Search PubMed⌕ Search

Biomedical subjects

W Stremmel

Publications and source records attributed to W Stremmel.

At least 235 records · Page 13Linked to original sources
PubMed1989

Cellular influx of sulfobromophthalein by the biliary epithelium carcinoma cell line Sk-Cha-1 reveals kinetic criteria of a carrier-mediated uptake mechanism.

Cellular uptake of the cholephilic organic anion sulphobromophthalein (BSP) by the human biliary epithelium carcinoma cell line Sk-Cha-1 was examined at 37 degrees C. In confluent monolayer cultures the cellular influx rate of increasing concentrations of [35S]BSP followed saturation kinetics with a Km value of 18 microM and a Vmax value of 243 pmol.min-1.mg protein-1. Uptake of [35S]BSP was competitively inhibited by the presence of bilirubin diglucuronide, but not by taurocholate or cholate. Furthermore, uptake was temperature dependent with maximal cellular influx rates at 37 degrees C.

Biliary Tract Neoplasms↗
PubMed1989

Fatty acid uptake by human hepatoma cell lines represents a carrier-mediated uptake process.

Cellular influx kinetics of a representative long chain fatty acid, [3H]oleate, were examined in monolayer cultures of three different human hepatoma cell lines (Hep G2; PLC/PRF 5; Mz-Hep-1). The cultures were incubated with 173 microM [3H]oleate in the presence of various concentrations of albumin which served to modulate the unbound oleate concentration in the medium. For all [3H]oleate-albumin complexes incubated, it was shown that cellular uptake of [3H]oleate over the initial 30 s incubation period was maximal, linear and independent of intracellular fatty acid metabolism, representing cellular influx. With increasing unbound oleate concentrations in the medium cellular influx by all three cell lines revealed similar saturation kinetics with Km values of 112.6 +/- 14.5 nM and Vmax values of 7.19 +/- 0.32 nmol.min-1 per mg cell protein. When these hepatoma cell lines were pretreated with the IgG fraction of a monospecific antibody to the rat liver membrane fatty acid binding protein (MFABP), initial uptake of [3H]oleate was selectively inhibited compared to controls pretreated with the IgG fraction of the preimmune serum. Furthermore, immunoblot analysis with the monospecific antibody to the rat MFABP revealed reactivity with a single 40 kDa protein in the homogenates of all three cell lines. These data suggest that uptake of fatty acids by human hepatoma cells may be mediated by a specific membrane fatty acid binding protein.

Carcinoma, Hepatocellular↗
PubMed1989

Mechanism of hepatic fatty acid uptake.

In recent years a new concept of the mechanism of hepatic fatty acid uptake has been described. It was shown that this major class of energy yielding substrates enters hepatocytes by a carrier-mediated uptake system. After the dissociation of the fatty acid-albumin complex at the sinusoidal liver cell plasma membrane, fatty acid binds with high affinity to a specific, newly identified, 40 kDa membrane fatty acid binding protein (MFABP). This protein functions as transmembrane transporter for long chain fatty acids. Hepatocellular uptake of fatty acids was shown to be sodium-dependent and electrogenic, compatible with a Na+-fatty acid cotransport system.

Animals↗
PubMed1989

[Epidemiology and clinical aspects of chronic hepatitis B and non-A, non-B virus infections].

Hepatitis B and Non-A-non-B infections often become chronic and proceed to cirrhosis associated with a shortened life expectancy. Both infections are transmitted by parenteral or sexual routes. New insights in the structure of the hepatitis B virus (HBV) as well as in the immune response mechanism of the organism permit by serological testing a clear definition of the replicative state of the virus. Together with the parameters of inflammation (e.g. transaminases, liver histology) it is possible to determine the activity of the hepatitis. The most effective treatment of chronic HBV-infection today is the therapy with alpha- or beta-interferon. The aim of this treatment is the inhibition of HBV replication and accellerated elimination of the virus, indicated by seroconversion of HBEAg to anti-HBEAg. The most significant advance in the knowledge of percutaneous Non-A-non-B hepatitis is the identification of the responsible virus and the development of a diagnostic test for its serological detection. Since this type of hepatitis becomes chronic in 50-60% of the cases, therapy is urgently required. Clinical studies showed that also for Non-A-non-B virus infection alpha-interferon is most effective. Currently the optimal dosage, duration and point in time for interferon treatment is being evaluated.

Follow-Up Studies↗
PubMed1988

[Orthotopic liver transplantation in Wilson's disease and acute liver failure].

