Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023890 (cirrhosis)
 42,195 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. alpha 1-antitrypsin is an antiprotease that inhibits the neutrophil elastase enzyme, and belongs to a family of structurally related serine proteinase inhibitors (serpins). Its methionine358 residue determines the specificity for elastase. 2. The normal M-type alpha 1-antitrypsin is mainly synthesized in the liver parenchymal cells and transported to the plasma. Abnormal Z-mutant alpha 1-antitrypsin is retained in the endoplasmic reticulum, which leads to its intracellular accumulation and to markedly decreased plasma levels. 3. In normal conditions, alpha 1-antitrypsin protects the lungs from destruction by the proteolytic neutrophil elastase. A protease/antiprotease imbalance in the lung is responsible for the development of emphysema in severe alpha 1-antitrypsin deficiency and in cigarette smokers, and accounts for the marked acceleration of the lung disease in smoking alpha 1-antitrypsin deficient patients. Smoking has to be avoided in alpha 1-antitrypsin deficient patients. Replacement therapy with plasma-derived alpha 1-antitrypsin seems indicated in alpha 1-antitrypsin deficient patients with emphysema. 4. Intracellular accumulation of abnormal Z-alpha 1-antitrypsin molecules in liver parenchymal cells may lead to liver disease, ranging from neonatal cholestasis to adulthood cirrhosis and hepatocellular carcinoma. End-stage liver disease can be treated by liver transplantation, which is followed by a phenotypic conversion. 5. Diagnosis of alpha 1-antitrypsin deficiency related disease relies on the presence of a low serum concentration of alpha 1-antitrypsin, and of periodic-acid Schiff positive globules in the liver parenchymal cells. Isoelectric focusing of the serum identifies the protease inhibitor phenotype. The protease inhibitor phenotype is determined by the independent expression of the two parental alpha 1-antitrypsin alleles. It is determinant of the serum level and of the risk for development of lung or liver disease.
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PMID:Alpha 1-antitrypsin deficiency: an overview. 839 99

The clinical pattern and the pathophysiological mechanism of the hereditary disorder alpha 1-antitrypsin deficiency are outlined. It appeared that the patient described suffered not only from emphysema, cirrhosis of the liver and hepatocellular carcinoma, but also from acute haemorrhagic pancreatitis. The combination of acute pancreatitis and alpha 1-antitrypsin deficiency has not been described before. Screening of relatives is important because of possible treatment.
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PMID:[Acute pancreatitis in a patient with alpha 1-antitrypsin deficiency. Is there a causal relationship?]. 841 21

Main variants of alpha-1-proteinase inhibitor are reviewed. Some clinical aspects of alpha-1-proteinase inhibitor deficiency concerned with emphysema, hepatic cirrhosis and panniculitis are discussed.
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PMID:[Clinical features of the genetic variants of alpha-1-proteinase inhibitor]. 841 21

Alpha-1-antitrypsin is a glycoprotein which inactivates proteolytic enzymes, especially neutrophil elastase. Infants deficient in this enzyme commonly develop neonatal hepatitis. In adults, the deficiency typically results in emphysema. Only rarely will an adult manifest liver disease. We present a case of adult liver cirrhosis due to Alpha-1-antitrypsin deficiency in a 63-year-old man. Manifestations of alpha-1-antitrypsin deficiency and liver disease are discussed.
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PMID:Alpha-1-antitrypsin deficiency: rare cause of adult cirrhosis--a case report. 842 51

A review of the perioperative morbidity and mortality and long-term survival in elderly and high-risk patients with colorectal neoplasia was undertaken. Elderly high-risk patients with localized disease were compared with those with advanced disease. Over a five-year period, 82 high-risk (at least one major organ system disease), or elderly (age > or = 70 years) patients underwent an operation for colorectal neoplasia. Overall, 43 of 82 (52 percent) had advanced disease (obstruction, perforation, hemorrhage, or metastatic disease), while 39 of 82 (48 percent) had localized disease. The mean age of all patients was 78.2 years. Preoperative comorbid diseases included: coronary atherosclerosis, 59 (72 percent); previous myocardial infarction, 17 (21 percent); previous arrhythmia, 10 (12 percent); emphysema, 32 (39 percent); renal failure, 6 (7 percent); and cirrhosis, 3 (4 percent). At the time of surgery, 26 patients (32 percent) had metastatic disease. Six patients (7 percent) died in the perioperative period. The presence of advanced neoplasia did not significantly affect 30-day mortality. There was no difference in major morbidity between patients operated on for localized and for advanced disease. The mean actuarial 18-month survival was less for patients with advanced disease (P < 0.05). Sixty-eight patients (83 percent) are alive at a follow-up of 17.7 +/- 29 months postoperatively. The morbidity and mortality associated with resection of colorectal neoplasia in high-risk elderly patients are acceptable even in the presence of advanced disease. In select patients, resection offers the best palliation and may improve the quality of remaining life.
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PMID:Advanced colorectal neoplasia in the high-risk elderly patient: is surgical resection justified? 842 20

