Search PubMed⌕ Search

Biomedical subjects

W Stremmel

Publications and source records attributed to W Stremmel.

At least 163 records · Page 9Linked to original sources
PubMed1996

Kinetics of primary bile acids in patients after orthotopic liver transplantation.

Administration of cyclosporin A (CsA) may induce cholestasis, and this effect has been attributed to impaired hepatocellular uptake, transport, secretion and intestinal absorption of bile acids. Disturbances of the enterohepatic circulation may affect metabolism of bile acids. To test whether liver transplantation and treatment with CsA alters pool sizes or synthesis and turnover rates, we determined kinetics of primary bile acids in patients after orthotopic liver transplantation on CsA. Two male and four female patients were studied 6-20 months after transplantation. They had no overt signs of cholestasis, graft dysfunction or rejection. Kinetics of cholic acid (CA) and chenodeoxycholic acid (CDCA) were simultaneously determined after oral administration of [24-13C]-CA and [24-13C]-CDCA on the basis of isotope dilution in a single pool of bile acids. Ten healthy volunteers served as controls. After orthotopic liver transplantation, pool sizes, fractional turnover rates and synthesis rates of both primary bile acids, CA and CDCA were not significantly different from control subjects. In spite of the known interference of CsA with the enterohepatic circulation of bile acids, in the majority of patients after orthotopic liver transplantation without cholestasis, graft dysfunction of rejection, treatment with CsA does not disturb kinetics of primary bile acids.

Adult↗
PubMed1996

Long-term survival in patients with hereditary hemochromatosis.

BACKGROUND & AIMS: The course of hereditary hemochromatosis may depend on the degree of iron overload and the time of therapeutic intervention. This analysis evaluates the impact of early diagnosis and iron removal on survival and complications in hereditary hemochromatosis. METHODS: A Cohort of 251 patients with hemochromatosis was followed up for 14.1 +/- 6.8 years. RESULTS: Survival was reduced in the total group of patients when compared with a matched normal population. Survival in noncirrhotic and nondiabetic patients and in patients diagnosed between 1982 and 1991 was identical with rates expected. Survival was reduced in patients with severe iron overload vs. those with less severe overload. The percentage of early diagnoses increased threefold between 1947 and 1969 to that between 1970 and 1981; there was only a further 20%-25% increase in the last decade. Deaths caused by liver cancer, cardiomyopathy, liver cirrhosis, and diabetes mellitus were increased as compared with expected rates. Liver cancers were associated with cirrhosis and amount of mobilizable iron but not with hepatitis B or C markers. CONCLUSIONS: Prognosis of hemochromatosis and most of its complications, including liver cancer, depend on the amount and duration of iron excess. Early diagnosis and therapy largely prevent the adverse consequences of iron overload.

Adolescent↗
PubMed1996

Sodium, hydrogen antiporter activation by extracellular adenosine triphosphate in biliary epithelial cells.

BACKGROUND & AIMS: Extracellular nucleotides are secretagogues and influence ion permeability. The aim of this study was to investigate whether secretagogues activate transmembrane acid-base carriers, e.g., sodium, hydrogen antiporter in cholangiocytes. METHODS: Cells were loaded with pH and Ca(2+)-sensitive dyes. Intracellular changes in ion concentrations were monitored by confocal laser scanning microscopy. Adenosine 3', 5'-cyclic monophosphate was determined by standard methods. RESULTS: Baseline intracellular pH (pH1) averaged 7.28 +/- 0.17 pH units. Adenosine triphosphate (ATP; 10 mumol/L) increased baseline pH1 by 0.28 +/- 0.06 pH units/10 min (P < 0.01). Ten and 100 mumol/L ATP increased Na+, H+ antiporter-mediated proton flux from 9.4 +/- 4.9 mmol. L-1 min-1 to 17.2 +/- 11.8 and 16.7 +/- 10.3 mmol. L(-1)-min(-1) (P < 0.001), respectively. Under control and ATP-stimulated conditions, 1 mmol/L amiloride blocked pH1 recovery, indicating true activation of Na+, H+ antiporter by extracellular ATP. Inhibition of basolateral Na+, H+ antiporter isoform inhibited stimulation by ATP. Na+, H+ antiporter-mediated proton flux was stimulated by adenosine, uridine triphosphate, adenosine-5'-0-(3-thiotriphosphate), alpha, beta-methylene-ATP, and 2-methylthio-ATP but not prevented by adenosine receptor blocking. Activation by ATP was not influenced by the Ca2+/protein kinase C/calmodulin system but could be mimicked by addition of N6,2'-O-dibutyryladenosine-3',5'-cyclic monophosphate and was inhibited by pertussis toxin. CONCLUSIONS: Extracellular nucleotides may modulate secretory and absorptive function of cholangiocytes by activating Na+/H+ exchange mechanisms.

