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Biomedical subjects

W A Olsen

Publications and source records attributed to W A Olsen.

At least 37 records · Page 2Linked to original sources
PubMed1982

Sucrase metabolism in germfree rats.

We studied degradation of the intestinal brush-border protein sucrase-isomaltase in germfree animals as well as in ex-germfree animals and conventional controls to determine the mechanism by which intestinal bacteria alter disaccharidase levels. Our results indicate that sucrase-isomaltase turnover is as rapid in germfree animals as in the other groups and are consistent with surface removal of disaccharidases by pancreatic proteases under physiological conditions. Our results also suggest that elevated disaccharidase levels in germfree animals are in large part the consequence of an increased number of mature enterocytes, which persists for at least 2 wk after exposure of animals to a conventional microbial flora.

Animals↗
PubMed1982

In vivo responses of rat intestinal epithelium to intraluminal dietary lectins.

Although a variety of plant lectins are consumed as part of the normal human diet and are capable of binding to intestinal cell surfaces in vitro, little information exists on their effects on intact intestine. We have studied the acute effects of intraluminal administration of wheat germ agglutinin and concanavalin A in normal rats. Both lectins caused increased shedding of brush border membrane and, at higher concentrations, reduction in surface area, acceleration of cell loss, and shortening of villi. These changes were prevented by simultaneous administration of the appropriate sugar to inhibit binding, indicating that the effects were related to binding to carbohydrate residues of intestinal cells. Similar changes of brush borders were found after intraluminal administration of antiserum to sucrase-isomaltase, a surface protein of the brush border membrane, suggesting that the lectin effects resulted from cell surface receptor-lectin interaction rather than a primary intracellular effect. Our results suggest that dietary lectins may be in part responsible for normal turnover of brush border membrane, and support, in addition, the possibility that certain intestinal diseases such as celiac sprue may be the consequence of increased levels of lectin receptor allowing a dietary lectin to exert a toxic effect.

Animals↗
PubMed1981

The effect of bilirubin on the function of hamster small intestine.

Jaundice phototherapy is associated with a significant incidence of watery diarrhea. We have postulated that acute intestinal secretion, rather than malabsorption of dietary carbohydrate, is an effect of a photoproduct of bilirubin upon the intestinal mucosa. Because of major effect of phototherapy is the hepatic excretion of nonconjugated bilirubin, we investigated the effect of bilirubin on small intestinal function in the hamster in vivo. The entire small intestine was luminally perfused in vivo with solutions containing bilirubin (0.125 to 0.75 mmole/liter) and net water and sodium fluxes were measured. Control animals absorbed both water (J H2O(net) = 58.9 microliter/min/g) and sodium (J Na(net) = 4.55 microEq/min/g), but animals perfused with bilirubin (greater than or equal to 0.25 mmole/liter) exhibited secretion of water (J H2O(net) = -39.0--85.9) and sodium (J Na(net)=-9.91--18.24). The rate of water secretion was positively related to the concentration of bilirubin in the infusate (r=0.749; p less than 0.001). The concentration of bilirubin in ultrafiltrates of perfusate was likewise positively related to its concentration in the infusate (r = 0.844; p less than 0.001), indicating the potential importance of soluble forms of bilirubin in inducing secretion. Possible epithelial injury was studied by measuring the concentration of DNA in the perfusate and the activity of disaccharidases in postperfusion mucosa, and the possible role of cyclic adenosine monophosphate as a mediator of the secretory process was investigated by determining its concentration in postperfusion mucosa. Perfusion with 0.5 mM bilirubin, which produced significant secretion, did not cause loss of DNA (0.284 versus 0.244 mg/liter) or mucosal lactase activity (56 versus 53 units/g) or enhancement of cyclic adenosine monophosphate concentration (14.9 versus 14.12 pmoles/mg protein).

Animals↗
PubMed1980

Circadian rhythm of intestinal sucrase activity in rats. Mechanism of enzyme change.

