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Biomedical subjects

A F Hofmann

Publications and source records attributed to A F Hofmann.

At least 253 records · Page 14Linked to original sources
PubMed1977

Effect of deoxycholic acid ingestion on bile acid metabolism and biliary lipid secretion in normal subjects.

The effect of deoxycholate ingestion, 750 mg per day, on bile acid kinetics, biliary bile acid composition, and biliary lipid secretion was studied in 7 healthy volunteers. Bile acid kinetics were measured by isotope dilution, and hourly outputs of bile acid, cholesterol, and phospholipid were quantitated by a duodenal perfusion technique during a 24-hr period which included three liquid meals and an overnight fast. Biliary bile acid composition was assessed by coupled gas chromatography-mass spectrometry. After deoxycholic acid ingestion, biliary bile acids became composed of predominantly deoxycholyl conjugates, and deoxycholic acid pools increased 4-fold. Both chenodeoxycholic and cholic acid pools decreased, and daily synthesis of each of the primary bile acids was inhibited by 50%. Total bile acid pools did not change in any consistent manner. Daily bile acid secretion increased slightly during deoxycholic acid ingestion, and recycling frequency varied reciprocally with the total bile acid pool both before and during deoxycholic acid treatment. Deoxycholic acid ingestion caused no change in either the daily secretion of cholesterol or lecithin, or the cholesterol saturation of fasting-state bile, which remained unsaturated throughout the study. SGOT levels increased to 4 times the upper limits of normal in 2 of 7 subjects, but these levels promptly returned to normal when deoxycholate feeding was stopped. Serum cholesterol levels decreased in every subject (average 15%) during deoxycholic acid administration. No evidence for a direct role of deoxycholate in the pathogenesis of cholesterol cholelithiasis was obtained in these studies.

Bile↗
PubMed1977

The enterohepatic circulation of bile acids in man.

The enterohepatic circulation of bile acids may now be described in its broad outlines. Methodology presently available appears sufficient for overall characterization in health and disease. The challenge of the future is to gain insight into the control of the enterohepatic circulation so that new therapeutic approaches to liver, biliary and intestinal disease may be developed.

Amino Acids↗
PubMed1977

The enterohepatic circulation of conjugated bile acids in healthy man: quantitative description and functions.

A multicompartmental model describing the enterohepatic circulation of conjugated bile acids in man under steady-state conditions is proposed. The model encompasses conjugation; deconjugation and reconjugation; dehydroxylation; sulfation, desulfation and resulfation; dehydrogenation; and stereoselective rehydrogenation. A dynamic description of the enterohepatic circulation and a brief description of bile acid functions in health and dysfunctions in disease are also discussed.

Bile↗
PubMed1977

Lactase deficiency: a common genetic trait of the American Indian.

Intestinal lactase activity was assessed indirectly in 156 American Indians by measuring breath hydrogen after an oral lactose load. Lactase deficiency was present in 66% of subjects and correlated highly with the percentage of Indian blood. Lactase deficiency was present by the age of 5 years and was unrelated to sex. Most lactase-deficient subjects (81%), but only a minority (23%) of lactase-sufficient subjects, developed symptoms after the oral lactose load, and among lactase-deficient subjects, symptoms occurred more frequently in adults than in children (P = 0.05). Indeed, by history, 53% of lactase-deficient adults, but only 10% of lactase-deficient children under 18 years of age, were aware of milk intolerance. Despite these differences, milk consumption was only slightly less (19 g) in the lactase-deficient subjects than in those with normal lactase activity (25 g) (P less than 0.05). The results indicate that lactase deficiency is a common autosomal genetic trait in the American Indian that becomes manifest in early childhood. Tolerance to dietary lactose appears to decline in the American Indian as he reaches adulthood, but in this population the decline in tolerance had only minor influence on lactose intake.

Adolescent↗
PubMed1977

Metabolism of steroid and amino acid moieties of conjugated bile acids in man. V. Equations for the perturbed enterohepatic circulation and their application.

Equations previously developed to describe the enterohepatic circulation of the major biliary bile acids in man (Gastroenterology 67:887, 1974) were modified in order to predict the effect on biliary bile acid composition and pattern of amino acid conjugation after prototypic perturbations of the enterohepatic circulation in man. For the steroid moiety, the effects of bile acid feeding, increased recycling frequency, decreased intestinal conservation, and increased dehydroxylation were simulated. For the glycine or taurine moiety, the effect of increased deconjugation or preferential loss of one of the amino acid moieties was simulated. For the steroid moiety, the steady state biliary bile acid composition reflects the balance between input and conservation for each bile acid. Similarly, the distribution of bile acids between glycine and taurine conjugates reflects the balance between conjugation and conservation for each amino acid moiety. Because these values may vary widely and independently, analysis of biliary bile acid composition in terms of the steroid moiety or the glycine-taurine ratio per se cannot be used to infer the relative rates of input or conjugation.

Amino Acids↗
PubMed1977

A facile hydrolysis-solvolysis procedure for conjugated bile acid sulfates.

Methods for hydrolyzing and solvolyzing conjugated bile acid sulfates were compared on reference mixtures of conjugated and unconjugated bile acid sulfates gas-liquid chromatography to assess recovery, and thin-layer chromatography and zonal scanning to define the products occurring after hydrolysis. Conventional methods in which solvolysis preceded vigorous alkaline saponification gave incomplete recoveries. However, essentially complete recovery of primary and secondary bile acid sulfates was obtained with a mild alkaline saponification procedure followed by acidification and extraction into ether, in shich complete solvolysis was shown to occur within 12 hours. Based on these findings, we developed and validated a simple hydrolysis-solvolysis procedure; the method features mild alkaline hydrolysis, acidification to pH 1, and extraction with ether followed by a 1-hour incubation.

