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Biomedical subjects

W Stäubli

Publications and source records attributed to W Stäubli.

At least 37 records · Page 2Linked to original sources
PubMed1984

Inhibitory effect of nafenopin upon the development of diethylnitrosamine-induced enzyme-altered foci within the rat liver.

The effect of nafenopin and phenobarbitone upon the distribution of gamma-glutamyltranspeptidase activity and epoxide hydrolase antigenic sites in the liver and upon the development of enzyme-altered foci during hepatocarcinogenesis have been compared. Phenobarbitone induced gamma-glutamyltranspeptidase activity in perilobular hepatocytes. Nafenopin did not alter the distribution of this enzyme. Both compounds appeared to induce epoxide hydrolase; phenobarbitone increased the enzyme content of centrilobular cells, whilst nafenopin altered immunostaining mainly in portal regions. Hepatic lesions were induced by treating one day-old rats with diethylnitrosamine. Phenobarbitone and nafenopin were then administered in the diet upon weaning. Animals were killed after either 2, 4 or 8 weeks feeding and liver sections were stained for the two enzymes. Only sections from nitrosamine-treated animals contained enzyme-altered foci. In general, gamma-glutamyltranspeptidase-containing foci stained also for epoxide hydrolase; but many hydrolase-positive foci did not stain for gamma-glutamyltranspeptidase activity. Phenobarbitone treatment stimulated the formation of enzyme-altered foci. This effect was more marked in male animals. Nafenopin treatment suppressed the development of foci at all time points, such that less hepatic lesions were seen than in animals which received only diethylnitrosamine. The results cast doubt upon the generality of gamma-glutamyltranspeptidase as a marker for preneoplastic lesions within the liver.

Animals↗
PubMed1984

Use of primary cultures of adult rat hepatocytes to investigate mechanisms of action of nafenopin, a hepatocarcinogenic peroxisome proliferator.

The effect of nafenopin upon primary cultures of adult rat hepatocytes has been investigated. Nafenopin treatment resulted in a proliferation of peroxisomes within the cultured cells. This proliferation was the result of an increase in both the number and size of the peroxisomes. Nafenopin treatment also caused an increased level of thymidine incorporation into the cultures, which was a consequence of replicative DNA synthesis rather than DNA repair. Finally, nafenopin appeared to delay the appearance of gamma-glutamyltranspeptidase activity within the cultured cells. Consequently three effects of nafenopin upon the liver were reproduced using monolayers of adult rat hepatocytes, which suggests that this culture system may be useful to further investigate the molecular processes underlying peroxisome proliferation, and their involvement in the hepatocarcinogenicity of peroxisome proliferators.

Animals↗
PubMed1983

Epoxide hydrolase activity in isolated peroxisomes of mouse liver.

Using trans-stilbene oxide as substrate, the subcellular distribution of epoxide hydrolase was investigated in livers from DBA/2 mice. The highest specific activities were found in cytosolic and light mitochondrial fractions. Isopycnic subfractionation of the light mitochondrial fraction showed that the organelle-bound trans-stilbene oxide hydrolase is localized in peroxisomes.

Animals↗
PubMed1982

Immuno-electron-microscopic studies on the subcellular distribution of rat liver epoxide hydrolase and the effect of phenobarbitone and 2-acetamidofluorene treatment.

The distribution of rat liver epoxide hydrolase in various subcellular fractions was investigated by immuno-electron-microscopy. Ferritin-linked monospecific anti-(epoxide hydrolase) immunoglobulins bound specifically to the cytoplasmic surfaces of total microsomal preparations and smooth and rough microsomal fractions as well as the nuclear envelope. Specific binding was not observed when the ferritin conjugates were incubated with peroxisomes, lysosomes and mitochondria. The average specific ferritin load of the individual subcellular fractions correlated well with the measured epoxide hydrolase activities. This correlation was observed with fractions prepared from control, phenobarbitone-treated and 2-acetamidofluorene-treated rats.

2-Acetylaminofluorene↗
PubMed1982

Purification and characterization of a soluble epoxide hydrolase from rabbit liver.

A method for the extensive purification of rabbit liver cytoplasmic epoxide hydrolase is described. The end-product, which was purified 550-fold with respect to the cytosolic fraction, appeared to be more than 85% pure. Results indicate that the enzyme is a dimer of molecular weight 110 000 and consists of two subunits, which are identical or very similar (Mr 57 000) and possess N-terminal serine. Evidence for the existence of aggregates of higher molecular weight was also obtained. The catalytic properties of the cytoplasmic enzyme with styrene oxide as substrate (Km = 3.4 mM; V = 3480 nmol mg-1 min-1) differed markedly from the values published for the microsomal hydrolase.

Amino Acids↗
PubMed1979

In vivo and in vitro studies on endothelial regeneration.

