PubMed HealthSearch

Biomedical subjects

T F Boat

Publications and source records attributed to T F Boat.

At least 19 recordsLinked to original sources

Development of mucociliary transport in the postnatal ferret trachea.

Little is known of the developmental aspects of mucociliary transport. Previous studies have documented that newborn ferret trachea has very few ciliated cells but numerous immature secretory cells in the epithelium and only rudimentary submucosal glands. Rapid and complete maturation occurs in the first postnatal month. This study examines mucociliary transport during this period of rapid maturation. We made direct observations of particle movement across the epithelium of ferret tracheas. No mucus transport could be demonstrated on the first day of life. Transport was discernible, although sporadic and slow, by 7 days and reached adult levels (10.7 +/- 3.7 mm/min) by 28 postnatal days. The emergence of transport capability correlated well with previously described developmental changes in ciliation, mucus secretion, and ion permeability and transport. Threshold mucus transport occurred at 1 wk of age when 20-25% of the surface cells are ciliated. The neonatal ferret appears to be a useful model for assessing integrated epithelial structure-function relationships that are important not only during early development but also during repair after airway injury involving deciliation.

Aging

Developmental changes of ferret tracheal mucin composition and biosynthesis.

We characterized the chemical composition of mucins secreted by ferret tracheal explants and the activities of key mucin glycosyltransferases in ferret tracheal epithelium during a period of rapid postnatal maturation of the mucin-secreting structures. Ferret tracheal explants secrete three major groups of high molecular weight glycoconjugates: (1) those susceptible to bovine testicular hyaluronidase; (2) those resistant to hyaluronidase and exhibiting high density (p greater than or equal to 1.60 g/mL); and (3) those resistant to hyaluronidase and exhibiting low density (1.45 less than or equal to p less than 1.60 g/mL). The hyaluronidase-resistant, low-density glycoconjugates have typical mucin properties and constitute 36% of total glycoconjugates released in newborns but only 8% in adult ferrets. Mucin secretory rate per unit surface area of trachea progressively decreases with age. Mucin amino acid and total carbohydrate contents do not vary; however, the sialic acid content increases, and fucose content as well as blood group A activity of the mucins decreases with age. Four glycosyltransferases involved in mucin biosynthesis [Gal beta 3GalNAc:(GlcNAc-GalNAc)beta 6 N-acetylglucosaminyl-, GalNAc:beta 3 galactosyl-, Gal:alpha 2 fucosyl-, and GalNAc alpha 2----6 neuraminyltransferase] are present in tracheal epithelium of ferrets at all ages. Activities of all but the neuraminyltransferase decrease with age. The relatively greater neuraminyltransferase activity is consistent with increased incorporation of sialic acid into secreted mucins over the same age span. Conversely, diminution of fucosyltransferase relative to galactosyltransferase activity may contribute to the lower fucose content and lower blood group A activity of mucins secreted by mature ferret tracheas.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acids

Epithelial cell dysfunction in cystic fibrosis: implications for airways disease.

An important pathophysiologic factor in CF airways is the failure to clear poorly hydrated secretions. The water deficit in CF mucous secretions can now be ascribed to a fundamental defect of epithelial cell regulatory processes which promotes sodium reabsorption from surface liquids and interferes with chloride secretion onto the luminal surface. In addition, it is now known that CF airway epithelial cells oversulfate high molecular weight glycoconjugates, both secreted and cell surface-associated. Oversulfation of glycoconjugates may contribute to the altered clearance properties of CF airways mucus and in addition could favor colonization of airways by organisms such as P. aeruginosa.

Airway Obstruction

Increased sulfation of glycoconjugates by cultured nasal epithelial cells from patients with cystic fibrosis.

Cystic fibrosis (CF) respiratory epithelia exhibit abnormal anion transport that may be linked to abnormal lung defense. In these studies, we investigated whether primary cultures of CF respiratory epithelial cells regulate abnormally the sulfate content of high molecular weight glycoconjugates (HMG) participating in airways' mucosal defense. HMG, including glycosaminoglycans and mucin-type glycoproteins released spontaneously into medium and HMG released from cell surfaces by trypsin, were metabolically labeled with 35SO4- and [6-3H]-glucosamine (GlcN) or 35SO4- and [3H]serine. All three classes of HMG from CF cells exhibited 35S/3H labeling ratios 1.5-4-fold greater than HMG from normal or disease control cells. Differences for labeling ratios of HMG from CF cells were shown to be the consequence of increased 35SO4- incorporation rather than decreased peptide synthesis and release or HMG glycosylation. The buoyant density of CF mucin-type HMG also was increased, consistent with increased sulfation. These observations suggest that oversulfation of a spectrum of HMG is a genetically determined characteristic of CF epithelial cells and may play an important pathophysiological role by altering the properties of mucous secretions and/or the interactions between selected bacteria and HMG at the airways' surface.

Adolescent

Development, organization, and function of tight junctional complexes in the tracheal epithelium of infant ferrets.

