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

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.
 ...
PMID:[Deficiency of alpha-1-antitrypsin and the allele Pi nul]. 108 63

Combined hepatocellular-cholangiocarcinoma is a rare form of primary liver cancer showing features of both hepatocellular and biliary epithelial differentiation. In a review of 24 cases of this tumor, three histologic types were encountered. Four cases were Type I or "collision tumors," apparently a coincidental occurrence of both hepatocellular carcinoma and cholangiocarcinoma in the same patient. Twelve cases were Type II or "transitional tumors," in which there were areas of intermediate differentiation and an identifiable transition between hepatocellular carcinoma and cholangiocarcinoma. Eight cases were Type III or "fibrolamellar tumors" which resembled the fibrolamellar variant of hepatocellular carcinoma but which also contained mucin-producing pseudoglands. Type III tumors differ from other combined tumors, occurring at a younger age, in the absence of cirrhosis, and having a slightly longer survival. Immunohistochemical (immunoperoxidase) staining for intracellular antigens showed that alpha-fetoprotein is a fairly specific, although insensitive, marker of hepatocellular differentiation in primary liver cancers, being present in 50% of typical hepatocellular carcinomas and in hepatocellular areas in 29% of combined tumors, but in no cholangiocarcinomas or cholangiocellular areas of combined tumors. Keratin is a good marker of biliary epithelial differentiation, being found in 90% of cholangiocarcinomas and in 52% of combined hepatocellular cholangiocarcinomas, but in no hepatocellular carcinomas. Alpha-1-antitrypsin, fibrinogen, IgG, and carcinoembryonic antigen may be found in both hepatocellular carcinoma, cholangiocarcinoma, and in combined tumors; these antigens are therefore of limited use in differential diagnosis.
 ...
PMID:Combined hepatocellular-cholangiocarcinoma. A histologic and immunohistochemical study. 257 78

Alpha-1-antitrypsin (AAT) is the predominant protease inhibitor in human sera. The major physiological role of this inhibitor is to protect elastin fibers in the alveolar structure of the lung from excessive degradation by neutrophil elastase. AAT is synthesized predominantly by hepatocytes, although the AAT gene is expressed to a small degree in the epithelial cells of various tissues. Recent studies have shown that the enhanced liver-specific expression of the AAT gene is controlled by the binding of hepatic nuclear proteins to specific DNA sequences upstream from the structural gene. A variety of mutations within the AAT gene have been identified that result in a partial deficiency or total absence of the inhibitor in sera. Inheritance of a particular combination of these alleles can result in a predisposition towards the development of destructive lung disease. Interestingly, the most common AAT deficiency variant, designated PiZ, causes the mutant protein to accumulate as an insoluble aggregate within the lumen of the hepatic rough endoplasmic reticulum, which is an etiological agent for the development of liver disease. Overall, investigation into the genetic control of AAT has led to an increased understanding of the factors that control hepatic gene expression, as well as mechanisms involved in the pathophysiology of emphysema and liver cirrhosis.
 ...
PMID:Genetic control of human alpha-1-antitrypsin. 269 88

Alpha-1-antitrypsin is a glycoprotein of blood exhibiting the properties of a proteolytic enzymes inhibitor. It occurs in a number of polymorphic variants transmitted genetically, the differentiation of which enables to use electrophoretic methods. The authors surveys literature, involving also her own experience, on the diagnostic use of alpha-1-antitrypsin phenotypes. The variants related to alpha-1-AT deficiency are associated with an increased incidence of certain diseases: obstructive pulmonary disease, liver cirrhosis in children, cancer. An early establishment of alpha-1-antitrypsin phenotype may be significant for occupational prevention, furthermore, it may be helpful in the highlighting of etiology of certain liver diseases in early childhood.
 ...
PMID:[Alpha 1-antitrypsin phenotypes and their role in medical diagnosis]. 332 31

Alpha-1-antitrypsin level and serum trypsin inhibitory activity were measured in patients with viral hepatitis, chronic hepatitis and liver cirrhosis. The most pronounced discrepancy between these two parameters were observed in patients with liver cirrhosis: the increase of alpha-1-At level was not accompanied by adequate increase of trypsin inhibitory activity. Some mechanisms potentially responsible for this discrepancy are discussed.
 ...
PMID:Serum trypsin inhibitory activity and alpha-1-antitrypsin level in liver diseases. 349 Apr 9