Adenosine↗
PubMed1996

A novel two-nucleotide deletion in the ornithine transcarbamylase gene causing fatal hyperammonia in early pregnancy.

Ornithine transcarbamylase (OTC) deficiency shows X-linked inheritance. Typically, symptomatic females (who constitute 15%-20% of all carriers) have markedly reduced enzyme activity and show first symptoms in late infancy or early childhood. Here we present the case of a previously asymptomatic 24-year-old woman who died of severe hyperammonemia associated with orotic aciduria but normal OTC activity in the fourth month of pregnancy. DNA analysis revealed a novel mutation in form of the deletion of two nucleotides (T892, G893) in exon 9 of the OTC gene, leading to a frame shift and an aberrant gene product. We suggest that OTC deficiency should be suspected in any patient who presents with hyperammonia in the presence of otherwise normal liver function.

Adult↗
PubMed1996

Thyroid morphology and function after surgical treatment of thyroid diseases.

In 1992 we performed a prospective study with 300 patients after thyroid resection. Indication for the operation was a benign nodular goiter in 280 cases, Graves' disease in 11 cases and a differentiated thyroid carcinoma in 9 cases. 269 patients (89.6%) returned for a follow-up visit which contained an ultrasound of the thyroid region and a determination of the serum thyrotropin concentration. Patients with less than 10 ml had a thyroxine replacement of 100 yg daily for six months. This therapy was discontinued for the next three months and they received their follow-up nine months after the operation. All other patients with benign diseases had their follow-up without thyroxine replacement eight weeks after the operation. The mean remnant volume was 2.4 ml for selective resected lobes, 0.8 ml after near total resection and 0.2 ml after lobectomy. We found residual or recurrent nodular tissue in 7.2% of the partially resected lobes. Visualization of the recurrent nerve and ligation of the inferior thyroid artery reduced the risk of nodular tissue in the remnant thyroid tissue significantly. Only 153 patients (62%) were treated according to our postoperative treatment schedule. Thyroxine replacement therapy was given to 96 patients at the time of their follow-up. 34% of the patients without replacement therapy had signs of insufficient hormone production of the remnant thyroid tissue. However, 22% of the patients under thyroxine replacement therapy showed signs of iatrogenic subclinical hyperthyroidism. We found a significant correlation between the volume of the remnant tissue and the serum thyrotropin concentration in patients without continuous thyroxine replacement. The corresponding calculated volume for a functionally potent remnant thyroid volume was 7.3 ml. This value was significantly higher in patients with both inferior thyroid arteries ligated at 9.8 ml. An individual postoperative therapy with iodine and/or thyroxine, which results in neither a high rate of thyrotropin elevation nor an unnescessary and undesirable part of the patients with suppressed serum thyrotropin concentrations is an indispensable component of the surgical treatment of benign nodular thyroid disease in areas of endemic iodine deficiency. As a result of this study we changed our postoperative treatment schedule. Patients with less than 10 ml remnant thyroid volume will have a continuous replacement therapy with a reduced dose of 75 yg thyroxine daily.

Adenoma↗
PubMed1996

Low prevalence of alterations in the pancreatic duct system in patients with primary sclerosing cholangitis.

BACKGROUND AND STUDY AIMS: Primary sclerosing cholangitis (PSC) is a rare disease of unknown origin that involves the intrahepatic or extrahepatic biliary system, or both. To obtain more precise information on concomitant involvement of the pancreatic duct system, a comparatively large group of 44 patients was studied. PATIENTS AND METHODS: Between 1989 and 1995, 44 patients took part in a study of the therapeutic effect of ursodeoxycholic acid, and their data were analyzed. In 42 of the 44 patients, both the pancreatic and biliary system were visualized by endoscopic retrograde cholangiopancreatography (ERCP). RESULTS: Pancreas divisum was detected in four patients (9.5%) with an otherwise normal major pancreatic duct. Three (7.1%) patients had pancreatic duct changes of the type seen in chronic pancreatitis. When risk factors such as alcohol abuse were excluded, there was only one patient with PSC and pancreatic duct alterations. CONCLUSION: In PSC patients, the prevalence of chronic pancreatitis is low.

