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)

Twelve percent of a sample of New Zealand Europeans were found to have variant forms of alpha-1-antitrypsin. The distribution of different variants was similar to that found in other Northern European populations. Four percent were heterozygotes for the deficiency state (Z allele) which predisposes to both emphysema and cirrhosis. An initial survey of New Zealand Maoris suggests that although they have a lower overall incidence of variants, there is an increased frequency of the deficiency Z allele. This may be a contributory factor to the susceptibility of the Maori to respiratory and liver disease.
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PMID:Alpha-1-antitrypsin variants in New Zealand. 108 13

Alpha-1-antitrypsin is a glycoprotein in human serum that inhibits several proteases. It is a polymorphic protein. A single autosomal locus (Pi), with multiple codominant alleles is responsible of the synthesis of alpha-1-antitrypsin. Of particular interest are alleles that lead to lower than normal concentrations of alpha-1-antitrypsin in serum, namely, PiS, PiP and PiZ. Some of these subjects carry a high risk of developing chronic obstructive pulmonary disease, especially when they are homozygotes for PiZ. In children, cirrhosis of the liver are also found in association with homozygosity for PiZ. recently, TALAMO discovered a subject whose serum contained no alpha-1-antitrypsin; this was the first case of total deficiency, and the patient carried a double dose of the so-called Pi--allele (Pi nul). We were able to demonstrate that a single dose of this allele exists in three families which we have studied in this paper. In a fourth family, the propositus carries Pi-- in duplicate. We report here the second case of the strange homozygous phenotype, Pi--. Surprisingly, we have found that alpha-1-antitrypsin is not completely absent in this serum; its concentration is 200 times lower than normal (less than 10 microgrammes per ml). At the moment, the existence of the Pi-- allele is obvious, but the significance of this small quantity of alpha-1-antitrypsin in the serum of such a patient remains unknown.
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PMID:[Deficiency of alpha-1-antitrypsin and the allele Pi nul]. 108 63

The molecular basis for the accumulation of a substance which displays the immunological reactivity of alpha-1-antitrypsin within vesicles of liver parenchymal cells of individuals with hepatic cirrhosis and serum alpha-1-antitrypsin deficiency remains unclear. We recently reported that serum from a patient with alpha-1-antitrypsin deficiency and hepatic cirrhosis was substantially deficient in sialyltransferease (EC 2.4.99.1) an enzyme which transfers sialic acid from cytidine 5'-monophosphate-N-acetylneuraminic acid to a variety of asialoglycoprotein acceptors. In the present report we have extended these studies to include serum from five additional patients with alpha-1-antitrypsin deficiency and juvenile hepatic cirrhosis as well as a liver specimen obtained at autopsy of one of these patients. We find the sialytransferase activity in serum from six patients with alpha-1-antitrypsin deficiency and hepatic cirrhosis to be 50% of healthy pediatric control values and 30% of pediatric patients with liver disease. However, serum from family members homozygous for alpha-1-antitrypsin deficiency but without hepatic cirrhosis, and serum from patients with a variety of other kinds of liver disease, failed to exhibit the marked sialytransferase deficiency. Similar assays carried out on a homogenate of a liver sample from one patient with alpha-1-antitrypsin deficiency and hepatic cirrhosis indicated that the deficiency of sialyltransferase activity was not demonstrable in liver. Furthermore, a comparative kinetic analysis of serum and liver sialytransferase in normal and afflicted individuals failed to detect differences in substrate affinities which might account for a decrease in functional sialyltransferase capacity in individuals with alpha-1-antitrypsin deficiency and hepatic cirrhosis. These observations suggest that the serum sialyltransferase deficiency in such patients probably arises after chronic and extensive liver disease involving hepatic accumulation of alpha-1-antitrypsin rather than the enzyme deficiency being the primary cause of the hepatic cirrhosis and alpha-1-antitrypsin deficiency.
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PMID:Cytidine-5'-monophosphate-N-acetylneuraminic acid. Asialoglycoprotein sialic acid transferase activity in liver and serum of patients with juvenile hepatic cirrhosis and alpha-1-antitrypsin deficiency. 108 50

A 63 year old woman with cryptogenic cirrhosis, ascites, portal hypertension, and intermediate levels of alpha-1-antitrypsin of protease inhibitor SZ phenotype who died of esophageal variceal hemorrhage is described. The partial deficiency of alpha-1-antitrypsin and the diagnosis of cirrhosis were suspected one year prior to death because a needle biopsy of liver showed PAS positive, diastase resistant cytoplasmic bodies within hepatocytes. This report illustrates three previously undescribed features: (1) Heterozygous protease inhibitor SZ phenotype may be associated with coarsely nodular cirrhosis in the older adult. (2) The large intracytoplasmic glycoprotein droplets that are distinctive by light microscopy are probably formalin induced aggregates of submicroscopic flocculent material. (3) In the older patients with aberrant alpha-1-antitrypsin the flocculent material is present not only in the granular endoplasmic reticulum but also in smooth endoplasmic reticulum vesicles and cytolysosomes.
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PMID:Cirrhosis associated with partial deficiency of alpha-1-antitrypsin: a clinical and autopsy study. 108 82

