Research in Cystic Fibrosis

Pa, di Sant'Agnese; Pb, Davis

doi:10.1056/nejm197609022951005

Cited by 78 publications

(31 citation statements)

References 64 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The earliest lesion in exocrine tissues in CF is the microobstruction of glandular tissue by cellular products that are less soluble than those produced by normal cells (1)(2)(3)(4). Dilatation of ducts (the "cysts") and fibrosis ensue.…”

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

Mitrochondrial NADH dehydrogenase in cystic fibrosis.

Shapiro¹,

Feigal²,

Lam³

1979

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

We have shown that skin fibroblasts from patients with cystic fibrosis (CF) and from carriers for CF [heterozygotes (HZ)] consume more 02 than do their controls. When the mitochondrial electron transport inhibitor rotenone was added to the cells, the relative inhibition of 02 consumption was CF > HZ > controls (P < 0.005 in both comparisons). Because rotenone specifically inhibits NADH dehydrogenase, [NADH:(acceptor) oxidoreductase, EC 1.6.99.31, which is the enzyme of energy-conserving site 1 of the mitochondrial electron transport system, activity and kinetics of this enzyme system were studied in fibroblast homogenates. NADH dehydrogenase activity was equal in cells from the three genotypes. At pH 8.0, affinity of the enzyme for its substrate was CF < HZ = controls; at pH 8.6, affinity was CF> HZ = controls (P < 0.005 for the differences). pH optima for the genotypes were without exception 8.6 (CF), 8.3 (HZ), and 8.0 (control). HZ and control lines were distinguished unequivocally in a blind test on the basis of differences in pH optima. Purified mitochondrial preparations revealed pH optima identical to those found in whole cell homogenates. These data suggest that the mutant gene responsible for CF is expressed in the complex mitochondrial NADH dehydrogenase system.

show abstract

Section: Resultsmentioning

confidence: 99%

“…Although CF is considered to be a generalized disease of exocrine glands (1)(2)(3)(4), a number of laboratories including ours have used skin fibroblasts as a model system for CF studies. Fibroblasts are not exocrine cells but they do secrete their products by mechanisms similar to those operating in exocrine cells (5).…”

mentioning

confidence: 99%

Mitrochondrial NADH dehydrogenase in cystic fibrosis.

Shapiro¹,

Feigal²,

Lam³

1979

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

show abstract

“…Several lines of evidence have indieated that mucins from eystic fibrotie individuals are tnore heavily sulfated (Havez et al 1968, Lamblin et al 1972, Latnb & Reid 1972. Such structural differenees tnay form the basis for the ehanges in muein rheologieal properties seen in these patients (e.g., extreme inerease in viseosity) (Di Sant'agnese & Davis 1976). In this regard.…”

Section: /// Structural Modulatiott Of Tnuein Futtctiottmentioning

confidence: 94%

Role of salivary mucins in the protection of the oral cavity

Tabak

Levine

Mandel

et al. 1982

J Oral Pathology Medicine

477

263

View full text Add to dashboard Cite

Mucins are the principal organic constituents of mucus, the slimy visco‐elastic material that coats all mucosal surfaces. Compelling evidence suggests that they play an integral role in non‐immune protection of the oral cavity. Specific protective functions include: 1) protection against desiccation and environmental insult, 2) lubrication, and 3) antimicrobial effects against potential pathogens. Biosynthesis of mucin is regulated by both intrinsic (“cooperative sequential specificity”) and extrinsic (“structural modulation”) controls. These controls form the basis by which mucin's structure can be modified to meet a dynamically changing biological need.

show abstract

“…Cystic fibrosis (CF), the most common semilethal genetic disease in the United States, is transmitted as an autosomal recessive trait. About 5% of the general population are carriers of the gene (2). The unknown basic defect affects exocrine glands, primarily, and most clinical manifestations are secondary to obstruction of organ passages by mucous secretions that have abnormal physicochemical behavior.…”

Section: Introductionmentioning

confidence: 99%