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Biomedical subjects

E P Bosman-Jacobs

Publications and source records attributed to E P Bosman-Jacobs.

5 recordsLinked to original sources

Na+-dependent bile acid transport in the ileum: the balance between diarrhea and constipation.

Ileal Na+-dependent bile acid transport was quantified in vitro as the uptake of 3H-taurocholate into brush-border membrane vesicles. Vesicles were prepared from ileal biopsies of 158 patients placed in 10 diagnostic categories. Active bile acid transport (expressed as picomoles taurocholate uptake per milligram brush-border membrane protein per 15 s, median and interquartile ranges indicated) did not differ significantly in 6 categories: irritable bowel syndrome (71, 35-97; n = 21), colon polyps (42, 30-89; n = 29), colitis (62, 33-91; n = 31), postvagotomy or postcholecystectomy (69, 37-97; n = 11), diarrhea without increased bile acid loss (58, 48-85; n = 12), and lack of gastrointestinal pathology (74, 45-103; n = 22). A decreased active bile acid transport was found in 3 categories: ileal disease (4, 1-36; n = 11), partial ileal resection (5, 1-35; n = 5), and constipation (41, 22-50; n = 8). Bile acid transport was increased in patients with bile acid-losing diarrhea with endoscopically and histologically normal ilea (111, 94-135; n = 8). These findings indicate that a low fecal bile acid loss, presumed to be present in constipated patients, is associated with a low Na+-dependent ileal bile acid transport and a high bile acid loss is associated with a high active bile acid transport. Ileal bile acid transport might be regulated by the availability of bile acids to the ileal enterocytes.

Bile Acids and Salts↗

[75Se]-selenohomotaurocholic acid degradation by bacterial enzymes in vitro and in vivo. Is it still a specific indicator for active ileal bile acid uptake?

The stability of the bile acid analogue [75Se]-selenohomotaurocholic acid (75SeH-CAT) was studied in man. When 75SeHCAT was administered to patients for diagnostic purposes the majority of labeled material present in the feces was found deconjugated. In vitro incubation of 75SeHCAT, by addition of fecal homogenate or with addition of purified enzyme, showed identical deconjugation. The relative differences in polarities of 75SeHCAT, [75Se]-selenohomocholic acid (75SeHCA), [14C]-taurocholic acid (14C-TCA) and [14C]-cholic acid (14C-CA) were estimated by isoelectric focusing and selective chloroform extractions at various pH values. The pI values representing the pH where these molecules become uncharged were for 75SeHCA and 75SeHCAT 3.1, for 14C-TCA 3.0 and for 14C-CA 3.9. These results suggest that from these bile acids only 14C-CA is a candidate for passive absorption in the colon, while 75SeHCA would be far too polar for passive diffusion. Indeed, we could demonstrate the inability of 75SeHCA for passive absorption in healthy persons. In conclusion, 75SeHCAT, specifically selected to monitor active ileal bile acid transport, functions as a good indicator of this process in its conjugated form. In contrast to published data it is susceptible to bacterial degradation, and therefore gives rise to a diminished whole-body retention.

Amidohydrolases↗

Bile acid malabsorption in cystic fibrosis; membrane vesicles, a tool for revealing the role of the ileal brush border membrane.

Increased fecal bile acid loss in cystic fibrosis (CF) may result from ileal dysfunction. A method to quantitate in vitro Na+-dependent taurocholate uptake into brush border membrane vesicles prepared from frozen ileum and ileal biopsy specimen is described. This transport across the ileal brush border membrane can be measured selectively, in contrast to in vivo measurements which represent a complex overall process. Preliminary results obtained with ileal specimen of 2 CF patients, suggest that in vitro bile acid uptake is low but not abnormal.

Bile Acids and Salts↗

Endogenous bile acid tolerance test for liver function.

Fasting and postprandial (stimulated) serum conjugated bile acids (CBA) were measured by a solid-phase radioimmunoassay in 329 patients undergoing liver biopsy, and the results were analyzed for 231 who fitted into 10 diagnostic categories. In healthy volunteers the mean fasting CBA of 1.8 +/- 0.7 mumol/liter rose to 3.0 +/- 0.8 mumol/liter postprandially. In patients mean fasting and stimulated CBA were only significantly raised in moderate to severe chronic and acute liver disease. Diagnostic sensitivity was poor in mild liver disease. Individuals with normal results were found in 8 of 11 disease categories. The ratio of stimulated to fasting CBA expressed in a stimulation quotient did not rise in more advanced liver disease. These findings are best explained by a constant fractional clearance of bile acids by the liver. We conclude that the serum conjugated bile acid determination as a test of liver cell function is not sensitive enough to identify all cases of biopsy-proven liver disease.

Bile Acids and Salts↗

Solid phase radioimmunoassay for determination of conjugated cholic acid in serum.

A modified radioimmunoassay for conjugated cholates is presented. In this modification the antibody is chemically bound to Sepharose which enablproducibility (the coefficient of variation between samples is 4%). The whole procedure is carried out at room temperature and with a short incubation time (45 min). Serum can by analysed directly (no extractions or modifications needed). The assay is a suitable tool for liver function testing. A rough indication of total bile acid concentration in serum or bile can also be obtained with this assay.

Cholic Acids↗