[Ultrastructure of liver damage in chronic vinyl chloride intoxication (author's transl)]. / Die Ultrastruktur der Leberschädigung bei der chronischen Vinylchlorid-Intoxikation

Liver biopsies taken from 15 workers at a PVC-producing factory were examined by electron microscopy. The hepatocytes showed focal hydropic swelling, disseminated toxic steatosis, peculiar para-crystalline inclusions in enlarged mitochondria, focal cytoplasmic degradations, and occasional single cell necroses. These regressive changes were more prominent in cases with a shorter interval of non-exposure prior to the biopsy. Further, a focal compensatory hyperplasia of the smooth endoplasmatic reticulum was found. With increase of the non-exposure time interval, a regression of the degree of steatosis as well as an age-independent excessive lipofuscin deposition was seen in the hepatocytes. Apparently, these are sequelae of increased autophagia of lipids and increased lipid oxidation by the vinylchloride. In the sinusoids, activation, enlargement and proliferation of Kupffer cells was noted. The tendency of these cells to proliferate is apparently caused by the cancerogenic stimulation by vinylchloride. The prominent hyperplasia of lipocytes is probably connected with the deposition of collagen and the peculiar perisinusoidal fibrosis.

[Investigations with 3H-thymidine and electron microscopical studies in rat livers following thermocoagulation of the thoracic duct at the base of the neck (author's transl)]. / Autoradiographische und elektronenmikroskopische Untersuchungen an der Rattenleber nach experimenteller Blockade des Ductus thoracicus in Höhe des linken Venenwinkels

Autoradiographic studies with 3H-thymidine were done in 90 male and female white Sprague Dawley rats following thermocoagulation of the thoracic duct at the base of the neck. In the acute stages of these experiments we were unable to find any significant influence of a lymphedema on the hepatocytes and Kupffer cells. In the longterm experiments the labelling indices of the hepatocytes were slightly above those of healthy controls of the same age. In another 14 male and female white Sprague Dawley rats we did electron microscopical investigations of the liver. In the acute phase of the experiment we found an intra- and extrahepatic edema as well as damages of the hepatocytes at the periphery of the liver acini. After 12-15 days these findings have regressed. It seems therefore that an intrahepatic lymphedema does not influence the regenerative capacity of the liver to a marked extent.

Uptake of cortisol by isolated rat liver cells. A phenomenon indicative of carrier-mediation and simple diffusion.

The uptake of cortisol by isolated rat liver cells was studied. Cortisol was taken up rapidly; the uptake increased with increasing temperature and reached a plateau after 45 s at 37 degrees, C, after 60 s at 27 degrees C, and after 90 s at 22 degrees C; at 5 degrees C the uptake increased linearly with time. The uptake was linear up to 1.5 mg of cell protein. Analysis of uptake as a function of increasing concentration of cortisol in the external medium indicated the presence of two saturable systems: a high-affinity system with an apparent Km value of 190 +/- 25 nM and a low-affinity system with an apparent Km value of 2200 +/- 180 nM. Above 600 nM, the rate of uptake of cortisol increased almost linearly with increasing cortisol concentration. Treatment of cells with KCN or 2,4-dinitrophenol inhibited the two saturable components, leaving the nonsaturable system unaffected. The affinity constants, Ka, were 6 X 10(6) M-1 and 0.6 X 10(6) M-1 for the high and low affinity components, respectively. These values increased approximately two-fold when uptake rates were corrected for diffusion. Cortisone and corticosterone inhibited the uptake of cortisol by liver cells competitively; dexamethasone inhibited cortisol uptake noncompetitively. Similarly, oestrone, oestradiol and testosterone decreased the uptake of cortisol, at a concentration of 2000 nM in the external medium, by 20, 49 and 35 percent, respectively; the inhibition was noncompetitive. p-Chloromercuribenzoate, N-ethylmaleimide and 1-fluoro-2,4-dinitrobenzene decreased the uptake of cortisol. Ouabain did not influence the uptake of cortisol; varying the external sodium concentration also did not affect uptake of cortisol. Cyclic-3',5'-adenosine monophosphate had a stimulatory effect. The results show that the first step, before cortisol is bound to intracellular binding proteins, is the uptake of cortisol by proteins in the plasma membrane. At lower concentrations of cortisol, uptake takes place by saturable processes; at higher concentrations saturation is not achieved, indicating that simple diffusion becomes the major route of transport into the cell. The proteins in the plasma membrane probably function as carriers to transport the glucocorticoid into the cell.

[Alpha-antitrypsin deficiency in infancy]. / Alpha1-Antitrypsin-Mangel im Säuglingsalter. Klinische, biochemische, morphologische, immunhistochemische und genetische Befunde bei zwei Säuglingen

Clinical, histological (including electron-microscopic), immunohistochemical and genetic studies were performed on two infants with alpha1-antitrypsin deficiency. The clinical picture was one of neonatal biliary stasis. Liver biopsies revealed multiple cytoplasmic acidophilic bodies within many cells of the liver parenchyma which were strongly periodic acid-Schiff-positive, diastase-resistant and stained selectively with fluorescein-labelled rabbit antihuman alpha1-antitrypsin. Ultrastructurally, the bodies were situated within enlarged cisterns of the endoplasmatic reticulum. Both infants were of the protease inhibitor (Pi) phenotype ZZ, having inherited on PiZ gene from each parent. Results of Pi typing of both families were consistent with an autosomal co-dominant inheritance. Both infants are clinically well except for slight hepatomegaly at one year of age. But transaminase and gamma-glutamyl transpeptidase activities have remained elevated.