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Biomedical subjects

K Ziegler

Publications and source records attributed to K Ziegler.

At least 19 recordsLinked to original sources
PubMed1992

Tissue-selective action of pravastatin due to hepatocellular uptake via a sodium-independent bile acid transporter.

Pravastatin is a foreign substrate of a sodium-independent transport system for bile acids. The tissue selectivity of pravastatin in inhibiting 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase is due to the uptake via a transport system which exists predominantly in liver cells. Pravastatin competitively inhibits the sodium-independent hepatocellular uptake of cholate, taurocholate and ouabain, whereas the total uptake of cholate is non-competitively blocked. The affinity of pravastatin to the sodium-dependent taurocholate transporter is, however, low. Millimolar concentrations of pravastatin are needed to inhibit the sodium-taurocholate cotransporter. Pravastatin has no affinity to other transport systems in liver cells such as those for long-chain fatty acids, amino acids, rifampicin and bivalent organic cations.

Animals↗
PubMed1992

Radiation inactivation of multispecific transport systems for bile acids and xenobiotics in basolateral rat liver plasma membrane vesicles.

The functional molecular mass of the cholate, phallotoxin, iodipamide, and ouabain transport proteins in isolated basolateral plasma membrane vesicles was determined by radiation inactivation. Purified basolateral plasma membrane vesicles were irradiated (-90 to -120 degrees C) with high energy electrons from a 10-MeV linear accelerator at doses from 0 to 30 megarads. After each dose, the initial uptake, the equilibrium binding, and the binding of the substrates at 4 degrees C were checked. The size of the transporting function was, for cholate, 107 +/- 8.9 kDa; for phallotoxin, 104 +/- 7 kDa; and for ouabain, 120 +/- 4.7 kDa. The target size for the binding proteins was 56 +/- 4.2, 57 +/- 5, and 47.2 +/- 1.95 kDa for cholate, phallotoxin, and taurocholate, respectively. In the case of iodipamide, the functional molecular mass for both the transport and binding proteins was 54 +/- 4.8 kDa.

Amanitins↗
PubMed1992

Binding proteins for linear renin-inhibiting peptides in basolateral plasma membranes of rat liver.

A linear hydrophobic peptide, (Code no. EMD 55068), a synthetic renin-antagonist, competitively inhibits the uptake of taurocholate and of another linear peptide (EMD 51921) but not of oleic acid, serine or thiamin hydrochloride into isolated rat liver cells. EMD 55068 was attached to a gel matrix at a position that is not involved in the protein ligand interaction. The gel matrix used did not interact nonspecifically with solubilized proteins from rat liver. The quantity of bound ligand was determined to be 3.6 mg/ml of gel matrix. In the fraction of EDTA extracted hydrophilic membrane-associated proteins, no binding proteins were detected. Affinity chromatography of integral plasma membrane proteins resulted in four protein bands with molecular masses of 46, 49, 53 and 56 kDa in SDS-PAGE. In contrast, solubilized plasma membrane proteins from AS-30D ascites hepatoma cells, which are unable to transport bile acids and linear peptides, did not bind specifically to the affinity matrix.

Animals↗
PubMed1992

Functional molecular mass of the 14C-azidobenzamidotaurocholic acid binding proteins in hepatocellular bile acid transport systems.

The apparent target size of 14C-azidobenzamidotaurocholate binding proteins in basolateral rat liver plasma membranes (blPm) was determined by analysis of the radiation induced decrease of the binding of this photoreactive taurocholate analog to blPm. Radiation causes a dose-dependent mono-exponential reduction of binding of ABATC to the protein subunits with molecular masses of 48-50 and 52-54 kDa in SDS-PAGE. The minimal functional molecular mass of the 48-50 and 52-54 kDa ABATC binding proteins was determined to be 99 +/- 8.2 and 93.2 +/- 7 kDa, respectively.

Animals↗
PubMed1992

Endoscopic laser resection of a duodenal membrane.

This report documents the first resection of a duodenal membrane by laser. Subsequently, however, a laparotomy was required because of an annular pancreas. Nevertheless, it demonstrates that the laser endoscopical resection of a duodenal membrane is technically feasible.

Duodenum↗
PubMed1992

[Short term cultivation of Plasmodium for the determination of chloroquine resistance].

The in-vivo-test of Plasmodium drug resistance is one of the essential basic controls, assisting therapeutic measures in tropical malaria. An initial in-vitro-check up of drugs provided for antimalarial therapy is another useful help to the clinician. Even when manufactured WHO test kits are not available, the analysis of drug resistance can be performed under simple working conditions. Its application is demonstrated in a patients history.

