PubMed Health⌕ Search

Biomedical subjects

S H Wright

Publications and source records attributed to S H Wright.

At least 91 records · Page 5Linked to original sources
PubMed1983

Pneumatic dilatation in patients with symptomatic diffuse esophageal spasm and lower esophageal sphincter dysfunction.

Nine patients with severe symptoms of diffuse esophageal spasm and lower esophageal sphincter dysfunction who were unresponsive to medical therapy and bougienage dilatation were treated by forceful pneumatic dilatation. Treatment with pneumatic dilatation in eight of the nine patients produced a marked improvement in dysphagia and regurgitation (average follow-up of 37.4 months). Esophageal motility performed up to three years (average 12.4 months) after clinically successful pneumatic dilatation revealed a decrease in lower esophageal sphincter pressure from 34.0 +/- 4.0 mm Hg (mean +/- standard error) to 19.2 +/- 2.7 mm Hg (P less than 0.01). There were no significant changes in either the percentage of lower esophageal sphincter relaxation or the type of esophageal motor pattern. We conclude from this study that pneumatic dilatation is an effective form of therapy for a select group of patients with severe symptomatic diffuse esophageal spasm with lower esophageal sphincter dysfunction who are unresponsive to conventional medical therapy.

Adult↗
PubMed1983

Specificity of the Na+-dependent monocarboxylic acid transport pathway in rabbit renal brush border membranes.

The substrate specificity of a Na+-dependent transport pathway for L-lactate was studied in rabbit renal brush border membrane vesicles. Jmax for L-lactate transport was unaffected by the presence of a fixed concentration of two different short-chain monocarboxylic acids, while the apparent Kt(Ka) for L-lactate increased, and this is compatible with competitive inhibition. The inhibitor constants ("Ki"'s) for the transport pathway for the two solutes examined closely corresponded to the respective "Ki"'s derived from a Dixon plot. A broad range of compounds were then tested as potential inhibitors of L-lactate transport, and the "Ki"'s thereby derived yielded specific information regarding optimal substrate recognition by the carrier. A single carboxyl group is an absolute requirement for recognition, and preference is given to 3 to 6 C chain molecules. Addition of ketone, hydroxyl and, particularly, amine groups at any carbon position, diminishes substrate-carrier interaction. Intramolecular forces, notably the inductive effects of halogens, may play a role in enhancing substrate-carrier interaction; however, no correlation was found between pKa and "Ki" for the substrates examined. We conclude that a separate monocarboxylic acid transport pathway, discrete from either the D-glucose, alpha or beta neutral amino-acid, or dicarboxylic acid carriers, exists in the renal brush border, and this handles a broad range of monocarboxylates.

Amino Acids↗
PubMed1983

Simultaneous determination of net uptake of 16 amino acids by a marine bivalve.

High-performance liquid chromatography was used to measure the simultaneous transport of 16 amino acids from seawater into the mussel Mytilus edulis. All the substrates, including representative neutral, basic, and acidic amino acids, were accumulated from ambient concentrations as low as 5 nM. Influx of four radioactively labeled amino acids was compared with their net flux. In each case the influx of the 14C-labeled substrate, determined from the removal of isotope from test solutions, accurately represented the net flux of that substrate as measured by direct chemical analysis. Ammonia was the only compound observed to be routinely lost from these animals. Rates of uptake of individual amino acids, each at concentrations of 10 nM, ranged from 2.4 to 7.0 nmol . g dry flesh wt-1 . min-1. The studies show that M. edulis is capable of a net uptake of dissolved amino acid from the very low concentrations characteristic of seawater. Moreover, net accumulation can occur against chemical gradients calculated to be in excess of one million to one. The rates of amino acid uptake may contribute significantly to the animals' energy requirements.

Amino Acids↗
PubMed1982

Stoichiometry of Na+-succinate cotransport in renal brush-border membranes.