Adult↗
PubMed1996

Effect of surface and intracellular pH on hepatocellular fatty acid uptake.

Fatty acids enter hepatocytes, at least in part, by a carrier-mediated uptake mechanism. The importance of driving forces for fatty acid uptake is still controversial. To evaluate possible driving mechanisms for fatty acid transport across plasma membranes, we examined the role of transmembrane proton gradients on fatty acid influx in primary cultured rat hepatocytes. After hepatocytes were loaded with SNARF-1 acetoxymethyl ester, changes in intracellular pH (pHi) under different experimental conditions were measured and recorded by confocal laser scanning microscopy. Fatty acid transport was increased by 45% during cellular alkalosis, achieved by adding 20 mM NH4Cl to the medium, and a concomitant paracellular acidification was observed. Fatty acid uptake was decreased by 30% during cellular acidosis after withdrawal of NH4Cl from the medium. Cellular acidosis activates the Na+/H+ antiporter to export excessive protons to the outer cell surface. Inhibition of Na+/H+ antiporter activity by amiloride diminishes pHi recovery and thereby accumulation of protons at the outer surface of the plasma membrane. Under these conditions, fatty acid uptake was further inhibited by 57% of control conditions. This suggests stimulation of fatty acid influx by an inwardly directed proton gradient. The accelerating effect of protons at the outer surface of the plasma membrane was confirmed by studies in which pH of the medium was varied at constant pHi. Significantly higher fatty acid influx rates were observed at low buffer pH. Recorded differences in fatty acid uptake appeared to be independent of changes in membrane potential, because BaCl2 did not influence initial uptake velocity during cellular alkalosis and paracellular acidosis. Moreover, addition of oleate-albumin mixtures to the NH4Cl incubation buffer did not change the observed intracellular alkalinization. In contrast, after cells were acid loaded, addition of oleate-albumin solutions to the recovery buffer increased pHi recovery rates from 0.21 +/- 0.02 to 0.36 +/- 0.05 pH units/min (P < 0.05), indicating that fatty acids further stimulate Na+/H+ antiporter activity during pHi recovery from an acid load. It is concluded that carrier-mediated uptake of fatty acids in hepatocytes follows an inwardly directed transmembrane proton gradient and is stimulated by the presence of H+ at the outer surface of the plasma membrane.

Animals↗
PubMed1996

-Therapy with ursodeoxycholic acid in primary biliary cirrhosis in pregnancy-.

Pregnancy is very uncommon in patients with primary biliary cirrhosis (PBC) and only few reports exist about pregnancy and PBC. However, no data are available on therapy and potential risks of treatment with ursodeoxycholic acid (UDCA) in PBC, especially in the first trimester of pregnancy. Furthermore, it is not known, whether UDCA is secreted into the breast milk during lactation. We report a 41 year old patient with the diagnosis of PBC stage III, who had been treated with UDCA (750 mg/day) for three years. At the time of diagnosis of pregnancy (5th gestational week), UDCA was withdrawn. Within nine days, severe pruritus developed, alkaline phosphatase and gamma-glutamyltransferase increased. UDCA was administered again (750 mg/day). The pruritus disappeared completely within one week. Liver enzymes decreased to baseline values and remained stable throughout the remainder of the pregnancy. No drug-related side effects were observed. Caesarean section for placental insufficiency unrelated to PBC was performed at the 34th week of pregnancy. The newborn thrived normally during a follow-up period of six months. When the patient's breast milk was analyzed by high pressure liquid chromatography, cholic acid, deoxycholic acid and lithocholic acid, but not UDCA were detected in trace amounts. It is concluded that UDCA therapy in PBC may be continued in the early pregnancy and during the breast feeding period. UDCA may be effective for the prevention of cholestasis in PBC during pregnancy.

Adult↗
PubMed1996

Release of thrombomodulin from endothelial cells by concerted action of TNF-alpha and neutrophils: in vivo and in vitro studies.

