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Biomedical subjects

W Vogel

Publications and source records attributed to W Vogel.

At least 19 recordsLinked to original sources
PubMed1995

[Hepatocellular carcinoma].

Hepatocellular carcinoma (HCC) is one of the most common malignant tumors in the world. The profile of risk factors associated with HCC includes not only chronic infection with hepatitis B virus and/or hepatitis C virus with subsequent cirrhosis, but also metabolic and alcoholic chronic liver diseases. While the risk of developing cancer is high in patients with cirrhosis, the aim of most screening programmes is to detect small, potentially resectable tumors. Serum alpha 1-fetoprotein lacks both sensitivity and specificity as a screening test and two-thirds of patients with small HCCs have levels below 200 ng/ml. Hepatic resection or liver transplantation at an early stage of HCC, without extrahepatic metastasis, provide complete cure of the disease.

Adult↗
PubMed1995

Protein-tyrosine phosphatase 1D modulates its own state of tyrosine phosphorylation.

The insulin receptor-mediated signal transduction pathway involves insulin receptor substrate 1 and a variety of proteins containing Src homology-2 (SH2) domains, such as phosphatidylinositol 3-kinase, Grb2, and protein-tyrosine phosphatase 1D (PTP1D). Upon insulin stimulation of baby hamster kidney cells overexpressing the IR, the catalytically inactive mutant of PTP1D, C463A, becomes tyrosine-phosphorylated and coprecipitates with Grb2. Tyrosine phosphorylation of this mutant is significantly reduced when wild type PTP1D is coexpressed. Substitution of tyrosine residues 546 and 584 with phenylalanine abrogates tyrosine phosphorylation of the catalytically inactive mutant and abolishes its interaction with Grb2.

Animals↗
PubMed1995

Single voltage-activated Na+ and K+ channels in the somata of rat motoneurones.

1. Voltage-activated Na+ and K+ channels were investigated in the soma membrane of motoneurones using the patch-clamp technique applied to thin slices of neonatal rat spinal cord. 2. One type of TTX-sensitive Na+ channel, with a conductance of 14.0 pS, was found to underlie the macroscopic Na+ conductance in the somata of motoneurones. These channels activated within a potential range between -60 and -20 mV with a potential of half-maximal activation (E50) of -38.9 mV and steepness factor (k) of 6.1 mV. 3. Kinetics of Na+ channel inactivation could be fitted with a single exponential function at all potentials investigated. The curve of the steady-state inactivation had the following parameters: a half-maximal potential (Eh,50) of -81.6 mV and k of -10.2 mV. 4. Kinetics of recovery of Na+ channels from inactivation at a potential of -80 mV were double exponential with fast and slow components of 16.2 (76%) and 153.7 ms (24%), respectively. It is suggested that the recovery of Na+ channels from inactivation plays a major role in defining the limiting firing frequency of action potentials in motoneurones. 5. Whole-cell K+ currents consisted of transient (A)- and delayed-rectifier (DR)-components. The A-component activated between -60 and +20 mV with an E50 of -33.3 mV and k of 15.7 mV. The curve of steady-state inactivation was best fitted with an Eh,50 of -82.5 mV and k of -10.2 mV. The DR-component of K+ current activated smoothly at more positive potentials. E50 and k for DR-currents were +1.4 and 16.9 mV, respectively. 6. The most frequent single K+ channel found in the somata of motoneurones was the fast inactivating A-channel with a conductance of 19.2 pS in external Ringer solution. In symmetrical high-K+ solutions the conductance was 50.9 and 39.6 pS for inward and outward currents, respectively. The channel activation took place between -60 and +20 mV. The curve of steady-state inactivation of single A-channels had an Eh,50 of -87.1 mV and k of -12.8 mV. In high-Ko+ solution A-channels demonstrated a rapid deactivation at potentials between -110 and -60 mV. The time constant of the channel deactivation depended on the membrane potential and changed from 1.5 ms at -110 mV to 6.3 ms at -60 mV. 7. Delayed-rectifier K+ channels were found in the soma membrane at a moderate density.(ABSTRACT TRUNCATED AT 250 WORDS)

4-Aminopyridine↗
PubMed1995

Visualization of the conservation of synteny between humans and pigs by heterologous chromosomal painting.