The coupled transport of Na+ with succinate and citrate into rabbit renal brush-border membrane vesicles was studied. Initial rates of transport (J) were estimated from 1-s uptakes under well defined transmembrane conditions (membrane potential, pH, ionic composition). A Na+ gradient increased J up to 700 times compared to Na+ replacement with sorbitol. J was a sigmoid function of increasing Na+ concentration; the kinetic interaction of Na+ with the succinate-citrate transport system was described by the equation: J = Jmax/(1 + (Ks/[Na]))3. Assuming that the Na+ interaction involves equivalent, noninteracting binding sites, these results indicate that 3 Na+ ions are translocated/molecule of organic substrate. Consistent with the latter observation was the direct demonstration of a stoichiometric coupling between simultaneously determined fluxes of 22Na+ and 14C-labeled substrates. In excess of 2 Na+ ions were transported/molecule of organic substrate. These results explain the electrogenicity of the transport of succinate and citrate as evidenced by the response of J to K+ diffusion potentials and the effects of transport on the fluorescence of a potential-sensitive cyanine dye.

Animals↗
PubMed1982

Effect of pH on the transport of Krebs cycle intermediates in renal brush border membranes.

Lowering extravesicular pH stimulated Na+-dependent citrate transport in renal brush border membrane vesicles: e.g., at pHout = 5.5, the initial rate of citrate uptake was increased 10-fold compared to parallel control experiments at pH 7.5. The same experimental conditions had little effect on succinate uptake. The influence of pH on citrate transport is a product of the extravesicular H+ concentration; pH gradients did not potentiate the effects nor were proton gradients capable of driving transport in the absence of Na+. The effect of pH is adequately explained if only the mono- and divalent species of citrate (Cit1-, Cit2-) are considered acceptable substrates for transport. The stimulatory influence of pH on transport correlated quite well with pH-related increases in the concentrations of Cit1- and Cit2-, and over the same pH range [Cit3-] was inversely related to citrate uptake. A model of the Na+-dependent dicarboxylate transport system is discussed in which three sodium ions are translocated per molecule of dicarboxylic acid.

Animals↗
PubMed1982

Interactions between lithium and renal transport of Krebs cycle intermediates.

The effect of lithium on the renal transport of Krebs cycle intermediates was studied in brush border membrane vesicles isolated from the rabbit renal cortex. The di- and tricarboxylic acids are avidly transported across renal brush border membranes by a sodium cotransport system. Lithium acted as a potent, specific, competitive inhibitor (Ki = 1.2 mM) of succinate/sodium cotransport when added to the uptake medium. Similar effects were observed for citrate but not D-glucose, L-phenylalanine, L-proline, L-alanine, or L-lactate transport. Intravesicular lithium behaved as a noncompetitive inhibitor of succinate transport in the absence of sodium. These results account for the observation that therapeutic doses of lithium increase the renal excretion of Krebs cycle intermediates. The existence of a transport system for alpha-ketoglutarate in synaptosomes suggests a possible target for lithium in the central nervous system.

Biological Transport, Active↗
PubMed1982

Pathways for carboxylic acid transport by rabbit renal brush border membrane vesicles.

Brush border membrane vesicles were purified from rabbit renal cortex using a calcium-precipitation procedure, and the uptake of carboxylic acids was determined by a rapid-filtration method. L-Lactate, pyruvate (monocarboxylic acids), and succinate (dicarboxylic acid) demonstrated features of Na+ cotransport: enhanced initial rate (1 s) of uptake with an inward Na+ gradient compared with the Na+ -free control condition and transient accumulation of substrate within the vesicles. Kinetic parameters derived for L-lactate and succinate show that each substrate is transported via single pathway and that the two substrates exhibit marginal cross-inhibition. A range of monocarboxylic acids including pyruvate and ketone bodies appear to interact with the monocarboxylic acid carrier. The kinetics of Nat-dependent pyruvate uptake suggest at least two transport pathways-namely, that this monocarboxylate shares both the mono- and dicarboxylic acid carriers. We conclude that isolated rabbit renal microvillus membranes possess independent transport systems for mono- and polycarboxylic acids.

Animals↗
PubMed1982

Organic and inorganic solute transport in renal and intestinal membrane vesicles preserved in liquid nitrogen.

