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Biomedical subjects

H Denk

Publications and source records attributed to H Denk.

At least 127 records · Page 7Linked to original sources
PubMed1981

Keratin-like proteins in normal and neoplastic cells of human and rat mammary gland as revealed by immunofluorescence microscopy.

Normal and neoplastic human breast tissue as well as lactating and nonlactating rat mammary glands and 7,12-dimethylbenz(alpha)-anthracene-induced mammary adenocarcinomas of rat, were examined by indirect immunofluorescence microscopy using guinea pig antibodies to human and bovine epidermal prekeratin and to cytokeratin polypeptide D from mouse hepatocytes. In normal mammary glands of both species, lactating rats included, the antibodies raised against human and bovine epidermal prekeratins strongly stained ductal and myoepithelial cells, whereas antibodies to hepatic cytokeratin D revealed, in addition, fibrillar staining in cells of the alveolus-like terminal lobular units and in milk secreting cells of the rat. The presence of some finely dispersed intermediate-sized filaments of the cytokeratin type in lactating alveolar cells of rat mammary gland was also demonstrated by electron microscopy. In human intraductal mammary carcinomas the antibodies to epidermal prekeratins showed staining in myoepithelial cells and intralumenal papillary protrusions of the tumor, whereas the antibodies to hepatic cytokeratin D presented an almost complementary pattern in that they showed strongest staining in the more basally located layers of tumor cells. Intraductal adenocarcinomas of rats showed strong staining with all keratin antibodies examined. In contrast to previous studies using exclusively antisera raised against epidermal prekeratin, out results show that all types of neoplastic and non-neoplastic epithelial cells of mammary gland of both species contain-at least some-filaments of the cytokeratin type identifiable by immunologic reaction, if antibodies are used that recognize a broad range of epidermal and nonepidermal cytokeratins. Consequently, such broad range antibodies to keratin-like proteins provide adequate tools to identify and characterize neoplastic and non-neoplastic epithelial cells and to eliminate false negative immunocytochemical findings in tumor diagnosis. In addition, our observation that in the same human carcinoma two cell types can be distinguished by their reaction with two different antibodies to cytokeratins from epidermis and liver, respectively, indicates that the cells of a given carcinoma can differ in their cytoskeletal composition, thus presenting further criteria for diagnostic differentiation.

Adenocarcinoma↗
PubMed1981

Rearrangement of the hepatocyte cytoskeleton after toxic damage: involution, dispersal and peripheral accumulation of Mallory body material after drug withdrawal.

Large cytoplasmic aggregates (Mallory bodies) containing randomly arranged 10 to 20 nm thick filaments are characteristic structures of hepatocytes in certain liver diseases, especially alcoholic hepatitis of man and griseofulvin intoxication of mouse. Biochemical and immunological studies have shown that such Mallory bodies contain structural proteins related to the cytokeratins present in epithelial cells of various kinds, normal hepatocytes included. We have studied the mode of reorganization of the hepatocyte cytoskeleton during involution of Mallory bodies experimentally induced in mice by prolonged griseofulvin feeding after withdrawal of the drug, using immunofluorescence microscopy and electron microscopy. Dispersal of Mallory bodies into small granules accumulating in the hepatocyte periphery is a characteristic feature of Mallory body involution. Dispersed heaps of Mallory body material are seen in hepatocyte cortices at lateral (hepatocyte-to-hepatocyte) as well as at sinusoidal cell surfaces. Mallory body material dispersed to the cell periphery exhibits a filamentous ultrastructure an often shows conspicuous associations with desmosomes. Three different types of desmosome complexes can be discriminated in livers of mice allowed to recover from the intoxication: (i) desmosomes with normally looking bundles of tonofilaments; (ii) desmosomes associated with Mallory body filaments but few, if any, tono-filaments; and (iii) desmosomes lacking tonofilaments as well as Mallory body filaments. The associations between Mallory body filaments and desmosomes during Mallory body involution further strengthen the relationship between Mallory body filaments and tonofilaments. The observations suggest that Mallory body material, at least in part, may be utilized for rearrangement of the hepatocyte cytoskeleton, especially tonofilament-desmosome complexes.

Animals↗
PubMed1981

Effect of Griseofulvin on 5-aminolevulinate synthase and on ferrochelatase in mouse liver neoplastic nodules.