Animals↗
PubMed1991

Hepatocellular uptake of peptides by bile acid transporters: relationship of carrier-mediated transport of linear peptides with renin-inhibiting activity to multispecific bile acid carriers.

The uptake of a linear peptide with renin-inhibiting activity (code number EMD 51921) was characterized in isolated rat liver cells. Isolated hepatocytes take up EMD 51921 in a time-, concentration-, energy- and temperature-dependent manner. Transport of the peptide follows mixed-type kinetics. Diffusion occurs at a rate of 8.123 x 10(-6) cm/sec at 6 degrees C. For the saturable part of uptake, a Km of 2.0 microM and a Vmax of 160 pmol/mg per min were calculated. Various substrate analogues inhibit the uptake of EMD 51921. Absence of oxygen or decreased cellular ATP content (e.g., by metabolic inhibitors or xylulose) blocks hepatocellular uptake of EMD 51921. Temperatures above 20 degrees C accelerate the uptake. The activation energy was calculated to be 58.3 kJ/mol. The apparently active uptake of EMD 51921 was not sodium dependent. The membrane potential is a driving force for the accumulation of EMD 51921. Mutual competitive transport inhibition of EMD 51921, cholate and taurocholate is indicative of a common transport system. Benzamidotaurocholate and a cyclosomatostatin analog 008, not phalloidin and iodipamide, however, considerably decrease the uptake of EMD 51921. AS 30D ascites hepatoma cells, unable to accumulate bile acids and certain cyclopeptides, also fail to transport EMD 51921. BSP, a foreign substrate of the bilirubin carrier, noncompetitively inhibits the transport of EMD 51921. The inhibition of the uptake of EMD 51921 by rifampicin, a further substrate of the bilirubin carrier, is mixed: competitive at high EMD 51921 concentrations and uncompetitive at low EMD 51921 concentrations. The uptake of rifampicin into isolated rat liver cells, however, is not influenced by EMD 51921. Substrates of the transport systems for cations, amino acids, long chain fatty acids and hexoses did not influence the transport of EMD 51921.

Animals↗
PubMed1991

Hepatocellular transport of cyclosomatostatins: evidence for a carrier system related to the multispecific bile acid transporter.

The uptake of the cyclopeptide c(Phe-Thr-Lys-Trp-Phe-D-Pro) (008), an analog of somatostatin with retro sequence, was studied in isolated hepatocytes. 008 is taken up by hepatocytes in a concentration-, time-, energy- and temperature- dependent manner. Since 008 is hydrophobic, it binds rapidly to liver cells. This is evident by the positive intercept at the gamma-axis in the uptake curves. At higher concentrations, a minor part of the transport occurs by diffusion at a rate of 8.307.10(-6) cm/s. This part of diffusion is measured at 4 degrees C and can be subtracted from the uptake at 37 degrees C resulting in the carrier mediated part of uptake which is saturable. Kinetic parameters for the saturable part of uptake are Km 1.5 microM and Vmax 40.0 pmol/mg per min. The transport is decreased in the absence of oxygen and in the presence of metabolic inhibitors. Uptake is accelerated at temperatures above 20 degrees C. The activation energy was determined to be 30.77 kJ/mol. The membrane potential and not a sodium gradient is the main driving force for 008 transport. Cholate (a typical substrate of the multispecific bile acid transporter) and taurocholate are mutual competitive inhibitors of 008 uptake. Phalloidin, antamanide and iodipamide, typical foreign substrates of the transporter, interfere with the uptake of 008. AS 30D ascites hepatoma cells, known to be unable to transport bile acids, phalloidin and iodipamide, are also unfit to transport 008. Interestingly, sulfobromophthalein (BSP) but not rifampicin, both foreign substrates of the bilirubin carrier, inhibits the transport of 008 in a competitive manner.

Animals↗
PubMed1991

New substrates of the multispecific bile acid transporter in liver cells: interference of some linear renin inhibiting peptides with transport protein(s) for bile acids.

