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)

alpha 1-Antitrypsin is a serum protein protease inhibitor. The homozygous deficiency state for alpha 1-antitrypsin is associated with the development of chronic obstructive lung disease and liver cirrhosis. Familial hypercholesterolemia is a genetic defect in which the nonhepatic tissues of affected persons are partially or completely deficient in cellular receptors for low-density lipoproteins, the major plasma cholesterol transport protein. Homozygotes and heterozygotes for familial hypercholesterolemia experience premature coronary artery disease. We have identified a young patient who manifested heterozygous deficiencies for both of these gene products. The occurrence of these defects in tandem has not been previously reported.
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PMID:Heterozygous defects in alpha 1-antitrypsin and low-density lipoprotein receptor. Simultaneous occurrence in a pediatric patient. 625 88

A 2-month-old white girl had severe liver disease (but without signs of hepatic necrosis, infection or cirrhosis), urinary cytomegalovirus, transient reduction of alpha 1-antitrypsin concentration and transient abnormal alpha 1-antitrypsin phenotype that were not present in her parents. Five serum specimens that were obtained during the 11/2 months of acute phase liver disease indicated, by polyacrylamide gel isoelectric focusing (PAG-IEF), acid starch gel and agarose electrophoresis as well as immunofixation, an unusual alpha 1-antitrypsin phenotype that we labeled delta (delta). It migrated adjacent to Z, i.e., cathodal of Z and Zpratt on PAG-IEF; anodal of Z but cathodal of X, S, Zpratt on starch gel. We labeled the girl's complete phenotype M delta. After clinical recovery, her phenotype was MM and identical to that of her parents. Hepatic electronmicroscopy of the acute phase specimen showed dilated bile canaliculi. We observed the following in hepatocytes: clusters of globular inclusions surrounded by myelin sheets that, to a lesser extent, also appeared in the liver of CMV-infected children with phenotype MM; dilated endoplasmic reticulum cisternae that contained floccular material; and marked steatosis. These changes were less severe in the convalescent liver specimen.
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PMID:Alpha 1-antitrypsin phenotype: transient cathodal shift in serum of infant girl with urinary cytomegalovirus and fatty liver. 627 90

A deficiency in the plasma protease inhibitor alpha 1-antitrypsin can cause chronic obstructive emphysema or infantile liver cirrhosis. This deficiency results from a single amino acid substitution created by a G to A transition in the gene for alpha 1-antitrypsin. Chemically synthesized specific oligonucleotide probes (19-mer) have been used to develop a sensitive and direct test for the presence or absence of the mutant gene in any individual, which can be used for prenatal diagnosis of the deficiency syndrome.
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PMID:alpha 1-antitrypsin deficiency detection by direct analysis of the mutation in the gene. 630 78

alpha 1-Antitrypsin, the major serum protease inhibitor, is a glycoprotein synthesized in the liver. Severe deficiency results in protease-antiprotease imbalance, which predisposes to severe emphysema at a young age. Reduced serum levels reflect inadequate release of alpha 1-antitrypsin by the liver, which may be caused by specific defects in biosynthesis. The deficiency is inherited, with multiple codominant alleles at a single autosomal locus. Homozygous individuals, with severely reduced alpha 1-antitrypsin levels, have dyspnea, pulmonary function abnormalities, and respiratory disability from emphysema, usually in the fifth decade of life, with smokers being affected one decade earlier. Heterozygous individuals have intermediate alpha 1-antitrypsin levels and a more benign clinical course. Heterozygous smokers may have mild pulmonary function abnormalities, but these are of uncertain clinical significance. Hepatic involvement with transient neonatal hepatitis and cirrhosis with subsequent liver failure in adulthood represent the major extrapulmonary manifestations, occurring in 10% of homozygous individuals.
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PMID:alpha 1-Antitrypsin deficiency. 632 84

Urinary excretion of bile acids was investigated in seven infants with alpha 1-antitrypsin deficiency and neonatal cholestasis. The infants were followed prospectively and the bile acid analysis was repeated after 2-8 years in four of the patients. Bile acid excretion during 24 h was quantified by gas-liquid chromatography and the bile acids were identified by gas-liquid chromatography-mass spectrometry. In contrast to healthy controls, all the patients excreted tetrahydroxylated bile acids during cholestasis and in the postcholestatic period. The patients who developed cirrhosis during the observation period had lower concentration of tetrahydroxylated bile acids than those with a more favourable course. Our findings suggest that tetrahydroxylation of bile acids might be an alternative pathway for elimination of bile acids in cholestasis of infancy, and that those infants exhibiting a good capacity of polyhydroxylation might have a better prognosis.
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PMID:Urinary excretion of tetrahydroxylated bile acids in children with alpha 1-antitrypsin deficiency and neonatal cholestasis. 633 65

