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At least 19 recordsLinked to original sources
PubMed1979

IgE mediated hypersensitivity to pancreatic extract (PE) in parents of cystic fibrosis (CF) children.

On exposure to pancreatic extract (PE), four parents of cystic fibrosis (CF) children developed immediate hypersensitivity-like symptoms: i.e. rhinoconjunctivitis, asthma, and/or anaphylaxis. IgE to PE was demonstrated in the subjects by skin testing, leucocyte histamine release and radioallergosorbent test (RAST). No serum precipitating antibodies were found. Bronchial challenge caused an immediate asthmatic response. No delayed asthmatic response or hypersensitivity pneumonitis-like reaction occurred. The responsible antigen for PE induced asthma is unknown; trypsin failed to inhibit PE-RAST and is therefore not responsible in these subjects. Caution should be exercised in using PE for skin testing and bronchial challenge in subjects with suspected hypersensitivity to PE. Certain measures were found useful in preventing the occurrence of symptoms in the four subjects.

Adult↗
PubMed1977

Cystic fibrosis. An expanding challenge for internal medicine.

The number of adults with cystic fibrosis (CF) receiving care from the US Cystic Fibrosis Centers has been increasing at an average rate of about 200 patients each year. A model based on the continuation of this rate of increase predicts that almost 4,000 adults will be receiving care at the centers by the end of 1985. Four other models developed are based on continuation of a steady state with two variations: a 50% reduction in mortality and universal newborn screening. These models show the boundaries of an equilibrium population to be between 24,000 and 64,000 patients, with 7,000 to 18,000 adults.

Adult↗
PubMed1976

Electrophoretic studies of the cystic fibrosis ciliary inhibitor and its interaction with immunoglobulin G.

The cystic fibrosis ciliary inhibitor (CFCI) has been partially purified from serum and plasma of cystic fibrosis (CF) homozygotes and heterozygotes, and from media of cultured fibroblasts derived from cystic fibrosis genotypes. Characterization and comparison of fractions containing the CFCI were carried out by polyacrylamide gel electrophoresis. Gel electrophoresis confirmed previous molecular weight estimations of 4,500 to 11,000 for the CFCI and provided an estimate of the number of proteins present in the fractions. Low molecular weight proteins from serum and media were combined with IgG preparations. No specific binding to IgG by the media fraction containing the CFCI could be demonstrated by the techniques employed. There was decreased binding of the low molecular weight serum fraction containing CFCI to native IgG molecules from cystic fibrosis patients as compared to IgG from normal individuals. However, IgG from CF individuals demonstrated increased binding of the cfci-containing low molecular weight serum fraction after gel filtration in the presence of guanidinium chloride. This suggests: 1) that very low concentrations of CFCI are present in media fractions; and 2) that native CF IgG cannot bind the low molecular weight CFCI fractions to the same degree as native IgG from normals or CF IgG that has been dissociated from non-covalently bound components.

Blood Proteins↗
PubMed2024

In vivo editing of lung stem cells for durable gene correction in mice.

In vivo genome correction holds promise for generating durable disease cures; yet, effective stem cell editing remains challenging. In this work, we demonstrate that optimized lung-targeting lipid nanoparticles (LNPs) enable high levels of genome editing in stem cells, yielding durable responses. Intravenously administered gene-editing LNPs in activatable tdTomato mice achieved >70% lung stem cell editing, sustaining tdTomato expression in >80% of lung epithelial cells for 660 days. Addressing cystic fibrosis (CF), NG-ABE8e messenger RNA (mRNA)-sgR553X LNPs mediated >95% cystic fibrosis transmembrane conductance regulator (CFTR) DNA correction, restored CFTR function in primary patient-derived bronchial epithelial cells equivalent to Trikafta for F508del, corrected intestinal organoids and corrected R553X nonsense mutations in 50% of lung stem cells in CF mice. These findings introduce LNP-enabled tissue stem cell editing for disease-modifying genome correction.

Animals↗
PubMed1978

Cystic fibrosis presenting with the meconium plug syndrome.

The meconium plug syndrome (MPS) is a common cause of low intestinal obstruction in newborn infants. Usually, it is benign and not associated with other intestinal dysfunction. We describe the cases of three infants in whom there was intestinal obstruction consistent with the MPS and in which cystic fibrosis (CF) was later documented. We suggest that there is an association between the MPS and CF, and that the condition of all infants with the MPS be evaluated for the possibility of both Hirschsprung's disease and CF.

Cystic Fibrosis↗
PubMed2025

Cellular imbalance in proximal and distal lung of CFTR-/- sheep in utero and at birth.