By comparative gene mapping, extended conservation of synteny between different mammalian species has become apparent. Mapping in these species could be accelerated by exact visualization of the chromosomal segments that exhibit conserved synteny. We have hybridized human chromosome-specific DNA libraries onto porcine metaphase spreads to examine the extent of conservation of synteny between the two species. The hybridization signals on pig chromosomes are of variable quality, but the analysis allowed us to assign for all human autosomes homologous chromosomal segments in the pig karyotype. Extended conservation of synteny was observed, often comprising whole chromosomes. In our analysis 47 segments of conserved synteny common to the human and pig karyotype were identified. Intrachromosomal rearrangements by inversion within and between these segments are described. These rearrangements are common events during evolution. Our analysis shows that conservation of synteny between human and pig is three times more than between humans and mice and, consequently, is characterized by fewer, but larger conserved segments.

Animals↗
PubMed1995

Distinct structural characteristics of discoidin I subfamily receptor tyrosine kinases and complementary expression in human cancer.

Mammary carcinoma kinase 10 (MCK-10) and colon carcinoma kinase 2 (CCK-2) constitute a subclass of receptor tyrosine kinases characterized by a discoidin I motif in the extracellular domain and a large cytoplasmic juxtamembrane (JM) region. While the ectodomain structure suggests a common role in cell aggregation, the JM domains of MCK-10 and CCK-2 are structurally most divergent and display features that suggest an involvement in signal generation and definition. MCK-10 occurs in at least three isoforms, which contain alternatively spliced consensus sequences for internalization and SH3 domain interaction. The presence of the 37 amino acid insert affects receptor autophosphorylation and changes ectodomain glycosylation. Proteolytic cleavage within the extracellular domain of MCK-10 generates a membrane-anchored kinase domain and releases a soluble ectodomain fragment including the discoidin I homology domain. CCK-2 and MCK-10 expression was found in connective and epithelial tissues, respectively, which in cancers of epithelial origin results in mutually exclusive expression in stroma and tumor cells, indicating a possible involvement of this class of RTKs in tumor invasion.

Amino Acid Sequence↗
PubMed1995

Interferon-alpha induces circulating tumor necrosis factor receptor p55 in humans.

In the present studies we investigated the effect of interferon-alpha (IFN alpha) on the release of the soluble (extracellular) form of the tumor necrosis factor p55 receptor (TNFsRp55), because TNFsRp55 is a natural antagonist of tumor necrosis factor (TNF)-induced inflammation and also might be part of the antiinflammatory properties of IFN alpha. Plasma levels of TNFsRp55 were measured by a specific radioimmunoassay in five healthy volunteers and in five patients with chronic hepatitis C treated with IFN alpha. Levels showed a significant increase after a single injection of 5.0 million U IFN alpha in both healthy and hepatitis patient groups. Peak values (3.5 to 4.5 ng/mL) were observed within 12 hours of beginning treatment. Thereafter, levels promptly declined, reaching baseline values within 24 hours. TNF alpha and C-reactive protein (CRP) levels were below the detection limit in the same plasma samples. In addition, IFN alpha suppressed significantly interleukin (IL)-1 alpha-induced TNF alpha protein synthesis by human peripheral blood mononuclear cells. These results suggest that the antiinflammatory properties of IFN alpha may be, in part, also due to the induction and/or release of TNF soluble receptors and the suppression of TNF alpha synthesis.

C-Reactive Protein↗
PubMed1995

The X-chromosomal human biglycan gene BGN is subject to X inactivation but is transcribed like an X-Y homologous gene.

We report the mRNA and protein expression levels of human biglycan (BGN) in patients with different numbers of sex chromosomes. BGN maps to the distal long arm of the X chromosome, band Xq28, near the second pseudoautosomal region. BGN expression levels are reduced in 45,X Turner patients and increased in patients with additional sex chromosomes. This is suggestive of a pseudoautosomal gene or a gene that escapes X inactivation and that has an active Y chromosomal copy. However, we also provide evidence from hybrid cell lines that BGN is subject to X inactivation and that there is no homolog on the Y chromosome. This evidence excludes an escape from X inactivation. Moreover, additional Y chromosomes increase BGN expression levels, despite the absence of a Y chromosomal BGN gene. Therefore, another explanation has to be invoked. The "pseudoautosomal expression" of BGN may be attributed to a gene or genes that escape X inactivation and that regulate the transcriptional activity of BGN. This is the first report concerning an X chromosomal gene that does not show the conventional correlation between gene dosage and expression rate known from other X chromosomal genes.

Adult↗
PubMed1995

Reversible hepatic veno-occlusive disease in an infant after consumption of pyrrolizidine-containing herbal tea.