Treatment of mice with griseofulvin for 8 months induced hepatocellular nodules in the liver which persist after discontinuation of griseofulvin feeding. We investigated the porphyrogenic effect of griseofulvin on these nodules and surrounding nonneoplastic liver after renewed short-term exposure of tumor-bearing mice to this agent. Griseofulvin treatment for 4 days led to marked elevation of the activity of 5-aminolevulinate synthase in peritumoral (3.8-fold) and control (6-fold) liver. The increase in enzyme activity was much less pronounced in the nodules (1.5-fold). Ferrochelatase activity was markedly decreased under the same experimental conditions in both peritumoral and control livers (to 18 and 13.5%, respectively, of the pretreatment values), but the effect was considerably smaller in nodules (to 40% of the pretreatment value). These results may explain the lack of porphyrin accumulation in tumor tissue.

5-Aminolevulinate Synthetase↗
PubMed1980

Epithelial blood group antigens in human carcinomas of the distal colon: further studies on their pathologic significance.

Blood group antigen content of human carcinomas located in the distal large bowel (descending colon, sigmoid colon, and rectum) was determined by the specific red cell adherence reaction and was compared to several morphologic features of prognostic significance, e.g., differentiation, extent of tumor spread, peritumoral lymphoplasmocytic infiltration, and growth patterns. About 50% of the carcinomas expressed blood group antigens in either diffuse or patchy distribution. Classification of tumors according to the extent of local spread revealed that 60% of Dukes stage A tumors were blood group antigen-negative, whereas 58% of those in Dukes stage B were positive. Dukes stage C lesions had an intermediate position, and this limits the prognostic usefulness of blood group antigen determinations. No significant correlations were found between blood group antigenicity and the degree of histologic differentiation, the degree of peritumoral lymphoplasmocytic infiltration, and the mode of tumor growth.

Adenocarcinoma↗
PubMed1980

Microsomal mixed-function oxidase and activities of some related enzymes in hyperplastic nodules induced by long-term griseofulvin administration in mouse liver.

Hepatic hyperplastic nodules induced in mice by long-term griseofulvin administration were examined for selected microsomal activities and responses to enzyme inducers. Despite a decrease in microsomal cytochrome P-450 in hyperplastic nodules, aminopyrine N-demethylase was at control levels. Benzopyrene hydroxylase activity was slightly lower in microsomes derived from hyperplastic nodules than in those of control liver. Reduced nicotinamide adenine dinucleotide-cytochrome b5 reductase was at control level, but reduced nicotinamide adenine dinucleotide- and reduced nicotinamide adenine dinucleotide phosphate (NADPH)-cytochrome c reductases and the NADPH-ferricyanide reductase were increased. NADPH-supported lipid peroxidation was lower in microsomes from hyperplastic nodules than in those from control liver, whereas microsomal stearoyl coenzyme A desaturase activity was almost doubled in the nodules. NADPH-cytochrome c reductases isolated and semipurified from hyperplastic nodule and from control liver microsomes showed almost identical affinity for NADPH. Microsomal enzymes of hyperplastic nodules responded readily to phenobarbital induction, but sodium dodecyl sulfate-polyacrylamide gel electrophoresis disclosed differences in the polypeptide patterns in the molecular weight range from 47,000 to 54,000 between microsomes derived from hyperplastic nodules and control livers.

Animals↗
PubMed1979

Effect of protease pretreatment on immunomorphologic demonstration of hepatitis-B-surface antigen in conventional paraffin-embedded liver biopsy material: quantitative evaluation.

The effect of protease pretreatment on the demonstration of hepatitis-B-surface antigen by immunofluorescence (IF) and the unlabeled peroxidase-antiperoxidase technique (PAP) in conventionally processed (formalin-fixed, paraffin-emmbedded) liver biopsy material was quantitatively assessed by microphotometry. Protease digestion significantly enhances the intensity of specific staining by both methods, and, in addition, suppresses non-specific background fluorescence. The sensitivity of the immunomorphologic test is significantly enhanced, and antigen in low amounts, for example hepatitis-B-surface antigen associated with liver cell membrane ('membrane' staining), is easily detected.

Animals↗
PubMed1979

Formation and involution of Mallory bodies ("alcoholic hyalin") in murine and human liver revealed by immunofluorescence microscopy with antibodies to prekeratin.