BACKGROUND: The Lung is the major focus of therapeutic approaches for the inherited disorder cystic fibrosis (CF) as without treatment lung disease is life-limiting. However, the initiating events that predispose the CF lung to cycles of infection, inflammation and resultant tissue damage are still unclear. Inflammation may occur in the CF lung prior to birth in human and several large animal models suggesting an in utero origin for the disease and encouraging further studies prior to birth. METHODS: Here we used the sheep model of CF (CFTR-/-) and age-matched wild-type (WT) sheep of the same breed to investigate the single cell transcriptomes of proximal and distal lung tissue at 80 days and 120 days of gestation and at term (147 days). Single cell RNA-seq was performed on tissues from 4 to 7 animals of each genotype (WT and CFTR-/-) at each time point. RESULTS: At term, FOXJ1-expressing ciliated cells are overrepresented in both lung regions from CFTR-/- lambs, while secretory epithelial and basal cells are underrepresented in proximal lung, as are T cells and monocytes in distal lung. The imbalance in ciliated and basal cells was confirmed by immunohistochemistry. At 120 days of gestation, lymphoid cells are slightly more abundant in proximal and distal lung from CFTR-/- animals compared to WT, consistent with the transient CF-associated inflammatory response in utero. At 80 days of gestation, T and B cells are underrepresented in both lung regions. CONCLUSIONS: The differences in epithelial cell abundance observed in the CFTR-/- lambs at term may reflect sequelae from the loss of CFTR on lung development and differentiation in utero. These findings provide novel insights into the cellular mechanisms of pathology and may be relevant to the design of new therapeutic approaches for CF lung disease.

Animals↗
PubMed1976

Carcinoembryonic antigen and cystic fibrosis protein in blood from cystic fibrosis homozygotes and heterozygote carriers.

Carcinoembryonic antigen (CEA) activity was measured by radioimmunoassay in blood from cystic fibrosis (CF) homozygotes, heterozygote carriers of CF, normal healthy controls, and other patient controls with carcinomas involving gastrointestinal organs. All samples were also screened by electrofocusing for cystic fibrosis protein (CFP), a metabolic marker previously shown to be associated with the CF gene. Significantly increased levels of CEA activity were found in all CFP-positive groups; however, with one exception all patient controls with marked increases in CEA activity were CFP-negative. Immunodiffusion of perchloric acid extracts of CEA-like material from heterozygote carrier blood indicated that the CEA-like material, which was elevated in homozygotes and heterozygotes for CF, showed only partial identity with two separate CEA preparations obtained from colon carcinomas and was not identical to either A, B, or O(H) blood group substances. This glycoprotein material did, however, react with three different anti-CEA antisera. Our finding of an abnormally increased glycoprotein in cystic fibrosis, taken together with previous reports demonstrating abnormalities in the carbohydrate portion of glycoproteins found in various exocrine secretions in CF, further suggests that the primary defect in this disease is manifested partly as a defect in glycoprotein metabolism. This defect may result from an abnormality in one or more of the glycosyltransferases, possibly caused by a more primary defect in polyamine metabolism.

Adolescent↗
PubMed1978

Electrolytes in nails analysed by X-ray microanalysis in electron microscopy. Considerations on a new method for the diagnosis of cystic fibrosis.

Patients with cystic fibrosis (CF) have an increased concentration of sodium in their nails. Hitherto, only neutron activation analysis has been considered for the diagnosis of cystic fibrosis by analysis of electrolytes in nails. It has been thoroughly tested methodologically and clinically. However, the intrinsic advantages of X-ray microanalysis and the results obtained in this study suggest that this method, after further testing, may be a useful diagnostic acid for cystic fibrosis. In comparison with neutron activation analysis, X-ray microanalysis has the advantage of simultaneously giving the concentrations of several elements and may be accessible at any hospital with an electron microscope fitted with the necessary equipment. Nails of CF-patients are here shown to have increased concentrations of Na, K and Cl, which will make the diagnosis of cystic fibrosis more reliable. The possibility of using sulphur as a reference element may eliminate the weighing procedure necessary in neutron activation analysis.

Child, Preschool↗
PubMed1978

Dexamethasone-resistant cystic fibrosis fibroblasts show cross-resistance to sex steroids.

Diploid skin fibroblasts derived from individuals with the autosomal recessive disease, cystic fibrosis (CF), were shown previously to be significantly more resistant to the cytotoxicity of dexamethasone, a glucocorticoid hormone, than were normal human fibroblasts. Here cystic fibrosis fibroblasts are also shown to be more resistant than normal human fibroblasts to the cytotoxic effects of the sex hormones, 17 beta-estradiol, dihydrotestosterone and progesterone. Since cells are believed to contain different receptors for each of the steroid hormones, it is not probable than the resistance of CF cells to these hormones results from a receptor deficiency. This was shown by the fact that CF cells were found to exhibit the same receptor activity as normal cells for 3-H-dexamethasone. Furthermore, neither normal human nor CF fibroblasts could be demonstrated to contain detectable receptor activity for 3H-17 beta-estradiol. In addition, the studies of fibroblast killing by hormones led to the further interesting observation that normal human diploid fibroblasts, regardless of the sex of the tissue donor, are sensitive to killing by each of the sex hormones. These findings suggest that the cytotoxic effects of the steroid hormones may be observed independently of the specific hormone receptors. The studies reported here thus suggest that the resistance of CF cells to the different steroid hormones is probably the result of a defect in a pathway in cellular steroid hormone metabolism other than that involving receptors.

