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F A Wilson

Publications and source records attributed to F A Wilson.

At least 55 records · Page 3Linked to original sources
PubMed1982

Retinopathy following jejunoileal bypass surgery: report of a case.

Vitamin A deficiency associated with retinopathy and night blindness was observed in a patient 4 yr after jejunoileal bypass. Upon further investigation, a multiple vitamin deficiency state was established. Daily supplementation with 30 000 units of vitamin A resulted in normal levels of vitamin A and retinol-binding protein. The patient's night blindness improved, but his retinopathy remained unchanged as demonstrated by fluorescein angiography. We conclude that patients who have undergone jejunoileal bypass should be supplemented with vitamin A since the vitamin A deficiency is preventable and the retinopathy associated with the deficiency may not be totally reversible.

Adult↗
PubMed1981

Intestinal transport of bile acids.

The intestinal absorption of bile acids is determined by two resistances: diffusion through an unstirred water layer and penetration of the cell membrane. Passive jejunal uptake of polar bile acids is limited by the mucosal membrane, whereas the unstirred layer exerts resistance on uptake of more nonpolar species. After correction for the diffusion layer, the membrane permeability coefficients were derived to calculate the delta delta Fw leads to 1 associated with uptake of the -OH (+874 cal.mol-1), glycine (+897), and taurine (+1,498) groups. The delta delta F1 (-6,126 cal.mol-1) for the -OH group suggested that the jejunal mucosa is a relatively polar membrane. The unstirred layer is even more rate limiting for bile acid uptake from micellar solutions. Once the micelle reaches the aqueous-membrane interface, it is not absorbed intact, but rather uptake is explained in terms of monomers in the aqueous phase that are in equilibrium with the micelle. The presence of the unstirred water layer introduces artifactually high Km values for active transport. Structure-activity studies suggest that the ileal recognition site consists of a component for the steroid moiety, a positive charge, and an adjacent anionic charge. The energy for active transport arises from the Na+ gradient across the brush-border membrane that, in turn, is dependent on the activity of Na+-K+-ATPase. The Na+ stimulation of bile acid transport across the ileal brush-border membrane is due to influx coupling via a cotransport system rather than electrical coupling to satisfy overall electrical neutrality.

Bile Acids and Salts↗
PubMed1981

Sodium-coupled taurocholate transport in the proximal convolution of the rat kidney in vivo and in vitro.

Using the standing droplet technique in the renal proximal convolution and simultaneous microperfusion of the peritubular capillaries, the zero net flux transtubular concentration difference of taurocholate (DeltaC(TC-)) at 45 s was determined as a measure of active bile acid reabsorption in vivo. Starting with 0.1 mmol/liter taurocholate in both perfusates the control DeltaC(TC-) of 0.042 mmol/liter fell to 0.006 mmol/liter (P < 0.001) when the Na(+) concentration in the perfusates was reduced to zero. Removal of bicarbonate from the perfusates to alter pH had no influence on DeltaC(TC-). When glycocholate was added to the perfusates DeltaC(TC-) was decreased, while probenecid increased DeltaC(TC-). These observations were extended by studies performed with brush border membrane vesicles derived from renal cortex. The initial (20 s) uptake of 0.01 mmol/liter taurocholate in the presence of a Na(o) (+) > Na(i) (+) gradient was stimulated twofold compared with its uptake in the absence of a Na(+) gradient. Uptake of taurocholate was osmotically and temperature sensitive. Membranes preloaded with unlabeled glycocholate showed accelerated entry of labeled taurocholate (trans-stimulation) only in the presence of Na(+). Replacement of Na(+) in the media with K(+), Li(+), and choline(+) decreased initial taurocholate uptake by 49, 53, and 62%, respectively. Stimulation of taurocholate transport by cation gradient diffusion potentials was unlikely inasmuch as the addition of valinomycin under K(+) gradient conditions had no effect. A transmembrane pH gradient (pH(o) < pH(i)) did not influence initial uptake of taurocholate. Finally, in the presence of Na(+) taurocholate transport showed cis-inhibition with unlabeled bile acids and saturation kinetics with respect to increasing taurocholate concentrations. The micropuncture and vesicle data indicate that the net transport of taurocholate in the proximal tubule is the result of an electroneutral Na(+)-taurocholate cotransport across the brush border membrane.

Animals↗
PubMed1981

Studies of relationship among bile-acid uptake, Na+, K+-ATPase, and Na+ gradient in isolated cells from rat ileum.

