Residual chloride secretion in intestinal tissue of ΔF508 homozygous twins and siblings with cystic fibrosis

Bronsveld, Inez; Mekus, Frauke; Bijman, J.; Ballmann, Manfred; Greipel, Joachim; Hundrieser, J.; Halley, Dicky; Laabs, Ulrike; Busche, Roger; Jonge, Hugo R. de; Tümmler, Burkhard; Veeze, Henk J.

doi:10.1053/gast.2000.8524

Cited by 87 publications

(97 citation statements)

References 33 publications

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“…One maintains that ⌬F508 CFTR protein reaches the PM in airway and intestinal epithelial cells in a tissue-specific manner to produce some Cl Ϫ channel function in CF subjects (Kalin et al, 1999;Bronsveld et al, 2000). The alternative hypothesis maintains that regardless of the tissue, ⌬F508 CFTR protein does not fully mature and escape the endoplasmic reticulum quality control mechanisms, and hence, reach the PM to express Cl Ϫ channel activity (Mall et al, 2004).…”

Section: Discussionmentioning

confidence: 99%

“…An immunohistochemical study detected CFTR in the apical PM at similar intensities in airway and intestinal epithelia from ⌬F508 homozygous and normal subjects, suggesting that the maturation defect of ⌬F508 CFTR is tissuespecific (Kalin et al, 1999). Similarly, recent functional studies concluded that residual CFTR-mediated Cl Ϫ secretion was present in rectal and nasal epithelia from a large subgroup of ⌬F508 homozygous CF subjects (Bronsveld et al, 2000(Bronsveld et al, , 2001.…”

Section: Introductionmentioning

confidence: 90%

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Characterization of Wild-Type and ΔF508 Cystic Fibrosis Transmembrane Regulator in Human Respiratory Epithelia

Kreda

Mall

Mengos

et al. 2005

MBoC

234

210

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Previous studies in native tissues have produced conflicting data on the localization and metabolic fate of WT and ⌬F508 cystic fibrosis transmembrane regulator (CFTR) in the lung. Combining immunocytochemical and biochemical studies utilizing new high-affinity CFTR mAbs with ion transport assays, we examined both 1) the cell type and region specific expression of CFTR in normal airways and 2) the metabolic fate of ⌬F508 CFTR and associated ERM proteins in the cystic fibrosis lung. Studies of lungs from a large number of normal subjects revealed that WT CFTR protein localized to the apical membrane of ciliated cells within the superficial epithelium and gland ducts. In contrast, other cell types in the superficial, gland acinar, and alveolar epithelia expressed little WT CFTR protein. No ⌬F508 CFTR mature protein or function could be detected in airway specimens freshly excised from a large number of ⌬F508 homozygous subjects, despite an intact ERM complex. In sum, our data demonstrate that WT CFTR is predominantly expressed in ciliated cells, and ⌬F508 CFTR pathogenesis in native tissues, like heterologous cells, reflects loss of normal protein processing.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 90%

Characterization of Wild-Type and ΔF508 Cystic Fibrosis Transmembrane Regulator in Human Respiratory Epithelia

Kreda

Mall

Mengos

et al. 2005

MBoC

234

210

View full text Add to dashboard Cite

show abstract

“…In fact, although CFTR mutations belonging to class I, II, and III have variable effects on gene transcription, mRNA translation or intracellular trafficking of the nascent protein, they would all be expected to confer complete loss of cAMP-regulated chloride channel function. However, several studies suggest that homozygotes for DF508 mutations (the most frequent class II genotype) retain in some tissues a residual functional protein expression on the cell membrane (42)(43)(44). Unfortunately, not enough class IV and V mutations carriers (conferring residual function) could be evaluated.…”

Section: Discussionmentioning

confidence: 99%

Spontaneous hypoglycemia in patients with cystic fibrosis

Battezzati¹,

Battezzati²,

Costantini³

et al. 2007

eur j endocrinol

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Objective: Diabetes frequently complicates cystic fibrosis (CF) without fasting hyperglycemia or despite spontaneous hypoglycemia (anecdotally ascribed to malnutrition), whose prevalence, clinical meaning, and relationship with glucose tolerance and clinical/nutritional status were not previously investigated. The relationship of CF genotype with insulin secretion control is also unclear. Design and methods: A total of 129 CF patients without stable diabetes received 188 oral glucose tolerance tests. Distribution of fasting plasma glucose (FPG), glucose, insulin and C-peptide responses, clinical/nutritional variables, and their relationships were analyzed. Results: FPG!60 mg/dl (3.3 mmo/l) was detected in 14% of studies and reactive hypoglycemia (PG!50 mg/dl (2.8 mmo/l)) in 15%. OGTT-based diabetes frequency was similar in the lowest quartile (Q1) and Q2-3 for FPG (10 and 8%), with higher glucose increment and area under the curve in Q1. Insulin and C-peptide levels were similar among FPG quartiles. Class I cystic fibrosis transmembrane conductance regulator mutation carriers had higher insulin concentrations than class II, especially in Q1 for FPG. Age, sex, nutritional, and anthropometric parameters including fat and lean body mass were unrelated to FPG. Lower FPG was associated with more frequent hospitalization rates (PZ0.002) and lower Shwachman scores (PZ0.041). Steroids weaning was accurately evaluated but then excluded as a possible cause of hypoglycemia. Conclusions/interpretation: Fasting asymptomatic hypoglycemia is frequent and possibly related to inappropriate insulin secretion control in class I mutation carriers. Low FPG does not exclude impaired glucose tolerance (IGT) and diabetes in CF and reflects worse clinical status.

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“…Monozygous (MZ) and dizygous (DZ) twins can differentiate the relative contribution of genetic factors since twins have a high degree of shared environment, but MZ and DZ twins differ in their degree of gene sharing (100% versus 50%) (18)(19)(20)(21). On the other hand, siblings have the same degree of gene sharing as DZ twins (50%), but a lower degree of shared environment so that a comparison of DZ twins and siblings can estimate environmental contribution.…”

Section: Introductionmentioning

confidence: 99%

Relative Contribution of Genetic and Nongenetic Modifiers to Intestinal Obstruction in Cystic Fibrosis

et al. 2006

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Residual chloride secretion in intestinal tissue of ΔF508 homozygous twins and siblings with cystic fibrosis

Cited by 87 publications

References 33 publications

Characterization of Wild-Type and ΔF508 Cystic Fibrosis Transmembrane Regulator in Human Respiratory Epithelia

Characterization of Wild-Type and ΔF508 Cystic Fibrosis Transmembrane Regulator in Human Respiratory Epithelia

Spontaneous hypoglycemia in patients with cystic fibrosis

Relative Contribution of Genetic and Nongenetic Modifiers to Intestinal Obstruction in Cystic Fibrosis

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