UNLABELLED: Veno-occlusive disease was diagnosed in an 18-month-old boy who had regularly consumed a herbal tea mixture since the 3rd month of life. The boy developed portal hypertension with severe ascites. Histology of the liver showed centrilobular sinusoidal congestion with perivenular bleeding and parenchymal necrosis without cirrhosis. The tea contained peppermint and what the mother thought was coltsfoot (Tussilago farfara). The parents believed the tea aided the healthy development of their child. Pharmacological analysis of the tea compounds revealed high amounts of pyrrolizidine alkaloids. Seneciphylline and the corresponding N-oxide were identified as the major components by thin-layer chromatography, mass spectrometry and NMR spectroscopy. We calculated that the child had consumed at least 60 micrograms/kg body weight per day of the toxic pyrrolizidine alkaloid mixture over 15 months. Macroscopic and microscopic analysis of the leaf material indicated that Adenostyles alliariae (Alpendost) had been erroneously gathered by the parents in place of coltsfoot. The two plants can easily be confused especially after the flowering period. The child was given conservative treatment only and recovered completely within 2 months. CONCLUSION: In all cases of veno-occlusive disease pyrrolizidine alkaloids ingestion should be excluded. The identity of collected plant material should be verified by pharmaceutically trained experts and information of composition, dosage and mode of administration should be included in guidelines for herbal preparations.

Hepatic Veno-Occlusive Disease↗
PubMed1995

Fulminant hepatic failure in a child as a potential adverse effect of trimethoprim-sulphamethoxazole.

UNLABELLED: Trimethoprim-sulphamethoxazole (TMP-SMZ) is considered a safe drug for treatment of infectious bacterial diseases in children. Side-effects are rare and generally take the form of a hypersensitivity reaction to the sulphamethoxazole component of the drug. Hepatic injury usually presents as a transient elevation of liver enzymes, which is of little clinical relevance. Fulminant liver failure due to TMP-SMZ has been reported in only six adults and never in children. We here report a 5-year-old girl who developed fulminant liver failure 3 weeks after her third exposure to TMP-SMZ. After a biphasic clinical course she underwent successful liver transplantation. CONCLUSION: Trimethoprim-Sulphamethoxazole may cause fulminant liver failure in children. The disease can run a biphasic clinical course and liver transplantation must be considered as the therapeutic option for these patients.

Biopsy↗
PubMed1995

Prognosis and life expectancy in chronic liver disease.

The aim of the present was to define prognosis and life expectancy in patients with chronic liver disease of different etiologies and to relate them to an age- and sex-matched normal population. After a follow-up of 15 years, life expectancy of 620 patients with chronic liver disease was retrospectively calculated and compared with an age- and sex-matched normal population. Among patients with cirrhosis, prognosis was dependent upon Child classification (P = 0.001). Patients with alcoholic cirrhosis and fatty liver disease were younger (P = 0.01) and had a lower life expectancy than patients with other causes of chronic liver disease (P = 0.004). Patients with hepatitis B and hepatitis C cirrhosis showed a comparable prognosis and a significantly lower life expectancy than the age- and sex-matched population. Cryptogenic and autoimmune liver diseases showed a comparable life expectancy but a significantly shorter life expectancy than the normal population. In patients with alpha 1-antitrypsin deficiency-associated cirrhosis, a high viral coinfection rate was found (P = 0.01). For patients with noncirrhotic hemochromatosis, prognosis was poorer than that for the age- and sex-matched population. In patients with asymptomatic primary biliary cirrhosis, chronic persistent hepatitis B, and alpha 1-antitrypsin deficiency without cirrhosis, life expectancy was equal to that of the normal population. Prognosis and life expectancy in chronic liver disease depend on stage, cause, and symptoms of chronic liver disease; age; and possibilities of treatment. In patients with hereditary liver disease, additional viral infection of alcohol abuse lead to a significant deterioration of life expectancy. Patients with alcoholic chronic liver disease have the poorest prognosis.

Autoimmune Diseases↗
PubMed1995

Local anesthetics potently block a potential insensitive potassium channel in myelinated nerve.