Past investigation has revealed that the circadian rhythm of intestinal sucrase activity in rats is primarily cued by the time of feeding. We examined the mechanism of the circadian rhythm by methods involving quantitative immunoprecipitation of sucrase-isomaltase protein and study of decay of radioactively labeled protein. Rats were placed on a controlled feeding regimen (1000-1500 h) and then sacrificed at 3-h intervals over a 24-h period. Immunotitration experiments indicated that the circadian rhythm was the result of changes in the absolute amount of sucrase-isomaltase protein present and not of changes in the enzyme's catalytic efficiency. To study the mechanism of this circadian variation in sucrase-isomaltase mass, [(14)C]sodium carbonate was injected and, after maximum incorporation into brush border protein, the rats were sacrified at 3-h intervals. Sucrase-isomaltase protein was isolated by immunoprecipitation, and the decrease in total disintegrations per minute over time was used to study degradation of the protein. Enzyme degradation was not constant but exhibited a clear circadian rhythm. The period of increasing enzyme mass was characterized by virtual cessation of enzyme degradation (t((1/2)) of 38 h), and the period of declining enzyme mass by rapid degradation (t((1/2)) of 6 h or less). We found similar changes in enzyme degradation in fasted animals, demonstrating that the changes were not the result of decreased isotope reutilization during feeding. We found no evidence of a circadian rhythm in [(14)C]leucine incorporation into the protein, suggesting that enzyme synthesis was constant. These results indicate that the circadian rhythm of sucrase activity represents changes in the total amount of enzyme protein that are, at least in large part, secondary to changes in the enzyme's degradation rate.

Animals↗
PubMed1977

The intestinal brush border membrane in diabetes. Studies of sucrase-isomaltase metabolism in rats with streptozotocin diabetes.

Diabetes stimulates the functional activity of the intestinal brush border membrane with enhancement of both hydrolytic enzyme activity and membrane transport systems. To determine the mechanism of this effect, we studied the effects of streptozotocin diabetes on the metabolism of one membrane protein, sucrase-isomaltase, which increases its activity in diabetes. The protein was purified and an antiserum prepared. Sucrase-isomaltase from control and diabetic rats was immunologically identical as shown by Ouchterlony double-diffusion analysis of papain-solubilized mucosal proteins. The increase in sucrase enzyme activity in diabetic animals (31.0+/-1.4 U SEM 5 days after streptozotocin vs. 13.1+/-1.0 in controls) was the consequence of increased enzyme protein and not an alteration in catalytic efficiency as demonstrated by quantitative immunoprecipitin reactions. To account for increased sucrase-isomaltase protein in diabetes we studied papain-solubilized mucosal proteins labeled by injection of [(14)C]carbonate and [(14)C]leucine and analyzed incorporation into sucrase-isomaltase protein (anti-serum precipitable) and total protein (trichloroacetic acid precipitable). We found that diabetes did not affect the decay of labeled total protein, but prolonged the decay of labeled sucrase-isomaltase. t((1/2)) of sucrase-isomaltase was 4.4 h in control animals after [(14)C]carbonate injection and 8.8 and 10.2 h, respectively, 2 and 5 days after induction of streptozotocin diabetes. We obtained similar results in experiments with [(14)C]leucine with diabetes increasing t((1/2)) from 6 to 13.6 h. Diabetes did not appear to increase the rate of addition of sucrase-isomaltase to the brush border membrane, since it did not affect the 10- and 60-min incorporations of isotope into sucrase-isomaltase protein relative to incorporation into total protein and did not alter rate constants for synthesis calculated from the t((1/2)) and the change in enzyme mass over time.Thus, enhanced sucrase activity in the diabetic animal is the consequence of an increase in sucrase-isomaltase protein which develops because of a decrease in its rate of degradation.

Animals↗
PubMed1977

Effects of anionic surfactants on hamster small intestinal membrane structure and function: relationship to surface activity.