Inflammatory cytokines decrease the expression of thrombomodulin (TM) on the endothelial cell surface by suppression of TM transcription and translation or internalization with subsequent degradation. Nevertheless, elevated serum TM levels are found in diseases associated with systemical or locally increased levels of inflammatory cytokines. To study directly the in vivo effects of tumour necrosis factor-alpha (TNF-alpha) we determined the course of serum TM after systemic recombinant human (rh)TNF-alpha therapy. The TM levels were determined by enzyme-linked immunosorbent assay (ELISA). Systemic rhTNF-alpha therapy resulted in a marked and significant increase of serum TM. Using a mouse model we studied whether increased serum TM is associated with a decreased expression of TM on the endothelial surface in vivo. The immunohistochemical staining of the vasculature of meth-A sarcoma transplanted in mice showed a loss of TM immunoreactivity 4 hr after intravenous TNF-alpha application. To study the mechanism of TNF-alpha mediated release of TM, cultured endothelial cells were incubated with neutrophils and TNF-alpha. Incubation with TNF-alpha alone did not lead to an increase of TM in vitro. However TM was released into the culture supernatant when endothelial cells pretreated with TNF-alpha were exposed to neutrophils. This was associated with morphological evidence of endothelial cell damage. Therefore, the concerted action of cytokine-stimulated endothelial cells and neutrophils results in release of TM from cultured endothelial cells after rhTNF-alpha therapy. This might explain the increased serum TM levels observed in diseases associated with increased systemic or local levels of inflammatory cytokines despite the induced internalization and the direct inhibitory effects of TNF-alpha on TM transcription and translation.

Adult↗
PubMed1996

Absorptive and secretory mechanisms in biliary epithelial cells.

Biliary epithelial cells line the intra- and extrahepatic biliary tree. They are involved in bile formation and are of importance in different cholestatic conditions (vanishing bile duct syndrome). In recent years, progress has been made to elucidate more precisely the physiological role of biliary epithelial cells. Biliary epithelial cells are involved in the cholehepatic shunting of bile acids, they reabsorb sugar and glutamate from bile. Secretin-induced electrolyte secretion is regulated by intracellular cAMP levels in these cells. Intracellular Ca2+ levels, which are increased by different agonists, e.g. carbachol, regulate transmembrane ion channels. ATP acts as secretagogue in these cells by activating ion channels and Na+, H+ antiporter. Further studies have to investigate in which parts of the biliary tree absorptive or secretory mechanisms are predominant.

Absorption↗
PubMed1996

[How good is the prognosis in differentiated thyroid gland carcinoma].

Between 1980 and 1995, 4233 thyroid operations were carried out in our hospital and in 152 patients a thyroid carcinoma was treated. The choice of therapy concerning differentiated thyroid carcinoma, excluding the papillary microcarcinoma, is the thyroidectomy with resection of the central lymph node compartment. Since the introduction of routine, recurrent nerve representation, the rate of permanent nerve injury could be reduced from 7.2% to 1.3%. The permanent therapy of hypoparathyroidism was necessary for 9.9% of the patients. The well-known good prognosis of the differentiated and especially papillary thyroid cancer could be confirmed in our study.

Adenocarcinoma, Follicular↗
PubMed1995

Involvement of the CD95 (APO-1/Fas) receptor and ligand in liver damage.

Apoptosis occurs in the normal liver and in various forms of liver disease. The CD95 (APO-1/Fas) (CD95) receptor mediates apoptosis, and liver cells in animal models are acutely sensitive to apoptosis initiated by this receptor. We have used primary human hepatocytes as a model system to investigate CD95-mediated apoptotic liver damage. Treatment of fresh human hepatocytes with low concentrations of agonistic antibodies against CD95 resulted in apoptosis of > 95% of the cultured liver cells within 4 and 7.5 h. Immunohistology of a panel of explanted liver tissues revealed that hepatocytes in normal livers (n = 5) and in alcoholic cirrhosis (n = 13) expressed low constitutive levels of CD95. CD95 receptor expression was highly elevated in hepatocytes in hepatitis B virus-related cirrhosis (n = 9) and in acute liver failure (n = 8). By in situ hybridization CD95 ligand messenger RNA expression was absent in normal liver but detected at high levels in livers with ongoing liver damage. In cases of hepatitis B virus-related cirrhosis and acute hepatic failure, ligand expression was found primarily in areas with lymphocytic infiltration. In contrast, in patients with alcoholic liver damage, high CD95 ligand messenger RNA expression was found in hepatocytes. These findings suggest that liver destruction in hepatitis B may primarily involve killing of hepatocytes by T lymphocytes using the CD95 receptor-ligand system. In alcoholic liver damage, death of hepatocytes might occur by fratricide and paracrine or autocrine mechanisms mediated by the hepatocytes themselves.

