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Biomedical subjects

L Müller

Publications and source records attributed to L Müller.

At least 145 records · Page 8Linked to original sources
PubMed1986

Consequences of cadmium toxicity in rat hepatocytes: effects of cadmium on the glutathione-peroxidase system.

Cadmium (Cd; 10-100 microM) produced in isolated hepatocytes the formation of thiobarbituric acid-reactants (lipid peroxidation; LPO) and a decrease in SH groups in a time- and concentration-dependent manner. However, glutathione peroxidase (GSH-Px) was not affected indicating that LPO does not originate from GSH-Px injury. In contrast, in presence of Cd a time- and concentration-dependent decrease of glucose-6-phosphate dehydrogenase (G6PDH) and, most strongly, of glutathione reductase (GSSG-R), both members of the GSH-Px system, was observed. These effects could not be inhibited by (+)-cyanidanol-3, a compound known as inhibitor of LPO. Therefore, our data show that Cd-induced LPO is not a function of GSH-Px injury and inhibition of GSSG-R and G6PDH-activity is not a function of LPO. They also indicate that Cd-induced depletion of cellular SH groups are associated with toxic effects of Cd on GSSG-R and G6PDH different from LPO-induction.

Animals↗
PubMed1986

Cell cycle-dependent initiation of adenosine triphosphatase-deficient populations in adult rat liver by a single dose of N-methyl-N-nitrosourea.

Changes in the sensitivity of hepatocytes to initiation during the cell cycle were investigated in partially resected hydroxyurea-synchronized regenerating rat liver. At defined periods of the cell cycle the animals were given injections of a single dose of N-methyl-N-nitrosourea (MNU) (25 mg/kg) and were subsequently exposed to diethylnitrosamine for 30 days (2 mg/kg/day) or to phenobarbital (0.05% in the diet) for 80 days. Adenosine triphosphatase-deficient cell populations in the liver, determined 90 days after MNU treatment, served as a marker for the initiating action of the carcinogen. Few foci were observed when MNU treatment was performed during early G1. Their frequency increased steeply after MNU injection at G1-S boundary and reached a maximum after carcinogen exposure in early S phase, when the number of adenosine triphosphatase-deficient foci was higher by a factor of 5 (after diethylnitrosamine feeding) or 10 (after phenobarbital feeding) than after MNU exposure in early G1 phase. A rapid decline was observed in middle S phase. The frequency of altered foci after MNU in late S phase and during G2-M was in the same range as in early G1. Their size distribution was similar in all groups. The results confirm and extend earlier observations of an increased initiating effect of a carcinogen during liver regeneration. Under in vivo conditions, hepatocytes are, after HU synchronization, at the highest risk of being initiated by a carcinogen when they traverse the early S phase of the cell cycle.

Adenosine Triphosphatases↗
PubMed1985

Cell proliferation and DNA repair in the liver during early stages of chemical carcinogenesis.

X-chromosomal phosphoglycerate kinase mocaicisms in organ samples of female heterozygous mice provided a means to prove, because of a selective expression of one of the two allozymes, the clonal origin of carcinogen-induced preneoplastic hepatocellular populations (see also ref. 61). The occurrence of these clonal preneoplastic foci was used in rats to determine cell cycle dependent differences of transformation sensitivity and DNA repair. The highest transformation rate was found after carcinogen exposure in late G1/early S phase of the cell cycle. Experimental disturbance of DNA precursor pools by continuous thymidine infusion during carcinogen exposure results in an increased formation of preneoplastic clones. This is a further argument in favor of an essential role of base-mispairing during initiation. Cell cycle dependent fluctuations of O6-methylguanine DNA transferase with an increasing enzyme activity in late G1 and a maximum in early S phase indicate that cells possess an increased potential for eliminating promutagenic O6-methylguanine during the most transformation sensitive parts of the cell cycle to prevent base-mispairing during DNA replication or transcription. However, this putatively protective effect is limited because the enzyme is rapidly expended in the reaction and drops again in later stages of the cell cycle.

2-Acetylaminofluorene↗
PubMed1985

Regional and cellular differences in fucosylation of glycomacromolecules in the mouse brain. A biochemical and autoradiographic study of early postnatal and adolescent animals.