The relationship of the surface properties of a group of anionic surfactants to their effects on intestinal water transport was studied. Dose-response inhibition of water transport in everted hamster jejunal segments was obtained with two long chain detergents (sodium dodecyl sulfate and dioctyl sodium sulfocuccinate), a fatty acid (ricinoleate), and dihydroxy bile salts (deoxycholate, chenodeoxycholate, and taurodeoxycholate), whereas no activity was seen with trihydroxy (cholate, glycocholate, and taurocholate) and tri-keto (dehydrocholate) bile salts. The relative effects on water transport were paralleled by their abilities to lyse the erythrocyte, a membrane model. These two biological effects were related to the surface properties of the agents, as determined by critical micelle concentration and surface tension reduction. We further characterized the action of deoxycholate on hamster small intestine, in vivo. Net water secretion was accompanied by increases in permeability of the mucosa to inulin, dextran, and albumin. These secretory and permeability changes were accompanied by both biochemical and histological alterations: exfoliation (DNA release), membrane effects (sucrase release), and shortened villi. Electron microscopy revealed extensive alteration of the brush border membrane with a decrease in binding of lanthanum and the development of permeability to tracer in villus tip cells. In contrast, taurocholate, which did not alter water transport, did not affect intestinal permeability or the brush border membrane. We believe that the surface properties of anionic surfactants cause changes in absorptive cell membranes which result in intestinal secretion.

Animals↗
PubMed1977

[Absorption and malabsorption of vitamins (author's transl)].

Vitamins are absorbed by different mechanisms ranging from simple diffusion for most of the water soluble vitamins to more complex processes in the case of vitamin B12, folate, and the fat soluble vitamins. These processes are discussed. Malabsorptive disorders result in significant deficiency of only these latter vitamins which require specialized digestive or transport mechanisms. The underlying disease also determines which, if any, deficiency is likely to occur. The effects of different types of pancreatic, biliary, and intestinal disease on vitamin absorption are discussed.

Avitaminosis↗
PubMed1976

The effects of sodium ricinoleate on small intestinal function and structure.

The mechanism of hydroxy fatty acid-induced secretion was investigated in perfused hamster small intestine in vivo. Sodium ricinoleate at an 8-mM concentration resulted in not only secretion of water and sodium, but an increase in intestinal clearance of inulin and a 16,000 mol wt dextran as well. A concentration of ricinoleate (2 mM) which did not affect water transport, however, did not alter intestinal permeability. Ricinoleate-induced intestinal secretion was also accompanied by increased mucosal cell exfoliation as measured by the appearance of DNA in the perfusate and by apparent injury to epithelial cell membranes as judged by measurement of sucrase activity and phospholipid in cell-free aliquots of luminal fluid. Light and electron microscopic studies demonstrated substantial mucosal architectural changes with 8 mM ricinoleate with villus shortening and injury to epithelial cells at the villus tips. In contrast, cholera enterotoxin caused marked secretion of sodium and water, presumably by a cyclic AMP mechanism, but did not alter inulin clearance or enhance DNA or sucrase appearance in the lumen. These studies suggest that at least a component of ricinoleate-induced intestinal secretion is related to structural alterations of the mucosa.

Animals↗
PubMed1975

Inhibitory actions of laxatives on motility and water and electrolyte transport in the gastrointestinal tract.

Castor oil and magnesium sulfate were studied for their effects on gastrointestinal contractile activity in vivo. Ricinoleic acid, the active ingredient in castor oil, magnesium sulfate and mannitol were studied and compared for their effects on net water and electrolyte absorption in vitro. Extraluminal strain gauge transducers were implanted in dogs and used to monitor the circular smooth muscle activity of the antrum, duodenum, ileum and colon after water, castor oil or a 30 percent solution of magnesium sulfate. Substances were tested during the interdigestive (fasted) and digestive (fed) states. Decreases in total activity were found for both cathartics in the antrum and ileum. Further analysis revealed that decreases in the ileum occurred primarily by a decrease in contractile rate, whereas antral decreases could be attributed primarily to a decrease in force per contraction. Proximal colonic activity tended to decrease after laxatives and feeding. The effects of ricinoleic acid, isotonic and hypertonic solutions of magnesium sulfate and mannitol on net water and electrolyte absorption were tested on everted segments of hamster jejunum. Sodium ricinoleate (2.0 mM) reduced net water transport by 48 percent (P smaller than .01). Magnesium sulfate, like mannitol, only reduced net water absorption when present as a component of a hypertonic mucosal solution. The results suggest that both inhibition of water absorption and reduced circular smooth muscle activity may be important factors in castor oil- and magnesium sulfate-induced catharsis.