Since proteolytic processes are prominent in psoriasis, sera of forty-five psoriatics were examined for alpha 1-antitrypsin (alpha 1-AT) phenotype and eighteen sera, for alpha 1-AT content and function. Five sera (11.1%) had heterozygous phenotypes (2 MZ and 3 MS), a prevalence of Z and S variants similar to that reported in nonpsoriatic populations. Two of three variants examined for content and function exhibited marked reductions. Since MZ heterozygotes are almost always, and MS phenotypes sometimes, associated with decreased serum alpha 1-AT levels, and since Z and MZ phenotypes are associated with increased hepatic fibrosis or cirrhosis, these variants may be relevant to problems of spontaneous fibrosis or methotrexate-induced hepatotoxicity in psoriasis. alpha 1-AT deficiency may also contribute to guttate flares with infection and to increased O-2 . production by psoriatic sera-stimulated polymorphonuclear leukocytes (PMNs). Although no evidence exists that psoriasis is more prevalent among persons with hypomorphic alpha 1-AT phenotypes, such defects may contribute to severity of inflammation and hyperplasia.
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PMID:Alpha 1-antitrypsin deficiency genes: contributory defect in a subset of psoriatics? 633 40

Antibodies to a liver-specific lipoprotein complex (LSP) were determined by radioimmunoassay in the sera of 65 children with possible chronic liver disease. Thirteen had "autoimmune" chronic active hepatitis (CAH), 21 alpha 1-antitrypsin deficiency PiZ (alpha 1-ATD), all having significant liver disease, while 10 of 31 children with cystic fibrosis (CF) had abnormal biochemical tests of liver function, six having cirrhosis. Sera from 12 (92%) of 13 untreated CAH patients contained detectable anti-LSP antibodies, the highest titres occurring in those with anti-liver/kidney microsomal or smooth muscle antibodies. Titre of anti-LSP antibodies correlated with piecemeal necrosis of periportal hepatocytes in liver biopsies, but not with standard biochemical tests of liver function or serum immunoglobulin concentrations. The incidence of LSP antibodies fell as liver damage improved with immunosuppressant therapy, being positive in 18 of 26 sera from children in whom the transaminases were still above normal, but positive in only two of 20 in whom transaminase values were within the normal range (chi 2 = 16, p less than 0.001). Sera from two of 31 patients (6%) with CF contained anti-LSP antibodies as did sera from six of 21 patients with alpha 1-ATD. Antibody concentrations were lower than in CAH, and in alpha 1-ATD the presence of anti-LSP could not be correlated with the presence or absence of piecemeal necrosis on liver biopsy. Our data suggest that autoimmune mechanisms involving antibody to hepatocyte membrane components have a role in the pathogenesis of chronic liver disease in autoimmune CAH in children as in adults.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Antibodies to liver-specific lipoprotein in children with chronic liver disease due to "autoimmune" chronic active hepatitis, cystic fibrosis, and alpha 1-antitrypsin deficiency. 633 53

We studied, over a four-year period, two adolescents with alpha 1-antitrypsin (AAT) deficiency who subsequently died from complications of hepatic cirrhosis. Serial pulmonary function studies indicated mild obstructive lung disease involving peripheral airways in both patients. Postmortem histologic and pulmonary morphometric studies indicated mild diffuse airspace and bronchial gland enlargement, and slight dilation of small airways. This airspace enlargement may represent the early stage of lung disease in AAT-deficient subjects and suggests that pulmonary anatomic changes may occur long before the onset of clinically and pathologically significant emphysema.
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PMID:Unusual abnormalities in adolescent siblings with alpha 1-antitrypsin deficiency. 660 Jun 73

We observed 45 children with a history of neonatal cholestasis associated with alpha 1-antitrypsin deficiency (phenotype PiZ). Twenty-five developed cirrhosis (group 1), and in the other 20, without cirrhosis (group 2), the outcome was considered to be good. Certain clinical, biochemical, and histologic features of each group were studied to permit early assessment of hepatic evolution. Liver biopsy showed that fibrosis was more frequent and severe in group 1 during neonatal cholestasis. Later this group was characterized by possible persistence of jaundice, early development of splenomegaly, and persistence of hard hepatomegaly and liver function abnormalities. Of the latter, sustained elevation of SGPT and direct bilirubin values were the most striking findings. The characteristics of group 2 were harder to identify: clinical recovery and return to normal biochemical values were always signs of a good outcome, as confirmed by the histologic findings; on the other hand, although some of the children in this group without cirrhosis had only minimal abnormalities, histologic evidence of significant portal fibrosis in some patients made long-term prognosis less certain.
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PMID:Early assessment of evolution of liver disease associated with alpha 1-antitrypsin deficiency in childhood. 660 2

alpha 1-Antitrypsin is a major plasma protease inhibitor synthesized in the liver. Genetic deficiency of this protein predisposes the affected individuals to development of infantile liver cirrhosis or chronic obstructive pulmonary emphysema. The human chromosomal alpha 1-antitrypsin gene has been cloned and shown to contain three introns in the peptide-coding region. When the cloned alpha 1-antitrypsin gene was used as a hybridization probe to analyze Eco RI-digested genomic DNA from different individuals, two distinct bands of 9.6 kilobases (kb) and 8.5 kb in length were observed in every case. Further analysis using only labeled intronic DNA as the hybridization probe has indicated that the authentic alpha 1-antitrypsin gene resides within the 9.6-kb fragment. Thus the 8.5-kb fragment must contain another gene that is closely related in sequence to the alpha 1-antitrypsin gene. Using a series of human-Chinese hamster somatic cell hybrids containing unique combinations of human chromosomes, the alpha 1-antitrypsin gene as well as the sequence-related gene have been assigned to human chromosome 14 by Southern hybridization and synteny analysis.
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PMID:Assignment of the alpha 1-antitrypsin gene and a sequence-related gene to human chromosome 14 by molecular hybridization. 660 46


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