Search PubMed⌕ Search

Biomedical subjects

H P Buscher

Publications and source records attributed to H P Buscher.

33 records · Page 2Linked to original sources
PubMed1989

The histoautoradiographic localization of taurocholate in rat liver after bile duct ligation. Evidence for ongoing secretion and reabsorption processes.

To determine whether in complete obstructive cholestasis taurocholate is taken up by hepatocytes and if so whether it is secreted into bile, tritium-labelled taurocholate was localized by histoautoradiography on cryoslices from normal rat livers and from those after bile duct ligation. In non-cholestatic livers the hepatocytes of acinar zones 1 as well as the lumina and the epithelia of bile ductules and ducts became intensely labelled directly after injection of [3H]taurocholate into a mesenterial vein. Four hours and 4 days after bile duct ligation, hepatocytes of all three acinar zones became labelled, but in contrast to the normal state, pericanalicular concentration of silver grains was not observed, not even within 5 min. Fifteen days after bile duct obstruction, cryoslices taken 2 min after injection of [3H]taurocholate exhibited an intense silver grain labelling of all acinar zones, with the highest density at bile canalicular areas of the liver cell plates as well as the proliferated bile ductules and bile ducts. The biliary epithelium of small bile ductules and ducts of non-cholestatic and of bile duct-obstructed livers were also covered with silver grains; the epithelium of larger ducts exhibited significant labelling predominantly at the lateral sites of the cells. The biliary epithelium of the common bile duct was not significantly labelled. The results indicate that in complete obstructive cholestasis (a) taurocholate continues to be taken up from blood by hepatocytes and secreted into bile, but in terms of varying duration of obstruction, (b) all acinar zones are involved in bile salt transport, (c) in the initial phase (4 h and 4 days respectively after bile duct obstruction) hepatocytes fail to concentrate taurocholate at the canalicular site, (d) in a consecutive phase, in which bile ductules and ducts proliferate (demonstrated for a 15-day cholestasis), the taurocholate concentration at the canalicular site of hepatocytes is re-established and biliary secretion seems to be enhanced, (e) the biliary epithelium of bile ductules and ducts may play a significant role in the reabsorption and/or regurgitation of bile salts from bile to blood. Reabsorption/regurgitation of biliary constituents may also be operative in the non-cholestatic state but may become significantly enhanced with bile ductular proliferation.

Animals↗
PubMed1988

Transport systems for amphipathic compounds in normal and neoplastic hepatocytes.

Photoaffinity labeling of plasma membrane subfractions from liver and of intact liver tissue with a photolabile bile salt derivative, the sodium salt of (7,7-azo-3 alpha,12 alpha-dihydroxy-5 beta-cholan-24-oyl)-2-aminoethanesulfonic acid, revealed that the hepatobiliary transport of bile salts is accomplished by transport systems different for sinusoidal uptake and canalicular secretion. Polypeptides with apparent Mr values 54,000 and 48,000 interact with bile salts at sinusoidal membrane, whereas a polypeptide with an apparent Mr of 100,000 is involved in bile salt secretion through the canalicular membrane. Photoaffinity labeling with photolabile derivatives of uncharged and cationic compounds provided evidence that the sinusoidal membrane polypeptides exhibit a broad binding specificity. Photoaffinity labeling studies and kinetic studies suggest that hepatic uptake of different amphipathic anions, uncharged compounds and even of cations is mediated by the sinusoidal transport systems which are involved in the uptake of bile salts. Relatively little is known about the specificity of the canalicular bile salt transport system. The fluorescent bile salt derivative, the sodium salt of (N-[7-(4-nitrobenzo-2-oxa-1,3-diazol)]-3 beta-amino-7 alpha, 12 alpha-dihydroxy-5 beta-cholan-24-oyl)-2-aminoethanesulfonic acid, is readily taken up into the hepatocytes of all acinar zones and may be used for the evaluation of the functional state of bile salt transport by fluorescence microscopy. Fluorescent microscopic studies with the fluorescent bile salt derivative showed that ascites hepatoma AS 30D cells do not have the ability to take up bile salts and demonstrated the absence of hepatobiliary bile salt transport in the solid Morris hepatoma 7777. Photoaffinity labeling studies revealed that in both tumor cell models, in hepatoma AS 30D and in Morris hepatoma 7777, the plasma membranes were devoid of the polypeptides having affinities to bile salts and amphipathic cations. A slight labeling of bile salt binding membrane polypeptides in plasma membranes from Morris hepatomas 9618A and TC 5123 opens the possibility to study transport in neoplastic hepatocytes.

Animals↗
PubMed1988

[Cholestasis].

Explore the source record for details and available documents.

Bile Acids and Salts↗
PubMed1982

Bile-salt-binding polypeptides in plasma membranes of hepatocytes revealed by photoaffinity labelling.