Antibodies, Monoclonal↗
PubMed1995

Characterization and partial purification of a ferrireductase from human duodenal microvillus membranes.

Reduction of ferric iron in the presence of HuTu 80 cells or duodenal microvillus membranes (MVMs) was investigated. With both systems, NADH-dependent reduction of Fe3+/NTA (nitrilotriacetic acid) was demonstrated, using the ferrous iron chelator ferrozine. Uptake of Fe3+ from Fe3+/NTA by HuTu 80 cells was strongly inhibited by addition of ferrozine, indicating that Fe2+ is the substrate for the iron uptake system. With isolated plasma membranes it is shown that the reductase activity is sensitive to trypsin and incubation at 65 degrees C. The reductase activity could be extracted from the plasma membrane and partially purified by ammonium sulphate precipitation and isoelectric focusing. From the purification and inhibition characteristics we conclude that reduction of ferric iron on the surface of duodenal plasma membranes is catalysed by a membrane protein.

Catalysis↗
PubMed1995

Oleic acid uptake into rat and rabbit jejunal brush border membrane.

Oleic acid uptake was studied using adult rabbit and rat jejunal brush border membrane vesicles. There was a reduction of oleic acid uptake following trypsin-treatment. Opposing Na+/H+ gradients (inward Na+ and outward H+ gradients) increased oleic acid uptake by about 40%, as compared with only an inward Na+ gradient, only an outward H+ gradient, or the absence of either Na+ or H+ gradients. The addition of mucin further increased the enhanced uptake of oleic acid observed in the presence of opposing Na+/H+ gradients. Amiloride, an inhibitor of the Na+/H+ exchanger, reduced by about 40% the uptake of oleic acid into sheets of rat jejunum, and this inhibitory effect was observed over a range of rates of stirring of the bulk phase. In rabbit jejunal brush border membrane vesicles, amiloride reduced oleic acid uptake in the presence but not in the absence of opposing Na+/H+ gradients, with a Ki of approx. 36 microM. Thus, oleic acid uptake occurs largely by partitioning of the lipid into the brush border membrane, influenced by a process which involves the activation of the brush border membrane Na+/H+ exchanger.

Amiloride↗
PubMed1995

Evidence for a hepatocyte membrane fatty acid transport protein using rat liver mRNA expression in Xenopus laevis oocytes.

The aim of the present study was to directly demonstrate that hepatocellular uptake of long-chain fatty acids represents a non-diffusional uptake mechanism. Xenopus laevis oocytes were used for expression of rat liver mRNA to identify the liver fatty acid uptake system. Injection of total rat liver poly(A)+ RNA into oocytes resulted in a dose-dependent increase in fatty acid uptake. The most active mRNA was found in the 1.1-2.1 kb subfraction. In contrast, expression of the liver cytosolic fatty acid binding protein (L-FABP) or the previously suggested candidate carrier protein, mitochondrial aspartate aminotransferase (mGOT), did not induce fatty acid uptake. It is concluded that in rat liver, fatty acid transport represents a protein-mediated transport system.

Animals↗
PubMed1995

Effect of ursodeoxycholic acid on biochemical parameters, hepatocyte proliferation and liver histology in galactosamine hepatitis in the rat.

The effect of oral administration of ursodeoxycholic acid (UDCA) on biochemical parameters, liver histology and liver cell proliferation was investigated in rats with galactosamine hepatitis. Treatment with UDCA led to a decrease of aminotransferases, but did not show any significant changes in liver histology or liver cell proliferation. The improvement of liver enzymes without change of histology in this animal model of hepatitis following treatment with UDCA is in agreement with results obtained from clinical trials with UDCA in patients with chronic viral hepatitis.

Alanine Transaminase↗