Mice of CBA strain of both sex were injected with [3H]fucose at age 2, 6, 12 or 30 days and the incorporation was determined biochemically 45, 90 and 180 min later. Biochemical measurements of the whole brain (at 90 min postinjection interval) revealed a stepwise age decrease in the amount of incorporated isotope (per mg protein). The amount of [3H]fucose available in the brain has however been found to decrease with age while the degree of its utilization increases. Thus, after correction of the data on [3H]fucose incorporation for the pool of the free isotope, a transient increase in fucosylation rate appeared at postnatal day 12 while the differences among 2-, 6- and 30-day-old animals became negligible. Further, the synthesis of fucosylated soluble glycomacromolecules appeared relatively higher at postnatal day 2 than in older age groups. Examination of different brain regions revealed that the rate of fucosylation is relatively highest in the olfactory bulbs; this prevalence starts appearing with age and becomes most evident in 30-day-old mice. Autoradiography carried out with 6- and 12-day-old animals revealed that the incorporation of [3H]fucose into meningovascular apparatus and the choroid plexus is a few times higher than into brain parenchyma. The regional differences appeared to be similar to those indicated by the biochemical data. Cellular analysis has shown that the incorporation is relatively higher in the cytoplasm of large projecting neurons of the cerebellum, hippocampus and the olfactory bulbs; in the latter region high amounts of macromolecule-bound [3H]fucose also appeared in the synaptic glomeruli.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1985

Alpha-fetoprotein in the brain of embryonic pigs.

Alpha-fetoprotein (AFP) has been screened in the brain of pig embryos by immunocytofluorescence, crossed immunoelectrophoresis and the immunoblotting technique. Immunocytochemistry showed that the cell and tissue localization of AFP changes with age of the embryos, and/or maturation of the brain. At the earliest stages studied (embryonic days (ED) 26 to 28), the AFP in the brain prevails near the cerebral ventricles, while later (ED 35-46) AFP also appears in higher concentrations in the differentiating parenchyma of some regions of the brain (especially in deep layers of the cortical plate or the region of the differentiating hippocampus) and spinal cord. Its intracellular presence was well evident in the large neuroblasts of these regions. During the 3rd month of embryonic life AFP starts to disappear from the brain parenchyma. At all ages studied, bright fluorescence in the choroid plexus and the meningovascular apparatus is evident. In the choroid plexus as well as ependymal cells a mosaic-like pattern of fluorescence appeared, especially near its invagination into the lateral ventricles; the latter suggests transependymal transport of AFP by some cells. Single and crossed immunoelectrophoresis revealed one reacting band in the water extract of homogenate of the brain of 35-day-old pig embryos. Similarly, only one band has been stained in SDS electrophoretograms prepared from such extracts and stained by the immunoblotting technique; its molecular weight corresponded to the pig AFP. In contrast to the brain the AFP band in the liver was also found in the membrane fraction. It is concluded that maximal tissue concentrations of AFP in the pig brain are attained during the second embryonic month and that, in addition to extracellular fluids, it is also transitionally present in the cytoplasmic compartment of brain cells, especially those more advanced in maturation.

Animals↗
PubMed1985

Lectin binding sites and anionic components related to differentiation in the prenatal rat cerebral cortex.

The location of lectin binding sites and of anionic components was studied in the embryonic rat cerebral cortex after the formation of the cortical plate at embryonic day 18. The cortical layers advanced in differentiation, i.e. the sub-plate region and the marginal zone, showed a predominant staining with peroxidase conjugates of wheat germ agglutinin (WGA), peanut agglutinin (PNA), and after immunocytochemical detection of PNA binding sites. This pattern was obtained also with the colloidal iron hydroxide staining method. In contrast to this, the binding of concanavalin A and of succinylated WGA did not reveal a prevalent staining of the sub-plate region and the marginal zone. The further histochemical analysis of the substances responsible for the selective staining of these layers was performed by lipid extractions and by enzymatic treatment of the tissue sections with trypsin, hyaluronidase or neuraminidase prior to the binding of lectins or colloidal iron. The results obtained indicated high concentrations of sialylated galactosylglycoproteins in coexistence with glycosaminoglycans. Electron microscopy was performed with peroxidase conjugates of WGA and PNA. Binding sites of both of the lectins in the sub-plate region and in the marginal zone were located mainly at cell surfaces of the different cellular structures. The most intensive binding of WGA and PNA was detected at the surface membranes and at intracellular material of amoeboid microglial cells and astrocyte-like cell processes. It can be concluded that in distinct brain areas during early differentiation specific glycoproteins in coexistence with glycosaminoglycans are situated at, or associated with cell surfaces in high concentrations. The identical histochemical features previously described in mesenchymal tissues suggest that these glycoconjugates might be related to common morphogenetic processes in which non-neuronal cells of brain and body are specifically involved.