Liver histology demonstrated progressive cirrhosis in a 19-year-old girl with a subacute form of Wilson's disease. Despite D-penicillamine administration her liver functions rapidly deteriorated further. Orthotopic liver transplantation was performed. Postoperatively there were two mild rejection episodes, an organic psychiatric syndrome and generalized tremor. Copper metabolism and clinical symptoms became normal postoperatively. Five months after the transplantation she was in a good general condition, able to continue her education.

Acute Disease↗
PubMed1988

What's new in the hepatocellular uptake mechanism of bilirubin and fatty acids?

Although hepatocellular uptake of bilirubin and fatty acids represents a major function of the liver, little was known about the molecular mechanism of their translocation across the plasma membrane. This review provides evidence that these classes of albumin-bound organic anions enter hepatocytes via specific membrane associated carrier systems. After dissociation of the albumin-ligand complexes at the cell surface, bilirubin and related cholephilic organic anions bind to a 55 kDa membrane glycoprotein, while fatty acids bind to a 40 kDa membrane protein. Both proteins function as carrier of their respective ligand across the plasma membrane. Although the driving forces for the influx of bilirubin are still unknown, it could be demonstrated that the translocation of fatty acids across the plasma membrane is driven by an active, potential-sensitive, sodium-dependent transport system.

Bilirubin↗
PubMed1988

Abnormalities in estrogen, androgen, and insulin metabolism in idiopathic hemochromatosis.

Of 44 male patients with idiopathic hemochromatosis who were diagnosed at an early stage without morphological or biochemical evidence of liver disease, 25% suffered from impotence and 34% manifested glucose intolerance. Impotence was correlated with a 50% reduction in plasma testosterone, resulting from a 63% decrease in testosterone production. Testicular atrophy was caused by insufficient secretion of gonadotropins due to the selective accumulation of iron in gonadotropic cells of the pituitary gland. However, peripheral sexual hormone metabolism, in particular the conversion of androgens to estrogens, remained unaltered. It was therefore possible to employ substitution therapy successfully with testosterone in these men, and hyperestrogenism was not observed as a side effect. The pathogenetic factors in the development of diabetes mellitus in patients with idiopathic hemochromatosis include impaired insulin secretion caused by the selective deposition of iron in B-cells of the pancreas and insulin resistance due to iron accumulation in the liver. In particular, the insulin resistance is markedly improved after depletion of body iron stores by phlebotomy treatment, resulting in lower insulin requirements in patients with insulin-dependent diabetes as well as improvement of carbohydrate metabolisms in about half of the patients with non-insulin-dependent diabetes. We have concluded that hypogonadism and carbohydrate intolerance are caused by the specific distribution pattern of excess iron in the organism, accompanied by functional impairment of affected parenchymal cells.

Adult↗
PubMed1988

Survival and causes of death in hemochromatosis. Observations in 163 patients.

Survival and causes of death were analyzed among 163 patients with hemochromatosis diagnosed between 1959 and 1983. Mean followup was 10.5 +/- 5.6 years (+/- SD). Cumulative survival was 76% at 10 years and 49% at 20 years. Life expectancy was reduced in patients who presented with cirrhosis or diabetes compared to patients who presented without these complications at the time of diagnosis. Patients who could be depleted of iron during the first 18 months of venesection therapy had a markedly better prognosis compared to those patients who could not be depleted during this time period, probably due to greater amounts of excessive iron. Prognosis was not influenced by sex. Patients without cirrhosis or diabetes had a life expectancy that was virtually identical to that of an age-matched normal population. Analysis of the causes of death in 53 patients showed that liver cancer (n = 16) was 219 times more frequent, cardiomyopathy (n = 3) was 306 times more frequent, liver cirrhosis (n = 10) was 13 times more frequent, and diabetes mellitus (n = 3) was seven times more frequent compared to death rates expected for an age-matched normal population. The risk of death from other causes, including extrahepatic cancer (n = 7), did not differ from rates expected. Thus, patients with hemochromatosis diagnosed in a precirrhotic stage and treated by venesection have a normal life expectancy. Cirrhotic patients had a shortened life expectancy and a high risk of death from liver cancer even when complete iron depletion has been achieved.

Adult↗
PubMed1988

Regional myocardial free fatty acid extraction in normal and ischemic myocardium.

