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Biomedical subjects

L Theilmann

Publications and source records attributed to L Theilmann.

At least 109 records · Page 6Linked to original sources
PubMed1991

Prevalence of antibodies to hepatitis C virus in hemodialysis patients.

Due to frequent parenteral contact with blood transfusions hemodialysis patients are prone to acquire hepatitis C virus (HCV) infection. To determine the role of HCV infection we investigated the prevalence of antibodies to HCV in 188 hemodialysis patients. The prevalence of antibodies to HCV was 7.4%. As compared to anti-HCV-negative patients, anti-HCV-positive patients had slightly elevated transaminases which were independent of the presence of markers for hepatitis B virus infection. We conclude that HCV infection is common among dialysis patients.

Female↗
PubMed1991

Interactions of hepatitis B virus with hepatocytes: mechanism and clinical relevance.

A receptor for hepatitis B virus (HBV) on hepatocytes has been postulated. There is increasing evidence that the binding of the virus to the target cell surface is mediated by epitopes of the pre-S proteins of the HBV envelope. In contrast to vaccination with HBsAg, passive immunization for the prevention of HBV infection is less effective. Using antibodies against the pre-S proteins, representing the putative attachment site for HBV binding to hepatocytes, a more efficient means of protection might be achieved.

Epitopes↗
PubMed1991

Antibodies in anti-HBe-positive patient sera bind to an HBe protein expressed on the cell surface of human hepatoma cells: implications for virus clearance.

The relevance of the recently described membrane-bound form of the HBe protein for the antiviral immune response was examined. The data show that antibodies in anti-HBe, but not in anti-HBc-positive human sera efficiently bind to the membrane expressed HBe. No evidence was obtained that the HBc can reach the cell surface in a form that can be detected with human antibodies. The findings suggest that the decline of virus titer that is usually observed after seroconversion from HBe to anti-HBe might be the result of an antibody-mediated elimination of infected cells.

Biological Transport↗
PubMed1990

Biliary excretion of iron in healthy man and in patients with alcoholic cirrhosis of the liver.

We measured the biliary excretion of iron in 11 patients with alcoholic cirrhosis of the liver and in 10 healthy controls using an intestinal perfusion technique. In the patients with cirrhosis increased amounts of iron in liver tissue were present. The concentrations of iron in the bile samples were determined by atomic absorption spectrometry. The biliary excretion of iron in the healthy controls was 0.32 +/- 0.09 mumol/h and in the patients with cirrhosis it was 0.45 +/- 0.14 mumol/h. The biliary excretion of iron in the patients with cirrhosis was not reduced, indicating that other mechanisms than a reduced biliary excretion of iron must be responsible for the accumulation of iron in liver tissue in alcoholic cirrhosis.

Adult↗
PubMed1990

Ursodeoxycholate reduces hepatotoxicity of bile salts in primary human hepatocytes.

Primary human hepatocytes were used to study bile salt hepatotoxicity and the hepatoprotective potential of ursodeoxycholate in vitro. Hepatocytes were obtained by collagenase perfusion of healthy human liver tissue and were treated with glycochenodeoxycholate for 24 hr 1 day after plating. Clear signs of cytotoxicity were observed at concentrations of about 100 mumol/L glycochenodeoxycholate. Toxicity was determined by release of alkaline phosphatase, gamma-glutamyl transferase, AST, ALT or lactate dehydrogenase into the culture medium, by measuring DNA synthesis of the cultured liver cells and by testing the viability of the hepatocytes using trypan-blue dye exclusion. Addition of ursodeoxycholate, which by itself proved to be of little toxicity, significantly reduced the hepatotoxic effects of glycochenodeoxycholate: 72% +/- 6% of the cells survived treatment with 500 mumol/L glycochenodeoxycholate alone, but addition of 100 mumol/L ursodeoxycholate increased the survival rate to 87% +/- 4% (p less than 0.05). Moreover, all enzymes tested were secreted at a significantly lower level when ursodeoxycholate was present. Similarly, the cellular DNA synthesis was maintained at significantly higher levels as a result of ursodeoxycholate treatment. We conclude that (a) primary human hepatocytes are a suitable model for studying hepatotoxicity of bile salts in vitro, (b) ursodeoxycholate reduces hepatotoxicity of other bile salts and (c) ursodeoxycholate can act hepatoprotectively by itself (i.e., alteration of the metabolism of other bile salts is not necessarily required).

Bile Acids and Salts↗
PubMed1990

Detection of large intrahepatic cholangiectases in patients with primary sclerosing cholangitis by endoscopic retrograde cholangiography.

