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Biomedical subjects

I W Percy-Robb

Publications and source records attributed to I W Percy-Robb.

At least 37 records · Page 2Linked to original sources

Differential timing of maximal postprandial concentrations of plasma chenodeoxycholate and cholate: its variability and implications.

The concentrations of conjugated chenodeoxycholate and cholate in serum have been measured in 26 controls and 19 patients with liver disease before and after taking a fat-containing meal. The times at which maximum bile salt concentrations occurred varied considerably between individuals. In the majority of cases maximal concentrations of the two bile salts occurred simultaneously but in 3 subjects maximal concentrations of chenodeoxycholate were found 15-60 min prior to maximal cholate concentrations. The measurement of bile salt concentration in a single sample taken 2 h after the fatty test meal would have produced two false-negative results in the patients with liver disease. It is concluded that the jejunal absorption of dihydroxylated bile salts may not be significant in the majority of individuals and that the protocol for assessment of liver function by postprandial bile salt analysis should include at least two blood samples collected at 1.5 and 2 h after ingestion of the test meal.

Chenodeoxycholic Acid↗

The glyceryl [14C]tripalmitate breath test: a reassessment.

Several reports have been published commending the use of 14C-labelled triglyceride breath tests in the assessment of fat malabsorption. We report further studies using gyceryl [14C]tripalmitate. Corrections for age, weight or metabolic rate failed to improve the test's ability to discriminate between malabsorbers and control subjects. A correction for respiratory quotient improved the linear correlation observed between the breath test results and daily faecal fat excretion. The significance of these findings is discussed and a number of problems identified which, at present, are preventing the introduction of breath tests for fat malabsorption into routine clinical practice.

Adult↗

The effect of age on the intravenous sodium glycocholate test.

The clearance of an injected dose of sodium glycocholate has been studied in a group of 23 control subjects who had no evidence of liver disease. A significant correlation was found between bile salt clearance and age. No significant difference was found between the bile salt clearance of male and female subjects. Data derived from a simple compartmental model indicated that decreased clearance of bile salt with age was not specifically related to degenerative changes in hepatocellular integrity, hepatic uptake of bile salts or bile flow.

Adolescent↗

Cholic acid binding by glutathione S-transferases from rat liver cytosol.

Cholic acid-binding activity in cytosol from rat livers appears to be mainly associated with enzymes having glutathione S-transferase activity; at least four of the enzymes in this group can bind the bile acid. Examination of the subunit compositions of different glutathione S-transferases indicated that cholic acid binding and the ability to conjugate reduced glutathione with 1,2-dichloro-4-nitrobenzene may be ascribed to different subunits.

Animals↗

Bile salt transport in the Dubin-Johnson syndrome.

Serum bile salt measurements and intravenous clearance of glycocholate were performed in a woman with Dubin-Johnson syndrome. Fasting conjugated cholate concentration was raised and prolonged intravenous clearance of sodium glycocholate revealed a secondary rise in conjugated cholate concentration after two hours. The intravenous clearance of bromsulphthalein also showed a secondary rise. These findings support the proposal that Dubin-Johnson syndrome is not homogeneous and that in some patients a abnormality of bile salt clearance coexists with an abnormality of bilirubin nd bromsulphthalein clearance.

Aged↗

Are serum bile salt concentrations raised in hyperlipidaemia?

We have studied serum fasting and postprandial primary bile salt concentrations in a group of 10 consecutive hyperlipidaemic subjects. The efficiency of hepatic bile salt clearance in the same subjects was aslo studied using an injected dose of sodium glycocholate. No increase in serum fasting or postprandial concentrations of the primary bile salts were observed and hepatic bile salt clearance was only marginally abnormal in one subject. The presence of hyperlipidaemia does not invalidate the use of serum conjugated bile salt analysis for the detection of liver diseases.

Aged↗

Weight loss in primary biliary cirrhosis.

Duodenal bile salt concentrations were measured throughout one day in six patients with primary biliary cirrhosis while they were eating a normal ward diet. Five of them had lost weight; none had ascites. Each patient had a radiologically normal small bowel and a normal jejunal biopsy. No clear relationship between high faecal fat excretion and abnormally low duodenal bile salt concentration was found. Xylose absorption was abnormal in five patients. If weight loss in primary biliary cirrhosis is due to malabsorption, factors other than a reduced small intestinal bile salt concentration must be important.

Aged↗

Contribution of biliary lipids to calcium binding in bile.

As part of a detailed study into the solubility of calcium in bile, the contribution of the biliary lipids, bile salt, lecithin, and cholesterole to calcium binding in bile has been assessed. Micellar binding could account for 80% of the calcium binding in hepatic bile but only 50% in gallbladder bile. It is suggested that such binding, in soluble form, lowers the activity of calcium in bile, and therefore its liability to precipitation as gallstone nuclei.

Adult↗

Studies in the rat on the hepatic subcellular distribution and billary excretion of lithocholic acid.

