Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0034067 (emphysema)
 11,506 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. In 1991 there were 2,127 heart, 402 lung, and 51 heart-lung transplants performed in the United States. These numbers reflect increases of 27% for heart, over 1000% for lung, and a decrease of 31% for heart-lung transplants since 1988. 2. The number of programs performing heart transplants has increased by 16% since 1988, whereas the number of programs performing lung transplants has tripled over that time. 3. The most frequent primary indications for thoracic transplantation were: cardiomyopathy (45%) and coronary artery disease (41%) for heart; primary pulmonary hypertension (43%) and congenital/Eisenmenger's for heart-lung; and emphysema/chronic obstructive pulmonary disease (28%) and Alpha-1 antitrypsin deficiency (20%) for lung. 4. Average cold ischemic time increased gradually between 1988 and 1991: 2.7 hours for hearts transplanted in 1991 compared with 3.3 hours for heart-lungs, and 4.3 for lungs. 5. Between 1988 and December 1991, the following percentages increased significantly: pediatric heart and lung transplantations; non-White thoracic transplant recipients and donors; the use of thoracic organs from younger (< or = 5 yrs) as well as older (> or = 45 yrs) donors; and local utilization of thoracic organs. 6. For the entire period covered by this report, 1-year recipient survival rates were: heart 81.6%, heart-lung 55.4%, and lung 67.2%. Patient survival was significantly lower in heart retransplants or when the primary indication for transplantation was the treatment of congenital disease. Between 1988 and 1991, 1-year survival appeared to have increased significantly for heart-lung and lung recipients.
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PMID:Thoracic organ transplants in the United States from October 1987 through December 1991: a report from the UNOS Scientific Registry for Organ Transplants. 130 9

Alpha-1 antitrypsin (alpha 1AT) is an efficient inhibitor of the human neutrophil proteases, elastase and cathepsin G. The reactive centre P1 residue (Met358) of alpha 1AT is important in defining the specificity of inhibition; furthermore, oxidation of this residue results in a loss of inhibitor activity. There is evidence that oxidative inactivation of alpha 1AT may be involved in the pathogenesis of pulmonary emphysema associated with cigarette smoking. We have studied the effect of a series of amino acid replacements at the active centre on the inhibition properties of alpha 1AT. The mutant proteins were produced in E. coli following in vitro mutagenesis of the alpha 1AT cDNA. Alpha-1-AT (Ile358), (Ala358) and (Val358) were efficient inhibitors of both neutrophil and pancreatic elastase, but not cathepsin G. Alpha-1-AT (Ala356, Val358) and alpha 1AT (Phe358) were specific for pancreatic elastase and cathepsin G respectively. Alpha-1-AT (Leu358) inhibited both neutrophil elastase and cathepsin G. These data show that, for effective inhibition, a potential cleavage site for the protease must be displayed at the alpha 1AT active centre. In each case, replacement of Met358 led to resistance to oxidative inactivation. Since alpha 1AT (Leu358) inhibits both neutrophil proteases and is resistant to oxidation, this variant may be of increased potential for the therapy of destructive lung disorders.
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PMID:Antiprotease targeting: altered specificity of alpha 1-antitrypsin by amino acid replacement at the reactive centre. 354 50

Alpha-1 antitrypsin deficiency is a cause of liver disease in neonates and emphysema in adults. Protein phenotypes are identified by isoelectric focusing using polyacrylamide gels. The Pharmacia Phastsystem was utilized for electrophoresis in miniature gels to identify heterozygotes for the deficiency. Protein phenotypes were identified by isoelectric focusing in a fixed pH gradient from 4.3 to 5 using the Pharmacia Phastsystem for automated electrophoresis and staining of gels. The gradient is formed with Immobilines to create gels of dimensions 50 x 43 x 0.5 mm. The processing time for 16 specimens is one hour and 45 minutes. This method is a rapid, automated method for the analysis of alpha-1 antitrypsin phenotypes and for establishing the diagnosis of a genetic deficiency of this protein.
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PMID:Alpha-1 antitrypsin protease inhibitor typing in immobilized pH gradients. 843 Sep 98

We report panniculitis revealing alpha-1 antitrypsin deficiency in 3 patients with different Pi phenotypes. The first patient, a 16-year-old woman, had inflammatory skin lesions on the abdomen for 6 months. The lesions regressed spontaneously. Serum alph-1 antitrypsin level was normal but the Pi phenotype was MS. The second case was observed in a 56-year-old man who developed erythematous subcutaneous nodules on the abdomen, legs and buttocks in a trauma context. Serum alpha-1 antitrypsin was very low and the Pi phenotype was ZZ. The third patient was a 40-year-old woman who presented red swelling nodules on the legs. Her serum alpha-1 antitrypsin level was at the lower limit of normal and the Pi phenotype was MZ. Alpha-1 antitrypsin deficiency is an autosomic codominant inherited disorder characterized by inefficient or non-functional serum alpha-1 antitrypsin. The principal clinical manifestations are panlobular emphysema and cirrhoses. About 30 cases of panniculitis have been reported in the literature. In patients presenting panniculitis, we suggest studying the Pi phenotype to determine functional deficiency even if the serum level of alpha-1 antitrypsin is normal.
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PMID:[Panniculitis revealing alpha-1 antitrypsin deficiency. Report of 3 cases]. 1193 84