Cell Survival↗
PubMed1978

Reliable diagnosis of the major type of cystic fibrosis with fibroblast cultures. A double blind study.

A double blind study has been carried out to demonstrate that the most common type of cystic fibrosis (CF) can be reliably diagnosed with skin-derived fibroblast cultures. Alkaline phosphatase (AIP) activity has been measured in 6 normal controls, 12 CF-heterozygotes and 6 CF-homozygotes before and after stimulation with Tamm-Horsfall-glycoprotein (THP), isoproterenol and theophyline ("THP-induction test"). The mean AIP-activities after THP-induction were 8.8, 12.7 and 34.6 for the three different genotypes respectively. There was no overlap between the values of CF-homozygotes on the one hand, and the values of CF-heterozygotes and normal controls on the other hand. All 24 specimens were correctly diagnosed in the present double blind study, indicating the very high degree of reliability of the THP-induction test in the detection of the predominant type of cystic fibrosis with fibroblast cultures. Normal controls and CF-heterozygotes could not be discriminated on an individual basis, but as a group the CF-heterozygotes displayed higher AIP-values.

Adolescent↗
PubMed1979

Pathogenesis of cystic fibrosis: possible importance of alteration in epithelial surface topography.

As the pathogenesis in cystic fibrosis (CF) has been considered to lie in a disturbance in the behavior of secretions, particularly mucins, from exocrine glands, it has been proposed that an alteration in surface topography (form, number or distribution of microvilli or blebs) of epithelial cells lining ducts could impair distribution leading to retention of mucus leading to the clinical phenotype. Scanning electronmicroscopy of human epithelial suspension cultures now offers an opportunity to evaluate the role of plasmalemma topography in CF.

Cell Membrane↗
PubMed1978

Lysosomal hydrolases in cystic fibrosis livers.

The specific activity of several lysosomal hydrolases in normal and cystic fibrosis (CF) livers has been investigated. Neuraminidase activity with respect to two natural substrates (fetuin and bovine submaxillary mucin) is normal in CF livers. No significant differences were found between CF and normal livers in 4-methylumbelliferyl-alpha-D-mannosidase specific activities determined at three different pH values (4.3, 5.65 and 6.5) corresponding to lysosomal, golgi and cytosolic components of the enzyme, respectively. The specific activities of p-nitrophenyl-beta-D-mannosidase and 4-methylumbelliferyl-beta-N-acetylglucosaminidase were also both similar in CF and normal livers.

Acetylglucosaminidase↗
PubMed1976

The effect of spermidine and spermine on proliferation in vitro of fibroblasts from normal and cystic fibrosis patients.

The effects of spermidine and spermine at varying concentrations upon the replicative ability of human fibroblasts in cell culture have been studied. The average concentrations of spermidine causing a 50% inhibition of prolifertion (ID50) after 3 days of growth for three normal cell strains and three strains derived from patients with cystic fibrosis (CF) were 4.4 X 10(-6) +/- 1.2 M and 6.2 X 10(-6) +/- 2.1 M, respectively. The values for spermine were 2.0 X 10(-6) +/- 0.5 M for normal and 2.2 X 10(-6) +/- 0.1 M for fibroblasts from cystic fibrosis patients. No significant difference between the replicative ability of normal and CF cell strains was seen over a wide range of polyamine concentrations employed for a period of up to 3 days.

Cell Division↗
PubMed1977

Studies on cystic fibrosis using isoelectric focusing. III. Correlation between cystic fibrosis protein and ciliary dyskinesia activity in serum shown by a modified rabbit tracheal bioassay.