1. A compartmental model has been used to derive the in vivo subcellular distribution of lithocholic acid in rat liver. The model is based on the values of the partition coefficients for the distribution of lithocholic acid between subcellular fractions and buffer. It also permits calculation of the amount of lithocholic acid which is in free solution in cytosol. 2. The hypothesis that the rate of biliary excretion of a bile acid depends on the proportion in free solution was investigated by comparing the rates of biliary excretion of lithocholic acid and glycocholic acid. The rate for lithocholic acid was substantially less than for glycocholic acid while the percentages of each bile acid in free solution were 0.8% and 10%, respectively. 3. The validity of the model was supported by the observation that the amounts of lithocholic acid predicted to be present in the nuclear and cytosolic fractions were similar to the amounts found after intravenous injection of the bile acid.

Animals↗

Identification of two lithocholic acid-binding proteins. Separation of ligandin from glutathione S-transferase B.

1. Two lithocholic acid-binding proteins in rat liver cytosol, previously shown to have glutathione S-transferase activity, were resolved by CM-Sephadex chromatography. 2. Phenobarbitone administration resulted in induction of both binding proteins. 3. The two proteins had distinct subunit compositions indicating that they are dimers with mol.wts. 44 000 and 47 000. 4. The two lithocholic acid-binding proteins were identified by comparing their elution volumes from CM-Sephadex with those of purified ligandin and glutathione S-transferase B prepared by published procedures. Ligandin and glutathione S-transferase B were eluted separately, as single peaks of enzyme activity, at volumes equivalent to the two lithocholic acid-binding proteins. 5. Peptide 'mapping' revealed structural differences between the two proteins.

Animals↗

The interaction of calcium ions with glycocholate micelles in aqueous solution.

The formation of soluble complexes of Ca2+ ions and glycocholate has been demonstrated. The dissociation constant is 26 nmol/litre and a maximum of 2 Ca2+ ions are bound to each glycocholate micelle. The formation of this complex is shown to be reversible. Binding is increased by the introduction of phosphatidylcholine into the micelle; it is decreased by a decrease in pH and by increased counter-ion concentration. The biological significance of these effects is discussed.

Binding Sites↗

Partitioning of bile acids into subcellular organelles and the in vivo distribution of bile acids in rat liver.

1. The subcellular distribution of conjugates of cholic acid and chenodeoxycholic acid between cytosol, nuclei, mitochondria and microsomes in rat liver has been determined. 2. The partition coefficients for the distribution of these bile acids between subcellular fractions and buffer have been measured and used to construct a compartmental model of the amounts of conjugated bile acids present in the different subcellular organelles in vivo. 3. This model indicates that a large percentage of the bile acid in the rat liver is found in the nuclear fraction; 42% of the cholic acid conjugates and 27% of the chenodeoxycholic acid conjugates. Substantial amounts of bile acid are also present in microsomes and mitochondria suggesting that published estimates of the amounts of bile acids in these fractions are underestimates. 4. The model also allows the amount of bile acid which is in free solution in cytosol to be determined; 10.9% of the cholic acid conjugates and 4.1% of the chenodeoxycholic acid conjugates in rat liver were present in this fraction. Knowlege of the amount of free bile acid allows possible roles of the cytosolic bile binding proteins to be assessed.

Animals↗

The preparation of 125I-labelled bile acid ligands for use in the radioimmunoassay of bile acids.

A general method for the preparation of 125I-labelled bile acid-histamine or 125I-labelled bile acid-tyramine conjugates is presented. The method is simple, quick and produces ligands in good yield (30%). The characteristics of a radioimmunoassay for conjugated chenodeoxycholic acid, based on an 125I-labelled ligand prepared by the method, are also described. The assay produced values for fasting serum concentrations of conjugated chenodeoxycholic acid that agree well with previous data.

Bile Acids and Salts↗

Nuclear and cytosolic distribution of conjugated cholic acid and radiolabelled glycocholic acid in rat liver.

1. Normally fed and cholestyramine-treated rats were injected through the superior mesenteric vein with different amounts of radiolabelled glycoholic acid and the appearance of radioactivity in bile was measured. 2. In normally fed rats radioactivity appeared in bile within 30 s of injection and reached a maximum after 2 1/2 min; in the cholestyramine-treated animals the appearance of radioactivity was slower and less of the injected material was excreted into bile. 3. At 10 min after injection, livers were removed and the amounts of radioactive glycoholic acid and endogenous cholic acid conjugates in nuclei and cytosol were determined; most of the bile acid was found in the cytosol, only small amounts being found in nuclei. 4. Nuclear preparations from both normally fed and cholestyramine-fed rats were extracted with KCl (0.4 M) in an attempt to identify a putative bile acid receptor, but no such receptor was found. 5. Regulation of bile acid synthesis does not involve nuclear binding of bile acids.

Animals↗

A constant-volume ultrafiltration technique for the calculation of equilbrium binding data.

A constant-volume ultrafiltration technique is described, and details of its assessment presented. The retention characteristics of two membranes were evaluated using molecules of known molecular weight. The technique is rapid, precise, economical of material and yields equilibrium data. In these respects, it compares favourably with conventional techniques such as equilibrium dialysis.

Albumins↗