The rate constant for free fatty acid influx (k1) was studied in normal and ischemic myocardium. In 15 normal subjects and 30 patients with coronary artery disease, 201Tl and 15-(p-123I-iodophenyl)-pentadecanoic acid (IPPA) were administered during exercise under fasting conditions and at rest. In 10 patients, the study was repeated after percutaneous transluminal coronary angioplasty; in three patients, the study was repeated after infarction. The initial accumulation of IPPA, related to that of 201Tl (both background and crossover corrected), was used for determinations of the regional rate constant of IPPA influx into myocardial tissue (k1*). In normal subjects, no significant differences in k1* between major myocardial segments were found; the average value of k1* was 0.57 +/- 0.13/min (mean +/- SD) at rest and 0.42 +/- 0.06/min at exercise (average workload, 123 +/- 47 W). With increasing free fatty acid plasma concentration and perfusion, free fatty acid influx increased in a saturable fashion. The Michaelis-Menten constant (KM*) and the maximal velocity (Vmax*) for IPPA influx into myocardial tissue were estimated to be 470 nmol/g and 430 nmol/g.min, respectively. In ischemic areas, k1* was reduced to 57 +/- 18% of k1* value in nonaffected segments. The areas were larger than those showing reduced 201Tl uptake. Preinfarction and postinfarction studies showed that the size of 201Tl defects in postinfarction images corresponded with the size of the area with reduced k1* observed in preinfarction scintigrams. Revascularization led to an increase of 201Tl uptake and to normalization of k1*.

Coronary Disease↗
PubMed1988

Fatty acid uptake by isolated rat heart myocytes represents a carrier-mediated transport process.

The mechanism by which fatty acids enter cardiomyocytes is unclear. Therefore, the influx kinetics of [3H]oleate into isolated rat heart myocytes were examined. Cells were incubated at 37 degrees C with [3H]oleate bound to albumin in various molar ratios and the initial rate of uptake (V0) was determined as a function of the unbound oleate concentration in the medium. V0 was saturable with increasing oleate concentrations incubated (Km 78 nM; Vmax 1.9 nmol X min-1 per 10(6) cells) and temperature dependent with an optimum at 37 degrees C. Furthermore, binding of [3H]oleate to isolated plasma membranes of cardiomyocytes was saturable, revealing a KD of 42 nM, and was inhibited by heat denaturation or trypsin pretreatment of the membranes. From these membranes a single 40-kD protein with high affinity for a variety of long chain fatty acids was isolated. With a monospecific antibody to this membrane protein, binding as well as cellular influx of [3H]oleate was selectively inhibited. These data indicate that at least a portion of myocardial fatty acid uptake is mediated by a specific membrane protein.

Albumins↗
PubMed1988

Uptake of fatty acids by jejunal mucosal cells is mediated by a fatty acid binding membrane protein.

The previous identification of a membrane fatty acid binding protein (MFABP) in brush border plasma membranes of the jejunum suggested that mucosal cell uptake of fatty acids might represent a carrier-mediated transport system. For evaluation of this hypothesis cellular influx kinetics (V0) of [3H]-oleate were examined in isolated rat jejunal mucosal cells. With increasing unbound oleate concentration in the medium V0 was saturable (Km = 93 nM; Vmax = 2.1 nmol X min-1 per 10(6) cells) and temperature dependent with an optimum at 37 degrees C. Pretreatment of the cells with a monospecific antibody to MFABP significantly inhibited V0 of oleate, other long-chain fatty acids, and D-monopalmitin, but not of L-alanine. Moreover, in the in vivo system of isolated perfused jejunal segments the physiologic significance of MFABP in the directed overall intestinal absorption process of fatty acids was documented. In the presence of the anti-MFABP oleate absorption was markedly reduced, whereas uptake of L-alanine remained unaltered. By antibody inhibition studies it was suggested that this membrane carrier also reveals transport competence for various other long-chain fatty acids, D-monopalmitin, L-lysophosphatidylcholine, and cholesterol. These data support the hypothesis that absorption of fatty acids is mediated by a fatty acid binding membrane protein.

Animals↗
PubMed1987

Insulin binding to erythrocytes in hyperinsulinemic patients with precirrhotic hemochromatosis and cirrhosis.

This study investigated insulin receptor binding (number and affinity) to erythrocytes in patients with precirrhotic hemochromatosis, patients with cirrhosis, and healthy subjects. To evaluate plasma glucose and insulin levels, an oral glucose tolerance test (OGTT) was performed in all subjects. In the fasting state, all patients exhibited normal glucose levels. Precirrhotic patients showed slight impairment of glucose tolerance while cirrhotic patients were strikingly glucose intolerant. In both patient groups, fasting plasma insulin levels were increased. Following the glucose load, plasma insulin levels were significantly enhanced in precirrhotic patients at 90 and 120 min and increased at all times in cirrhotic patients. In the postabsorptive state (in the presence of hyperinsulinemia) insulin binding and the number and affinity of insulin receptors of erythrocytes were not different in precirrhotic or cirrhotic patients when compared to controls. We conclude that studies of insulin binding on erythrocytes do not contribute to the evaluation of the pathogenesis of insulin resistance in liver disease.

Blood Glucose↗