Human plasma contains a number of proteinase inhibitors which together form 10% of the total plasma proteins. Serine proteases are a group of closely related proteolytic enzymes, with serine in their active site. These play a key role in coagulation, fibrinolysin, kinin and complement activation. Serine protease inhibitors or "serpins" are specific inhibitors which control the activities of these enzymes. Among the serine protease inhibitors. Alpha-1 antitrypsin (alpha1 ATD) is found in highest concentration in plasma. It is the major physiologic inhibitor for neutrophil elastase. It has control over the elastase mediated degradation of elastic tissue in the lung. Alpha1ATD deficiency is a common genetic disorder and potentially lethal disease predominantly found in North European population--where the incidence is one in 2500; worldwide figures suggest that one in 6000 people have classic alpha1ATD. In cases of deficiency, antielastase activity is reduced in the lungs which results in increased elastin breakdown and development of emphysema. Cigarette smoking contributes to destructive changes in emphysema by suppressing the proteinase inhibitory activity of human serum and by inducing certain bronchoalveolar changes. Prevalence and severity of asthma increases in persons with abnormal alpha1ATD phenotype.
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PMID:Alpha-1 antitrypsin deficiency in emphysema. 1216 15

Alpha-1 antitrypsin (AAT) deficiency is an inherited genetic disorder currently diagnosed in approximately 5,000 people in the United States. Although some individuals with AAT deficiency are asymptomatic, the condition often leads to deterioration of lung function in adults and is associated with emphysema, asthma, chronic obstructive pulmonary disease, and other respiratory diseases. In children, AAT deficiency can result in severe liver disease, including fatal cirrhosis in newborn infants. Although much is known about the clinical pathology of AAT deficiency, researchers are just beginning to characterize environmental, occupational, and genetic modifiers affecting the onset and progression of diseases related to AAT deficiency. On 19 August 2002, a group of basic scientists, clinicians, environmental health researchers, and public interest groups gathered at the National Institute of Environmental Health Sciences in Research Triangle Park, North Carolina, to discuss ongoing research on these topics. The goals of this workshop were to a) assess the present state of knowledge regarding environmental and occupational risk factors contributing to AAT deficiency morbidity and mortality, b) define future research needs in this area, and c) explore collaborative opportunities to advance understanding of risk factors affecting the progression of AAT deficiency-related disease. Participants agreed that new research initiatives in these areas represent an opportunity to benefit both basic science, through enhanced understanding of gene-environment interaction, and the AAT deficiency patient community, through innovative new approaches to disease management and treatment.
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PMID:Environmental, occupational, and genetic risk factors for alpha-1 antitrypsin deficiency. 1459 26

Alpha-1 antitrypsin (AAT) deficiency is a hereditary disorder characterized by an early onset of emphysema. While this disease is common in the Caucasian population, it is quite rare in Japan. To date, only 15 traits have been reported and it can be speculated that many cases of this genetic deficiency may have been overlooked. We report an additional case of AAT deficiency with severe emphysema that is genetically determined as S(iiyama) variant by allele-specific polymerase chain reaction (PCR) analysis.
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PMID:Alpha-1 antitrypsin deficiency with severe pulmonary emphysema. 1509 5

Alpha-1 antitrypsin (AAT) is a protein that prevents enzymes such as elastin from degrading normal host tissue. Individuals who are deficient in AAT (those with levels < 11 micromol/L) are at risk for developing such clinical manifestations as emphysema, cirrhosis, panniculitis, and anticytoplasmic neutrophilic antibody (C-ANCA)-positive vasculitis (Wegener's granulomatosis). Estimates suggest that 75 to 85% of those with severe deficiency of AAT will develop emphysema. Smoking appears to be the most important risk factor for the development of emphysema among AAT deficient persons. Severe deficiency of AAT also seems to be associated with a shorter lifespan. Among smokers, mild to moderate reductions in AAT levels may be associated with a more rapid decline in lung function. Diagnosis of AAT deficiency is made by measuring serum levels of AAT and, if reduced, an effort should then be made to identify the genetic abnormality responsible for the reduction. A recent evidence-based review has offered testing recommendations for AAT deficiency and includes the recommendation that all patients with COPD be tested for AAT deficiency. Augmentation with an intravenous form of purified pooled human plasma has been shown to increase the serum levels of AAT among deficient patients and its use appears to impact the rate of forced expiratory volume in 1 second (FEV (1)) decline and overall survival; to date, no confirmatory, large, prospective, randomized trials are available.
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PMID:A review of alpha-1 antitrypsin deficiency. 1608 34

Alpha-1 antitrypsin (AAT) deficiency is a common but under-recognized disease. This hereditary disorder is characterized by low levels of AAT, and increased risks of panacinar emphysema at an early age, liver disease, vasculitis and panniculitis. Destruction of lung parenchyma and consequent emphysema result from an imbalance between different inflammatory proteases (in particular, leukocyte elastase), and the major natural antiprotease, AAT. To offer a review of key aspects of this important condition, we present the epidemiology, natural history, and pathogenesis of AAT deficiency and, in the context of recent data and the publication of an international standards document regarding the diagnosis and management of individuals with AAT deficiency, review current therapy of AAT deficiency.
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PMID:A review of alpha-1 antitrypsin deficiency. 1713 53

Alpha-1 antitrypsin deficiency--an autosomal codominant condition that predisposes to emphysema and also to liver disease--affects 100,000 Americans, yet in many cases the condition is either not diagnosed or the time between first symptoms and diagnosis is long. Because primary care physicians care for large numbers of patients with chronic obstructive pulmonary disease, enhanced suspicion of and testing for alpha-1 antitrypsin deficiency in the primary care setting would help identify people affected with this condition. The authors discuss impediments to diagnosis and drivers to making the diagnosis of alpha-1 antitrypsin deficiency, and they suggest several measures to enhance clinicians' recognition of the condition.
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PMID:Primary care diagnosis of alpha-1 antitrypsin deficiency: issues and opportunities. 1818 37


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