Effects of some local anesthetics were studied in patch clamp experiments on enzymatically demyelinated peripheral amphibian nerve fibers. Micromolar concentrations of external bupivacaine depolarized the excised membrane considerably. The flicker K+ channel was found to be the most sensitive ion channel to local anesthetics in this preparation. Half-maximum inhibiting concentrations (IC50) for extracellular application of bupivacaine, ropivacaine, etidocaine, mepivacaine, lidocaine, and QX-314 were 0.21, 4.2, 8.6, 56, 220, and > 10,000 microM, respectively. The corresponding concentration-effect curves could be fitted under the assumption of a 1:1 reaction. Application from the axoplasmic side resulted in clearly lower potencies with IC50 values of 2.1, 6.6, 16, 300, 1,200, and 1,250 microM, respectively. The log(IC50)-values of the local anesthetics linearly depended on the logarithm of their octanol:buffer distribution coefficients with two regression lines for the piperidine derivatives and the standard amino-amides indicating an inherently higher potency of the cyclic piperidine series. Amide-linked local anesthetics did not impair the amplitude of the single-channel current but prolonged the time of the channel to be in the closed state derived as time constants tau c from closed-time histograms. With etidocaine and lidocaine tau c was 133 and 7.2 ms, and proved to be independent of concentration. With the most potent bupivacaine time constants of wash in and wash out were 1.8 and 5.2 s for 600 nM bupivacaine. After lowering the extracellular pH from 7.4 to 6.6, externally applied bupivacaine showed a reduced potency, whereas at higher pH of 8.2 the block was slightly enhanced. Intracellular pH of 6.4, 7.2, 8.0 had almost no effect on internal bupivacaine block. It is concluded that local anesthetics block the flicker K+ channel by impeding its gating but not its conductance. The slow blocker bupivacaine and the fast blocker lidocaine compete for the same receptor. Lipophilic interactions are of importance for blockade but besides a hydrophobic pathway, there exists also a hydrophilic pathway to the binding site which could only be reached from the cytoplasmic side of the membrane. Under physiological conditions, blockade of the flicker K+ channel which is more sensitive to bupivacaine than the Na+ channel might lead via membrane depolarization and the resulting sodium channel inactivation to a pronounced block of conduction in thin fibers.

Anesthetics, Local↗
PubMed1995

Serum neopterin concentrations in chronic liver disease.

Neopterin is produced by macrophages after stimulation with interferon gamma or lipopolysaccharide. Its production is increased in many infectious, autoimmune, and malignant diseases. The aim of this study was to examine whether, on the basis of neopterin as a marker, liver diseases could be classified according to aetiology and stage of disease. A cohort of 264 patients with chronic liver diseases (viral, metabolic, autoimmune, toxic) and 150 normal controls were studied; 136 of the patients had cirrhosis. Increased serum neopterin concentrations were found in 41% of all patients (controls 6.0 (2.2) nmol/l), with patients in the cirrhotic stage of disease showing higher neopterin values (mean (SD) 15.7 (23.6) nmol/ml) than those in the non-cirrhotic stage (9.9 (5.5)). There were no statistically significant differences in the serum neopterin concentrations that could be considered characteristic for different stages of disease classified according to the Child criteria. Such differences in concentrations of neopterin that were found in patients with liver diseases grouped according to underlying causes were only marginal. Serum neopterin concentrations were found to be significantly lower than in any other disease group only in patients with Wilson's disease. The results suggest that activated macrophages participate in the development of chronic liver disease. Measurement of serum neopterin does not offer a reliable method for differentiating between various aetiologies of chronic liver diseases and does not help to predict severity of cirrhosis.

Biopterins↗
PubMed1995

Kringle 4 of human apolipoprotein[a] shares a linear antigenic site with human catalase.

Monoclonal antibody (mab) 1A2, directed against human apolipoprotein[a] (apo[a]), revealed a strong reaction with peroxisomes as shown by immuno-gold labeled cryosections of human liver biopsies. This reactivity was not due to the presence of apo[a] in peroxisomes but to a cross-reactivity of mab 1A2. Immunoblot analysis of peroxisomal fractions and purified human catalase demonstrated that mab 1A2 reacts with catalase. Conversely, an anti-catalase antibody also recognized apo[a]. By sequence comparison we identified a 4-amino acid motif (Y-Y-P-N) that is shared between the highly repetitive kringle 4 motif of apo[a] and the carboxy-terminal third of the peroxisomal marker enzyme catalase. No other identical sequences were identified in these proteins. Results from the following experiments indicated that 1A2 recognizes this short linear epitope. i) Mab 1A2 reacted only with the 4 amino acid peptide sequence in a pin-ELISA using immobilized overlapping peptides. ii) A synthetic peptide including this sequence completely inhibited the 1A2 immunoreactivity to apo[a] and catalase. iii) A recombinant fusion protein tagged with the putative epitope was recognized by mab 1A2. Our findings demonstrate that unknown linear epitopes in native proteins can be identified by sequence comparison between known proteins. The practical implication is that antibodies against apo[a] must be controlled for this cross-reactivity before using them for immunohistochemical studies of intracellular apo[a] in tissues or cells.

Amino Acid Sequence↗