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J D Conway

Publications and source records attributed to J D Conway.

6 recordsLinked to original sources
PubMed1997

Protein kinase C and Ca2+ activation of mucin secretion in airway goblet cells.

Airway goblet cells secrete mucin in response to ATP and uridine 5'-triphosphate (UTP), but the underlying signal transduction pathways are poorly understood. Cultures of SPOC1 cells (L. H. Abdullah, S. W. Davis, L. Burch, M. Yamauchi, S. H. Randell, P. Nettesheim, and C. W. Davis. Biochem. J. 316: 943-951, 1996) secreted mucin on exposure to phorbol 12-myristate 13-acetate (PMA) [apparent affinity (K0.5) approximately 100 nM] and ionomycin (K0.5 approximately 5 microM) almost fivefold over baseline. Thapsigargin also elicited secretion (K0.5 approximately 20 nM). Ionomycin and PMA together elicited approximately twice the secretion of either agent alone. Overnight exposure to half-maximal PMA abolished the response to maximal doses of UTP and PMA, whereas ionomycin was fully effective. Protein kinase C (PKC) activity in the membrane fraction was increased by maximal doses of PMA and UTP, whereas ionomycin had no effect. PKC inhibitors were relatively ineffective against PMA- and UTP-induced mucin secretion. Human and canine goblet cells in epithelial explants, by video microscopy, underwent exocytosis with ionomycin (1 microM) and PMA (0.1 or 1 microM). SPOC1 cell mucin secretion was not stimulated by forskolin, 8-(4-chlorophenylthio)-adenosine 3',5'-cyclic monophosphate, or 8-bromoguanosine 3',5'-cyclic monophosphate. Cystic fibrosis transmembrane conductance regulator was not detected in SPOC1 cells by Western blotting, and its mRNA was detected by reverse transcriptase polymerase chain reaction (PCR) only as a very weak band and after 55 PCR cycles. Multidrug resistance (MDR1), however, was readily detected by Western blotting, and its mRNA was detected as a major band after 35 PCR cycles. Thus airway goblet cell mucin secretion, distal to receptor activation, may be regulated independently by Ca(2+)- and PKC-dependent pathways. Cystic fibrosis transmembrane conductance regulator and cyclic nucleotides, however, may not play a major role in this secretion.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1996

The role of plasma renin activity in evaluating the adequacy of mineralocorticoid replacement in primary adrenal insufficiency.

BACKGROUND: Elevation of plasma renin activity (PRA) is a feature of mineralocorticoid deficiency in patients with primary adrenal insufficiency. This study was designed to assess the usefulness of PRA as an index of adequacy of fludrocortisone (FC) replacement in patients with primary adrenal failure, paying particular attention to the variability in PRA levels during FC and glucocorticoid treatment. METHODS: Twenty-two patients with mineralocorticoid deficiency due to primary adrenal diseases were studied at 3 time points: 8, 24 and 32 hours following the administration of FC replacement. Body weight, blood pressure while supine and erect, PRA, and plasma or serum levels of aldosterone, urea, sodium and potassium were measured at each time. The clinical and biochemical consequences of adjusting the FC dose were monitored in 5 patients with PRA levels above the range seen in normal subjects and in one hypokalaemic patient with normal PRA levels. RESULTS: At 8 and 32 hours following FC administration, PRA levels were not significantly different. PRA levels were significantly higher at 32 hours following FC administration (4.7 +/- 1.1 nmol/l/h) than at 24 hours (4.2 +/- 1.1 nmol/l/h, mean +/- SEM, P < 0.05). At 8 and 32 hours following FC administration, potassium levels were similar. Potassium levels were significantly higher at 32 hours following FC administration (3.9 +/- 0.1 mmol/l) than at 24 hours (3.6 +/- 0.1 mmol/l, P < 0.05). No changes in measurements of sodium, urea, mean supine and erect arterial pressure or body mass index were noted at the different study points. Attempted lowering of elevated PRA in 5 normokalaemic subjects by raising the dose of FC led to normalization of PRA in all of these patients but 2 developed hypokalaemia and oedema. Lowering of FC dose in one hypokalaemic patient with normal PRA levels led to the PRA levels rising to a supranormal value while the hypokalaemia was corrected. CONCLUSIONS: These results indicate that when plasma renin activity is estimated in patients with primary adrenal insufficiency replaced with daily doses of fludrocortisone, the time of day of blood sampling is not critical. Lowering elevated plasma renin activity levels to normal in patients who were considered to be otherwise normal may lead to over-treatment in some patients. Therefore, optimal fludrocortisone replacement may be associated with mildly elevated plasma renin activity levels. The information obtained by monitoring plasma renin activity adds little to the assessment of patients based on clinical evaluation and measurement of urea and electrolyte levels in blood.

Adrenal Insufficiency↗