The transport of organic solutes (sugars, amino acids, and metabolic intermediates) and inorganic solutes (Na+/H+ exchange and Na+-SO = 4 cotransport) in renal brush border and in intestinal brush border and basal lateral membrane vesicles is preserved when the vesicles are stored in liquid nitrogen. The preservation allows comparisons among transport systems of renal and intestinal cells obtained from the same animal.

Amino Acids↗
PubMed1981

Na+-dependent transport of tricarboxylic acid cycle intermediates by renal brush border membranes. Effects on fluorescence of a potential-sensitive cyanine dye.

The effect of the transport of tricarboxylic acid cycle intermediates on the membrane potential of renal brush border vesicles was studied using fluorescence of the cyanine dye, 3,3'-dipropylthiadicarbocyanine iodide. The behavior of the dye in the preparation was established with valinomycin-induced K+-diffusion potentials; increases in fluorescence were associated with depolarizing conditions. Addition of 1 mm succinate or citrate to membrane/dye suspensions produced transient increases in fluorescence, indicative of a depolarizing event(s) associated with the transport of these substrates. The transient response in fluorescence was Na+ dependent, of greater magnitude under Na+-gradient as compared to Na+-equilibrium conditions, and was a saturable function of substrate concentration. The specificity of the fluorescence response was identical to that obtained from studies of the competitive inhibition of succinate transport by tricarboxylic acid cycle intermediates and analogs We conclude that the major tricarboxylic acid cycle intermediates are transported via a common Na+-dependent transport system in renal brush border membranes.

Animals↗
PubMed1980

Specificity of the transport system for tricarboxylic acid cycle intermediates in renal brush borders.

Uptake studies employing renal brush border membranes were used to examine the structural specificity of the TCA cycle intermediate transport system. The kinetics of reciprocal inhibition between succinate and citrate revealed these compounds to be transported by a common mechanism. The Michaelis constant for succinate (0.11 mM) was significantly lower than that of citrate (0.28 mM), indicating that the system has a higher affinity for succinate than for citrate. The specificity of the transport system was determined from the relative inhibitory constants of 40 organic acids on the transport of succinate. The results established that the system is highly specific for 4-carbon, terminal dicarboxylic acids in the trans-configuration, including the major intermediates of the TCA cycle. The system is comparatively insensitive to monocarboxylates. Substitution of one of several polar, non-charged residues on the alpha-carbon of succinate permitted interaction of the substrate with the transport system, but substitutions on both the alpha and beta-carbons did not. The structural specificity of the system is fundamentally different from that of the dicarboxylate and tricarboxylate exchange systems of mitochondria. The role of this transport system in the reabsorption of TCA cycle intermediates from the proximal tubule is discussed.

Animals↗
PubMed1980

Influence of temperature and unstirred layers on the kinetics of glycine transport in isolated gills of Mytilus californianus.

The effect of temperature on the kinetics of glycine influx in isolated gills of Mytilus californianus was studied. Increases in temperature resulted in significant increases in the Jimax for glycine influx over the range 7--23 degrees C (Q10 = 5). Concomitant with this increase in Jimax was an increase in experimentally determined Kt, from 23 microM to 134 microM. The relationship between changes in Jimax and measured Kt was adequately described by an equation that takes into account the influence of unstirred layers on the kinetics of carrier-mediated transport. Use of this equation indicated that the changes in measured Kt could be explained by the presence of an unstirred layer approximately 400 micrometer thick over the transporting surfaces(s) of the isolated gill, and that the "true" Kt of the transport process is 1 microM. The very low values of Kt for amino acid uptake measured in intact muscles (1--3 microM) are revealed to be the product of transport processes of high affinity for substrate and a perfusion system which effectively minimizes the influence of unstirred layers, thereby permitting efficient utilization of substrate at the low concentrations characteristic of these animals' environment.

Animals↗
PubMed1980

Systemic mycosis complicating high dose corticosteroid treatment of chronic active liver disease.

