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At least 19 recordsLinked to original sources
PubMed1979

Increased resistance to influenza as a possible source of heterozygote advantage in cystic fibrosis.

Cystic fibrosis is the most common lethal or semi-lethal genetic disease in Caucasians of Central European origin, among whom it is inherited as an autosomal recessive trait at a frequency approximately 10 times that expected from recurrent mutation alone. A decreased sialic acid content has been observed in cell surface glycoproteins on cystic fibrosis fibroblasts and in numerous soluble glycoprotein preparations from cystic fibrosis homozygotes. Sialic acid residues on cell surface glycoconjugates play an essential role in the binding and infectivity of myxoviruses and paramyxoviruses, including those causing pandemic influenza. It is suggested that increased resistance to these viruses conferred by similar but quantitatively smaller alterations in sialoglycoconjugate structure in cystic fibrosis heterozygotes may have provided a selective advantage to maintain the high frequency of the cystic fibrosis gene in Caucasian populations.

Cystic Fibrosis↗
PubMed1977

Cystic fibrosis.

Cystic fibrosis has been regarded as a disease of infants. Yet, with improved management, a high percentage of patients how survive into young adulthood. In addition, mild cases may not be detected until long after infance. The older patient often has minimal symptoms, and the majority are socially active and productive.

Adolescent↗
PubMed1975

Defective essential-fatty-acid metabolism in cystic fibrosis.

Cystic fibrosis (C.F.) is characterised by low serum levels of essential fatty acids (E.F.A.). However, the fatty-acid pattern does not totally resemble that of dietary E.F.A. deficiency. The differences suggest a reduction in the desaturation of E.F.S. It is not known whether this defect is the primary lesion in C.F. or is the result of tissue damage in the disease. It is proposed that C.F. patients might have increased linoleic-acid requirements, and possibly specific requirements for its desaturation products.

Animals↗
PubMed1977

Serum complement depression during viral lower respiratory tract illness in cystic fibrosis.

Cystic fibrosis (CF) patients with viral lower respiratory tract illnesses (LRI) had depressed levels of the third and fourth components of complement, which returned to normal after recovery. There was no clinical evidence of immune complex disease. CF patients with LRI and no virus isolates, CF patients in stable status, and non-CF patients with LRI did not have complement depression. It is postulated that antigen-antibody complex activation of complement may occur in CF patients with viral LRI.

Adolescent↗
PubMed1992

Relationship between intestinal function and chloride secretion in patients with cystic fibrosis.

Cystic fibrosis (CF) is the most frequent inheritable disease with a lethal course. One of the major problems of the disease is malabsorption and malnutrition, due to pancreatic insufficiency which is already present at birth in more than 85% of the patients. Characteristically the mucoid secretion products of the epithelial tissues in lung, pancreas, liver and intestine have a high viscosity. The pathophysiology is characterized by obstruction of these organs with secondary damage and finally destruction. For a long period intestinal obstruction syndromes in CF were ascribed only to the pancreatic insufficiency. Malabsorption is not only caused by enzyme deficiency but is also related to transport processes to the surface of the enterocytes. This indicates that the intestinal disorders in CF are partly the result of mucoid plugging and not only of pancreatic insufficiency. Recently in vitro studies have shown a blockade of secretion through chloride channels in the mucosal membrane of CF tissues. In vivo measurements of chloride fluxes in the rectum showed a disturbed regulation in CF patients. The high viscosity of the mucus and plugging is directly related to the diminished chloride secretion. So it is postulated that the abnormal chloride secretion is responsible for the intestinal obstruction and partially also for the malabsorption.

Chlorides↗
PubMed1977

Studies on cystic fibrosis using isoelectric focusing. IV. Distinction between ciliary dyskinesia activity in cystic fibrosis and asthmatic sera and association of cystic fibrosis protein with the activity in cystic fibrosis serum.