Studies were performed to determine relationships among Na+, K+-ATPase, the transmucosal Na+ gradient, and bile-acid transport in metabolically viable cells isolated from rat ileum. Incubation of cells with 0, 10(-6), 10(-5), 10(-4) and 10(-3) M ouabain resulted, respectively, in a 0, 10.3, 42.1, 97.0, and 100% decrease in glycocholate uptake and a 0, 10.7, 46.4, 76.8, and 100% decrease in Na+, K+-ATPase activity. Thus, one-half maximal inhibition of glycocholate uptake and Na+, K+-ATPase activity occurred at 5.5 x 10(-5) M and 1.7 x 10(-5) M ouabain, respectively. A change in glycocholate uptake was correlated with a change in Na+, K+-ATPase activity after daily injections of methylprednisolone. After 4 days treated animals showed a 26% and 36% increase in glycocholate uptake and Na+, K+-ATPase activity, respectively, over pair-fed saline-treated controls (p less than 0.001). Methylprednisolone did not significantly alter the activity of (Mg++)-ATPase when compared with controls (p greater than 0.05). Glycocholate uptake was reduced by the omission of Na+ from the incubation medium. Preincubation of cells at 37 degrees C with gramicidin D, 10 micrograms/ml, to alter membrane permeability to Na+, resulted in a significant rise in cell Na+ (p less than 0.01) and a significant fall in glycocholate uptake from values in untreated cells (p less than 0.01) to approach values for glycocholate uptake at 0 degrees C. These data suggest that Na+, K+-ATPase may play a role in a bile-acid uptake into ileal cells possibly by maintaining a Na+ electrochemical potential gradient for coupled Na+-bile-acid transport.

Animals↗
PubMed1980

The effect of somatostatin on the intestinal transport of glucose in vivo and in vitro in the rat.

The possibility that somatostatin has a direct inhibitory effect on intestinal D-glucose absorption was studied in rats using intact intestinal loops and everted jejunal segments. Somatostatin infusion in vivo produced a significant fall in plasma glucose concentration (P less than 0.001) and a fall in pooled plasma insulin concentration to 51% of control values. However, somatostatin infusion did not alter significantly from control values the rate of glucose disappearance from the perfused jejunal lumen in vivo or the appearance of gut-derived plasma glucose. The lack of an inhibitory effect of somatostatin on glucose absorption in vivo was confirmed using two in vitro studies. When increasing concentrations of somatostatin (0-10(4) ng/ml-1) were added to both mucosal and serosal solutions, no significant differences were seen for net transmural flux or unidirectional flux of D-glucose in everted jejunal segments. These studies suggest that somatostatin in the rat does not influence plasma glucose concentration by inhibiting intestinal glucose transport at physiological concentrations of glucose and over a wide range of somatostatin concentrations.

Animals↗
PubMed1979

Glycodeoxycholate transport in brush border membrane vesicles isolated from rat jejunum and ileum.

The transport of the bile salt, glycodeoxycholate, was studied in vesicles derived from rat jejunal and ileal brush border membranes using a rapid filtration technique. The uptake was osmotically sensitive, linearly related to membrane protein and resembled D-glucose transport. In ileal, but not jejunal, vesicles glycodeoxycholate uptake showed a transient vesicle/medium ratio greater than 1 in the presence of an initial sodium gradient. The differences between glycodeoxycholate uptake in the presence and absence of a Na+ gradient yielded a saturable transport component. Kinetic analysis revealed a Km value similar to that described previously in everted whole intestinal segments and epithelial cells isolated from the ileum. These findings support the existence of a transport system in the brush border membrane that: (1) reflects kinetics and characteristics of bile salt transport in intact intestinal preparations, and (2) catalyzes the co-transport of Na+ and bile salt across the ileal membrane in a manner analogous to D-glucose transport.

Animals↗
PubMed1979

Microbial colonization and hepatic abnormalities in jejunoileal bypass with resection, ileal mucous fistula, and ileocolostomy.

A role for bacterial colonization of the intestines in the pathogenesis of hepatic abnormalities after jejunoileal bypass was sought. Dogs were divided into groups according to the disposition of the bypassed segment; resection (group I), exteriorization as an ileal mucous fistula (group II), and drainage via an ileocolonic anastomosis (group III). Weight loss, abnormalities in liver function, and hepatic steatosis were significantly greater in groups II and III than in group I. Concomitantly, there was a significant increase in the total number of bacterial colony-forming units in groups II and III. Moreover, a greater number of specific anaerobic genera was isolated in group III than in group II. It is concluded that: (1) retention of the bypassed intestinal segment is associated with greater changes in liver function and structure than when the segment is resected; (2) the changes in the liver correlated with bacterial proliferation in the bypassed intestinal segment; and (3) despite a greater number of anaerobic genera in the ileocolostomy than in the mucous fistula, both procedures were associated with hepatic abnormalities.

