronic obstructive pulmonary disease using dried blood specimensFrancisco 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...
- 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...
- A review of alpha-1 antitrypsin deficiencyJustin 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....
- The protease inhibitor PI*S allele and COPD: a meta-analysisM 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...
- Factors associated with advanced liver disease in adults with alpha1-antitrypsin deficiencyChristopher 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...
- Mortality in individuals with severe deficiency of alpha1-antitrypsin: findings from the National Heart, Lung, and Blood Institute RegistryJames 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)...
- Health implications of alpha1-antitrypsin deficiency in Sub-Sahara African countries and their emigrants in Europe and the New WorldFrederick 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...
- Prevalence and phenotype of subjects carrying rare variants in the Italian registry for alpha1-antitrypsin deficiencyI Ferrarotti
J Med Genet 42:282-7. 2005
- Volume adjustment of lung density by computed tomography scans in patients with emphysemaS 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...
- Influence of calibration on densitometric studies of emphysema progression using computed tomographyDavid 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...
- Alpha1-antitrypsin deficiency. 4: Molecular pathophysiologyD 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...
- Correlation between annual change in health status and computer tomography derived lung density in subjects with alpha1-antitrypsin deficiencyJ 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...
- Alpha 1-antitrypsin deficiency. 3: Clinical manifestations and natural historyM 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...
- Emphysema due to alpha-antitrypsin deficiency: familial study of the YBARCELONA variantMarc 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...
- Asthma features in severe alpha1-antitrypsin deficiency: experience of the National Heart, Lung, and Blood Institute RegistryEdward 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...
- Thirteen-year experience in lung transplantation for emphysemaStephen 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...
- Alpha1-antitrypsin deficiency: a report from the 2nd meeting of the Alpha One International Registry, Rapallo (Genoa, Italy), 2001M 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...
- Trends in the diagnosis of symptomatic patients with alpha1-antitrypsin deficiency between 1968 and 2003Michael 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...
- Outcome of bilateral lung volume reduction in patients with emphysema potentially eligible for lung transplantationB 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...
- Genetic epidemiology of severe, early-onset chronic obstructive pulmonary disease. Risk to relatives for airflow obstruction and chronic bronchitisE 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...
- The role of chlamydia in the pathogenesis of pulmonary emphysema. Electron microscopy and immunofluorescence reveal corresponding findings as in atherosclerosisD 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...
- Formation and current results of a patient-organized registry for alpha(1)-antitrypsin deficiencyJ K Stoller
Department of Pulmonary Medicine, The Cleveland Clinic Foundation, Cleveland, OH 44195, USA
Chest 118:843-8. 2000....
- Assessment of regional progression of pulmonary emphysema with CT densitometryM 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...
- IL10 polymorphisms are associated with airflow obstruction in severe alpha1-antitrypsin deficiencyDawn 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...
- Prevalence and impact of bronchiectasis in alpha1-antitrypsin deficiencyDavid 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...
- Modification of gene expression and increase in alpha1-antitrypsin (alpha1-AT) secretion after homologous recombination in alpha1-AT-deficient monocytesGillian 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...
- Inherited chronic obstructive pulmonary disease: new selective-sequencing workup for alpha1-antitrypsin deficiency identifies 2 previously unidentified null allelesJanke Prins
Department of Clinical Chemistry, Meander Medical Center, Utrechtseweg 160, Amersfoort, The Netherlands
Clin Chem 54:101-7. 2008..0 g/l...
- The alpha 1-antitrypsin gene and its deficiency statesR G Crystal
Trends Genet 5:411-7. 1989....
- Lung function, smoking and survival in severe alpha 1-antitrypsin deficiency, PiZZM 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...
- SERPINA1 gene variants in individuals from the general population with reduced alpha1-antitrypsin concentrationsMichele 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...
- Heteropolymerization of S, I, and Z alpha1-antitrypsin and liver cirrhosisR 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...
- Augmentation therapy reduces frequency of lung infections in antitrypsin deficiency: a new hypothesis with supporting dataJ 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...
- Cholangiocarcinoma in two siblings with emphysema and alpha-1-antitrypsin deficiencyD 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...
- Matrix metalloprotease polymorphisms are associated with gas transfer in alpha 1 antitrypsin deficiencyChristopher 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...
- Short-term supplementation therapy does not affect elastin degradation in severe alpha(1)-antitrypsin deficiency. The American-Italian AATD Study GroupD 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...