One-hundred-and-ten children between the ages of two months and 14 years with the following liver diseases were studied: 16 with acute viral hepatitis, 8 with persistent chronic hepatitis, 31 with active chronic hepatitis, 5 with hepatic steatosis, 11 with cirrhosis of the liver, 24 with newborn cholestasis, 3 with Wilson's disease, 2 with congenital hepatic fibrosis, 5 with metabolic diseases and 5 due to other causes. These children presented Pi system phenotypes in isoelectric focus using ultrafine polyacrylamide gels according to Kuepper's method, with modifications incorporated to determine Alpha-1-antitrypsin (A1-AT) serum level deficiencies in those presenting the Pi ZZ phenotype, a liver biopsy with P.A.S. coloration on digestion of diastase and a family history of the phenotype. Four (3.6%) of the children with Pi ZZ phenotypes showed a decrease of serum A1-AT and the presence of positive P.A.S. inclusions resistant to diastase in the cytoplasm of hepatocytes. Three had a history of postnatal icterus and the fourth presented hepatomegaly. The phenotypic study of the parents showed their being heterozygous (MZ), while siblings were normal (MM). The importance of the diagnosis of A1-AT deficiency and the diagnostic value of detecting Pi system phenotypes in every case of liver disease in children and adolescents is stressed.
 ...
PMID:[The value of the Pi system phenotype in alpha 1-antitrypsin deficiency]. 349 88

Alpha-1-antitrypsin is a blood glycoprotein synthesized in the liver. It is a protease inhibitor of the serpine group and has a specific action for elastase. Alpha-1-antitrypsin electrophoresis shows about 20 phenotypes, the normal one being PiM. The allele PiZ is usually responsible for liver or lung disease in children or adults, respectively. Eleven per cent of PiZZ infants present with prolonged neonatal cholestasis. Twenty-five of 45 PiZZ infants with prolonged neonatal cholestasis presented with later cirrhosis. Persistence of jaundice beyond the sixth month of age, early development of splenomegaly, persistence of hard hepatomegaly and liver function abnormalities, and early portal fibrosis have a poor prognostic significance. The most severe course occurs in infants with an early histologic pattern of paucity of interlobular bile ducts. Portal hypertension was present in 19 of 25 children presenting with cirrhosis; 8 of 25 PiZZ children with cirrhosis died during childhood.
 ...
PMID:[Alpha 1-antitrypsin deficiency in childhood]. 387 73

Alpha-1-antitrypsin (alpha-1-AT) deficiency can lead to juvenile liver cirrhosis and lung emphysema in adulthood. The deficiency Z allele is caused by a base transition. Temperature gradient gel electrophoresis (TGGE) and hybrid isoelectric focusing (HIEF) were used to detect carriers of the Z mutation of the alpha-1-AT gene. The resulting data were compared. To verify carriers at the sequence level, a manual nonradioactive sequencing strategy was established. Among our sample of carriers of the Z mutation, two were not detected by HIEF that could be identified by TGGE. DNA of all TGGE identified individuals harboring the Z mutation of the alpha-1-AT gene were sequenced nonradioactively. All carriers harbored a G to A transition at position 11.940. This mutation is described to cause the altered protein.
 ...
PMID:TGGE and HIEF: a comparison of two methods in the detection of carriers of the Z mutation in the alpha-1-antitrypsin gene. 816 37

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.
 ...
PMID:Alpha-1-antitrypsin deficiency: rare cause of adult cirrhosis--a case report. 842 51

Alpha-1-antitrypsin (alpha(1)-antitrypsin) is the archetypal member of the serine proteinase inhibitor or serpin superfamily. The most common severe deficiency variant is the Z allele, which results in the accumulation of mutant protein within hepatocytes. This 'protein overload' causes neonatal hepatitis, cirrhosis and hepatocellular carcinoma. The lack of circulating plasma alpha(1)-antitrypsin results in early-onset panlobular emphysema. The mechanism underlying the deficiency of Z alpha(1)-antitrypsin is due to an aberrant conformational transition within the protein and the formation of chains of polymers that tangle within the secretory pathway of hepatocytes. This mechanism also underlies the plasma deficiency of other members of the serpin superfamily to cause a class of diseases called the serpinopathies. Specifically mutant alleles of antithrombin, C1-inhibitor and alpha(1)-antichymotrypsin have been reported that favour the spontaneous formation of polymers and the retention of protein within hepatocytes. The consequent lack of plasma antithrombin, C1-inhibitor and alpha(1)-antichymotrypsin results in thrombosis, angio-oedema and emphysema, respectively. Moreover, the polymerisation of mutants of neuroserpin results in the retention of polymers within neurones to cause the inclusion body dementia, familial encephalopathy with neuroserpin inclusion bodies or FENIB. We review here the genetic and molecular basis and clinical features of alpha(1)-antitrypsin deficiency, and show how this provides a platform to understand the other serpinopathies.
 ...
PMID:Practical genetics: alpha-1-antitrypsin deficiency and the serpinopathies. 1469 55


1 2 Next >>