Bile Acids and Salts↗
PubMed1977

Biliary secretion of copper in healthy man. Quantitation by an intestinal perfusion technique.

A duodenal perfusion technique which permitted a normal daytime eating pattern of three liquid meals and an overnight fast was used to measure the 24-hr output of copper in bile in 19 studies in 14 persons with normal hepatic and gallbladder function. Daily biliary output was also determined by direct measurement on four 24-hr bile collections obtained from 3 patients with complete biliary diversion, and in 4 patients measurements of dietary copper intake and fecal copper output were also made. A mean bile copper output of 25 +/- 13 microng per kg-day (1.7 mg +/- 0.8) (mean +/- SD) was obtained in 19 perfusion studies; the range was 9.0 to 53.0 microng per kg-day. The values in the 24-hr bile collections were similiar to those obtained using the perfusion method. Biliary copper output was similar during the day and night, and there was no correlation between hourly rates of copper output and hourly rates of bile acid output, nor was there any correlation between daily copper output and daily bile acid output. The similar values for dietary intake, biliary output, and fecal output provide additional support for the current view that in healthy man copper balance is maintained by biliary secretion and subsequent fecal excretion of copper which has been absorbed in the stomach and proximal duodenum.

Bile↗
PubMed1977

Measurements of intestinal permeability using low molecular weight polyethylene glycols (PEG 400). I. Chemical analysis and biological properties of PEG 400.

A new approach to the measurement of intestinal permeability in man has been developed, using low molecular weight polyethylene glycol (PEG 400) as probe molecules. PEG 400 (range of molecular weight 232 to 594) is a mixture of water-soluble molecules of different sizes which can be extracted readily from biological fluids and analyzed by gas-liquid chromatography. PEG 400 is nontoxic, not degraded by intestinal bacteria, not metabolized after absorption, and rapidly excreted in urine. The different-sized molecular components cross the intestinal epithelium at different rates, allowing characterization of the passive permeability properties of the mucosa.

Animals↗
PubMed1977

Measurements of intestinal permeability using low molecular weight polyethylene glycols (PEG 400). II. Application to normal and abnormal permeability states in man and animals.

A new approach to the measurement of intestinal permeability using low molecular weight polyethylene glycols (PEG 400) has been applied to the study of normal and abnormal permeability states in man and animals. Successful assessments of gastric, jejunal, ileal, and colonic permeability suggest that the technique has application to any area of the gastrointestinal tract. The method has shown that bile acids alter mucosal permeability in the stomach and colon and that celiac sprue is associated with decreased intestinal permeability. These examples illustrate the potential of the technique for studying the function of diseases intestine in man.

Adult↗
PubMed1977

Radioimmunoassay of bile acids: development, validation, and preliminary application of an assay for conjugates of chenodeoxycholic acid.

A rapid, sensitive, precise radioimmunoassay for conjugates of chenodeoxycholic (chenic) acid has been developed and validated. Immunogen was prepared with chenylglycine couples to bovine serum albumin, emulsified in Freund's complete adjuvant, and injected intracutaneously in rabbits. Antibodies of moderate titer (used at 1:7500 final dilution) were obtained. Tracer of high specific activity was prepared by reductive tritiation of delta11-chenylglycine. The binding step required 1 hr at room temperature; separation of bound tracer was achieved by addition of ammonium sulfate. The limit of sensitivity of the assay was about 20 nmoles per liter, and the lower limit of the working range was 0.4 mumole per liter. The assay was validated by measuring levels in samples of fasting state serum to which known amounts of chenylglycine had been added; the assay was also validated by means of gas-liquid chromatography on sera from jaundiced patients. The median fasting state serum level in 56 Caucasians and blacks was 0.9 mumole per liter (upper limit of normal (95% confidence) being 2.3), which is in the same range as that reported by others using gas-liquid chromatography. A 5- to 10-fold increase in levels of chenyl conjugates was observed 1 hr after the ingestion of a liquid meal in healthy persons.

Ammonium Sulfate↗
PubMed1977

Radioimmunoassay of unsulfated lithocholates.

A simple, rapid, precise radioimmunoassay for total unsulfate species of lithocholate (lithocholyglycine, lithocholyltaurine, and lithocholate) in serum is described. Antiserum was raised in rabbits by injection of lithocholylglycine coupled to bovine serum albumin (prepared by a carbodiimide method) and emulsified in complete Freund's adjuvant; antisera capable of measuring 40-120 pmol at 1:400 dilution were obtained. The tracer was [11, 12-3[H]lithocholyglycine. The radioimmunoassay featured a 2-hr binding step at 42 decrease C and a 1-hr separation step using polyethylene glycol. The antibody had the following relative specificities: lithocholyglycine and lithocholytaurine, 1; lithocholate, 1.5; chenodeoxycholyglycine, 20; and deoxycholylglycine, 55. There was no binding of various other free or conjugated sulfated and unsulfated bile acids. The mean fasting-state level in 50 healthy subjects was 0.3 mu mol/l (0.14 microgram/ml), but 11 of the 50 subjects had level too low to measure by this technique.

Antibody Specificity↗