- Molecular diagnosis of intermediate and severe alpha(1)-antitrypsin deficiency: MZ individuals with chronic obstructive pulmonary disease may have lower lung function than MM individualsM 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...
- Respiratory symptoms and lung function in 30-year-old individuals with alpha-1-antitrypsin deficiencyElisabeth 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...
- Chronic liver disease in heterozygous alpha1-antitrypsin deficiency PiZH 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...
- Screening for Alpha 1 antitrypsin deficiency in Tunisian subjects with obstructive lung disease: a feasibility reportSabri 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...
- Ongoing research in Europe: Alpha One International Registry (AIR) objectives and developmentR 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...
- [Hereditary alpha-1-antitrypsin deficiency can cause COPD. Substitution treatment seems to result in fewer infections and prolonged survival]Sabina Janciauskiene
Wallenberglaboratoriet, Universitetssjukhuset MAS, Malmo
Lakartidningen 104:3631-4, 3637-8. 2007
- Alpha-1 antitrypsin: now available, but do we need it?Erich W Russi
Pulmonary Division, Department of Internal Medicine, University Hospital, Zurich, Switzerland
Swiss Med Wkly 138:191-6. 2008....
- Structure and variation of human alpha 1-antitrypsinR W Carrell
Nature 298:329-34. 1982..The nature of the reactive centre helps explain why cigarette smoking greatly accelerates the onset and severity of this degenerative process to give the disease emphysema...
- Alpha1-antitrypsin deficiency: incidence and implicationsRoberta J Richmond
Bellin College of Nursing
Dimens Crit Care Nurs 24:255-60; quiz 261-2. 2005..Critical care and advanced practice nurses will benefit from gaining a better understanding of the causes, pathophysiology, diagnosis, and treatment of this disorder...
- Alpha-1-antitrypsin deficiency in children: liver disease is not reflected by low serum levels of alpha-1-antitrypsin - a study on 48 pediatric patientsThomas Lang
Children s Hospital, Dr v Haunersches Kinderspital, University of Munich, Germany
Eur J Med Res 10:509-14. 2005..The aim of our study was to examine a correlation of total serum alpha1-AT, phenotype, and liver involvement in pediatric patients...
- PI*S(iiyama), a deficiency gene of alpha 1-antitrypsin: evidence for the occurrence in western JapanI 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...
- Homozygous deficiency of heparin cofactor II: relevance of P17 glutamate residue in serpins, relationship with conformational diseases, and role in thrombosisJavier 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...
- Case detection of alpha1-antitrypsin deficiency: does it help the patient or the doctor?J Stolk
Eur Respir J 26:561-2. 2005
- Isoelectric focusing phenotyping and denaturing gradient gel electrophoresis genotyping: a comparison of two methods in detection of alpha-1-antitrypsin variantsMila Ljujic
Institute of Molecular Genetics and Genetic Engineering, Belgrade, Serbia
Transl Res 151:255-9. 2008..Therefore, the optimal strategy for diagnostics of AAT deficiency should encompass detection of the most common AAT variants by IEF and screening for the less common variants by DGGE in combination with sequencing...
- National Emphysema Treatment Trial state of the art: genetics of emphysemaCraig P Hersh
Channing Laboratory, Center for Genomic Medicine, and Division of Pulmonary and Critical Care Medicine, Brigham and Women s Hospital, Harvard Medical School, Boston, MA 02115, USA
Proc Am Thorac Soc 5:486-93. 2008....
- [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...
- [Emphysema due to alpha-1-antitrypsin deficiency: is it really an uncommon disease?]Marc Miravitlles
Med Clin (Barc) 123:778-9. 2004
- Respiratory disease in aggregate quarry workers related to risk factors and Pi phenotypeIsabel 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...
- The new genetics and chronic obstructive pulmonary diseaseNoor Kalsheker
Division of Clinical Chemistry, Molecular Medical Sciences Institute of Genetics, Queens Medical Centre, University of Nottingham, Nottingham, UK
COPD 5:257-64. 2008....
- [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
- [Emphysema as a pulmonary manifestation of alpha-1 antitrypsin (alpha-1 AT) deficiency]Paweł Kuca
Oddziału Intensywnej Terapii Pneumonologiczno Kardiologicznej, Instytut Gruźlicy i Chorób Płuc w Warszawie
Pneumonol Alergol Pol 72:447-52. 2004
- [The variability of clinical presentation of chronic obstructive pulmonary disease in patients with hereditary alpha-1 antitrypsin deficiency]Paweł Kuca
Oddziału Intensywnej Terapii Pneumonologiczno Kardiologicznej, Warszawa
Pneumonol Alergol Pol 72:420-3. 2004..In all patients tobacco smoking history, spirometric and 6-minutes walking tests as well as HRCT of the lung were performed and compared. The influence of smoking on the functional status is underlined...