Animals↗
PubMed1978

ATP depletion, a possible role in the pathogenesis of hyperuricemia in glycogen storage disease type I.

Other investigators have shown that fructose infusion in normal man and rats acutely depletes hepatic ATP and P(i) and increases the rate of uric acid formation by the degradation of preformed nucleotides. We postulated that a similar mechanism of ATP depletion might be present in patients with glucose-6-phosphatase deficiency (GSD-I) as a result of ATP consumption during glycogenolysis and resulting excess glycolysis. The postulate was tested by measurement of: (a) hepatic content of ATP, glycogen, phosphorylated sugars, and phosphorylase activities before and after increasing glycolysis by glucagon infusion and (b) plasma urate levels and urate excretion before and after therapy designed to maintain blood glucose levels above 70 mg/dl and thus prevent excess glycogenolysis and glycolysis. Glucagon infusion in seven patients with GSD-I caused a decrease in hepatic ATP from 2.25 +/- 0.09 to 0.73 +/- 0.06 mumol/g liver (P <0.01), within 5 min, persisting in one patient to 20 min (1.3 mumol/g). Three patients with GSD other than GSD-I (controls), and 10 normal rats, showed no change in ATP levels after glucagon infusion. Glucagon caused an increase in hepatic phosphorylase activity from 163 +/- 21 to 311 +/- 17 mumol/min per g protein (P <0.01), and a decrease in glycogen content from 8.96 +/- 0.51 to 6.68 +/- 0.38% weight (P <0.01). Hepatic content of phosphorylated hexoses measured in two patients, showed the following mean increases in response to glucagon; glucose-6-phosphate (from 0.25 to 0.98 mumol/g liver), fructose-6-phosphate (from 0.17 to 0.45 mumol/g liver), and fructose-1,6-diphosphate (from 0.09 to 1.28 mumol/g) within 5 min. These changes, except for glucose-6-phosphate, returned toward preinfusion levels within 20 min. Treatment consisted of continuous intragastric feedings of a high glucose dietary mixture. Such treatment increased blood glucose from a mean level of 62 (range 28-96) to 86 (range 71-143) mg/dl (P <0.02), decreased plasma glucagon from a mean of 190 (range 171-208) to 56 (range 30-70) pg/ml (P <0.01), but caused no significant change in insulin levels. Urate output measured in three patients showed an initial increase, coinciding with a decrease in plasma lactate and triglyceride levels, then decreased to normal within 3 days after treatment. Normalization of urate excretion was associated with normalization of serum uric acid. We suggest that the maintenance of blood glucose levels above 70 mg/dl is effective in reducing serum urate levels and that transient and recurrent depletion of hepatic ATP due to glycogenolysis is contributory in the genesis of hyperuricemia in untreated patients with GSD-I.

Adenosine Triphosphate↗
PubMed1977

Characterization of bile acid binding to rat intestinal brush border membranes.

Studies were performed to characterize the binding1 of bile acids to intestinal brush border membranes. Total 14C-taurodeoxycholate binding was: 1) similar for brush borders prepared from jejunum and ileum, 2) linear with respect to monomer concentration, 3) uninhibited by a structural analog, and 4) not depressed by boiling or trypsin. A linear relationship existed between binding and the number of hydrogen bonds formed by a bile acid and the slope of the line corresponded to delta deltaF of 300 cal/mol. The binding of bile acids to the 105,000 x g supernatant fraction of sonicated brush borders was similar to the binding of phospholipid liposomes using gel chromatography. These data suggest that: 1) the kinetics and characteristics of binding of bile acid to ileal brush borders do not reflect the kinetics and characteristics of active ileal transport previously obtained in whole tissue preparations, but instead reflect the kinetics and characteristics of passive jejunal transport; 2) a determinant of binding is hydrogen bonding with water; 3) isolated intact brush borders are relatively polar membranes; and 4) binding to solubilized brush borders may represent partitioning between the aqueous phase and membrane lipid.

