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Biomedical subjects

M Field

Publications and source records attributed to M Field.

At least 37 records · Page 2Linked to original sources
PubMed1979

Sodium-coupled chloride transport by epithelial tissues.

There is compelling evidence that active Cl absorption by a variety of epithelia, widely distributed throughout the animal kingdom, is the result of an electrically neutral Na-coupled transport process at the luminal membrane and that the energy for transcellular Cl movement is derived from the Na gradient across that barrier. These co-transport processes are found predominantly in "leaky" or "moderately leaky" epithelia and permit these tissues to absorb Na and Cl with high degrees of efficacy. In addition, there is a growing body of evidence that cyclic AMP and Ca-induced electrogenic Cl secretion by a wide variety of epithelia may involve electrically neutral, Na-coupled Cl entry across the contraluminal membrane and that the energy for these secretory processes is derived from the Na-gradient across that barrier. A model for electrogenic Cl secretion that accounts for the available data is presented.

Absorption↗
PubMed1978

Ion transport across the isolated intestinal mucosa of the winter flounder, Pseudopleuronectes americanus. I. Functional and structural properties of cellular and paracellular pathways for Na and Cl.

The isolated intestinal mucosa of the flounder, Pseudopleuronectes americanus, when bathed in a 20 mM HCO3-Ringer's solution bubbled with 1% CO2 in O2, generated a serosa-negative PD and, when short-circuited, absorbed Cl at almost 3 times the rate of Na. Reducing HCO3 to 5 mM decreased the net Cl flux by more than 60%. The following results suggest that, despite the PD, Na and Cl transport processes are nonelectrically coupled: replacing all Na with choline abolished both the PD and net Cl flux; replacing all Cl with SO4 and mannitol abolished the PD and the net Na flux; and adding ouabain (to 0.5 mM) abolished the PD and the net Cl flux. Nearly all of the unidirectional serosa-to-mucosa Cl flux (JClsm) seemed to be paracellular since it varied with PD and Cl concentration in a manner consistent with simple diffusion. JClsm was only about one-fourth of JNasm, suggesting that the paracellular pathway is highly cation-selective. The data can be explained by the following model: (i) Na and Cl uptake across the brush border are coupled 1 : 1; Na is pumped into the lateral space and Cl follows passively, elevating the salt concentration there; (ii) the tight junction is permeable to Na but relatively impermeable to Cl; and (iii) resistance to Na diffusion is greater in the lateral space (considered in its entirety) than in the tight junction. If these assumptions are correct, the serosa-negative transmural PD is due mainly to a salt diffusion potential across the tight junction and, under short-circuit condition, most of the Na pumped into the lateral space diffuses back into the luminal solution, whereas most of the Cl enters the serosal solution. Morphological features of the epithelium support this interpretation: the cells are unusually long (60 micrometer); there is little distension of the apical 12 micrometer of the lateral space during active fluid absorption; and distension distal to this region is intermittently constricted by desmosomes.

Animals↗
PubMed1978

Heat-stable enterotoxin of Escherichia coli: in vitro effects on guanylate cyclase activity, cyclic GMP concentration, and ion transport in small intestine.

A partially purified preparation of the heat-stable enterotoxin of Escherichia coli caused a rapid and persistent increase in electric potential difference and short-circuit current when added in vitro to the luminal surface of isolated rabbit ileal mucosa. As little as 1 ng/ml produced an easily detectable response. Under short-circuit condition, the enterotoxin abolished net Cl- absorption; this change was half that produced by theophylline, which stimulated net secretion. The enterotoxin did not change cyclic AMP concentration but caused large and persistent increases in cyclic GMP concentration. The electrical and nucleotide responses exhibited similar and unusually broad concentration-dependences and maximal effects could not be demonstrated. Theophylline elevated cyclic GMP concentration 3-fold both in the presence and absense of the enterotoxin, suggesting no effect of the toxin on cyclic GMP phosphodiesterase. Guanylate cyclase [GTP pyrophosphatelyase(cyclizing); EC 4.6.1.2] activity in a crude membrane fraction from intestinal epithelial cells was stimulated 7-fold by the enterotoxin. These results suggest that guanylate cyclase stimulation is the basis for the toxin's diarrheagenic effect.

Bacterial Toxins↗
PubMed1978

Isolation of nontoxinogenic mutants of Vibrio cholerae in a colorimetric assay for cholera toxin using the S49 mouse lymphosarcoma cell line.

A mouse lymphosarcoma (S49) cell line that is growth-inhibited by agents that elevate intracellular concentrations of adenosine 3':5'-cyclic phosphate was used in a sensitive and convenient colorimetric assay for cholera toxin. S49 cells suspended in Dulbecco's modified Eagle's minimal essential medium containing 10(-5)--10(-6) M RO 20-1724, an analogue of 4-(3,4-demethoxybenzyl)-2-imidazolidinone and a phosphodiesterase inhibitor, were growth-inhibited by subnanogram concentrations of cholera toxin. Effects of toxin were detected by the absence of a yellow pH change (phenol red indicator) which normally accompanies the production of acid metabolites by lymphoma cells. An assay using S49 cells grown in microtiter plates, which is capable of detecting 10 pg of cholera toxin or 0.01 units of cholera antitoxin, was used in screening for nontoxinogenic mutants of Vibrio cholerae strain 569B. The properties of two mutants of the Tox--phenotype, which lacked biologically and immunologically detectable toxin products, are described.