- The TNFalpha gene relates to clinical phenotype in alpha-1-antitrypsin deficiencyAlice M Wood
Division of Medical Sciences, The Medical School, University of Birmingham, Birmingham, B15 2TT, UK
Respir Res 9:52. 2008..phenotypic variation in chronic obstructive pulmonary disease (COPD) in subjects with and without alpha 1 antitrypsin deficiency (AATD)...
- Emphysema associated with complete absence of alpha 1- antitrypsin in serum and the homozygous inheritance [corrected] of a stop codon in an alpha 1-antitrypsin-coding exonK Satoh
Pulmonary Branch, National Heart, Lung and Blood Institute, Bethesda, MD 20892
Am J Hum Genet 42:77-83. 1988..Although the consequences to the individual (i.e., emphysema) are identical to those associated with the common homozygous Z mutation, the homozygous null bellingham form of alpha 1AT deficiency has a very different genetic basis...
- Alpha-1-antitrypsin deficiency (Siiyama) as indication for lung transplantation: proper timing for surgical interventionG 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...
- 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....
- Hereditary alpha-1-antitrypsin deficiency and its clinical consequencesLaura 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...
- Pathogenesis of COPD. Part I. The role of protease-antiprotease imbalance in emphysemaR T Abboud
Division of Respiratory Medicine, Department of Medicine, Vancouver General Hospital, University of British Columbia, Vancouver, British Columbia, Canada
Int J Tuberc Lung Dis 12:361-7. 2008....
- Phase 2 Study of rAAV1-CB-hAAT for Treatment of Alpha-1 Antitrypsin DeficiencyJeffrey D Chulay; Fiscal Year: 2010..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. ..
- Preclinical & Phase I/II Trials of AAV-AAT VectorsTerence Flotte; Fiscal Year: 2005..It is hoped that the combined data from these two studies will provide important dose-ranging information for all human uses of rAAV vectors by the IM route. ..
- Rare Liver Disease NetworkRonald Sokol; Fiscal Year: 2007..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. ..
- Rare Lung Disease Clinical Research NetworkBruce Trapnell; Fiscal Year: 2006..Ongoing clinical, basic and translational studies at the centers chosen have already yielded critical insights into molecular mechanisms underlying lung function and defense in health and disease. ..
- NEWBORN SCREENING BY MULTIPLEX MOLECULAR ANALYSISEdwin 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 ..
- Liver regeneration with stems cells of uniparental originHolger Willenbring; Fiscal Year: 2009..These embryonic stem cells would be derived from the respective patient's sperm or oocytes, and thus limit rejection problems associated with the use of existing embryonic stem cell lines. ..
- Liver regeneration with stems cells of uniparental originHolger Willenbring; Fiscal Year: 2010..These embryonic stem cells would be derived from the respective patient's sperm or oocytes, and thus limit rejection problems associated with the use of existing embryonic stem cell lines. ..
- ABCA3 and the Response to Lung InjuryRASHMIN SAVANI; Fiscal Year: 2009..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. ..
- Genetic Modifiers of Alpha 1-Antitrypsin DeficiencyEdwin Silverman; Fiscal Year: 2005....
- APPROACHES TO THE GENETICS OF COPDEdwin Silverman; Fiscal Year: 2003..abstract_text> ..
- Pulmonary Alveolar Proteinosis Research ConferenceBruce 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. ..
- RIBOZYMES AND RNA GENE THERAPIES FOR LIVER DISEASESAndrea 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. ..
- Environmental factors in alpha 1-antitrypsin deficiencyLee 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. ..
- The Molecular Basis of Serpin Function and DisfunctionPatrick Wintrode; Fiscal Year: 2009..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. ..
- Genetic Determinants of COPD in Diverse Ethnic GroupsEdwin Silverman; Fiscal Year: 2007..The overall goal of this proposal is to test the hypothesis that shared genetic determinants influence the development of COPD in diverse ethnic groups. ..
- The Molecular Basis of Serpin Function and DisfunctionPatrick Wintrode; Fiscal Year: 2009..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. ..
- AAT Deficiency & Liver Diseases Caused by ProteinsBruce Trapnell; Fiscal Year: 2006....
- ABCA3 and the Response to Lung InjuryRashmin C Savani; Fiscal Year: 2010..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. ..