The deficiency of alpha 1-antitrypsin, a strong protease inhibitor, is known to cause pulmonary emphysema, neonatal hepatitis and liver cirrhosis. Among 75 variants reported so far, amino acid or DNA variations have been determined in about 30 variants. Many are caused by single base substitutions which then cause single amino acid replacements. In most of the null variants, base substitutions, base deletions or base insertions make stop codons appear somewhere beyond the mutation sites, which cause truncated proteins. Only several variants, including PiZ and PiMmalton, characterized as having cytoplasmic globules in hepatocytes, cause liver diseases. Recent analyses on the tertiary structure of alpha 1-antitrypsin have elucidated the mechanism of the formation of insoluble polymers in PiZ patients. The accumulation theory seems more relevant to the mechanism of the liver damage than the protease-antiprotease imbalance theory.
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PMID:[Genetic analyses of alpha 1-antitrypsin deficiency]. 846 63

Alpha 1-antitrypsin deficiency is associated with pulmonary emphysema and liver cirrhosis. The pathogenesis and treatment is reviewed with particular emphasis on gene therapy for emphysema. The technology of gene transfer using viruses and liposomes is developing fast and animal experiments have confirmed the feasibility of gene therapy for alpha 1-antitrypsin deficiency (AATD). So far only subtherapeutic levels of protein have been produced but human trials are starting and progress can be expected.
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PMID:Gene therapy for alpha 1-antitrypsin deficiency. 854 24

It is known that alpha1-antitrypsin deficiency is associated with emphysema in adults and liver cirrhosis in neonates. The phenotypes PiZZ and PiSZ are considered to be high risk groups. alpha1-antitrypsin deficiency is one of the most common lethal congenital disorders in Europe and the USA, occurring in approximately 1 in 2,000 caucasians of North European descent. Studies in Malaysia have found that the phenotypes PiZ and PiS are present in our population. Out of 950 samples analyzed, it was found that 10 samples were shown to be apparently Z homozygous phenotype. The phenotype is determined by high resolution isoelectrofocusing on an ultra-thin polyacrylamide gel embedded with narrow range Pi phamarlyte. The isoelectrofocused bands are confirmed by immunofixation and the plasma alpha1-antitrypsin levels determined by electroimmunoassay. The abnormal phenotypes are further confirmed by polymerase chain reaction using allele specific oligonucleotides.
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PMID:The Malaysian experience in the typing of genetic variants of alpha-1-antitrypsin. 862 32

Alpha 1 antitrypsin deficiency (AT) is an autosomal recessive disease associated with chronic liver disease in adults and children and emphysema in adults. The disease is one of the most common inherited disorders of the Caucasian population of North Europe and North America and is the most common genetic reason for pediatric orthotopic liver transplantation (OLTx), although it is a rare indication in adults. The natural history of the disease is unpredictable and the pathogenesis of the liver injury unclear. Thirty-five patients with histologically apparent alpha 1 AT accumulation in the liver (22 adults, 13 children) have been transplanted in this center. Clinical features were correlated with the pretransplant phenotype, serum alpha 1 antitrypsin levels and potential precipitating factors. All children were PiZZ homozygotes, most of whom had presented with neonatal hepatitis. The majority of adult patients were heterozygotes presenting with portal hypertension and liver cirrhosis. Current one-year posttransplant survival figures are 73% for adults and 87.5% for children. Replacement of the cirrhotic liver results in acquisition of the donor phenotype, a rise in serum levels of alpha 1 antitrypsin, and apparent prevention of associated disease.
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PMID:Transplantation for end stage liver disease related to alpha 1 antitrypsin. 863 77

Alpha 1-Antitrypsin deficiency predisposes to pulmonary emphysema, liver cirrhosis and hepatocellular carcinoma. Anecdotal evidence and a large autopsy study suggest that severe lung and liver disease rarely coexist in the same subject, but this has not been studied in patients. Therefore we investigated 27 patients with severe alpha 1-deficiency (Pi ZZ) and pulmonary emphysema for signs of liver disease and impaired hepatic function. A subgroup of 7 patients underwent quantitative liver function tests. On physical examination or ultrasonography, cirrhosis or tumor was not suspected in any patient. Conventional liver function tests were completely normal in 17 patients. Elevated serum activities of gamma-glutamyltranspeptidase and/or aminotransferases were seen in 10 patients. In some, the elevation was only marginal and in none more than twice normal. The serum bilirubin concentration and activity of alkaline phosphatase were increased in 1 patient. Serum protein, albumin, fibrinogen, antithrombin III, alpha 1-fetoprotein concentrations, serum activities of cholinesterase and glutamate dehydrogenase, activated partial thromboplastin time and prothrombin time were normal in all patients. The indocyanine green half-life was abnormal only in 1 of 6 patients, suggesting that hepatic blood flow was not impaired in the study group. However, the lidocaine half-life and galactose elimination capacity, parameters of hepatic metabolization, were impaired in 4 and 6 of 7 patients, respectively. We conclude that liver disease or impaired liver function is not a clinically relevant problem in most patients with pulmonary emphysema due to alpha 1-antitrypsin deficiency. But results of quantitative liver function tests, although performed in only a small group of patients, suggest that hepatic metabolization might be impaired even in those patients who present with pulmonary disease.
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PMID:Liver function in patients with pulmonary emphysema due to severe alpha-1-antitrypsin deficiency (Pi ZZ). 873 89


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