PubMed Health⌕ Search

Biomedical subjects

M Somerville

Publications and source records attributed to M Somerville.

10 recordsLinked to original sources
PubMed1992

Release of mucus glycoconjugates by Pseudomonas aeruginosa rhamnolipid into feline trachea in vivo and human bronchus in vitro.

Pseudomonas aeruginosa colonizes the lower respiratory tracts of patients with severe bronchiectasis, including cystic fibrosis, a condition associated with increased airway mucus output. We have shown that an extract containing chloroform-soluble extracellular products of P. aeruginosa releases glycoconjugates into the cat trachea in vivo. This activity was not related to pyocyanin, a major component of the extract, but was associated with the rhamnolipids. Purified monorhamnolipid (100 micrograms/ml) released radiolabeled and periodic acid-Schiff (PAS)-reactive glycoconjugates (delta 3H = +490 +/- 70%, delta 35S = +170 +/- 40%, delta PAS = +8.6 +/- 1.7 micrograms/min; n = 6, P less than 0.02 for each). Dirhamnolipid (200 micrograms/ml) was also effective (delta 3H = +640 +/- 70%, delta 35S = +130 +/- 20%, delta PAS = +9.3 +/- 1.5 micrograms/min; n = 6, P less than 0.02 for each). Monorhamnolipid (100 micrograms/ml) also released 35S-labeled and PAS-reactive glycoconjugates from human bronchial tissue in vitro (delta 35S = +189 +/- 47%, delta PAS = +26.3 +/- 8.5 micrograms/min; n = 7, P less than 0.001 versus control tissues in which no stimulus was given). The cat tracheal glycoconjugates released by the rhamnolipids differed from those released by pilocarpine 50 microM, in having a higher 3H:35S ratio (P less than 0.001). After gel chromatography on a Sepharose CL-4B column, the void volume fractions of the glycoconjugates also had different profiles in a cesium chloride density gradient. Those released by rhamnolipid banded at 1.62 g/ml, while those released by pilocarpine banded mainly at 1.50 g/ml, with some of the higher density material also present.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Stimulation of secretion into human and feline airways by Pseudomonas aeruginosa proteases.

We have investigated the effect of elastase and alkaline protease from Pseudomonas aeruginosa on airway secretion into the trachea of anesthetized cats and from human bronchial mucosa in vitro. Secretory macromolecules were radiolabeled biosynthetically with two precursors in the cat, [3H]glucose and [35S]sulfate, and with [35S]-sulfate only in human tissue. Both enzymes (2.6 x 10(-9) to 1.3 x 10(-6)M elastase and 8 x 10(-9) to 2.4 x 10(-6)M alkaline protease) released radiolabeled macromolecules in a concentration-dependent manner from the two preparations. Purified elastase, 1.3 x 10(-6)M, released radiolabeled macromolecules (delta 3H = +397 +/- 72%, delta 35S 225 +/- 40% over control, P less than 0.001) and periodic acid-Schiff- (PAS) reactive glycoconjugates (delta PAS = +4.1 +/- 0.96 micrograms/min or +102 +/- 20%; P less than 0.01) from cat trachea, as did alkaline protease, 2.4 x 10(-6)M (delta 3H = +356 +/- 57%, delta 35S = +176 +/- 25%, delta PAS = +7.5 +/- 1.3 micrograms/min or 194 +/- 36%, P less than 0.001). Increases in 3H exceeded those of 35S, suggesting surface epithelium as the main source of secretion. Inhibition of enzyme activity abolished secretory effects. Both enzymes also stimulated secretion from human bronchus (e.g., with elastase, 1.3 x 10(-6)M: delta 35S = +331 +/- 67%, delta PAS = +4.3 +/- 0.92 micrograms/min or +131 +/- 24%, P less than 0.001; with alkaline protease, 2.4 x 10(-6)M: delta 35S = +220 +/- 67%, delta PAS = +12.7 +/- 3.2 micrograms/min or +575 +/- 245%, P less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Mucin structure. The structure and heterogeneity of respiratory mucus glycoproteins.

Respiratory mucus glycoproteins purified from both "normal" respiratory secretions and sputa of patients with a variety of hypersecretory conditions are high Mr linear molecules adopting a random coil configuration in solution. Studies on their polydispersity show them to have an Mr in the range 3 to 32 x 10(6) and a distribution of length from 200 nm to beyond 10 microns. These macromolecules are fragmented by reduction of intermolecular disulfide bonds into subunits, with Mr approximately 2 x 10(6) and length from 200 to 600 nm. Reduction not only cleaves the mucin molecule but opens, presumably by breaking intramolecular disulfide bonds, cryptic "naked" protein regions. Trypsin digestion of subunits yields high Mr glycopeptides (Mr, 300 to 500,000), presumably by cleavage of the peptide core within the unfolded "naked" protein domains. Respiratory mucus glycoproteins from infected sputum samples are usually heterogeneous in CsCl density gradients, in contrast to those from "normal" tracheobronchial secretions. The former are characterized by the presence of a number of different mucin species, and the basis for the separation of these mucins appears to be the variable presence of sialic acid and sulfate moieties in the oligosaccharide clusters. This heterogeneity may reflect a difference in cellular origin of the mucins and also may be clinically significant.