We have developed a modified rabbit tracheal bioassay for use in investigating a possible correlation between cystic fibrosis protein (CFP) and ciliary dyskinesia factor (CDF) in human serum. The bioassay requires high standards of tissue selection, and all epithelial tissue must be free of underlying connective tissue. When serum samples were collected and processed carefully and warmed to 37 degrees before assay, CDF could be reliably detected in 31 of 31 sera from cystic fibrosis (CF) homozygotes or obligate heterozygotes in 35 min or less without prior fractionation or concentration of sera, whereas 13 of 14 normal control sera were nonreactive. CDF-positive serum reacts in three consecutive phases: (1) initial increase in ciliary beat frequency, (2) ciliary dyskinesia, and (3) tissue destruction with extrusion of single ciliated cells, mucus, and debris. Our results confirm the association of CDF with cystic fibrosis. The bioassay is not specific for CF, however, when whole sera are bioassayed, since serum from several patients with bronchial asthma also caused ciliary dyskinesia. However, this finding need not preclude using rabbit tracheal ciliated epithelial tissue as an assay for following the purification of CDF. Isoelectric focusing showed that the presence or absence of CFP corresponded with that of dyskinesia activity in all sera tested except for the active samples from seven asthma patients, which were negative for CFP. The results indicate that CFP and CDF may be identical or closely related markers for the CF gene, and suggest that the activity detected by the rabbit tracheal bioassay in sera from patients with asthma and other diseases probably is caused by a substance different from a CF-specific CDF.

Animals↗
PubMed1976

Cultured cells in cystic fibrosis research: A review.

Cystic fibrosis (CF) is a common inherited disorder which is characterized by the production of exocrine secretions with elevated ion content and abnormally viscous mucus. Over the last few years cells obtained from the peripheral blood or cultured from tissues of cystic fibrosis patients have been used increasingly in the study of the disease. Investigations of the following properties of cystic fibrosis cells are reviewed: morphology, ultrastructure, growth kinetics, cellular metachromasia, the production of ciliary inhibitors, cellular composition, plasma membrane composition, the transport of inorganic ions and small organic molecules, lysosomal enzyme content, and RNA methylation. Studies of the effects on cultured cells and erythrocyte membranes of factors in CF cell culture medium and biological fluids from CF patients are discussed.

Animals↗
PubMed1977

Cystic fibrosis: studies with the oyster ciliary assay.

Bioassays using ciliary systems have detected a factor or factors in cystic fibrosis (CF) sera and tissue culture medium derived from CF cells. The typical shortcomings of an assay measuring biological activity have been studied, and the means to overcome the weaknesses of the oyster gill cilia assay have been established. The presence of the cystic fibrosis mucociliary inhibitor (CFMI) in experimental fractions may be determined by accepting data from only those assays in which authentic CF and normal (non-CF) fractions give defined reactions, by measuring the reaction of each sample at least three times, and by examining each experimental sample at a protein concentration greater than the minimum established in this study. The relative concentrations of the CFMI present in the first steps of purification of serum and medium have been calculated in terms of units of inhibition. Generally, the units of inhibition present in serum and medium fractions from heterozygotes are close to one-half of that in fractions from homozygous sources. Analogous fractions concentrated from a normal (non-CF) source never inhibited mucociliary activity, even when tested at nearly 100 times the CF concentration. Ciliary assays utilizing oyster gills are essential for monitoring fractionation procedures aimed at purifying the CFMI, and have been shown to be capable and reliable enough to do so.

Biological Assay↗
PubMed1976

The SIgA system and hypersensitivity in patients with cystic fibrosis.

A number of investigations have been used for the first time to examine the secretory IgA (SIgA) system in different body fluids from patients with cystic fibrosis (CF). Free J-chain was detected in all the sputum specimens examined. The isolated free secretory component (SC) from CF sputum differed in electrophoretic mobility from the SC isolated from normal human colostrum. In addition the free SC from some CF saliva formed precipitin lines of partial identity with normal human saliva or colostrum. A higher proportion of CF sera (33%) than of normal sera (10%) contained free SC. These investigations suggest that there may be some defect in the synthesis and/or the assembly of the SIgA immunoglobulins, which if confirmed, may help to explain the impaired Type I and Type III allergic manifestations in patients with CF.

Adolescent↗
PubMed1979

Quantitative evaluation of the development of the exocrine pancreas in cystic fibrosis and control infants.

The development of the exocrine pancreas has been determined quantitatively in 31 infants with cystic fibrosis (CF) both with and without meconium ileus and in 29 control infants. In the normal pancreas, the ratio of acinar to connective tissue volume is 0.5 at 32 weeks postconceptional age (PCA) and increases linearly to 2.0 at 52 weeks PGA. In cystic fibrosis infants, with or without meconium ileus, the ration is 0.5 at 35 weeks PCA anddecreases linearly to 0.3 at 52 weeks PCA. The volume of acinar and duct lumens is greater in CF than control infants but is independent of age or acinar volume. The development of the exocrine pancreas in infants with CF with and without meconium ileus diverges from the normal pattern: There is consistent lack of exocrine tissue before or a full-term birth, which persists throghout the age range of this study. CF infants above 42 weeks PCA can be discriminated from controls on the basis of the quantitative assessment of acinar volume.

Connective Tissue↗