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Biomedical subjects

T F Boat

Publications and source records attributed to T F Boat.

At least 37 records · Page 2Linked to original sources
PubMed1985

Altered urinary excretion of elastin cross-links in premature infants who develop bronchopulmonary dysplasia.

In order to determine whether elastin degradation is increased in infants whose respiratory insufficiency requires ventilation with high concentrations of O2, we quantitated, by amino acid analysis, the elastin degradation products (desmosines) excreted in the urine of 14 premature male infants during the first 3 wk of life. Eight of these infants, the "low-O2" infants, did not have severe lung disease and did not require more than 40% O2 beyond the first 8 h of life. The other 6 infants, selected retrospectively because they developed bronchopulmonary dysplasia (BPD), were ventilated with more than 60% O2 for at least the first 72 h of life. The pattern of desmosine excretion observed in infants who developed BPD differed significantly (p less than 0.05) from the excretion pattern seen in "low-O2" infants during the first 3 wk of life. At the end of the first week of life, desmosine excretion was significantly greater (p less than 0.05) in the infants who later developed BPD than in the "low-O2" infants without severe lung disease. From Days 7-9 to 20-22, desmosine excretion increased in the "low-O2" infants from 6.9 +/- 1.7 micrograms/kg to 9.0 +/- 3.5 micrograms/kg. In contrast, desmosine excretion did not remain elevated in the BPD infants, decreasing from 10.6 +/- 2.2 micrograms/kg to 6.1 +/- 2.9 micrograms/kg during the same period. In the BPD infants, elevated desmosine excretion through Day 9 is likely to reflect lung injury, whereas decreased desmosine excretion beyond Day 9 suggests that elastin synthesis and turnover is impaired, possibly as a result of nutritional deficiencies.(ABSTRACT TRUNCATED AT 250 WORDS)

Age Factors↗
PubMed1985

Immune complexes and complement abnormalities in patients with cystic fibrosis. Increased mortality associated with circulating immune complexes and decreased function of the alternative complement pathway.

Serum samples from 139 patients with cystic fibrosis (CF) were tested for complement abnormalities and circulating immune complexes (CIC). We found no consistent changes in whole complement activity. However, we found CIC in 29% of these patients and decreased activity of the alternative complement pathway (ACP) in 36%. During 5 yr of observation, mortality was much higher in patients whose sera contained CIC (p less than 0.001) or decreased ACP activity (p less than 0.01). Of patients with both abnormalities, 31% died; however, no deaths occurred in patients with normal ACP activity and negative tests for CIC (p less than 0.001). During a subsequent 2.5-yr period, 55% of patients greater than or equal to 21 yr old with both findings died. In contrast, no deaths occurred in older patients lacking this combination (p = 0.0062). Circulating immune complexes but not decreased ACP activity were an independent risk factor for death. Our findings support the hypothesis that humoral immune mechanisms may contribute to morbidity and mortality in CF.

Adolescent↗
PubMed1984

Proteinases release mucin from airways goblet cells.

The mucin-release effect of proteinases on airways epithelium was assessed in vitro. Using explants of rabbit tracheal mucosa-submucosa we determined that elastase and alkaline proteinase from Pseudomonas aeruginosa, pancreatic trypsin and elastase and the microbial proteinases subtilisin, thermolysin and pronase, all stimulate mucin release from goblet cells. On the other hand Streptomyces caespitosus proteinase pancreatic chymotrypsin and collagenase fail to trigger mucin release. Bovine trachea and human nasal polyp epithelium also release mucins in response to proteinases. Mucin release activity is dependent on proteolytic activity of enzymes which have a fairly broad, but generally similar, substrate specificity. The cellular mechanism of action is not known. We propose that mucin secretion in response to proteinases represents a useful defence mechanism but also forms the basis for hypersecretory states and airways obstruction in chronic endobronchial inflammatory states.

Animals↗
PubMed1984

The alpha 2-adrenergic system of the platelet in cystic fibrosis.