The authors evaluate the health status of children with alpha-1-antitrypsin deficiency, focused on liver disease in infant age. The children were selected by neonatal screening. Of 21 children one had severe neonatal hepatitis with progression to cirrhosis, 2 children had clinically apparent jaundice to the age of two months, 6 children had elevated total bilirubin and transaminase levels without clinical signs of the disease, 12 of the remaining children had no clinical and laboratory signs of liver disease. In the discussion the authors compare the results with data published abroad.
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PMID:[Liver diseases in children with alpha 1-antitrypsin deficiency in infancy]. 139 67

This paper reviews the genetic variants of alpha-1-antitrypsin (AAT) which have been sequenced with special emphasis on the s.c. deficiency variants. These result in AAT low plasma levels via three main mechanisms: 1) intracellular storage; 2) intracellular degradation; 3) lack of synthesis. Intracellular storage occurs with the classical Z variant and with a few variants called M-like, because of their isoelectric focusing (IF) pattern. The storage phenomenon causes liver damage and can be demonstrated at both light and electron microscopic level with the help of immunohistochemistry. We report a new deficiency variant of AAT (M-Cagliari) characterized by very low plasma levels, massive storage of AAT and liver cirrhosis. By using immunohistochemical techniques and DNA analysis we could demonstrate that M-Cagliari has antigenic and genetic properties other than the Z AAT.
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PMID:Genetic variants of alpha-1-antitrypsin (AAT). 144 62

Cystic fibrosis (CF) is the commonest, fatal, autosomal recessive disorder and is associated with lung sepsis, pancreatic failure and elevated sweat electrolytes. The CF gene on chromosome 7 encodes a protein identified as CF transmembrane conductance regulator (CFTR) which regulates chloride ion transport in epithelial cell membranes. Almost 100 mutations have been identified in this gene which cause defective chloride-channel control. Recently, this abnormality has been reversed in affected CF cells in vitro by retrovirus-mediated transfer of a normal gene. Fifty years ago, most cases died in childhood, but now up to 80% reach adulthood. Chronic lung sepsis is the principal cause of death, and intensive antibiotic therapy with chest physiotherapy is used to control this. Advanced lung disease can be successfully treated by heart-lung transplantation. Nebulised recombinant DNase and antineutrophil elastase agents such as alpha-1-antitrypsin and secretory leucoprotease inhibitor are potentially promising new therapies. Pancreatic insufficiency is managed by high-calorie diets and enteric coated enzyme supplements. Other prominent gastrointestinal complications include meconium ileus equivalent, biliary cirrhosis and cholelithiasis. Specially dedicated CF centres have led to improved survival rates and allow experienced staff to treat the many complications of CF while promoting research in this multisystem disorder.
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PMID:Cystic fibrosis in adolescents and adults. The coming of age of cystic fibrosis. 155 Dec 44

Low levels of alpha-1-antitrypsin can predispose deficient infants to the development of hepatitis and cirrhosis. Heterozygous PiMZ carriers can be affected by a subclinical liver involvement during their first half year of life. One pathogenic hypothesis of liver damage is that the process seems to be mediated by the activity of toxic oxygen waste products. In the present investigation it was found that the antioxidant vitamin E was able to significantly reduce the frequency of liver involvement in PiMZ carriers at two months of age but not at five months. These findings indicate that oxidative free radicals can promote liver damage in inadequately protected young infants, such as in alpha-1-antitrypsin deficiency. The protective role of vitamin E in relation to the developmental expression of other anti-oxidant scavengers is discussed.
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PMID:Oxidative radicals and liver involvement of infants with alpha-1-antitrypsin deficiency. 166 23

A patient with type PiZZ alpha-1-antitrypsin deficiency was found to have severe hypoxia despite normal pulmonary function testing and a normal chest radiograph. A nuclear medicine ventilation-perfusion study revealed a right-to-left shunt. Computed tomography showed minimal bleb formation, no diffuse changes, and hepatic changes of cirrhosis with portal hypertension. No nodular pulmonary masses or enlarged peripheral pulmonary vessels were found. The diagnosis of diffuse intrapulmonic arteriovenous shunts ("pulmonary spiders of cirrhosis") was suggested and then confirmed with a dynamic radionuclide flow study.
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PMID:Hypoxia and cyanosis in alpha-1-antitrypsin deficiency. Cirrhosis as an unusual etiologic factor. 193 89

The phenotypes of alpha-1-antitrypsin have been analyzed by isoelectric focusing on polyacrylamide gels in 232 healthy Japanese blood donors and in 240 Japanese patients with chronic liver diseases: 69 with chronic active hepatitis, 122 with liver cirrhosis, 41 with hepatocellular carcinoma and 8 with primary biliary cirrhosis. The liver cirrhosis patients had a gene frequency of 0.07 for P1*M3, which was significantly higher (P less than 0.01) than that (0.03) in blood donors. The gene frequency of P1*M3 was significantly increased in cryptogenic liver cirrhosis (P less than 0.05), and there was a tendency toward an increased frequency of P1*M3 in post-transfusion groups, and in primary biliary cirrhosis. There were also tendencies toward increased frequencies of P1*M3 in cryptogenic and post-transfusion groups of patients with chronic active hepatitis. The present study indicates that P1*M3 is a genetic or predisposing factor for chronic liver diseases, especially for cryptogenic and/or non A-non B viral chronic liver disease and also for primary biliary cirrhosis.
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PMID:An association between alpha 1-antitrypsin phenotype and chronic liver disease. 215 26


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