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Titolo:
Keratin 8 mutations in patients with cryptogenic liver disease.
Autore:
Ku, NO; Gish, R; Wright, TL; Omary, MB;
Indirizzi:
Vet Affairs Med Ctr, Gastroenterol Sect, Palo Alto, CA 94304 USA Vet Affairs Med Ctr Palo Alto CA USA 94304 Sect, Palo Alto, CA 94304 USA Stanford Univ, Sch Med, Palo Alto, CA 94304 USA Stanford Univ Palo Alto CA USA 94304 iv, Sch Med, Palo Alto, CA 94304 USA Calif Pacific Med Ctr, Dept Transplantat, San Francisco, CA USA Calif Pacific Med Ctr San Francisco CA USA lantat, San Francisco, CA USA Vet Affairs Med Ctr, Gastroenterol Sect, San Francisco, CA 94121 USA Vet Affairs Med Ctr San Francisco CA USA 94121 an Francisco, CA 94121 USA
Titolo Testata:
NEW ENGLAND JOURNAL OF MEDICINE
fascicolo: 21, volume: 344, anno: 2001,
pagine: 1580 - 1587
SICI:
0028-4793(20010524)344:21<1580:K8MIPW>2.0.ZU;2-M
Fonte:
ISI
Lingua:
ENG
Soggetto:
EPIDERMOLYSIS-BULLOSA SIMPLEX; GENETIC SKIN DISEASES; ENCODING LAMIN A/C; INTERMEDIATE FILAMENTS; TRANSGENIC MICE; PARTIAL LIPODYSTROPHY; HEPATOCYTE INTEGRITY; MISSENSE MUTATIONS; SKELETAL MYOPATHY; RAT HEPATOCYTES;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Life Sciences
Citazioni:
53
Recensione:
Indirizzi per estratti:
Indirizzo: Ku, NO Vet Affairs Med Ctr, Gastroenterol Sect, Mail Code 154J,3801 Miranda Ave, Palo Alto, CA 94304 USA Vet Affairs Med Ctr Mail Code 154J,3801 Miranda Ave Palo Alto CA USA 94304
Citazione:
N.O. Ku et al., "Keratin 8 mutations in patients with cryptogenic liver disease.", N ENG J MED, 344(21), 2001, pp. 1580-1587

Abstract

Background: About 10 percent of patients who undergo liver transplantationhave cryptogenic liver disease. In animal models, the absence of heteropolymeric keratins 8 and 18 or the presence of mutant keratins in hepatocytes causes or promotes liver disease. We have previously described a mutation in the keratin 18 gene in a patient with cryptogenic cirrhosis, but the importance of mutations in the keratin 8 and keratin 18 genes in such patients is unclear. Methods: We tested for mutations in the keratin 8 and keratin 18 genes in purified genomic DNA isolated from 150 explanted livers and 89 peripheral-blood specimens from three groups of patients: 55 patients with cryptogenic liver disease; 98 patients with noncryptogenic liver disease, with causes that included alcohol use, autoimmunity, drug use, and viral infections; and86 randomly selected inpatients and outpatients who provided blood to the hematology laboratory. Results: Of the 55 patients with cryptogenic liver disease, 3 had glycine-to-cysteine mutations at position 61 (a highly conserved glycine) of keratin 8, and 2 had tyrosine-to-histidine mutations at position 53 of keratin 8. These mutations were not detected in the patients with other liver diseases or in the randomly selected patients. In transfected cells, the glycine-to-cysteine mutation limited keratin-filament reorganization when the cells were exposed to oxidative stress. In contrast, the tyrosine-to-histidine mutation destabilized keratin filaments when transfected cells were exposed to heat or okadaic acid stress. Conclusions: Mutations in the keratin 8 gene may predispose people to liver disease and may account for cryptogenic liver disease in some patients. (N Engl J Med 2001;344:1580-7. ) Copyright (C) 2001 Massachusetts Medical Society.

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Documento generato il 12/08/20 alle ore 20:53:07