The ability of norepinephrine to inhibit prostaglandin E1 (PGE1)-stimulated accumulation of adenosine 3':5' cyclic monophosphate (cyclic AMP) in intact washed platelets was determined in 12 patients with cystic fibrosis, 6 parents of patients with cystic fibrosis, and a total of 21 healthy age-matched controls. Patients with cystic fibrosis and their parents did not differ from their age-matched controls in basal or PGE1-stimulated levels of cyclic AMP, nor in the dose dependent inhibition of cAMP accumulation by norepinephrine. Moreover, binding sites for [3H]-dihydroergocryptine were present in normal numbers and had normal ligand affinity in platelet membranes from patients with cystic fibrosis. In all measures tested, the alpha 2-adrenergic system in the platelet was normal in cystic fibrosis.

Adolescent↗
PubMed1984

Proteinases of Pseudomonas aeruginosa evoke mucin release by tracheal epithelium.

We have determined the potential of exoproducts from pathogenic bacteria to stimulate the release of high molecular weight mucins from goblet cells of airway epithelium in a rabbit tracheal explant system. Culture supernatants from proteolytic strains of Pseudomonas aeruginosa and Serratia marcescens, but not supernatants from a number of non-proteolytic strains, released mucins from goblet cells. Highly purified elastase and alkaline proteinase from P. aeruginosa stimulated goblet cell mucin release in a dose-dependent fashion. Lipopolysaccharide, exotoxin A, and alginate of P. aeruginosa did not possess mucin release properties. Proteolytic activity was required for mucin release by P. aeruginosa elastase, but such release in goblet cells was not mediated by cyclic AMP. Morphologic studies suggested rapid release of mucins from goblet cells was response to elastase by a process resembling apocrine secretion. Several nonbacterial proteinases mimicked the effect of Pseudomonas proteases. These studies provide support for the hypothesis that bacterial and other play a role in the pathogenesis of mucus hypersecretion in acute and chronic lung infections.

Adenylyl Cyclases↗
PubMed1984

Time course of hemosiderin production and clearance by human pulmonary macrophages.

Tracheal aspirates from four previously healthy infants with acute pulmonary hemorrhage, and small volume bronchial lavages from children undergoing flexible fiberoptic bronchoscopy were examined for pulmonary alveolar macrophages (PAM) containing hemosiderin. Hemosiderin formation was also studied in vitro. Macrophages containing hemosiderin were first seen in tracheal aspirates 50 hours after an acute pulmonary hemorrhage and after 72 hours in cultured macrophages. A small percentage of the PAM recovered by bronchoalveolar lavage from both adults and children contained hemosiderin. Hemosiderin was rapidly cleared from the lungs following an acute pulmonary hemorrhage.

Female↗
PubMed1984

Effects of alpha-tocopherol on platelet membrane function in cystic fibrosis.

Patients with cystic fibrosis and their parents were reported to have abnormal platelet aggregation responses to prostaglandin E1. To determine whether this is a property of the platelets, we studied the adenosine 3':5'-cyclic monophosphate (cAMP) response of washed platelets to prostaglandin E1. The cAMP response to prostaglandin E1 was the same in platelets from obligate heterozygotes for cystic fibrosis and from those of healthy controls. Patients with cystic fibrosis who had deficient vitamin E levels (plasma alpha-tocopherol, less than 500 micrograms/dl) had significantly (p less than 0.01) reduced platelet cAMP response to prostaglandin E1 compared with patients who had sufficient vitamin E, and supplementation with water-miscible vitamin E in these patients resulted in significant increases in plasma alpha-tocopherol levels (p less than 0.01) and in cAMP response to prostaglandin E1 (p less than 0.05). Plasma alpha-tocopherol levels correlated significantly with platelet cAMP response to prostaglandin E1 in patients with cystic fibrosis (r = 0.58, p less than 0.05). However, plasma alpha-tocopherol level was unrelated to the lymphocyte and granulocyte cAMP response to prostaglandin E1 or to the platelet cAMP response to alpha 2-adrenergic stimulation. Our data suggest that patients with cystic fibrosis have no inherited defect in platelet cAMP response to prostaglandin E1. In patients who have sufficient vitamin E, cAMP responses to prostaglandin E1 are normal in all the formed elements of the blood.

