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Biomedical subjects

G L Carlson

Publications and source records attributed to G L Carlson.

At least 73 records · Page 4Linked to original sources
PubMed1983

Synthesis, spectral properties, and use of 6-acryloyl-2-dimethylaminonaphthalene (Acrylodan). A thiol-selective, polarity-sensitive fluorescent probe.

Fluorophores processing a 6-acyl-2-dimethylaminonaphthalene moiety show fluorescence that is extremely sensitive to solvent polarity (Weber, G., and Farris, F. J. (1979) Biochemistry 18, 3075-3078). We have synthesized and characterized 6-acryloyl-2-dimethylaminonaphthalene (Acrylodan) which selectively labels thiol moieties in proteins. The quantum yield of this agent is markedly enhanced after reaction with thiols, and as expected, the fluorescent derivatives are very sensitive to dipolar perturbation from their environments. The usefulness of Acrylodan in the study of "hydrophobic" domains, conformational changes, and dipolar relaxation processes in proteins is demonstrated by measurements of fluorescence spectra and lifetimes of a mercaptoethanol adduct dissolved in different solvents and of adducts of this agent with parvalbumin, troponin C, papain, and carbonic anhydrase.

2-Naphthylamine↗
PubMed1983

A bean alpha-amylase inhibitor formulation (starch blocker) is ineffective in man.

A commercial alpha-amylase inhibitor with potent inhibitory activity in vitro was used in a randomized double-blind, cross-over clinical trial in six nonobese, healthy adult males. In these subjects, this inhibitor had no effect on the response of blood glucose, insulin, or breath hydrogen to a standardized starch meal. It is concluded that this formulation has no effect on starch digestion in humans.

Amylases↗
PubMed1982

Differing effects of ursodeoxycholic or chenodeoxycholic acid on biliary cholesterol saturation and bile acid metabolism in man. A dose-response study.

A dose-response study comparing ursodeoxycholic and chenodeoxycholic acid was carried out in six men with asymptomatic radiolucent gallstones present in well-visualizing gallbladders. The study tested the effects of a low (averaging 6 mg/kg/day) or medium dose (averaging 11 mg/kg/day) of each bile acid on the cholesterol saturation of bile as well as on bile acid metabolism, as inferred from biliary and fecal bile acid composition. Ursodeoxycholic acid, at low or medium doses, induced bile desaturation in most patients, whereas chenodeoxycholic acid did not. Despite the greater desaturation efficacy of ursodeoxycholic acid, biliary bile acids became less enriched with the administered bile acid during ursodeoxycholic acid treatment than during chenodeoxycholic acid treatment. Both bile acids were nearly completely 7-dehydroxylated to lithocholic acid by colonic bacteria, but biliary lithocholic increased only slightly (and similarly) with each bile acid. Fecal bile acid composition suggested that administered ursodeoxycholic acid suppressed endogenous bile acid synthesis much less than chenodeoxycholic acid. The results indicate that ursodeoxycholic acid and chenodeoxycholic acid have similar but not identical effects on bile acid metabolism, but that for a given dose, ursodeoxycholic acid is a more potent desaturating agent than chenodeoxycholic acid. The results suggest that cholesterol gallstone dissolution with ursodeoxycholic acid should occur with a dose of 8-10 mg/kg in most nonobese patients.

Aged↗
PubMed1982

Quantification of the fate of dietary fiber in humans by a newly developed radiolabeled fiber marker.

A radiolabeled cellulose (131I-fiber) that retains the essential physical and chemical properties of this class of fiber was developed in our laboratory. We quantified the fate of orally ingested 131I-fiber in healthy individuals by external gamma camera monitoring and fecal collections. The marker passes virtually intact through the human gastrointestinal tract with negligible release and absorption of the label in the gut. Comparison of the gastric emptying rate of 131I-fiber with that of a predominantly aqueous marker, 99mTc-diethylenetriamine pentaacetic acid (99mTc-DTPA), showed that 131I-fiber strands were evacuated more slowly than intragastric fluids. An important finding was that some 131I-fiber emptying occurred during most time periods, even before liquids were completely evacuated. This suggests that the human stomach is able to empty simultaneously liquids and fiber strands (1-15 mm in length) that are resistant to grinding by antral mechanical forces and to digestion by acid-peptic secretion. Thus, some nondigestible solids may be emptied with the bulk of a meal, although at a slower rate. 131I-Fiber may be a useful marker for quantifying gastric emptying of nondigestible solids. Further, the stability of 131I-fiber in the gut, as opposed to most other physiologic solid labels, should enable future investigation of intestinal and colonic transit of fiber, which is an important component of the human diet.