Antibodies raised against prekeratin intensely and specifically stain, in immunofluorescence microscopy, Mallory bodies ("alcoholic hyalin") present in livers of human alcoholics and griseofulyin-treated mice. The high sensitivity of this method allows the identification of small distinct cytoplasmic structures that are observed during early stages of Mallory body formation, especially frequent in the perinuclear cytoplasm, as well as during stages of Mallory body disintegration and disappearance, such as after withdrawal of the drug. In the latter situation, the prekeratin-containing small particles exhibit a characteristic pattern of arrangement in the hepatocyte periphery. Electron microscopy illustrates that such small bodies are heap-like aggregates of typical Mallory body filaments. Immunofluorescence studies with antibodies to isolated prekeratin polypeptides from bovine hoof or muzzle epidermis show that Mallory body filaments, in particular those in human liver, are immunologically more closely related to prekeratin of tonofilaments from living epidermal cells (stratum spinosum). The data indicate that Mallory bodies contain a pathologic form of prekeratin-like material. They also suggest that disorders of cytoskeletal structures of the intermediate-sized filament class are associated with specific diseases and can be visualized and characterized by immunofluorescence microscopy by using antibodies to constitutive proteins of such filaments.

Animals↗
PubMed1979

Ultrastructural, biochemical, and immunologic characterization of Mallory bodies in livers of griseofulvin-treated mice. Fimbriated rods of filaments containing prekeratin-like polypeptides.

Mallory bodies (MBs) induced in hepatocytes by long term feeding of mice with griseofulvin were isolated, purified, and examined by electron microscopy in ultrathin sections and negatively stained preparations. The major structural component of the MBs was randomly oriented, unbranched rods of filaments; these were usually 175 to 250 nm. long and 14 to 20 nm. thick and covered by a dense fimbriate coat of laterally projecting 1.5- to 3-nm. thick threads. Such lateral threads could extend for more than 20 nm. and seemed to be involved in the interconnection of adjacent filaments and their association and aggregation into MBs. Using sodium dodecyl sulfate-polyacrylamide gel electrophoresis, the purified filament material showed six major polypeptide bands with apparent molecular weights ranging from 48,000 to 66,000. When the portion of the MB filament material that was soluble in solutions containing 8 M urea was allowed to reaggregate upon removal of the urea, an enrichment of one of the polypeptide components (approximate molecular weight, 64,000) was observed. When frozen sections of liver tissue MBs were subjected to indirect immunofluorescence microscopy, they were specifically revealed by guinea pig antibodies directed against purified bovine prekeratin. No significant accumulation of MBs was observed with a series of other antisera, including those containing antibodies against tubulin, actin, and vimentin, the major protein of the intermediate sized filaments predominant in mesenchymal cells. The observations suggest that MBs in livers of griseofulvin-treated mice, and probably also of human alcoholic hepatitis, contain large amounts of prekeratin-like polypeptides which are assembled into a special form of fimbriated rods of 14- to 20-nm. filaments. These filaments are morphologically different from other forms of intermediate sized and thick filaments, including the prekeratin-containing 6- to 11-nm. tonofilament-like filaments present in various epithelial cells.

Animals↗
PubMed1979

[Histotopographic demonstration of hepatitis-B-surface-antigen (HBSAg) in liver-biopsies with the peroxidase-antiperoxidase (PAP)-method in symptomfree HBSAg-carriers].

In 241 paraffin-embedded liver-biopsies of HBSAg-positive, voluntary blood-donors hepacellular HBSAg was demonstrated with the immunomorphologic peroxidase-antiperoxidase (PAP)-method. In all sections, HBSAg-positive liver-cells were estimated, their distribution-pattern was assessed and different types of cytoplasmatic localisation of HBSAg were described. Despite high sensitivity of the PAP-method, 24% of seropostive cases were histologically negative. A correlation of HBSAg-content and histologic diagnosis was lacking. An association of high HBSAg-content with non-aggressive liver-disease and of low HBSAg-content with aggressive liver-disease in a single biopsy could not be found in our material in contrast to the literature. 34 patients were followed up through 4-6 years. Constant or improved liver-histology was associated with increased, deterioration with decreased HBSAg-tissue-content.

Biopsy↗