Adolescent↗
PubMed1984

Concentrations of alpha 1-proteinase inhibitor and alpha 2-macroglobulin in serum and lung secretions of intubated infants.

In order to determine the relative importance of the two proteinase inhibitors, alpha 1-proteinase inhibitor (alpha 1 PI) and alpha 2-macroglobulin (alpha 2M), in defending the infant lung against proteolytic attack, we measured concentrations of alpha 1PI and alpha 2M in both serum and lung secretions of infants intubated for respiratory insufficiency. In addition, we compared the concentration of each of the proteinase inhibitors in lung secretions with the serum concentrations of the proteinase inhibitor on the same day. Serum and secretions of all infants contained quantifiable levels of alpha 1PI. All serum samples had measurable amounts of alpha 2M. Ninety-two percent of the infants and 78% of all secretion samples tested contained alpha 2M. Molar ratios of alpha 1PI/albumin did not change as a function of gestational age in either serum or secretions. Serum alpha 2M/albumin also remained unchanged, but in lung secretions alpha 2M/albumin increased significantly with gestational age. With increasing postnatal age up to 44 days, mean levels of serum alpha 1PI, alpha 1PI/albumin, alpha 2M and alpha 2M/albumin increased. There was a greater increase in serum alpha 2M than in alpha 1PI as evidence by a decreasing molar ratio of alpha 1PI/alpha 2M with increasing postnatal age. In lung secretions, only alpha 1PI/albumin increased with postnatal age. Mean values for the molar ratio of alpha 1PI/alpha 2M in lung secretions ranged from 17 at 1-5 d to 22 at 11-44 d compared with the ratio of 200 reported for healthy adults (7).

Blood Proteins↗
PubMed1983

Surface architecture of the mucosal epithelium of the cat trachea: I. Cartilaginous portion.

The mucosal covering of the cartilaginous portion of the cat trachea was studied by correlated light, transmission-electron, and scanning-electron microscopy. While in some areas the ciliated pseudostratified epithelial lining is fairly smooth in contour, in other areas it contains longitudinally oriented, cilia-lined clefts. Ducts from submucosal glands sometimes open into the base of these clefts, or into funnel-shaped stomata that are lined by either ciliated or microvillus-rich cells. Specialized epithelial cells are occasionally associated with the clefts or with other regions of surface epithelium. In single sections, these cells appear to contain a cilium-lined vacuole, but serial sectioning has demonstrated that these apparent vacuoles actually are long intracellular invaginations in enormously elongated cells that extend longitudinally in the plane of the epithelium. The function of these cells is undetermined. Basal cells are attached to the lamina densa by means of hemidesmosomes that consistently lack peripheral densities; in contrast, the tall columnar cells have no hemidesmosomes.

Animals↗
PubMed1983

Surface architecture of the mucosal epithelium of the cat trachea: II. Structure and dynamics of the membranous portion.

Bronchoscopic examination of anesthetized cats revealed that the trachea is capable of considerable change in caliber via lateral expansion of the membranous trachea. The morphological basis for this expansile capacity was determined by correlated light microscopy and scanning and transmission electron microscopy. The organization of the membranous trachea differs from that of the cartilaginous trachea. The mucosa is arranged in a series of longitudinal folds that open like an accordion when stretched laterally. These fold are not random, but appear to depend on rows of nonciliated, microvillus-rich cells that form flexure lines in the surface epithelium. The mitochondria in such cell have a condensed configuration, indicating a high level of oxidative metabolism and suggesting that they may participate in transport processes that modify the luminal contents. Goblet cells, which are relatively sparse in the membranous trachea, have mitochondria in which the prominence of matrix granules and degree of mucus storage are inversely related. Mitochondrial morphology allows goblet cells that have discharged their mucin content to be readily distinguished from the microvillus-rich cells, even when their luminal surfaces lie outside the thickness of a section.

Animals↗
PubMed1983

Beta-adrenergic modulation of mucin secretion in cat trachea.

