Anamnesis, Sweat Electrolyte and Pulmonary Function Studies in Parents of Patients with Cystic Fibrosis of the Pancreas1

Orzalesi, M; Kohner, D.; Cook, Charles D.; Shwachman, Harry

doi:10.1111/j.1651-2227.1963.tb03779.x

Cited by 16 publications

(2 citation statements)

References 16 publications

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“…On the basis of the many comprehensive family studies, including segregation analysis (4--7), cystic fibrosis is clearly transmitted as an autosomal recessive trait. An increased prevalence of respiratory or gastrointestinal disease is not seen in the parents of patients with cystic fibrosis (29,30). Although the mean sweat sodium concentration (3,31) and the sodium content of nails (32) are frequently increased in obligatory heterozygotes, the degree of overlap with normal subjects invalidates these tests for the detection of carriers.…”

Section: Discussionmentioning

confidence: 99%

Cystic Fibrosis of the Pancreas

Danes

Bearn

1969

The Journal of Experimental Medicine

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103 individuals from 16 families with cystic fibrosis and 87 individuals without family history of cystic fibrosis have been studied using the methods of cell culture. Skin fibroblast cultures derived from 19 affected children, and fibroblast cultures from 11 different organs obtained at autopsy from two affected children, showed cellular metachromasia. The morphological appearance and the intracellular mucopolysaccharide content enabled these cultures to be divided into two distinct classes. Class I had discrete cytoplasmic metachromatic vesicles and a mucopolysaccharide content similar to that observed in normal fibroblasts. In class II the metachromasia was present in both vesicles and granules and was evenly distributed throughout the cytoplasm. The mucopolysaccharide content of these cells was markedly increased. The cultures derived from the parents, presumed heterozygotes, and other members of each family showed cells with the same type of metachromasia as that demonstrated by the propositus. These data strongly suggest that cystic fibrosis is not a homogeneous entity and, moreover, can be caused by homozygosity of genes at two distinct loci. The recognition of cytoplasmic abnormalities in skin fibroblasts derived from affected individuals and heterozygous carriers for cystic fibrosis should facilitate genetic and biochemical studies on the heterogeneity of this inborn error of metabolism.

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Section: Discussionmentioning

confidence: 99%

Cystic Fibrosis of the Pancreas

Danes

Bearn

1969

The Journal of Experimental Medicine

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“…In the 1960s, several groups investigated the hypothesis that CF heterozygotes may be predisposed to respiratory disease. Comparisons of parents of CF patients versus controls (mean age 34-36 yrs) did not reveal any significant differences in lung function or history of asthma or chronic bronchitis [86][87][88][89]. However, obligate heterozygotes have been shown to have increased bronchial reactivity to methacholine [90], and increased incidence of wheeze accompanied by decreased FEV1 and forced mid-expiratory flow (FEF25-75) [91].…”

Section: Cystic Fibrosis Transmembrane Regulatormentioning

confidence: 99%

Genetic risk factors for chronic obstructive pulmonary disease

Sandford¹,

Weir²,

Paré³

1997

Eur Respir J

191

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Cigarette smoking is the major risk factor for chronic obstructive pulmonary disease (COPD). However, only a minority of cigarette smokers develop symptomatic disease. Studies of families and twins suggest that genetic factors also contribute to the development of COPD. We present a detailed literature review of the genes which have been investigated as potential risk factors for this disease.The only established genetic risk factor for COPD is homozygosity for the Z allele of the α 1 -antitrypsin gene. Heterozygotes for the Z allele may also be at increased risk. Other mutations affecting the structure of α 1 -antitrypsin or the regulation of gene expression have been identified as risk factors.Genes, including those for α 1 -antichymotrypsin, α 2 -macroglobulin, vitamin Dbinding protein and blood group antigens, have also been associated with the development of COPD. Variants of the cystic fibrosis transmembrane regulator gene have been identified as risk factors for disseminated bronchiectasis.The genetic basis to chronic obstructive pulmonary disease has begun to be elucidated and it is likely that several genes will be implicated in the pathogenesis of this disease. The knowledge gained from such studies may also prove relevant to other inflammatory diseases. Eur Respir J 1997; 10: 1380-1391. REVIEWChronic obstructive pulmonary disease (COPD) is characterized by decreased expiratory flow rates, increased pulmonary resistance and hyperinflation. The most important risk factor for the development of COPD is cigarette smoking [1]. Cigarette smoke, in combination with other factors, leads to two pathophysiological processes in the lung. The first is proteolytic destruction of the lung parenchyma, which increases the size of the airspaces; these eventually coalesce to form emphysematous spaces. The development of emphysema is associated with a loss of lung elastic recoil. The second process is inflammatory narrowing of peripheral airways, which is characterized by oedema, mucus hypersecretion and fibrosis, scarring, distortion and obliteration of peripheral airways. The loss of lung elastic recoil and the narrowing of the peripheral airways combine to decrease maximal expiratory flow from the lung and contribute to hyperinflation. In conjunction with gas exchange abnormalities, hyperinflation produces the symptoms of COPD.Despite the clear association of smoking and airway obstruction, there remains marked interindividual variation in the response to cigarette smoke. This indicates that there are additional genetic or environmental cofactors, which contribute to the development of COPD. It has been estimated that only 10-20% of chronic heavy smokers will ever develop symptomatic COPD [2,3]. Co-factors, such as childhood viral respiratory infections and environmental and occupational pollution, undoubtedly play a role in determining this susceptible subset. Furthermore, there is evidence that genetic susceptibility is of major importance. The epidemiological and clinical data that demonstrate a heredit...

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Genetics of Disorders of Intestinal Digestion and Absorption

Frézal

Rey

1970

Advances in Human Genetics 1

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Anamnesis, Sweat Electrolyte and Pulmonary Function Studies in Parents of Patients with Cystic Fibrosis of the Pancreas1

Cited by 16 publications

References 16 publications

Cystic Fibrosis of the Pancreas

Cystic Fibrosis of the Pancreas

Genetic risk factors for chronic obstructive pulmonary disease

Genetics of Disorders of Intestinal Digestion and Absorption

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