Animals↗
PubMed1984

Differences in the distribution of methyl mercury in erythrocytes, plasma, and brain of Japanese quails and rats after a single oral dose.

Distribution of a single oral dose of methyl mercury (10 mg Hg/kg body weight) was followed from 90 min up to 120 h in plasma, erythrocytes, and brain of Japanese quails and rats. Significantly higher Hg concentrations were observed in plasma and brain of quails and red blood cells of rats. Blood/brain ratio decreased in quails from 6 to 2 at 24 h and 120 h respectively, whereas it increased in rats. Erythrocyte/plasma ratio in quails was about three times lower and averaged 54. The differences in Hg distribution were accompanied by a more than 3-fold higher acute toxicity in quails under adequate experimental conditions.

Animals↗
PubMed1984

The occurrence of long chain alpha, omega-diols in the lipids of steer and human meibomian glands.

A group of long chain alpha, omega-diols (C29 to C34) has been identified in the lipids of steer and human meibomian gland excreta (meibum). These new lipids were isolated from the steer meibum unsaponifiables. Proof of structure was provided by 1) the column chromatographic behavior and TLC of the diols and their diacetates; 2) GLC on glass capillary columns; 3) fragmentation patterns in GC-MS; 4) NMR data, and 5) ozonolysis studies of the unsaturates. Chain types for the steer sample were 51% straight monoenes, 8.5% straight saturates, 39% iso and anteiso saturates and 1.5% iso and anteiso unsaturates. GC for the human sample gave straight monoenes 83%, straight saturates 8%, and iso plus anteiso saturates 9%. Close correspondence of the alpha, omega-diol chain lengths and types with meibum omega-hydroxy fatty acids suggests a biochemical precursor relationship.

Animals↗
PubMed1984

Cadmium-induced alteration of the energy level in isolated hepatocytes.

The incubation of isolated hepatocytes with 10-100 microM cadmium (Cd) decreased the ATP/ADP-ratio, the ATP/AMP-ratio and the adenylate energy charge and enhanced the lactate/pyruvate-ratio in a time- and concentration-dependent manner. Likewise, the cellular oxygen-consumption was decreased at early incubation times, when the cell membrane was still intact, as judged by the Trypan Blue-exclusion test. Similarly, Cd-concentrations above 0.3 nmol/mg mitochondrial protein inhibited the succinate- and malate/pyruvate-stimulated respiration of isolated mitochondria. This critical concentration was also reached in mitochondria of hepatocytes, when exposed to 25 microM Cd for less than 30 min. We therefore suggest that the inhibition of cellular respiration and the breakdown of cellular energy generation is mediated by a severe disturbance of mitochondrial respiratory functions due to Cd. This effect seems to be an early event in Cd-toxicity in isolated hepatocytes.

Adenine Nucleotides↗
PubMed1984

Differential sensitivity of integrity criteria as indicators of cadmium-induced cell damage.

The reliability of the stainability by Trypan Blue (TB) to detect membrane damage in hepatocyte suspensions of different TB stainability and in freshly isolated cells exposed to 50 microM cadmium (Cd) for 60 min was assessed by comparison with the leakage of lactate dehydrogenase (LDH) and NADH-oxidation. The cellular nitrophenyl-phosphate (NPP) uptake and the digitonin-induced fluorescence of 8-anilinonaphthalene-sulfonate-1 (dig-ANS-F) were introduced as integrity parameters of hepatocytes and compared with TB stainability. Cd was without effect on all these parameters. LDH-leakage was a poor criterion, whereas NADH-oxidation and dig-ANS-F were as sensitive as TB stainability. The NPP-uptake was more sensitive than TB stainability to indicate toxic Cd-effects when the plasma membrane still seemed to be intact. Because of the enhanced extracellular NPP-degradation, which resulted from the release of alkaline phosphatase, NPP-uptake was useful as a measure of Cd-induced damage only under certain conditions. These results confirm TB stainability as a simple and reliable criterion for plasma membrane integrity and therefore viability of hepatocytes also in Cd-toxicity.

Anilino Naphthalenesulfonates↗
PubMed1984

Inhibitors of the rate of carbohydrate and lipid absorption by the intestine.