Glycoproteins↗
PubMed1990

Characterisation of Pseudomonas rhamnolipids.

The Gram negative organism, Pseudomonas aeruginosa, is often found in the lungs of patients with cystic fibrosis and other forms of severe bronchiectasis, where it secretes a number of extracellular toxins including the mono- and dirhamnolipids. The principal monorhamnolipid from P. aeruginosa has previously been identified as rhamnosyl-3-hydroxydecanoyl-3-hydroxydecanoate (Rh-C10.C10). A number of related mono- and dirhamnolipids have been purified from cultures of a clinical isolate of P. aeruginosa and identified by fast atom bombardment and electron impact mass spectrometry: these contain the 3-hydroxyoctanoyl-3-hydroxydecanoate (C8.C10) and 3-hydroxydecanoyl-3-hydroxydodecanoate (C10.C12) homologues. Structural isomers were also present where the order of the lipid linkage was transposed (Rh-C10.C8 and Rh-C12.C10). Unsaturated mono- and dirhamnolipids containing the 3-hydroxydecanoyl-3-hydroxydodec-5-enoate (C10.C12:1) lipid were also present.

Glycolipids↗
PubMed1990

The effects of local anaesthetic agents upon mucus secretion in the feline trachea in vivo.

The actions of lignocaine and tetrodotoxin (TTX) in a tracheal segment of the cat were tested on secretion of mucus macromolecules radiolabelled with 35S and 3H. Lignocaine, 4.3-43 mM, given into the segment, caused a concentration dependent increase of secretion of 3H-and 35S-labelled macromolecules. At 43 mM, lignocaine increased secretion: delta 3H = +433 +/- 191%, delta 35S = +327 +/- 34.5% (n = 8). This effect lessened over 15-45 min. Atropine (1 mg/kg) had little effect on these responses. All concentrations of lignocaine tested (4.3-43 mM) abolished the effect of vagus nerve stimulation on secretion and diminished the effect of a submaximal concentration of pilocarpine (5 microM) in the segment in a dose-dependent manner. TTX in the segment did not alter the resting secretion. At 50 microM it abolished, and at 10 microM diminished, vagal control of secretion without affecting the secretory response to pilocarpine. The study shows that lignocaine, in concentrations which block vagal control of secretion (greater than or equal to 4.3 mM), stimulates the release of mucus macromolecules. Resting secretion is unaltered by TTX, and so does not appear to be under neurogenic inhibition. Larger concentrations of lignocaine (greater than or equal to 13 mM) also diminish pilocarpine-induced secretion, whereas TTX may inhibit nervous control of mucus secretion selectively. The results suggest that clinical anaesthesia of the airways with lignocaine may stimulate mucus secretion.

Animals↗
PubMed1989

Local anaesthesia of the trachea and mucus secretion.

We have tested whether two local anaesthetics, in the lumen of cat trachea in vivo, would block the stimulation of mucus secretion by parasympathetic nerves without altering its stimulation by a cholinergic drug. Lignocaine, 4.3-43 mM (0.1-1%) in Krebs-Henseleit, increased the output of mucus macromolecules. It abolished secretion in response to vagus nerve stimulation, but also diminished the effect of 5 microM pilocarpine. Tetrodotoxin, 50 microM, abolished vagal control of secretion without inhibiting pilocarpine's action or changing resting secretion. Though lignocaine blocks nerve-mediated secretion, its action is not simply on nerve conduction. In contrast, the effect of tetrodotoxin may be restricted to the blocking of nerves.

Anesthetics, Local↗
PubMed1985

Exchange transfusion in severe falciparum malaria.

Three cases of severe falciparum malaria with high parasitaemia, one of them complicated by disseminated intravascular coagulation, were treated with exchange transfusion in addition to conventional chemotherapy. All three made a good recovery. There are few previous reports of this treatment which deserves wider attention and further assessment.

Adult↗
PubMed1977

Axoplasmic flow in myelinated and unmyelinated nerves.

[14C]Leucine was injected into the floor of the IVth ventricle of rabbits in order to label the axoplasmic flow of proteins in the efferent fibres of the vagus nerve. At intervals from 6 h to 180 days after injection, the rabbits were sacrificed and the cervical and abdominal vagus and recurrent laryngeal nerves removed. The radioactivity in the protein, lipid and low molecular weight fractions of the nerve segments was estimated by liquid scintillation counting. Two rates of axoplasmic flow were thus demonstrated in the abdominal vagus nerve; a fast rate of about 450 mm/day and a slow rate of 30 mm/day. This agrees very well with previous work. Peaks of activity in the recurrent laryngeal nerve corresponded to rates of 9 and 270 mm/day, but their level was low, being not significantly above sciatic nerve background levels. The number of efferent fibres in the two nerves and the corresponding axonal areas were calculated in order to estimate the amount of labelled material in the flow. The abdominal vagus was shown to contain 4-5 times as much label per unit area of axoplasm as the recurrent laryngeal. A difference was therefore demonstrated in the same anatomical nerve between myelinated fibres in the recurrent laryngeal and unmyelinated fibres in the abdominal vagus nerve, both in the rates of flow and in the amounts of material contained in the flow.

Animals↗