Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:2.6.1.1 (aspartate aminotransferase)
21,665 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This subject concerns the complex interrelationship of a genetically determined protein deficiency, enzymes which are inhibited by that protein, environmental challenges such as cigarette smoke and industrial pollutants, and the occurrence of obstructive lung disease (Fig. 1). Unequivocal establishment of an etiological role for AAT deficiency, especially of intermediate degree, has proven to be difficult. Confounding variables such as enzyme concentration in PMN and PAMs, duration of exposure to potential environmental hazards, differences in laboratory methods utilized in measuring AAT and in studying pulmonary function all require investigation. The definitive study, incorporating all of these and other factors, has yet to be conducted. No single, clear-cut conclusion can be drawn from analysis of present studies. In those circumstances in which heterozygotes appear to be predisposed to COPD, phenotypic screening of the population at potential risk, such as industrial workers may be appropriate. Conversely, in conditions in which no association is demonstrated, such screening would not be justified. Perhaps, the best one can do is to suggest a "Scotch verdict"; that is, the issue of causation is not proven.
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PMID:alpha 1-Antitrypsin deficiency and susceptibility to lung disease. 31 70

A total of 151 children with severe atopic bronchial asthma were screened for AAT levels by the STIC and RID methods. They were also phenotyped by the method of acid starch electrophoresis and crossed immunoelectrophoresis. The results were compared with those in a like control age group of children without known pulmonary problems. Both groups revealed similar incidences of AAT deficiency and 3% phenotype Z variants. The children with steroid-dependent severe asthma had a greater proportion of Z heterozygote variants than the non-steroid-dependent asthmatic and control population.
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PMID:Alpha-1 antitrypsin levels and prevalence of Pi variant phenotypes in asthmatic children. 81 96

The use of advanced recombinant DNA technology has provided an improved understanding of the human AAT deficiency phenotype by providing the amino acid sequence of several variant proteins and by allowing for the production of various cell and animal models to study the molecular and biochemical components of the retention, degradation, and accumulation of these variants in the hepatic ER. Human AAT deficiency will continue to serve as an excellent model for enhancing our current understanding of mechanisms utilized in regulating protein "traffic" in the ER and in elucidating the pathophysiologic components of AAT-related liver disease.
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PMID:Molecular biology and genetics of alpha 1-antitrypsin deficiency. 143 81

This is a case of decompensated chronic liver disease associated with FZ phenotype AAT deficiency. Histologic confirmation of the diagnosis was aided by immunostaining of the AAT globules. Liver transplantation was successful in reversing the disease process.
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PMID:End-stage liver disease in a 31-year-old man. 143 85

alpha 1 antitrypsin deficiency is associated with predisposition to the development of pulmonary emphysema and childhood cirrhosis. There are two common deficiency alleles in the European population, proteinase inhibitor (Pi) Z and S. In addition, there are rare Pinull or QO variants which can be difficult to diagnose. A family assigned as having the PiQO allele by AAT protein quantification and isoelectric focusing was shown by DNA sequencing to have the PiMheerlen mutation (Pro369-Leu). This highlights the difficulties of diagnosis of PiQO.
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PMID:What is Pi (proteinase inhibitor) null or PiQO?: a problem highlighted by the alpha 1 antitrypsin Mheerlen mutation. 155 39

A 43-year-old black man had an 18-year history of apical lung cystic-bullous disease. Following two episodes of spontaneous pneumothorax and two instances of thoracotomy for bullectomy and pleural abrasion, he was found to have an intermediate AAT deficiency with an MZ phenotype. It is believed that this is the first case of localized bullous lung disease to be reported in association with any degree of AAT deficiency. There is evidence that the cystic lesions progressed to form upper lobe bullae. It is postulated that the AAT deficiency may have played a role in this progression, as did the patient's cigarette smoking. Following two instances of surgery, CT scans of the lungs, compliance studies and complete pulmonary function tests show no further evidence of lung bullae or emphysema. The rarity of the Z variant of AAT in blacks is discussed.
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PMID:Intermediate alpha 1-antitrypsin deficiency with apical lung bullae and spontaneous pneumothorax. Presence of a Z variant in an American black. 203 55