Interactions between some stable linear peptides with renin inhibitory activity and a multispecific transport system in the basolateral plasma membrane of liver cells was studied on cell suspensions. The peptides used in our experiments were taken up by liver cells and subsequently eliminated without any biotransformation (e.g., proteolysis). No degradation products could be detected in the extracellular medium by thin-layer chromatography. All peptides tested inhibited the uptake of physiological and of some foreign substrates of the multispecific bile acid transporter (MT). The phalloidin response of liver cells was also inhibited to a similar degree in a concentration-dependent manner. The potency of inhibition did not correlate with the lipophilic properties of the peptides. On the other hand a tight correlation could be documented between the inhibition of cholate transport and that of the phalloidin response. Transport inhibition of typical substrates of the MT by the above renin inhibitors was competitive. In contrast, the transport of a typical substrate of the bilirubin carrier (rifampicin), of amino acids (alpha-aminoisobutyric acid), long chain fatty acids (oleic acid) and cationic compounds (thiamin hydrochloride) was not inhibited by the same renin inhibitors. These results indicate that linear renin inhibiting peptides are taken up into liver cells by carrier proteins related to the MT.

Aminoisobutyric Acids↗
PubMed1991

Evaluation of endosonography in sclerotherapy of esophageal varices.

During intravariceal sclerotherapy of esophageal varices with polidocanol in 32 patients with portal hypertension due to liver cirrhosis of various etiologies, endosonographic assessment of both esophageal and gastric intramural vessels was carried out in order to evaluate the usefulness of endosonography in the follow-up of the variceal status. In all cases endosonography demonstrated esophageal and gastric varices; in contrast, only five cases of gastric varices could be demonstrated by endoscopy. Furthermore, different stages of variceal obliteration following sclerotherapy could be demonstrated by means of endosonography, and it was possible to identify incomplete obliteration in about one-third of the patients in whom inadequate sclerotherapy was suspected endoscopically. In addition, the status of gastric varices during sclerotherapy was demonstrated by means of endosonography. Only in cases of adequate sclerotherapy of esophageal varices, as assessed by both endoscopic and endosonographic criteria, were gastric varices plugged. On the basis of these findings endosonography would appear to be a useful technique for the diagnosis and follow-up of esophageal and gastric varices during intravariceal sclerotherapy.

Esophageal and Gastric Varices↗
PubMed1991

Evaluation of endosonography in TN staging of oesophageal cancer.

Strategies for the treatment of cancer of the oesophagus depend on the tumour stage at the time of diagnosis. Resection, the only curative treatment, is confined to early tumour stages. Tumours with local infiltration are usually unresectable and require palliative treatment. Computed tomography has been widely used for preoperative staging but often fails to define this correctly. Endoscopic ultrasound allows direct visualisation of the parietal wall and may be useful in staging gastrointestinal tumours. In a comparative prospective study, 52 patients with tumours of the oesophagus were investigated preoperatively both by endoscopic ultrasound and computed tomography to determine the stage of tumour infiltration and local lymph node involvement. Thirty seven of these patients underwent operation, resection, or dissection and entered the study. The intraoperative findings or the histopathological assessment, or both, were taken as a reference. For all TN stages of oesophageal tumours, correct preoperative staging was accomplished by endoscopic ultrasound in 89% for T stage and 69% for N stage compared with 51% and 51% respectively by computed tomography (highly significant using Fisher's exact test). This study shows that endoscopic ultrasound is useful in preoperative TN staging of tumours of the oesophagus.

Adult↗
PubMed1990

2-Aminobenzoyl-CoA monooxygenase/reductase, a novel type of flavoenzyme. Identification of the reaction products.

In a previous report we have described some properties of a novel flavoenzyme from a denitrifying Pseudomonas species which catalyzes the oxygen- and NAD(P)H-dependent conversion of 2-aminobenzoyl-CoA [Buder, R., Ziegler, K., Fuchs, G., Langkau, B. & Ghisla, S. (1989) Eur. J. Biochem. 185, 637-634]. In this paper, we report on the identification of the three products formed from 2-aminobenzoyl-CoA in this reaction. The spectroscopic data and the chemical properties of these compounds and those of their degradation products are compatible with the structures of 2-amino-5-hydroxybenzoyl-CoA, 2-amino-5-hydroxycyclohex-1-enecarboxyl-CoA and of 2-amino-5-oxocyclohex-1-enecarboxyl-CoA. The latter is the main product and was found to be rather unstable since it hydrolyzes and decarboxylates readily at pH less than 5. Ammonia is released from the decarboxylation product in the neutral pH range to yield 1,4-cyclohexanedione. Conditions were optimized such that the CoA thioester of 2-amino-5-hydroxybenzoate is the product obtained at greater than 98% yield. 2-amino-5-hydroxycyclohex-1-enecarboxyl-CoA is the product which is formed when the mixture of the reaction products is treated with sodium borohydride before separation.