The rate of energy storage in adipose tissues is, at least in part, dependent on the concentration of nutrients and hormones in the blood. A delayed absorption of ingesta from the intestine should cause lower concentrations of fat, glucose and insulin and, thus, reduce the triglyceride storage rate. Non-selective agents retard the absorption irrespective of composition of food. Inhibitors of intestinal alpha-glucosidases delay the degradation of complex carbohydrates to absorbable monosaccharides and thus decrease the rate of their absorption. Inhibitors of pancreatic lipase interfere with the degradation of dietary triglycerides and decrease the postprandial triglyceride increment in blood and tissues. Recently a compound was found which inhibits the absorption of carbohydrates as well as triglycerides.

Acarbose↗
PubMed1983

A method for the dissection of the embryonic cerebral cortex into individual layers. An application to biochemical studies of glycan metabolism.

A method is presented for the isolation of defined cerebral cortical layers from the prenatal rat brain. By this procedure cells at different stages of proliferation and/or differentiation can be obtained as relatively homogeneous populations. The principle of the proposed isolation procedure consists of freezing the isolated embryonic brain in a mould which flattens the two hemispheres. The different cortical layers are then isolated by carefully cutting serial cryostat sections. On embryonic day 16 (ED 16), 3 individual layers could be sampled from the cortex: the marginal zone, the zone of DNA synthesis and the mitotic region of the ventricular germinative zone. On ED 18 and ED 20, a further 3 layers could be isolated: the cortical plate, the sub-plate region, and the intermediate zone. As an example of an application of the isolation procedure for biochemical studies, maturation-dependent changes in the protein and Concanavalin A-binding glycoprotein patterns together with the activity of beta-N-acetylglucosaminidase in the different cortical layers of the embryonic brain are demonstrated at different stages of brain development.

Acetylglucosaminidase↗
PubMed1983

Influence of paracetamol (acetaminophen) on cadmium-induced lipid peroxidation in hepatocytes from starved rats.

Isolated hepatocytes form thiobarbituric acid (TBA)-reactants, a parameter of lipid peroxidation (LPO), when exposed to cadmium (Cd). Paracetamol (Para) inhibits this response, dependent on time and concentration. Cd-induced SH-group decline, however, and enhanced plasma membrane permeability to Trypan Blue (TB) were not inhibited by Para. This indicates that Cd-induced cell damage and Cd-induced LPO are independent events. Experiments using cells with enhanced and lowered metabolism of Para after phenobarbital- and acetone- or heat-and metyrapone treatment, respectively, suggest a potentially inhibitory effect of both Para and its metabolite(s) on LPO. The antioxidative potency of Para turned out to be small compared to that of the radical scavenger (+)-cyanidanol-3.

Acetaminophen↗
PubMed1983

Termination of geniculocortical afferents on bipolar neurons in area 17 of the albino rat: a Golgi/EM study.

Degenerating terminals of specific afferents to the primary visual cortex of the albino rat were identified by electron microscopy after electrolytic lesions of the lateral geniculate nucleus. Bipolar neurons were marked by Golgi impregnation. We observed smooth dendrites of two bipolar cells postsynaptic to degenerating geniculate terminals. We conclude that this cortical cell type is directly contacted by thalamic afferents.

Animals↗
PubMed1983

Geniculocortical synapses involving apical dendrites of layer V pyramidal cells in area 17 of the albino rat visual cortex: a combined Golgi/EM study.

Using the combined Golgi/EM technique (Fairén et al. 1977) we have investigated whether apical dendrites of layer V pyramidal cells with different diameters receive different numbers of geniculocortical synapses. An electrolytic lesion was made in the lateral geniculate nucleus (LGN) of albino rats. After a survival time of two days degenerating boutons of LGN afferents onto visual cortex (area 17) were identified by electron microscopy. Postsynaptic layer V pyramidal cells marked by Golgi impregnation were studied. The location of nine identified pyramids was determined by light microscopy. The diameter of the apical dendrites - ranging from 0.9 to 2.5 mum - was measured on electron micrographs. The dendrites of eight out of the nine pyramids make synaptic contacts with geniculocortical afferents in layer IV and lower layer III. The degenerative geniculocortical terminals were mostly of the electron dense type; one times the electron lucent type was observed. These axon terminals synapse mainly with asymmetrical synaptic junctions on spines. Occasionally synaptic contacts were found on dendritic shafts. Most degenerating synapses are localized on the pyramidal cell with the thinnest apical dendrite. There was also an other thin apical dendrite, which did not receive any degenerating bouton. All out of one apical dendrites of different size are involved in geniculocortical synapses without giving any preference to dendrites of a defined diameter.

Animals↗