The mechanism of beta-adrenergic regulation of mucin secretion was investigated in cat trachea in vitro. beta-Adrenergic agonists increased the release of [35S]SO4-radiolabeled mucin and mucosa-submucosal adenosine 3',5'-cyclic monophosphate (cAMP) levels in a dose- and time-dependent manner. The relative potencies and efficacies of l-isoproterenol, l-epinephrine, l-norepinephrine, terbutaline, and dobutamine for physiological and biochemical events were similar. The effect of these agonists were blocked by d-l-propranolol. 3-Isobutyl-l-methylxanthine (IBMX) and 8-bromo-cAMP mimicked the effects of the agonists on mucin release. IBMX increased cAMP levels and potentiated the increase in cAMP levels effected by beta-adrenergic agonists. The half-maximal effects of l-isoproterenol on cAMP levels and mucin release were attained at 1.6 and 8.8 min, respectively. Three major mucosa-submucosal proteins of apparent molecular weights of 49,000, 54,000, and 59,000 daltons displayed reduced binding of the photoaffinity label 8-N3-[32P]cAMP when endogenous cAMP levels were increased with l-isoproterenol and/or IBMX. The first two proteins correspond in electrophoretic mobility to the regulatory subunits of type I and type II cAMP-dependent protein kinases, respectively. The 59,000-dalton cAMP binding protein may be the phosphorylated form of the regulatory subunit of type II cAMP-dependent protein kinase. These data are consistent with the hypothesis that beta-adrenergic modulation of tracheal mucin release is mediated by cAMP and suggest that activation of cAMP-dependent protein kinases may be involved in the neurohormonal effects.

Adrenergic beta-Agonists↗
PubMed1983

Beta adrenergic receptors in lymphocytes and granulocytes from patients with cystic fibrosis.

Intact lymphocytes from patients with cystic fibrosis (CF) produce significantly (P less than 0.001) less adenosine 3':5' cyclic monophosphate (cAMP) than normal lymphocytes in response to isoproterenol (10(-8)-10(-4) M), although the basal cAMP content and the response to prostaglandin E1 are normal. Obligate heterozygotes for CF have significantly (P less than 0.005) reduced cAMP response to isoproterenol as well, suggesting a genetic component in the beta adrenergic deficiency in CF. The number of beta adrenergic receptors, as determined by equilibrium binding of [3H]dihydroalprenolol to lymphocyte particulates, is the same in normal lymphocytes (969 +/- 165 receptors/cell) and lymphocytes from patients with CF (1,333 +/- 263 receptors/cell). Binding properties of the receptor for both antagonist and agonist, as assessed by KD for dihydroalprenolol and Ki for (-)-isoproterenol, are also normal in the CF lymphocytes. Similarly, in granulocytes from patients with CF, the cAMP response to isoproterenol (10(-8)-10(-4) M) is significantly reduced compared with healthy controls (P less than 0.03), as is the response of granulocytes from obligate heterozygotes (P less than 0.05). Again, the basal cAMP levels and the response to prostaglandin E1 are normal. The number of beta adrenergic receptors, as determined by equilibrium binding of [3H]dihydroalprenolol to granulocyte particulates, was the same in normal (1,462 +/- 249 receptors/cell) and CF (1,621 +/- 221 receptors/cell) preparations. Binding properties of the receptor for both agonist and antagonist, as assessed by KD for dihydroalprenolol and Ki for isoproterenol, are normal in CF granulocyte particulates. The lymphocyte and granulocyte beta adrenergic defect in CF cannot be explained by abnormalities of the beta adrenergic receptor or of adenylate cyclase itself. Receptor-cyclase coupling is the most likely site of the heritable beta adrenergic defect in CF.

Adolescent↗
PubMed1983

The carbohydrate content of IgG from patients with cystic fibrosis.