The cystic fibrosis protein (CFP) and ciliary dyskinesia activities (CDA) in sera from CF homozygotes, heterozygote carriers, and individuals with bronchial asthma have been partially purified. Concurrently, the CDA's in sera from patients with cystic fibrosis (CF) or bronchial asthma were shown to be different substances by ion-exchange or gel permeation chromatographic procedures. Sephadex G-200 chromatography indicated that the CF-CDA eluted with a protein fraction of molecular weight (MW) 68,000-150,000 and that the asthma CDA was found in a protein fraction of MV greater than 150,000. The two activities could also be separated by DEAE-cellulose chromatography. Prior acidification of whole normal, CF homozygote, obligate heterozygote, or asthmatic sera to pH 3.7 using EDTA, followed by fractionation of Sephadex G-200 removed all the CDA's from fractions of highermolecular weight and shifted the activities to a protein fraction of MW 1,100-13,700. This procedure afforded a 200-fold purification of the CDA's in sera from patients with asthma or CF. EDTA treatment, however, also generated a CDA in previously nonreactive normal sera. Subsequent fractionation of the various active G-200 fractions on Bio-Gel P10 allowed for the separation of three separate activities (Bio-Gel Fractions I, II-IV, and V). Fraction I was shown to represent the activity in sera from patients with asthma and was determined to be C3a (MW 9,000). Fraction I was also found in normal, CF, and carrier sera and therefore is not a specific CDA. Fraction II-IV is thought to represent a CF-specific CDA (MW 5,000) since it could not be demonstrated in either normal or asthmatic sera but was found in sera of obligate heterozygotes. Fraction III-IV also did not react with antisera to human C3a. Fraction V was generated from all serum types upon acidification of the serum with EDTA and is thought to be a nonspecific CDA. Bio-Gel P10 filtration of Sephadex G-200 fractions provided 823-fold and 650-fold purification of the asthmatic and CF CDA's, respectively. Concurrent analysis of column fractions for CDA's by bioassay and for CFP by electrofocusing showed CFP only in fractions that contained the CF-CDA. Combined analyses employing acid disc gel electrophoresis, isoelectric focusing, and EDTA treatment of active CF-immunoglobulin (Ig) G and Sephadex G-200 column fractions, followed by Bio-Gel P10 chromatography, provided evidence that CFP was associated with the CF-CDA. It is unknown as yet whether CFP itself is responsible for the CF-CDA activity.

Asthma↗
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↗
PubMed1977

Pseudomonas aeruginosa infection in cystic fibrosis. Bactericidal effect of serum from normal individuals and patients with cystic fibrosis on P. aeruginosa strains from patients with cystic fibrosis or other diseases.

P. aeruginosa strains originating from the respiratory tract of patients with cystic fibrosis (CF) and patients with other diseases (non-CF) were analysed with regard to their sensitivity to the bactericidal activity of human serum. P. aeruginosa strains isolated from CF patients were more sensitive than strains from non-CF patients to the bactericidal activity of normal human serum. The bactericidal activity was heatlabile. As regards the sensitivity to normal human serum, mucoid and non-mucoid variants were not found to differ. Strains originating from chronically infected CF patients with many precipitins against these bacteria did not differ with respect to serum sensitivity from strains originating from intermittently colonized CF patients without P. aeruginosa precipitins. Compared with normal sera, CF sera showed similar or higher bactericidal activity against a panel of P. aeruginosa strains. In this respect, any difference between CF sera with precipitins and CF sera without precipitins against P. aeurginosa was not found. Sera from three CF patients chronically infected with P. aeruginosa, and with many precipitins against these bacteria, showed a selective inability in bactericidal activity against the patients' own P. aeruginosa isolate possibly reflecting the presence of "bactericidal blocking" antibodies.

Adolescent↗
PubMed1976

Colloid and crystal formation in parotid saliva of cystic fibrosis patients and non-cystic fibrosis subjects. II. Electron microscopy and electrophoresis.