1. Photoaffinity labelling of a subfraction of plasma membranes of rat liver, enriched with sinusoidal surfaces, with the sodium salts of (3 beta-azido-7 alpha,12 alpha-dihydroxy-5 beta-cholan-24-oyl)-2-amino[2-3H(N)]ethanesulfonic acid, (7,7-azo-3 alpha,12 alpha-dihydroxy-5 beta-cholan-24-oyl)-2-amino[2-3H(N)]ethanesulfonic acid and (11 xi-azido-12-oxo-3 alpha,7 alpha-dihydroxy- 5 beta-cholan-24-oyl)-2-amino[2-3H(N)]ethanesulfonic acid resulted with each derivative in a clear covalent incorporation of radioactivity into polypeptides with the apparent molecular weights of 67,000, 52,000, 48,000, 43,000 and about 20,000. 2. Photoaffinity labelling of a membrane subfraction predominantly composed of bile canalicular membranes by the photolabile derivatives of the conjugated bile salts also showed covalent incorporation of radioactivity into polypeptides of the same apparent molecular weights as with the subfraction enriched with the sinusoidal membranes. 3. The extent of photoaffinity labelling of the different membrane polypeptides is dependent upon the photolabile bile-salt derivative used. However, with each of the photolabile derivatives the relative ratio of the labelling of the different membrane polypeptides was similar for both membrane subfractions. Provided that the uptake as well as the secretion of bile salts by hepatocytes are carrier-mediated processes, this suggests the participation of the same polypeptides in both processes.

Affinity Labels↗
PubMed1979

Bile salt binding to serum components. Taurocholate incorporation into high-density lipoprotein revealed by photoaffinity labelling.

1. Photoaffinity labelling of human serum albumin with the sodium salts of (3 beta-azido-7 alpha,12 alpha-dihydroxy-5 beta-cholan-24-oyl)-2-amino[2(-3)H (N)]ethanesulfonic acid, (7,7-azo-3 alpha,12 alpha-dihydroxy-5 beta-cholan-24-oyl)-2-amino[2(-3)H (N)]ethanesulfonic acid and (11 zeta-azido-12-oxo-3 alpha,7 alpha-dihydroxy-5 beta-cholan-24-oyl)-2-amino[2(-3)H (N)]ethanesulfonic acid resulted, in each case, in a considerable covalent incorporation of radioactivity into the protein. 2. Photoaffinity labelling of whole serum, obtained from fasting test persons, revealed with all three photolabile derivatives of taurocholate at the physiological concentration of 2.1 microM the incorporation of radioactivity not only into albumin but also into high-density lipoprotein, as demonstrated by density gradient centrifugation and by immunological characterization. 3. The bulk of radioactivity incorporated into high-density lipoprotein by photoaffinity labelling of whole serum was found to have been associated with the lipids. Only 10-20% of the label was covalently bound to apolipoproteins, predominantly to the apolipoproteins A-I and A-II. 4. The interaction of taurocholate with high-density lipoprotein has been confirmed by density gradient centrifugation using 14C-labelled taurcholate. It is assumed that the interaction of taurocholate with high-density lipoprotein is physiologically of significance.

Adult↗
PubMed1976

[Intrahepatic cholestasis due to N-propyl ajmaline].

In two patients intrahepatic cholestasis and cholestatic liver disease probably due to N-propyl ajmaline were observed. In both cases there was a four-week-interval between the first ingestion of the drug and the onset of jaundice. In one case with rigors there was a temporary rise in temperature and cholestasis. In the other there was a two to three week prodromal period of pruritus and gastro-intestinal symptoms. Both cases were characterised by blood and pronounced tissue eosinophilia in the periportal zones, a marked increase of cholestatic and hepatic cell enzymes, serum bilirubin and cholesterol, a moderate increase in erythrocyte sedimentation rate and absence of leucocytosis. Pathological laboratory findings returned to normal spontaneously within 5 weeks in one case and within two weeks under steroid therapy in the other.

Adult↗
PubMedDate not supplied

Bile salt shift from albumin to high-density lipoprotein in cholestasis.

The distribution of [3H]taurocholate between albumin and the lipoproteins of serum of patients with various diseases in which lipoprotein metabolism and/or bile salt concentrations were altered and of healthy control subjects was investigated by means of the density gradient centrifugation method. 1. In control sera, bile salts distribute mainly between albumin and high-density lipoprotein. An amount of 19.7 +/- 3.6% (mean +/- S.D., n = 6) of the total serum bile salts was found in the high-density lipoprotein fraction of the density gradient. 2. In sera of nonicteric patients, the distribution pattern of [3H]taurocholate in the fractions of the density gradient showed no essential differences to normal serum. The relative amounts of taurocholate in the albumin-containing fractions and the high-density lipoprotein fractions were dependent on the concentrations of albumin and high-density lipoprotein. 3. In sera of deeply jaundiced patients, the distribution pattern of [3H]taurocholate showed two distinct peaks in the high-density lipoprotein density range, one of which codistributed with high-density lipoprotein2 and the other with a high-density fraction of high-density lipoprotein3 in the density range of 1.19 to 1.23 gm per ml. The distribution of [3H]taurocholate between albumin and high-density lipoprotein was markedly shifted toward high-density lipoprotein. No [3H]taurocholate association with lipoprotein X was observed. 4. Bilirubin was found to cause a shift of taurocholate from albumin to high-density lipoprotein in vitro. It is proposed that bilirubin is responsible, at least in part, for the observed shift in icteric sera.

Adult↗