Adult↗
PubMed1982

Antacids and HCl.

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Aluminum Hydroxide↗
PubMed1980

Treatment of pruritus of cholestasis by plasma perfusion through USP-charcoal-coated glass beads.

The accumulation of bile acids has been implicated in the pathogenesis of pruritus of cholestasis. To study the effect of bile-acid depletion on pruritus, 8 patients with chronic cholestasis and intractable pruritus which had not responded to cholestyramine and/or phenobarbitone underwent plasma perfusion through USP-charcoal-coated glass beads. DSuring twenty-two perfusions, between 957 and 6100 ml of plasma were perfused through charcoal columns, resulting in the removal of 126-795 mumol of bile acids. The mean extraction of the perfused bile acids was 81%. After the perfusions, all patients had prompt relief of their pruritus, lasting from 24 h to 5 months. Although the clinical effect may be due to the removal of unidentified pruritogens other than bile acids, charcoal plasma perfusion may improve the quality of life of incapacitated patients with servere intractable pruritus of cholestasis.

Adult↗
PubMed1980

Radiolabeled fiber: a physiologic marker for gastric emptying and intestinal transit of solids.

We report here a study of radiolabeled cellulose as a marker for gastric emptying and intestinal transit of fiber in a dog model. A chemically stable radioisotopic label (131I) was employed to facilitate external monitoring of the tracer. 131I-labeled fiber was found to be biologically stable, since no iodine was absorbed during passage through the canine digestive system. In comparison with water-soluble tracers, gastric emptying of [131I]fiber is very slow. This is consistent with the expected behavior of fiber as a nondigestible solid. We anticipate this new radiolabeled marker will prove to be a useful tool for studies on gastric emptying, intestinal transit, fate and actions of dietary fiber in nonruminant experimental animals and, eventually, in man.

Animals↗
PubMed1980

Metabolism in man of 7-ketolithocholic acid: precursor of cheno- and ursodeoxycholic acids.

To define the metabolism of 7-ketolithocholic acid in man, studies were carried out in gallstone patients with normal liver function. 7-[24-14C]ketolithocholic acid or its glycine or taurine conjugates were injected intravenously, and the chemical form of radioactivity appearing in bile was determined to define hepatic biotransformation. To study intestinal absorption 7-[24-14C]ketolithocholic acid was infused into the jejunum and ileum, respectively, and the chemical form of radioactivity appearing in peripheral blood and bile was assessed. 7-Ketolithocholic acid was extensively reduced in the liver to chenic acid and, to lesser extent, to ursodeoxycholic acid. Hepatic reduction was similar for both unconjugated as well as glycine- and taurine-conjugated 7-ketolithocholic acid. 7-Ketolithocholic acid was well absorbed. There was no biotransformation in the small intestinal lumen or during absorption, because all radioactivity recovered from the lumen or in peripheral blood was in unchanged 7-ketolithocholic acid. Biotransformation products in bile after jejunal infusion were similar to those after intravenous injection. The studies indicate that 7-ketolithocholic acid is likely to be a physiological precursor of ursodeoxycholic acid in healthy man.

Carbon Radioisotopes↗
PubMed1980

Monooctanoin, a dissolution agent for retained cholesterol bile duct stones: physical properties and clinical application.

A commercial emulsifying agent consisting largely of glyceryl-l-monooctanoate (monooctanoin) was found to be an excellent cholesterol solvent. In vitro, the agent dissolved mixed cholesterol gallstones more than twice as fast as sodium cholate solutions, which have been previously used for dissolution of retained cholesterol bile duct stones by T-tube infusion. To test clinical efficacy, the solvent was infused, via T-tube, into 12 patients with retained bile duct stones. Some or all of the stones disappeared in 10 patients during biliary tract infusion of monooctanoin for 4--21 days. Stones from the 2 patients whose stones did not disappear were removed surgically and in vitro were found to be insoluble in monooctanoin. Monooctanoin infusions were well tolerated. This digestible solvent appears to be a useful substance for direct physical dissolution of retained bile duct stones by T-tube infusion.

Adult↗
PubMed1979

Diazontized (125I) diiodosulafanilic acid as a label for cell surface membranes. Studies on erythrocytes.