Centrifuged pellets of turbid parotid saliva from cystic fibrosis (CF) patients and non-CF subjects, obtained from saliva kept at 2 degrees for 10 min, had the electron microscope appearance of amorphous, round particles, and were thought to be colloidal aggregates of organic material. Drops of turbid saliva, from samples incubated for 2 hr at 2 degrees or 37 degrees, additionally contained discrete, electron-dense crystals having well defined angular morphology: usually cubic, retangular, or approximately hexagonal. The inhibitors, urea, guanidine hydrochloride, and EDTA, resulted in no crystals being observed. Selected area electron diffraction from individual crystals showed predominantly hexagonal, rectangular patterns could be indexed as coming from hydroxyapitite. A transition from the hexagonal to the rectangular pattern and back to the hexagonal pattern could be obtained from individual crystals tilted in the electron microscope. The square diffraction pattern may be from octa-calcium or brushite. Polyacrylamide gel disc electrophoresis of the parotid saliva indicated that the sparingly soluble proteins in the 2 degree and 37 degree pellets comprised proline-rich proteins and a calcium-precipitable, trichloroacetic acid (TCA)-precipitable phosphoprotein, which fluoresced with amido schwarz and Coomassie brilliant blue G250.

Adolescent↗
PubMed1976

Colloid and crystal formation in parotid saliva of cystic fibrosis patients and non-cystic fibrosis subjects. I. Physicochemistry.

Two types of turbidity were found in parotid saliva from both cystic fibrosis (CF) patients and non-CF subjects. On cooling saliva, a rapidly forming, reversible, cold-dependent turbidity appeared in increasing amounts with decreasing temperature and increasing protein concentration. At 37 degrees, a slowly forming, stable turbidity appeared in increased amounts in parotid saliva samples containing increased amounts of calcium. The 2 degree centrifuged pellet consisted predominantly of protein, whereas the 37 degree pellet contained calcium, inorganic phosphate, and protein. The cold-dependent turbidity at 2 degrees was not inhibited by EDTA, but 37 degrees turbidity was dramatically inhibited. Urea and guanidine hydrochloride reduced 2 degree turbidity, and, to a lesser extent, inhibited 37 degree turbidity. The tendency towards higher levels of protein, amylase, and calcium in CF compared with child control parotid saliva (4, 6) causes a greater incidence and degree of turbidity formation in saliva of CF patients. In this paper only the nature of the turbidity has been investigated, not its relative occurrence in each group of subjects.

Adolescent↗
PubMed1976

Inflammatory reaction and airway damage in cystic fibrosis.

In cystic fibrosis there is chronic infection and inflammatory reaction in the airways, accompanied by destruction and shedding of airway epithelium. Leukocytes migrate into the airways and some disintegrate, liberating deoxyribonucleoprotein that is incorporated into the gel structure of the bronchial mucus. We compared the status of these processes in cystic fibrosis with that in chronic bronchitis and bronchiectasis, by examining the sputum raised from the lower airways. Measurements also were made on sputum induced in normal subjects. The results indicate that migration of leukocytes into the airways and shedding of damaged airway epithelium were minimal in the normal subjects; they were significant in the patients with chronic bronchitis, higher in those with bronchiectasis, and still higher in those with cystic fibrosis. The large increases found in the total content of DNA and solids in the cystic fibrosis sputum were due to increases in the insoluble fraction containing the whole leukocytes and particulate debris that remained when the sputum mucus gel was solubilized with mercaptoethanol. Despite the large increases in the total content of DNA and solids, the contents of mucus gel components and of deoxyribonucleoprotein from disintegrated leukocytes actually present in the mucus gel structure of the cystic fibrosis sputum were not significantly higher than in the sputum from the patients with chronic bronchitis or brochiectasis.

Bronchi↗
PubMed1992

Biochemical characterization of the cystic fibrosis transmembrane conductance regulator in normal and cystic fibrosis epithelial cells.