Animals↗
PubMed1978

Agenesis of the corpus callosum: report of two pre-school children and review of the literature.

The results of neuropsychological examinations of two patients with agenesis of the corpus callosum showed low intelligence-test performance, impared visuo-motor co-ordination and impaired bimanual co-ordination. The most striking deficits were observed in Case A, particularly in her inability to identify objects verbally when placed in the non-dominant hand, and in her ability to complete a task with the non-dominant hand without vision, when she was unable to complete the same task with vision. This patient is unusual insofar as she manifests deficits noted in acallosal patients, as well as some noted in split-brain patients but not previously ascribed to acallosal patients.

Agenesis of Corpus Callosum↗
PubMed1978

Effects of methylprednisolone on hydrogen ion absorption in the canine stomach.

The effect of methylprednisolone (2 mg/kg per day given parenterally for 3 doses, 2 wk or 12 wk) on the permeability of mammalian gastric mucosa to hydrogen ion (H(+)) was examined with denervated fundic pouches in dogs with antrectomies. Transmucosal electric potential difference (PD) and net fluxes of H(+) and Na(+) were determined for luminal [H(+)] from 20 to 160 mM and [Na(+)] from 1 to 140 mM ([H(+)] and [Na(+)] were varied reciprocally). The PD was 50-60 mV lumen negative and was constant over the entire range of Na(+) and H(+) concentration tested. Net H(+) flux varied linearly with [H(+)]. Extrapolation indicated apparent H(+) loss at zero luminal concentration, suggesting a basal HCO(3) (-) secretion. Addition of acetylsalicylic acid (ASA) or taurocholate decreased the PD to 30-40 mV and increased threefold the slope of the relation between net H(+) flux and [H(+)] (k(H)). Calculation of PD-independent permeability constants for H(+) (P(H)) with the Goldman constant field equation indicated that this increase in k(H) could not be attributed solely to the associated decrease in PD. Prednisolone administered for 3 doses had no effect on either the basal mucosal permeability to H(+) or the altered permeability induced by ASA or taurocholate. Chronic administration induced a low rate of basal acid secretion (at 12 wk) but had no effect on either PD or k(H). However, the increase in k(H) and P(H) that developed upon addition of ASA or taurocholate in chronically treated dogs was more than one and a half times that of controls. These data suggest that prolonged treatment with glucocorticoids increases susceptibility of the gastric mucosa to damage by agents that increase permeability to H(+).

Absorption↗
PubMed1977

Cyclic AMP regulation of active chloride transport in the rectal gland of marine elasmobranchs.

Active transport of chloride in the salt secreting rectal gland of the dogfish Squalus acanthias is markedly stimulated by the addition of theophylline (0.01 to 5 mM) or dibutyryl cyclic AMP (0.05 mM) during in vitro perfusion. The effect occurs promptly and may persist for two hours. Specific hormonal effectors have not yet been identified. The isolated perfused rectal gland thus offers a unique opportunity to examine the cellular mechanisms of active chloride secretion.

Animals↗
PubMed1977

Ileal mucosal cyclic AMP and Cl secretion: serosal vs. mucosal addition of cholera toxin.

Changes in ion transport and cyclic AMP (cAMP) concentration produced by addition of cholera toxin to the serosal side of isolated rabbit ileal mucosa (CTs) were compared to the changes produced by addition to the mucosal side (CTm). CTs increased short-circuit current (SCC) as did CTm but it did so more slowly. CTs, unlike CTm, did not significantly decrease electrical conductance. Inhibition of the SCC response to theophylline, a measure of preexisting secretion, was almost complete 180 min after CTm but was not yet significant 180 min after CTs. Longer (280 min) after CTs, the SCC response to theophylline was reduced by 59%, a significant reduction but less than that caused by CTm. A statistically significant change in net Cl flux could not be demonstrated after CTs, although at 280 min the measured flux was halfway between the fluxes for control and CTm tissues. Cyclic AMP concentrations were determined at 190 min, 10 min after addition of theophylline. CTs, despite little or no effect on ion transport, increased cAMP to the same level as did CTm, and the effect on cAMP of adding toxin to both sides was additive. We conclude that 1) active secretion is probably stimulated by cholera toxin added on the serosal side, although more slowly than after addition to the mucosal side and 2) much of the toxin-stimulated cAMP content of the mucosa is not coupled to secretion.

Animals↗
PubMed1977

Mechanism of active chloride secretion by shark rectal gland: role of Na-K-ATPase in chloride transport.