Cholangiographic features of primary sclerosing cholangitis are multiple strictures and alternating dilated and normal segments of both intra- and extrahepatic bile ducts. Formerly, intrahepatic cholangiectases have been shown only in explanted livers, but we now describe the presence of large intrahepatic cholangiectases in a 22-year-old male patient with primary sclerosing cholangitis, visualized using a balloon catheter at endoscopic retrograde cholangiography. Cholangiectases in this patient appear to have been caused by the disease and not as a result of prestenotic dilatations. To treat possible early complications of this condition, we recommend looking for these cholangiectases when diagnostic endoscopic retrograde cholangiography is performed in primary sclerosing cholangitis.

Adult↗
PubMed1990

Inhibition of hepatitis B virus polymerase-activity by various agents. Transient expression of hepatitis B virus DNA in hepatoma cells as novel system for evaluation of antiviral drugs.

The effect of three putative antiviral drugs--aciclovir (acyclovir, CAS 59277-89-3), zidovudine (azidothymidine, CAS 30516-87-1) and sorangicin B (a macrocyclic lactone, CAS 100415-25-6)--on replication and gene expression of hepatitis B virus (HBV) was studied in HepG2 cells. Transfection of these cells with cloned circular HBV DNA resulted in the production and secretion of virions into the medium. When antiviral drugs were added in increasing concentrations (aciclovir at 0.5 microgram/ml to 150 micrograms/ml, zidovudine 0.1 microgram/ml to 30 micrograms/ml, sorangicin B 1 micrograms/ml to 30 micrograms/ml), the activity of the viral polymerase decreased in a dose-dependent manner. Production of viral proteins as measured by the secretion of HBsAg and HBeAg into the medium was unaffected, suggesting interference of these drugs with viral DNA/RNA synthesis. It is concluded that aciclovir, zidovudine and sorangicin B inhibit the replication of HBV. Furthermore, the cell system used in our study appears to be suitable for the rapid testing of antiviral drugs and their evaluation for possible studies in vivo.

Acyclovir↗
PubMed1990

[Alpha tumor necrosis factor in the serum of patients with sarcoidosis, tuberculosis or bronchial cancer].

Tumor-necrosis-factor-alpha (TNF-alpha), which is secreted by cells of the macrophage/phagocytic system, interact in a variety of different ways with other cytokines and immunologically active substances. To investigate a possible role of TNF-alpha in granulomatous lung diseases and to determine whether sarcoidosis can be differentiated from tuberculosis on the basis of serum TNF-alpha levels, we studied sera from patients with sarcoidosis and active tuberculosis. Ninety-one percent of the patients with sarcoidosis and 83% of the patients with tuberculosis exhibited significantly elevated TNF-alpha levels as compered with controls. Since these levels remained elevated irrespective of clinical stage and even under therapy, it is believed that patients with sarcoidosis and tuberculosis experience continuous activation of TNF-2-alpha-producing cells of the myelomonocytic system. In addition, determination of serum TNF-alpha levels does not permit differentiation between sarcoidosis, tuberculosis or malignant disease.

Adult↗
PubMed1989

Taurine and glycine conjugation and sulfation of lithocholate in primary hepatocyte cultures.

Rat primary liver cells were used to study taurine and glycine conjugation and sulfation of lithocholate. After addition of [14C]lithocholate to the tissue culture medium, synthesis and excretion of amidated and/or sulfated products were investigated for up to 24 h. After incubation for 1 h, more than 83% of the labeled bile salt was amidated but not sulfated and between 5 and 11% was sulfated, with more than 80% of the sulfated bile salts being also amidated. After 24 h, the proportion of sulfated lithocholate had increased to about 23% and more than 99% of the lithocholate sulfate was additionally conjugated with glycine or taurine. Both sulfates and non-sulfates were preferably amidated with taurine. We conclude that in primary rat hepatocytes, (1) lithocholate is rapidly and almost completely conjugated with glycine or taurine (amidated), whereas sulfation of lithocholate (and its amidates) proceeds slowly and even after 24 h represents only a small proportion of the total lithocholate metabolites, and (2) sulfated and unsulfated bile salts are both preferably amidated with taurine.

Amides↗
PubMed1989

Phase-I trial of intravenous continuous infusion of tumor necrosis factor in advanced metastatic carcinomas.