We compare the complete carbohydrate composition of IgG purified from the serum of patients with cystic fibrosis (CF) with that of control subjects. Our results indicate that IgG from cystic fibrosis patients is underglycosylated with respect to galactose and sialic acid, the two terminal sugars on the antennae of the complex-type oligosaccharide chains found on IgG. The galactose content, as determined by gas liquid chromatography, was 2.81 +/- 0.86 (S.D.) mole/mole of IgG for normal subjects versus 1.5 +/- 0.39 for CF subjects (P less than 0.025). Sialic acid content, as determined by the Warren procedure, was 1.33 +/- 0.39 for normals versus 0.47 +/- 0.10 for CF subjects (P less than 0.001). Neither galactose nor sialic acid values for the two groups overlapped. The contents of the core sugars, mannose and glucosamine, and of fucose were not significantly different. When the data are expressed as residues per 3 moles mannose, similar results are obtained. We suggest that immune complex formation, which has been documented in many CF patients, exposes sugar chains of IgG molecules to hydrolytic activity of serum glucosidases, resulting in partial removal of the more peripheral sugars. Because serum glycoproteins missing sialic acid and galactose are not readily cleared from the circulation, the observed changes may contribute to elevated levels of IgG and immune complexes in older people with CF.

Adolescent↗
PubMed1982

Neurohormonal receptors and cyclic AMP-binding proteins in rabbit tracheal mucosa-submucosa.

Neurohormones and drugs that alter in vitro tracheal electrolyte transport and mucus glycoprotein secretion were examined for their ability to alter cyclic nucleotide accumulation in a smooth muscle-free preparation of rabbit tracheal mucosa-submucosa. cAMP levels were increased by beta-adrenergic agonists, histamine, 2-Cl-adenosine and prostaglandin E1. cGMP levels were increased by carbachol. The phosphodiesterase inhibitor isobutylmethylxanthine increased cAMP and cGMP levels and potentiated only the beta-adrenergic effects. The beta-adrenergic effects were blocked by (+/-)-propranolol and the effects of histamine by diphenhydramine, atropine and (+/-)-propranolol. Atropine blocked the carbachol effects. The isolated surface epithelium from rabbit trachea had higher basal cAMP levels and greater response to beta-adrenergic agonists and isobutylmethylxanthine than the mucosa-submucosa. Two major cAMP-binding proteins in the tracheal mucosa-submucosa were identified with the photoaffinity label 8-N3-[32P]cAMP. Agents that increased cAMP levels also decreased photoaffinity labelling, suggesting that these two cAMP-binding proteins were being occupied in the intact cell. The molecular weights of the proteins were 50 000 and 54 000 and correspond in electrophoretic mobility to the regulatory subunits of Type-I and Type-II cAMP-dependent protein kinases, respectively. The results are consistent with the hypothesis that epithelial functions in the airways are modulated by a number of agonists which increase cyclic nucleotide levels. The effects of beta-adrenergic agonists is apparently mediated by activation of adenylate cyclase and subsequent activation of cAMP-dependent protein kinases.

Adrenergic beta-Agonists↗
PubMed1982

Obstructive azoospermia as a diagnostic criterion for the cystic fibrosis syndrome.

In some male patients with findings characteristic of cystic fibrosis, but normal sweat chloride concentrations, the demonstration of obstruction azoospermia has been pivotal in diagnosis. It is proposed that cystic fibrosis be diagnosed if the patient has at least two of three major criteria (marked rise in sweat chloride concentration, chronic obstructive pulmonary disease and pseudomonas infection, and unexplained obstructive azoospermia) or has one major criterion together with one of several minor criteria--including positive family history and childhood onset of exocrine pancreatic insufficiency. Inclusion of unusual variants within the cystic fibrosis syndrome has major theoretical implications for pathogenesis and practical importance for genetic counselling and patient care.

Adolescent↗
PubMed1982

Treatment and prognosis of nasal polyps in cystic fibrosis.

Nasal polyposis complicated the course of fibrosis in 157 (26%) of 605 patients. Onset before age 5 years or after age 20 years was rare. Polyposis was the initial symptom of cystic fibrosis in 13 patients. Common symptoms included obstruction to nasal air flow, mouth breathing, epistaxis, and rhinorrhea. Intranasal and oral corticosteroids and antihistamines were ineffective in preventing recurrences but did occasionally afford symptomatic relief of obstruction. Nineteen (31%) of 62 patients who never had surgery had spontaneous and permanent disappearance of polyps. Simple polypectomy was an adequate procedure for patients with substantial nasal symptoms. There were no visual complications. Other surgical complications were rare. Children and adolescents with nasal polyps should have sweat tests by pilocarpine iontophoresis to rule out cystic fibrosis.

Adolescent↗