The isolated rectal gland of Squalus acanthias was stimulated to secrete chloride against an electrical and a chemical gradient when perfused in vitro by theophylline and/or dibutyryl cyclic AMP. Chloride secretion was depressed by ouabain which inhibits Na-K-ATPase. Thiocyanate and furosemide also inhibited chloride secretion but ethoxzolamide, a carbonic anhydrase inhibitor, did not. Chloride transport was highly dependent on sodium concentration in the perfusate. The intracellular concentration of chloride averaged 70-80 meq/liter in intact glands, exceeding the level expected at electrochemical equilibrium and suggesting active transport of chloride into the cell. These features suggest a tentative hypothesis for chloride secretion by the rectal gland in which the uphill transport of chloride into the cytoplasm is coupled through a membrane carrier to the downhill movement of sodium along its electrochemical gradient. The latter is maintained by the Na-K-ATPase pump while chloride is extruded into the duct by electrical forces.

Adenosine Triphosphatases↗
PubMed1976

Cyclic AMP and growth of Ehrlich ascites tumor cells. Lack of cyclic AMP elevation in nutritionally deprived cells and mechanism of retardation of growth by dibutryl cyclic AMP.

Cyclic AMP levels in Ehrlich ascites tumor cells changed little after deprivation of cells of essential nutrients, serum, glucose and amino acids, deprival of each of which leads to marked inhibition of growth and protein synthesis. Cyclic AMP levels also changed little after the addition of these nutrients to deprived cells. Thus cyclic AMP is not likely to be the intracellular mediator for growth regulation by these three nutrients. Elevation of cyclic AMP levels for short periods by exposure of cells to choleratoxin or theophylline produced only slight changes in parameters of protein synthesis (polyribosome pattern and rate of [3H]leucine incorporation). An exposure for 1 day to dibutyryl cyclic AMP did not inhibit cell growth. However, prolonged exposure to dibutyryl cyclic AMP inhibited the multiplication of Ehrlich ascites cells both in suspension and in stationary cultures. No morphological effects were evident in the former; in the latter, cells attached firmly to the substratum and formed elongated cytoplasmic processes. Inhibition of cell multiplication by dibutyryl cyclic AMP was related to cell density and to serum concentration. Cells in dibutyryl cyclic AMP-containing media plated at low cell densities multiplied as rapidly as control cells. The final densities cells reached were determined by the serum concentration; in dibutyryl cyclic AMP-containing media these densities were about one-half those of respective control cells. Limitation of cell multiplication by dibutyryl cyclic AMP was reversed by the addition of serum, by resuspending cells at lower densities, or by resuspending cells in media without dibutyryl cyclic AMP. These findings suggested that dibutyryl cyclic AMP may affect the utilization of serum factors by cells. Dibutyryl cyclic AMP did not inactivate serum factors and did not change the rate at which cells depleted the growth medium of serum factors. Dibutyryl cyclic AMP may limit cell multiplication by increasing the cellular requirement for serum factors.

Amino Acids↗
PubMed1976

Regulation of active ion transport in the small intestine.

The epithelium of the small intestine can both actively absorb and actively secrete electrolytes and water. Secretion can be elicited in vitro by adding cyclic AMP or a stimulator of intestinal mucosal adenylate cyclase (cholera and Escherichia coli enterotoxins, prostaglandins, vasoactive intestinal peptide) or an inhibitor of cyclic AMP phosphodiesterase (theophylline). Cyclic AMP appears to alter intestinal ion transport at two different loci: it inhibits a coupled influx process for Na+ and Cl- at the luminal border, thereby reducing active absorption of NaCl, and it also stimulates the active secretion of anion (or Na+ and anion). A variety of evidence suggests that these two effects of cyclic AMP reside in different types of cells, the former in villus cells and the latter in crypt cells. The latter process is Na+-dependent and is inhibited by low concentrations of ouabain and ethacrynic acid. Active ion absorption in vitro can be enhanced by (1) stimulating Na+-coupled organic solute absorption with glucose, amino acids and possibly also oligo peptides; (2) reducing the HCO3- concentration and/or pH of the serosal bathing solution; and (3) introducing an alpha-adrenergic agonist. Cholera toxin-induced fluid production in vivo can be diminished by the first of these manoeuvres. The in vivo efficacies of the other two have not been evaluated.

Animals↗
PubMed1976

Intestinal mucosal cyclic GMP: regulation and relation to ion transport.

Stimulation of alpha-adrenergic and muscarinic cholinergic receptors in rabbit ileal mucosa in vitro produced 5- to 15-fold increases in cyclic GMP (cGMP) concentration that were maximal within 2 min and gone within 30 min. Cholecystokinin octapeptide and insulin caused similar increases in cGMP. None of these agents affected cAMP. The epinephrine-induced increase in cGMP was blocked by atropine at 100 but not at 1 muM concentration. Epinephrine stimulates active NaCl absorption and decreases short-circuit current (SCC) in vitro, the latter effect due to inhibition of HCO3 secretion. Atropine (100 muM) blocked the former but not the latter effect of epinephrine. In vitro additions of several concentrations of cGMP and 8-bromo-cGMP did not decrease SCC or alter Na fluxes. Thus, changes in cGMP concentration have been directly correlated with changes in active absorption of NaCl, but a causal relationship has not been proven.

Animals↗