Chemical Phenomena↗
PubMed1990

Cyclosporin binding to a protein component of the renal Na(+)-D-glucose cotransporter.

The immunosuppressive and nephrotoxic agent cyclosporin binds to a renal polypeptide with an apparent molecular weight of 75,000 which has been identified as a component of the renal Na(+)-D-glucose cotransporter (Neeb, M., Kunz, U., and Koepsell, H. (1987) J. Biol. Chem. 262, 10718-10729). The same Mr 75,000 polypeptide was covalently labeled with the D-glucose analog 10-N-(bromoacetyl)amino-1-decyl-beta-D-glucopyranoside and with the cyclosporin analog N epsilon-(diazotrifluoroethyl)benzyl-D-Lys8- cyclosporin (CSDZ). CSDZ labeling was decreased when the brush-border membrane proteins were incubated with monoclonal antibodies against the Na(+)-D-glucose cotransporter. In the presence of 145 mM Na+, CSDZ labeling was decreased by D-glucose (1 microM, 1 mM, or 100 mM) and by phlorizin (100 or 500 microM). In the absence of Na+, CSDZ labeling was distinctly increased by 50 microM phlorizin and was slightly increased by 1 mM D-glucose, whereas CSDZ labeling was decreased by 50 microM phloretin and by 500 microM phlorizin. Furthermore, Na(+)-dependent high affinity phlorizin binding to the Na(+)-D-glucose cotransporter was competitively inhibited by cyclosporin A (Ki = 0.04 microM) while Na(+)-D-glucose cotransport was not influenced. The data suggest that a part of the cyclosporin binding domain on the Na(+)-D-glucose cotransporter is identical to the phloretin binding domain of the high affinity phlorizin binding site. While phloretin or the phloretin moiety of phlorizin may directly displace cyclosporin, interaction of D-glucose or of the D-glucose moiety of phlorizin with the transporter may alter the conformation of the cyclosporin binding site and this conformational change may be modulated by Na+.

Affinity Labels↗
PubMed1990

Lack of autoreceptor mediated regulation of the spontaneous dopamine turnover in the isolated neurointermediate lobe of the rat pituitary gland in vitro.

Isolated neurointermediate lobes of the rat pituitary gland were incubated in Krebs-HEPES solution and the spontaneous outflow of endogenous dopamine and its metabolites (DOPAC, HVA and MOPET) was determined by HPLC with electrochemical detection. The spontaneous outflow of dopamine metabolites (about 1500 fmol/10 min) largely exceeded that of dopamine (about 60 fmol/10 min). Apomorphine concentration-dependently (IC50, 205 nmol/l) reduced the spontaneous outflow of the dopamine metabolites. The effect of apomorphine developed slowly and was progressive over an observation period of 70 min. After 1 h of exposure to a maximall effective concentration of apomorphine (10 mumol/l), the outflow of metabolites was inhibited by 43%. The effect of apomorphine was not affected by the dopamine D2 receptor antagonist (-)-sulpiride nor by the dopamine D1 receptor antagonist SCH 23390. Neither quinpirole nor fenoldopam significantly affected the spontaneous outflow of dopamine metabolites. It was previously shown that the high rate of spontaneous outflow of dopamine metabolites from the dopaminergic nerves in the neurointermediate lobe reflects largely the immediate catabolism of newly synthesized dopamine. This high rate of spontaneous dopamine synthesis in the neurointermediate lobe is not controlled by dopamine autoreceptors. Apomorphine appears to inhibit the spontaneous dopamine turnover by an inhibition not mediated by dopamine receptors.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1990

Preoperative staging of gastrointestinal tumors by endosonography.

Intracavitary application of ultrasound was first performed for diagnostic purposes in 1967; since that time, it has been more and more widely used. As far as the gastrointestinal tract is concerned, endoscopically controlled ultrasonic probes provide visualization of the various layers of the intestinal wall. It is therefore possible to describe lesions of the esophagus, stomach, and the rectum with regard to their nature and depth of infiltration. Furthermore, periesophageal and perigastric organs can be visualized. It has become evident that endosonography is particularly important for pretherapeutic staging of tumors of the esophagus, stomach, and rectum. Here prospective comparative studies confirm the superiority of this new diagnostic procedure when compared to the methods available to date.

Endoscopy, Gastrointestinal↗