Fifteen patients with advanced metastatic adenocarcinomas were treated in a phase-I study with continuous intravenous 24 h infusion of recombinant tumor necrosis factor alpha (TNF-alpha) in order to determine the maximum tolerated dose (MTD) and associated side-effects. Patients received 40-400 micrograms/m2 TNF-alpha once (arm A) or twice (arm B) weekly for a scheduled treatment period of 2 months. The observed systemic side-effects resembled those reported for interferons and included fever, chills, fatigue, headaches, myalgias, thrombocytopenia, prostration, and malaise. Dose-limiting toxicities, resulting in a median MTD of 200 micrograms/m2 for 24 h, were fever, chills, fatigue, myalgias, and thrombocytopenia. Out of 15 patients, 11 showed tumor progression, and 3 sustained in no change for over 2 months of treatment. A minor response was seen in 1 patient with a colorectal carcinoma and liver metastases. To reduce side-effects, patients were treated either with paracetamol or indomethacin. Higher MTDs were observed in patients treated with indomethacin. No detectable plasma TNF-alpha levels or TNF antibodies were measured under therapy (plasma TNF-alpha less than 20 pg/ml). We conclude that TNF-alpha appears to have some antineoplastic activity in patients with adenocarcinomas since 4 patients remained in no change or showed a minor response.

Antibodies↗
PubMed1989

Isolation and characterization of cytoplasmic and nuclear particles of hepatitis B virus.

The properties of hepatitis B virus (HBV) core particles from liver tissue of two patients with acute HBV infection were investigated. Cores were isolated from cytoplasm and nuclear fractions by centrifugation and two thirds of the cores were located in the cytoplasm. In all properties examined cores isolated from the cytoplasm or nucleus were the same. The cores had a density of 1.38 g/ml and had the same DNA and protein content when analyzed by Southern blotting and by Western blotting with C-specific antisera. Cores from both subcellular fractions had endogenous polymerase activity. We conclude that core particles with identical properties are found in both the cytoplasm and nucleus of cells during acute infection.

Blotting, Southern↗
PubMed1989

Detection of hepatitis B virus core gene products in sera and liver of HBV-infected individuals.

The C gene of hepatitis B virus (HBV) codes for at least two different proteins (p 21c and p 17e). To investigate the expression of C-gene-encoded proteins in vivo, serum and liver samples from HBsAg-positive patients as well as serial serum samples from an HBV-transfected chimpanzee were studied. Antibodies directed against bacterially synthesized C-fusion proteins were used in Western blots to test for the presence of p 21c and p 17e. In serial serum samples from the chimpanzee, p 21c and p 17e were detected concomitantly during the acute phase of the infection. When sera of patients with chronic HBV infection were studied, all sera containing p 17e were found to be positive also for p 21c. Sera positive for HBV DNA but negative for HBeAg were only positive for p 21c, indicating that HBeAg/p 17e is not an absolutely reliable marker for infectivity. In liver tissue specimens from 20 patients with HBV-related liver diseases, p 21c was detected in five cases, indicating viral replication. The p 17e antigen, however, was present only in low amounts in three of these five, suggesting that synthesis of p 21c and p 17e is not strictly coupled. C/Pol-gene-encoded fusion proteins were found in the liver tissue of only one patient with cirrhosis, supporting our previous finding that detectable levels of these proteins are expressed rarely.

Animals↗
PubMed1989

Detection of HBV DNA in HBsAg-positive sera after amplification using the polymerase chain reaction.

The presence of hepatitis B virus (HBV) DNA in serum as detected by molecular hybridization is considered the most reliable marker for the presence of complete virions and, therefore, infectivity. This technique, however, has a lower limit of detection of 0.1 pg HBV DNA. Using the polymerase chain reaction (PCR), a technique by which DNA sequences can be amplified selectively, we investigated sera from 30 HBsAg carriers, 6 also positive for HBeAg and 24 negative for HBeAg. After PCR followed by Southern blot, 27 sera were found to be positive for HBV DNA, whereas only 7 sera were positive for HBV DNA in the conventional dot blot. PCR followed by Southern blot analysis lowered the limit of detection to 0.5 fg HBV DNA. Amplified HBV DNA fragments from some samples were directly sequenced without previous cloning. We conclude that PCR is a suitable method to amplify parts of viral genomes present in human sera, and that PCR with subsequent Southern blot analysis allows the detection of hepatitis B virions in the majority of HBsAg-positive sera.

Blotting, Southern↗
PubMed1988

Elevated levels of head activator in human brain tumors and in serum of patients with brain and other neurally derived tumors.

In normal human tissue high concentrations of the neuropeptide head activator are found in the hypothalamus, in the retina, and in the gastro-intestinal tract. Up to 100-fold elevated levels of head activator over neighbouring tissue were found in tumors of the brain, especially in tumors of neural origin like astrocytoma and glioblastoma, but also in meningioma. Coincident with elevated tissue levels, an increased secretion into the general circulation was observed. Elevated levels of head activator in the blood were also observed in patients with tumors in peripheral locations, especially in tumors of gastrointestinal tract and/or of neuroendocrine origin. After tumor removal, the head activator levels in the blood dropped to normal values suggesting a possible role of head activator in neuroendocrine tumorigenesis.

Animals↗