Animals↗
PubMed1975

Actions of ricinoleic acid and structurally related fatty acids on the gastrointestinal tract. II. Effects on water and electrolyte absorption in vitro.

Ricinoleic acid, the active component of castor oil, and related fatty acids were studied to determine their relative inhibitory effects on water and electrolyte absorption using everted hamster jejunal and ileal segments. Differences were found between hydroxylated and nonhydroxylated congeners as well as between cis and trans geometric isomers. At a mucosal concentration of 2.0 mM, the unsaturated fatty acids had the following rank order of potency on inhibition of water absorption: ricionoleate greater than or equal to ricinelaidate- greater than equal to linoleate greater than oleate greater than linelaidate greater than elaidate. Ricinoleyl alcohol was effective at 2.0 mM but the methyl ester of ricinoleic acid was ineffective at this concentration. Among a series of saturated fatty acids including palmitate, stearate, a mixture of 9- and 10-hydroxystearate, and 12-hydroxystearate, only the last compound had any inhibitory effect on water absorption. The results define those portions of the ricinoleic acid molecule required for its effect on water and electrolyte absorption and suggest that classification of this cathartic as an "irritant" or "stimulant" should be re-evlauated.

Animals↗
PubMed1975

Enhancement of intestinal sucrase activity in experimental diabetes: the role of intraluminal factors.

Experimental diabetes alters intestinal mucosal function in a variety of ways including the enhancement of both active transport processes and the activity of brush-border hydrolases. These effects could result from changes in either intraluminal factors (food, bile, pancreatic enzymes) or extraluminal factors (blood flow, hormones, nervous impulses). To determine the role of intraluminal factors we studied the effect of diabetes on segments of jejunum completely excluded from luminal continuity, but with intact blood and nerve supply. Three weeks after construction of Thiry-Vella fistulas in rats, diabetes was induced with streptozotocin. Five days later sucrase activity was measured in both the excluded segment and in the proximal jejunum. Exclusion alone resulted in a 77 per cent decrease in mucosal protein content with no change in sucrase specific activity suggesting simply a diminished number of mucosal cells. Diabetes increased the specific activity of sucrase from 0.0643 mumoles per minute per milligram of protein plus or minus 0.0077 (SEM) to 0.1074 plus or minus 0.0182 (P smaller than 0.05) in the proximal jejunum and from 0.0467 plus or minus 0.0047 to 0.1040 plus or minus 0.0191 (P smaller than 0.02) in the excluded segment. These results provide conclusive evidence that the diabetic enhancement of sucrase activity is independent of intraluminal factors and must be the consequence of extraluminal changes.

Animals↗
PubMed1974

Small intestinal disease in T cell deficiency.

Biopsies of the proximal small bowel were obtained in four children with impairment of cell-mediated immunity, chronic diarrhia, and malabsorption; one child had an isolated T cell defect and three had significant B and T cell defects. All of them had malabsorption and, in addition to alterations of the small bowel epithelium, large vacuolated macrophages were seen in the lamina propria in all biopsies. Electron microscopy demonstrated lipid and patches of small pleomorphic inclusions within the macrophages. Since large vacuolated macrophages have also been described in Whipple's disease and chronic granulomatous disease, we suggest the possibility of a common thread of defective host defense and gastrointestinal malfunction in these three conditions.

B-Lymphocytes↗