1. Diazotized 2,6-diiodosulfanilic acid (DDISA) appears to have properties suitable to serve as an artificial, non-penetrating label of cell surface membranes. Therefore, the conditions for selective labeling of cell surface membranes as compared to intracellular proteins as well as a method for its chemical determination were explored in the present study. 2. DDISA reacts with alpha-naphthol at neutral pH to produce a compound (1-hydroxy-4-(2,6-diiodo-4-sulfo-1-phenylazo-(naphthylene)), DSPN) with a characteristic spectrum in the visible range (Amax 430 nm). The absorbance of the reaction product, DSPN, is linearly proportional to the concentration of DDISA and can be used as a method for the colorimetric determination of DDISA. Reaction of DDISA with a molar excess of alpha-naphthol was also used as a method for inactivating unreacted DDISA to terminate labeling prior to cell fractionation. 3. [125I]DDISA reacts avidly with a variety of basic, neutral and acidic proteins as well as with cell membranes to form an acid-stable covalent azo linkage. 4. Effectiveness of labeling of the surface membrane of intact erythrocytes after incubation with [125I]DDISA was assessed by th ratio of 125I incorporated into membrane proteins compared to intracellular proteins. When intact erythrocytes were exposed to [125I]DDISA, the optimal labeling of membranes occurred at 37 degrees C after 20 min of incubation time and at a concentration of 10(-4) M [125I]DDISA in the incubation media. Under these conditions the ratio of the specific activity (cpm 125I/mg protein) of the membrane fraction to the specific activity of the soluble protein fraction (membrane/supernatant ratio) was greater than 500. When incubations were conducted at 4 degrees C this ratio was less than 50. However, when osmotically lysed erythrocytes were incubated with [125I]DDISA the majority of the label reacted with the soluble protein fraction resulting in a membrane/supernatant ratio of 0.14. 5. The results thus suggest that [125I]DDISA used under the appropriate incubation conditions, including the inactivation and removal of [125I]DDISA by washing with alpha-naphthol, can serve as a highly selective membrane label with minimal incorporation into intracellular soluble proteins. The general applicability of this method for other cell types remains to be explored.

Diazonium Compounds↗
PubMed1979

Fate of oral neutralizing antacid and its effect on postprandial gastric secretion and emptying.

The fate and neutralizing efficiency of oral antacids (aluminum and magnesium hydroxides) as well as their effect on postprandial gastric function were quantified in 6 patients with duodenal ulcer disease. We employed a double-marker technique for measurement of gastric secretion and emptying and combined this with back-titration of the gastric samples and analysis of aluminum to trace the fate of antacid in the stomach and duodenum. These studies show that: (a) antacid therapy with aluminum and magnesium hydroxides significantly increases gastric secretion; (b) intragastric neutralization of gastric acid produces a significant and substantial decrease in net acid output (acid secreted minus acid neutralized), but the beneficial effects of neutralization are partially offset by incomplete intragastric formation of aluminum trichloride; (c) most but not all of the ingested antacid is utilized in acid neutralization in the stomach (average 78.6% in our 6 patients); and (d) antacid therapy does not modify the absolute rate of postprandial gastric emptying, but increases dilution of gastric contents, expanding the intragastric volume. Thus, the fractional gastric emptying rate declines, and this, in turn, should enhance antacid utilization by delaying its emptying.

Administration, Oral↗
PubMed1979

Antacid therapy.

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Adsorption↗
PubMed1979

Removal of bile acids and bilirubin by plasmaperfusion of U.S.P. charcoal-coated glass beads.

Removal of protein-bound cholephilic substances such as BA by sorbent perfusion might improve the quality of life of patients with severe inoperable cholestasis where the accumulation of BA is thought to be responsible for the often distressing pruritus. Since hemoperfusion is associated with hematological side effects, plasmaperfusion which, in addition, allows the use of novel, possibly more efficient sorbents, might be preferable, provided a substance with a high affinity for these protein-bound anions could be found. A number of sorbents suitable for plasma-perfusion were therefore tested in vitro as to their BA-adsorbing capacity. U.S.P. charcoal coated onto glass beads in order to facilitate perfusion removed BA from human plasma far better than conventional charcoal suitable for hemoperfusion, charged and uncharged resins, and immobilized albumin. The extraction of BA by the coated glass beads exceeded 90% up to a load of 0.18 mumol BA per milliliter of sorbent, and the BA-adsorbing capacity was 20.8 mumol/ml. In addition to BA, the U.S.P. charcoal columns almost quantitatively removed uric acid, creatinine, and corticosteroids and retained substantial amounts of BR and thyroxine, whereas electrolytes, clotting factors, and plasmaproteins were adsorbed only initially.

Adsorption↗