Four patients with severe chronic active liver disease, treated with 30-200 mg. of prednisone daily for one-half month to seven months because of lack of response to smaller doses, developed systemic mycosis. Presentation was variable, consisting of cryptococcal meningitis, cryptococcal pneumonia, aspergillus cerebral vasculitis and disseminated histoplasmosis originating from a histoplasma pneumonia. None of 114 patients in the Mayo Clinic trials on conventional treatment for at least six months, but only one of 25 patients (4%) on high dose prednisone, developed systemic mycosis. Low dose prednisone or its equivalent can be maintained to control hepatic inflammation during vigorous antifungal therapy without jeopardizing cure of the fungal infection. We conclude that systemic mycosis is infrequently associated with corticosteroid therapy for severe chronic active liver disease but can occur on high dose regimens as a subtle, progressively debilitating and potentially fatal complication that justifies prompt recognition and aggressive treatment with amphotericin-B alone or in combination with 5-fluorocytosine.

Adult↗
PubMed1979

The gastrocolic response: evidence for a neural mechanism.

The aim of this study is to determine the effect of anticholinergic therapy on the gastrocolonic response to a standard meal or its major constituent fat. A rapid increase in rectosigmoidal spike activity occurs after ingesting the standard meal or the fat meal (P less than 0.01). Distal colonic motility returns to fasting levels 50 min after both meals. There is no further increase in spike activity after the 1000-calorie meal, but spike activity increases again 70 min after ingesting the fat (P less than 0.02). The anticholinergic drug, clidinium bromide, inhibits the early increase in spike activity after both meals. However, the anticholinergic has no effect on the delayed peak of activity following the ingestion of fat. This study suggests that (a) the early gastrocolic response to a standard meal and a fat meal is cholinergically mediated and (b) the late increase in rectosigmoidal motility occurs only after fat ingestion and may be controlled by other neural mediators or possibly the gastrointestinal hormones.

Adult↗
PubMed1977

Characteristics of influex and net flux of amino acids in Mytilus californianus.

1. Intact mussels and an in vitro preparation of isolated gill tissue were employed to study characteristics of the influx and net flux of amino acids in Mytilus californianus. 2. The kinetics of influx of 14C-labelled amino acids were complicated by the presence of a rapidly labelled extracellular compartment. 3. Correction of influx data for the extracellular compartment revealed influx of 14C-cycloleucine and 14C-glycine to be mediated by a transport mechanism adequately described by Michaelis-Menten kinetics. Passive diffusion plays no significant role in influx. 4. Influx and net flux of glycine into intact Mytilus were examined. From high concentrations (greater than 20 micronM) the influx of 14C-glycine was equivalent to the net influx of primary amine as determined by fluorescamine. At low ambient concentrations (greater than 20 micronM), influx of 14C-glycine occurred more rapidly than net influx as determined by fluorescamine. The data suggest that influx of labelled substrate is accompanied by efflux of unknown primary amine(s). In the absence of labelled substrate, efflux continues until a steady-state concentration of 2-5 micronM in the medium is achieved.5. The rate of influx of 14C-cycloleucine into isolated gill tissue, and the concentration gradient which can be developed by gill tissue are reduced when sodium is replaced in the medium. 6. The efflux of primary amines from isolated gill tissue is stimulated by the replacement of sodium in the medium with choline. 7. The data are consistent with a sodium-coupled mechanism for the transport of amino acid into gill tissue. However, energetic considerations cast doubt on the adequacy of such a mechanism to account fully for the observed trans-epidermal transport.

Amino Acids↗
PubMed1975

Transport of amino acids by isolated gills of the mussel Mytilus californianus Conrad.

The unidirectional influx of cycloleucine into in vitro preparations of gill tissue of the mussel, Mytilus californianus, was determined. Influx was found to be linear for at least an hour, and the kinetics of cycloleucine influx conformed to Michaelis-Menten type kinetics. The transport mechanism(s) for cycloleucine is relatively specific for the L-enantiomorph of neutral amino acids, and is capable of accumulating cycloleucine to intracellular concentrations much higher than those of the surrounding medium. Evedence is presented that the transport of amino acids by gill tissue plays a significant role in whole animal nutrition.

Amino Acids↗