The surface epithelium of newborn ferret airways matures rapidly in the first month of life. Prominent developmental features include a transition from predominantly non-ciliated to ciliated cells, quantitative and qualitative changes in secretion of macromolecules, and a transition from secretory to absorptive patterns of ion transport. Freeze-fracture replicas of ferret tracheal epithelium from 0 to 28 days of age exhibited progressive developmental patterns in tight junctional structure from beaded, unclosed patterns in newborns to more closed patterns at 28 days. Strand number increased while the depth of tight junctional structures and the proportion of strands exhibiting discontinuity decreased postnatally. Total transepithelial conductance, paracellular conductance, and cell size decreased over the first month. Our data suggest that changes in physiological parameters that reflect epithelial tight junction permeability can be attributed, at least in part, to maturation of this intercellular junction during the postnatal period.

Animals

Postnatal development of tracheal surface epithelium and submucosal glands in the ferret.

We explored the usefulness of the postnatal ferret as a model for early developmental events in the large airways, using light and scanning electron microscopy. In the first 28 postnatal days, ferret tracheal surface epithelium and glands undergo dramatic growth and development. Tracheal surface area increases 8-fold. At birth, ciliated cells are sparse (9.4 +/- 1.2% of total epithelial cells). A significant increase in ciliated cells is observed at weekly intervals and by day 28 the ciliated cell is the predominant cell type (54.2 +/- 2.8% of total epithelial cells). Secretory cells decrease from 66.4 +/- 1.0% at birth to 22.2 +/- 2.8% of total epithelial cells. Histochemical staining of the granules of the epithelial secretory cells changes from predominantly non-acidic (staining with PAS but not Alcian blue) to predominantly acidic (staining also with Alcian blue). During the same time interval, tracheal glands develop from intraepithelial cellular aggregates devoid of secretory granules at birth into complex, submucosal tubuloacinar structures composed predominantly of cells containing non-acidic secretory granules at 28 days. Therefore, infant ferrets offer an opportunity to examine the structural and functional components of the mucociliary clearance mechanism at developmental stages which occur prenatally in many laboratory animals and in humans.

Alcian Blue

Evidence against a specific effect of serum from patients with cystic fibrosis on sodium-dependent glucose transport in the rat jejunum.

Sera from patients with cystic fibrosis of the pancreas (CF) and normal human sera were assayed for the ability to inhibit sodium-dependent glucose transport in rat brush-border membrane vesicles. Fresh CF and age- and sex-matched control sera were both inhibitory when compared to physiologic saline. The inhibition by CF serum was 44 +/- 13% (mean +/- SD) at a final serum concentration of 6.7%, 67 +/- 34% at 10% serum, and 68 +/- 28% at 20% serum. The ratio of the inhibition of CF sera compared to that of control sera was 1.00, 0.78, and 0.93 at 6.7, 10, and 20% serum concentrations, respectively. Although a slightly greater inhibition by CF serum was observed at a concentration of 10%, this is probably not significant because no difference could be detected at a concentration of 20% serum. Glucose transport in the presence of serum was sensitive to phlorizin indicating that the residual glucose transport was proceeding by the sodium-dependent glucose transport system. These findings suggest that CF serum does not specifically inhibit the sodium-dependent glucose transport system. The intravesicular space accessible to glucose was reduced in the presence of CF or control serum. Fresh CF serum was 1.4 times more effective than fresh control serum (P less than 0.01). The presence of substantial vesicle-shrinking activity in control serum indicates that this activity cannot be considered specific for CF.

Animals

Intermediate-range sweat chloride concentration and Pseudomonas bronchitis. A cystic fibrosis variant with preservation of exocrine pancreatic function.

We studied the clinical and laboratory characteristics of seven patients with sweat chloride concentration consistently between 40 and 60 mEq/liter. Each has chronic Pseudomonas bronchitis, and all lack digestive symptoms. Laboratory findings indicate the preservation of exocrine pancreatic function. The patients include two of five children in one family and two of four in another. In a third family, one of five siblings has an intermediate sweat chloride concentration, but another has a typical fibrosis value (105 mEq/liter). One patient died of respiratory failure; results of an autopsy showed bronchiolectasis typical of cystic fibrosis, but minimal pancreatic changes. The data suggest a genetic basis for this variant of cystic fibrosis. These patients may be homozygous for a portion of a closely linked multigene cystic fibrosis locus or may have modifier genes that ameliorate the pancreatic and sweat lesions.

Adolescent

Effect of blood group determinants on binding of human salivary mucous glycoproteins to influenza virus.

We have demonstrated that the inhibitor of influenza B virus hemagglutination in human saliva is inactivated by neuraminidase and is associated with the mucous glycoprotein fraction (blood group substance) of this secretion. Inhibitory activity of saliva was found to be roughly proportional to its sialic acid content (r = 0.456). However, the minimal quantity of salivary sialic acid, neutral sugar, or blood group antigen required to inhibit virus hemagglutination was greater for secretors of A and B than for secretors of H and Lea blood group substances. Removal of terminal galactose from blood group B substance with alpha-galactosidase markedly decreased blood group B activity but increased blood group H and virus hemagglutination inhibitory activities of this glycoprotein. These data suggest that terminal alpha-linked galactose and, probably, N-acetyl-galactosamine interfere with access of influenza virus to binding sites on oligosaccharide chains of the mucous glycoprotein.

ABO Blood-Group System