The diagnostic accuracy of laboratory investigations in the prelaparotomy differentiation between extrahepatic biliary atresia (EHBA) and intrahepatic disease (IHD) was assessed in 86 consecutive infants presenting with conjugated hyperbilirubinaemia. Forty five infants had EHBA and 41 IHD. The mean serum bilirubin concentration, gamma-glutamyltranspeptidase (GGT) activity, and the GGT/aspartate transaminase (AST) ratio were appreciably higher in infants with EHBA than in those with IHD. In infants with IHD, however, serum bilirubin concentrations were in the EHBA range in 19 (47%), as were GGT values in 29 (71%), and GGT/AST ratios in 33 (80%). In individual patients neither increasing nor decreasing GGT values were of diagnostic importance. Failure of biliary excretion of 99Tcm-p-Butyl-ida occurred in 29 of 30 (97%) patients with EHBA but also in 22 of 23 (67%) with IHD. In all 5 patients with IHD associated with alpha 1 antitrypsin deficiency these 4 investigations gave results in the EHBA range. Liver biopsy specimen interpretation, correct in 38 of 42 infants with EHBA, gave an overall accuracy of diagnosis of 86%: the results of 3 further biopsies were equivocal. In 33 of 40 infants with IHD bile duct obstruction was excluded; the remaining 7, including 4 with alpha 1 antitrypsin deficiency, showed equivocal changes. Faecal excretion of 131I rose bengal faecal excretion was less than 10% in 36 of 37 patients with EHBA and in 9 of 26 with IHD, giving an overall accuracy of diagnosis of 84%. In patients in whom genetic disorders, such as alpha 1 antitrypsin deficiency had been excluded, interpretation of liver biopsy specimens together with 131I rose bengal faecal excretion remain the most accurate means of identifying those who need surgery for EHBA and of avoiding unnecessary laparotomy in infants with IHD.
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PMID:The prelaparotomy diagnosis of extrahepatic biliary atresia. 613 97

In 500 consecutive autopsies there were 27 cases in which the livers contained PAS-positive, diastase-resistant globules within hepatocytes. On the basis of morphologic findings and immunoperoxidase staining the inclusions were separable into two groups. There were 14 (2.8%) cases in which the globules were periportal in location and stained positively with the specific AAT immunoperoxidase method (Type 1 globules). In 13 (2.6%) cases, the globules were located in the centrilobular region of the liver or at the edge of the central ischemic zone. These globules did not stain with the specific immunoperoxidase technic (Type 2 globules). Cirrhosis was found in 10 (71%) of the 14 livers containing Type 1 globules. Dysplastic liver cells were present in four cases. No liver cell cancer was present in any of the cases. No fibrosis or cirrhosis was found in any of the 13 livers containing Type 2 globules. They were always present in the centrilobular areas and most likely were the result of sinusoidal congestion and anoxia. The immunocytochemical method is useful in separating the two types of PAS-positive, diastase-resistant globules. Type 1 inclusions are associated with alpha 1 antitrypsin deficiency.
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PMID:Alpha 1 antitrypsin liver disease differential diagnosis of PAS-positive, diastase-resistant globules in liver cells. 618 89

Alpha 1-antitrypsin has been examined in formalin-fixed, paraffin-embedded liver specimens from Greek patients with cirrhosis (35 cases) and hepatoma (55 cases) by peroxidase-antiperoxidase (PAP) method. Ring-like AAT globules were found in the non-neoplastic cells in 12% of the cases of hepatoma and in 11% of the cases of cirrhosis. Atypical globules were seen in neoplastic cells in 5.4% of the cases of hepatoma and in 17% of the cases of liver cirrhosis. A diffuse fine granular pattern of AAT distribution was present in 31% of the cases of hepatoma in the neoplastic cells and in 27% of those in the non-neoplastic cells. The relatively high incidence of ring-like AAT-globules, and of atypical globules in cases of hepatoma and cirrhosis is not in agreement with the extremely low gene frequency of Z allele in a Greek population of patients with cirrhosis and hepatoma. Thus, there is some doubt whether AAT-globules in the liver represent a histopathologic marker of genetically determined AAT deficiency. A relationship between AAT deposits and the degree of differentiation of hepatoma was noted in this series. AAT-positive cells were found in 55% of moderately differentiated, in 29% of highly differentiated and in 20% of poorly differentiated hepatomas.
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PMID:Demonstration of alpha 1-antitrypsin in paraffin sections of hepatoma and cirrhosis. 629 75

Although alpha(1)-antitrypsin (AAT) deficiency is one of the most common hereditary diseases and a recognized cause of emphysema in Caucasians, variants of this deficiency are extremely rare among Orientals. We present here a Japanese emphysema patient with the AAT deficiency variant originally identified as S(iiyama). After an 8-year follow-up period, the patient suffered from repeated pulmonary Pseudomonas aeruginosa infection for 4 years. He died suddenly of massive pulmonary hemorrhage. The pathologic examination revealed a necrotic hematoma in the right S10 lobe, which exhibited pneumonia due to cytomegalovirus (CMV) infection. Pulmonary hemorrhage due to CMV can occur and be fatal in patients with emphysema and AAT deficiency.
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PMID:Massive pulmonary hemorrhage due to cytomegalovirus infection in a Japanese patient with alpha-1-antitrypsin-deficient emphysema. 1046 Oct 90


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