Endothelial regeneration was studied in rabbit aorta after intra-arterial balloon catheterization. Most of the regenerated endothelium originated from existing branches which was assessed by the Evans-blue uptake pattern and confirmed by transmission and scanning electron microscopy. Glucocorticoid treatment enhanced re-endothelialization whereas hyperlipemic diet inhibited. Sera from minipigs fed an atherogenic diet consistently have less ability than sera from control pigs to stimulate in vitro the regeneration of wounded endothelium-like monolayers of 3T3-B cells. The deficiency is probably due to an inhibitor which appears and disappears with changes in the diet.

Animals↗
PubMed1977

The proliferative response of hepatic peroxidomes of neonatal rats to treatment with SU-13 437 (nafenopin).

The repeated administration of the hypolipidemic agent Su-13 437 (nafenopin) to neonatal rats roughly doubled the number of peroxisomes in the liver tissue and caused a sixfold volumetric expansion of the peroxisomal compartment. During the proliferative response, the size-distribution of the peroxisomes was reversibly altered, enlarged particles appearing in numbers varying according to the dose given. By means of a new method for quantitative autoradiography, it was shown that (a) the concentration of silver grains over peroxisomes was comparable to that found over the endoplasmic reticulum; (b) the peak incorporation of [3H]arginine into the peroxisomes was dealyed in comparison with that into the endoplasmic reticulum; (c) the label, once incorporated into the expanding peroxisomal compartment, displayed the same shift to large particles as did the whole population. These results are compatible with the biosynthetic pathway for peroxisomal catalase proposed earlier (cf. reference 12), and with the notion that the drug-induced size-shift might have resulted from progressive growth of a particular class of peroxisomes formed in the presence of the agent. Evidence is presented to show that during the recovery period the larger peroxisomes are removed preferentially.

Animals↗
PubMed1969

Correlated morphometric and biochemical studies on the liver cell. I. Morphometric model, stereologic methods, and normal morphometric data for rat liver.

The basic morphological properties of liver cells are defined in the form of a morphometric model to permit integrated quantitative characterization of functionally important parameters. Stereologic methods which allow efficient and reliable quantitative evaluation of sectioned liver tissue are presented. Material, obtained by a rigorous three-stage sampling procedure from five normal rat livers, is systematically subjected to this analysis at four levels of magnification. This yields quantitative data which are expressed as "densities," i.e. content per 1 ml of tissue, as "specific dimensions" related to 100 g body weight, and as absolute dimensions per average "mononuclear" hepatocyte. Base line data relating to the normal rat liver are presented for the entire spectrum of parameters. As examples, 1 ml of liver tissue contains 169 x 10(6) hepatocyte nuclei, some 90 x 10(6) nuclei of other cells, and 280 x 10(9) mitochondria. Hepatocyte cytoplasm accounts for 77% of liver volume, and the mitochondria for 18%. The surface area of endoplasmic reticulum membranes in 1 ml of liver tissue measures 11 m(2) of which are (2/3) of the rough form carrying some 2 x 10(13) ribosomes. The surface area of mitochondrial cristae in the unit volume is estimated at 6 m(2). The validity and applicability of the method are discussed, and the data are compared with available information from other studies.

Animals↗
PubMed1969

Correlated morphometric and biochemical studies on the liver cell. II. Effects of phenobarbital on rat hepatocytes.

The changes occurring in rat hepatocytes during a 5 day period of treatment with phenobarbital were determined by morphometric and biochemical methods, particular attention being paid to the endoplasmic reticulum. The hepatocytic cytoplasm played an overwhelming part in the liver hypertrophy, while the hepatocytic nuclei contributed to only a moderate extent. The endoplasmic reticulum accounted for more than half of the increase in cytoplasmic volume. The increase in the volume and number of hepatocytic nuclei in the course of phenobarbital treatment was associated with changes in the ploidy pattern. Until the 2nd day of treatment both the rough-surfaced endoplasmic reticulum (RER) and the smooth-surfaced endoplasmic reticulum (SER) participated in the increase in volume and surface of the whole endoplasmic reticulum (ER). Subsequently, the values for RER fell again to control levels, whereas those for SER continued to increase, with the result that by the 5th day of treatment the SER constituted the dominant cytoplasmic element. The specific volume of mitochondria and microbodies (peroxisomes) remained constant throughout the duration of the experiment, while that of the dense bodies increased. The specific number of mitochondria and microbodies displayed a significant increase, associated with a decrease in their mean volume. The phenobarbital-induced increase in the phospholipid and cytochrome P-450 content of the microsomes, as well as in the activities of microsomal reduced nicotinamide-adenine dinucleotide phosphate-cytochrome c reductase and N-demethylase, was correlated with the morphometric data on the endoplasmic reticulum.

Animals↗