Affinity-purified polyclonal antibodies, raised against two synthetic peptides corresponding to the R domain and the C terminus of the human cystic fibrosis transmembrane conductance regulator (CFTR), were used to characterize and localize the protein in human epithelial cells. Employing an immunoblotting technique that ensures efficient detection of large hydrophobic proteins, both antibodies recognized and approximately 180-kDa protein in cell lysates and isolated membranes of airway epithelial cells from normal and cystic fibrosis (CF) patients and of T84 colon carcinoma cells. Reactivity with the anti-C terminus antibody, but not with the anti-R domain antibody, was eliminated by limited carboxypeptidase Y digestion. When normal CFTR cDNA was overexpressed via a retroviral vector in CF or normal airway epithelial cells or in mouse fibroblasts, the protein produced had an apparent molecular mass of about 180 kDa. The CFTR expressed in insect (Sf9) cells by a baculovirus vector had a molecular mass of about 140 kDa, probably representing a nonglycosylated form. The CFTR in epithelial cells appears to exist in several forms. N-glycosidase treatment of T84 cell membranes reduces the apparent molecular mass of the major CFTR band from 180 kDa to 140 kDa, but a fraction of the T84 cell CFTR could not be deglycosylated, and the CFTR in airway epithelial cell membranes could not be deglycosylated either. Moreover, wheat germ agglutinin absorbs the majority of the CFTR from detergent-solubilized T84 cell membranes but not from airway cell membranes. The CFTR in all epithelial cell types was found to be an integral membrane protein not solubilized by high salt or lithium diiodosalicylate treatment. Sucrose density gradient fractionation of crude membranes prepared from the airway epithelial cells, previously surface-labeled by enzymatic galactosidation, showed a plasma membrane localization for both the normal CFTR and the CFTR carrying the Phe508 deletion (delta F 508). The CFTR in all cases co-localized with the Na+, K(+)-ATPase and the plasma membrane calcium ATPase, while the endoplasmic reticulum calcium ATPase and mitochondrial membrane markers were enriched at higher sucrose densities. Thus, the CFTR appears to be localized in the plasma membrane both in normal and delta F 508 CF epithelial cells.

3T3 Cells↗
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↗
PubMed1977

Cystic fibrosis: the effect of medium from cultured cystic fibrosis fibroblasts on ATPase activity.

Culture medium from fibroblasts of cystic fibrosis patients and controls was examined for the ability to inhibit (calcium plus magnesium)-activated ATPase and (sodium plus potassium)-activated ATPase. The ATPase systems used were both a solubilised preparation from dog-fish and a membrane associated preparation from human erythrocyes. Contrary to other reports the medium from cystic fibrosis fibroblasts did not inhibit ATPase activity.

Adenosine Triphosphatases↗
PubMed1992

Mutations and sequence variations detected in the cystic fibrosis transmembrane conductance regulator (CFTR) gene: a report from the Cystic Fibrosis Genetic Analysis Consortium.

Cystic fibrosis is the most common autosomal disorder in the Caucasian population. Since the description of the major mutation of this disease in 1989, over 150 of additional mutations have been identified in the CFTR gene. This update summarizes the different mutations identified and reported before March 15 by members of the international Cystic Fibrosis Genetic Analysis Consortium. The report includes information on DNA sequence variations found in the gene.

Amino Acid Sequence↗
PubMed1977

The biologic activities of cystic fibrosis serum. I. The effects of cystic fibrosis sera and calcium ionophore A 23187 on rabbit tracheal explants.

An ionophore A23187-induced increase in membrane permeability to calcium ions in culture medium produced a rabbit tracheal mucociliary response indistinguishable from that caused by cystic fibrosis (CF) sera on three different occasions. Specific chelation of calcium ions with EGTA in the basal medium Eagle (BME) media with no additive or in native CF sera abolished the mucociliary disturbances in all cases. Increased membrane permeability to calcium may be important in the production of the mucociliary response by CF serum factor(s) in the tracheal assay system.

Animals↗