Animals↗
PubMed1977

Bacteriological studies in a patient with antibiotic-associated pseudomembranous colitis.

Detailed aerobic and anaerobic bacteriological studies on the operative specimen from a patient with antibiotic-associated pseudomembranous colitis revealed approximately 10(11) facultatively anaerobic bacteria, but less than 10(5) obligate anaerobes per g of involved colonic tissue. Fourteen isolates of Escherichia coli, three isolates of Pseudomonas aeruginosa, and two isolates of Streptococcus fecalis were identified. The majority of the organisms were resistant to most of the antibiotics that the patient had received. Examinations of E. coli for heat-labile and heat-stable enterotoxins and tissue invasiveness were negative, and enterotoxin tests on the P. aeruginosa isolates were negative. Inoculation of mice with the bacterial isolates revealed no unusual pathogenicity. These findings suggest that antibiotic-associated colitis is associated with a marked loss in anaerobic colonic flora, but the colitis could not be explained by the presence of enterotoxins, tissue invasiveness, and pathogenicity of remaining microorganisms.

Aged↗
PubMed1976

Thiamine transport in thiamine-deficient rats. Role of the unstirred water layer.

As part of a systematic study of alcoholism and thiamine absorption, the effect of diet-induced thiamine deficiency and the role of the unstirred water layer on the thiamine transport were investigated. Using 3H-labeled dextran as a marker of adherent mucosal volume, jejunal uptake of 14C-labeled thiamine hydrochloride was measured, in vitro, in thiamine-deficient rats and pair-fed controls. Uptake of low thiamine concentrations (0.2 and 0.5 muM) was greater in the thiamine-deficient rats than in the controls. In contrast, uptake rates for high thiamine concentrations (20 and 50 muM) were similar in both groups. While Jmax was unaltered, Km was decreased in thiamine deficiency, suggesting a decrease in unstirred water layer thickness. Accordingly, the thickness of the water layer was measured in both groups of animals and correlated with Jmax and Km under unstirred and stirred conditions. Without stirring, there was no difference in Jmax between the two groups. In contrast, both Km and the water layer were reduced in the thiamine-deficient rats. With stirring, Jmax was not affected, but both Km and the water layer thickness were reduced to similar values in both groups. Reversal of thiamine deficiency resulted in the return of thiamine uptake and the unstirred water layer thickness to control values. These data support the concept of a dual system of thiamine transport and emphasize the role of the unstirred water layer as an important determinant of transport kinetics not only under physiologic situations but also in diet-induced rat thiamine deficiency, a model for a clinical patholigical state. The decrease in the unstirred water layer thickness in thiamine deficiency may be also viewed as a possible adaptive mechanism to facilitate absorption of meager supplies of thiamine.

Animals↗
PubMed1975

Characterization of the passive and active transport mechanisms for bile acid uptake into rat isolated intestinal epithelial cells.

The unstirred water layer has been shown to lead to an underestimation of apparent Km (Km(app)) values for active transport processes in intestinal whole tissue preparations. Isolated cells offer several potential advantages in the study of transport processes including a decreased diffusion layer of water adjacent to their absorptive membranes. Initial studies in cells isolated from rat intestine involving measurements of CO2 and lactate production and O2 consumption showed that overall metabolic pathways were functioning. Next, unidirectional uptake rates of bile acids across the isolated cell membrane were determined following correction for extracellular fluid contamination with a non-absorbable marker. Using epithelial cells isolated from jejunum P(app) for eight bile acid monomers varied from 24.9 (taurocholate) to 1563 (deoxycholate) nmol/min/100 mg protein/mM. From these data the incremental free energy changes for the addition of a hydroxyl, glycine and taurine group to the bile acid molecule were calculated to be 982, 1040 and 1464 cal/mol, respectively, values similar to those obtained after correction for unstirred water layer resistance in whole tissue preparations. Following subtraction of the passive component in isolated ileal cells complete kinetic curves for taurocholate and taurodeoxycholate yielded V(app) values of 109 and 70 nmol/min per 100 mg, respectively. Km(app) values of 0.24 mM (taurocholate) and 0.10 mM (taurodeoxycholate) are lower than usually recorded in whole tissue. Bile acid uptake into cells from ileum, but not jejunum, was affected by temperature, metabolic and competitive inhibition. These studies indicate that isolated epithelial cells are a metabolically viable, relatively purified intestinal preparation which discriminates between active and passive transport processes for bile acids under conditions where unstirred water layer artifacts are minimized.

Animals↗