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Biomedical subjects

H Denk

Publications and source records attributed to H Denk.

At least 145 records · Page 8Linked to original sources

Erythrocyte adherence to the marginal zone of mouse spleen follicle mediated by receptor(s) for neuraminic acid.

Erythrocytes of different species (chicken, sheep, man, mouse, rat, guinea pig) except rabbit erythrocytes strongly adhere to the marginal zone of mouse spleen follicles in frozen sections. This adherence reaction (AR) is not restricted to red blood cells but is also observed with human lymphocytes. Pretreatment of the tissue sections with trypsin, mercaptoethanol, periodate, chloroform/methanol, acetone, and heating the sections abolishes AR whereas neuraminidase (VCN) treatment of the sections has an amplifying effect. AR is inhibited by preincubation of the neuraminidase- or untreated sections with neuraminic acid (NA). Treatment of the erythrocytes with VCN completely abolishes AR whereas treatment with other enzymes (hyaluronidase, collagenase) is ineffective in this respect. Determination of NA in the erythrocyte membrane before and after VCN treatment reveals a positive correlation between the amount of NA and AR. Rabbit red blood cells have the lowest NA content in their membranes and, in addition, there is little effect of VCN treatment in further reducing it. It is possible that a lectin-like substance is responsible for AR. The biologic significance of AR is hypothetical, but since AR occurs in an area of the spleen playing a role in antigen trapping it is conceivable that this trapping may be mediated by interaction of NA and NA receptor(s).

Animals↗

Immunomorphologic methods in routine pathology. Application of immunofluorescence and the unlabeled antibody-enzyme (peroxidase-antiperoxidase) technique to formalin fixed paraffin embedded kidney biopsies.

Immunofluorescence and the unlabeled antibody enzyme (peroxidase - antiperoxidase) method were applied to formalin fixed conventionally paraffin-embedded kidney biopsy material, and optimal working conditions are reported. Both methods were suitable for the demonstration of immunoglobulin and complement deposits within glomerula. They were equally sensitive on dewaxed pronase-treated sections. Pronase treatment decreased nonspecific background fluorescence and increased the sensitivity of both immunomorphologic techniques, possibly by enhancing antigenicity.

Complement System Proteins↗

[Rabies].

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Animal Diseases↗

Colchicine-induced Mallory body formation in the mouse.

Long term griseofulvin treatment of mice results in the development of Mallory bodies (MB), Griseofulvin application apparently "primed" the liver cell for MB formation, and the hepatocytes were then able to respond almost immediately with MB to a griseofulvin challenge even after a 1-month griseofulvin-free period. Colchicine, in contrast to cytochalasin B, also induced MB under these latter experimental conditions. Since intermediate filaments increase in various types of cells in response to antitubulin agents, this observation further supports the hypothesis that MB are related to intermediate filaments.

Animals↗

4-methyl-5-amino-1-formylisoquinoline thiosemicarbazone, a second-generation antineoplastic agent of the alpha-(N)-heterocyclic carboxaldehyde thiosemicarbazone series.

4-Methyl-5-amino-1-formylisoquinoline thiosemicarbazone (MAIQ-1) was studied to determine its potential for clinical trail as a second-generation antineoplastic agent of the alpha-(N)-heterocyclic carboxaldehyde thiosemicarbazone class. MAIQ-1 was shown to be among the most potent known inhibitors of the major target for the expression of antineoplastic activity by this class of agents, the enzyme ribonucleoside diphosphate reductase, requiring only 0.06 micronM for 50% inhibition. This potency at the enzymatic level was consistent with its antineoplastic activity against the murine neoplasms Sarcoma 180, Leukemia L1210, Leukemia P388, and the B16 melanoma. The acetylation of the 5-amino group of the model substrate 5-amino-1,4-dimethylisoquinoline was lower than that of 5-amino-1-methylisoquinoline when incubated with acetyl-coenzyme A and rat liver homogenate. This finding suggests that the presence of the 4-methyl function offers steric hinderance to enzymatic substitution of the adjacent 5-amino group. In vivo metabolism of MAIQ-1 in mice, studied with [3'-14C]MAIQ-1 showed that relatively slow excretion of this agent occurred, since the cumulative urinary excretion of radioactivity was only 35% in 48 HR. About 51% of excreted urinary radioactivity was present in chromatograms in an area corresponding to the iron chelate of MAIQ-1, and only a minor quantity of material migrating like acetylated MAIQ-1 was present in urine, a finding consistent with enzymatic data with liver homogenates. The results indicate that MAIQ-1 has the antineoplastic activity, enzyme inhibitory potency, and relative resistance to metabolic inactivation required of an agent of this class for clinical trials.

Animals↗

[Metabolism of hypnotic and sedative drugs in cholestasis (author's transl)].

Alterations of hepatic microsomal biotransformation in cholestasis were discussed. In experimental animals biotransformation of hypnotic and sedative drugs is impaired under cholestatic conditions in vivo. The endplasmic reticulum of the hepatocytes is hypertropic but is hypoactive with respect to drug metabolism, a condition which is partly due to interference to substances retained in cholestatic livers (bile salts) with drug biotransformation and to cytochrome P-450 diminution in the microsomal membranes. The activity of conjugating enzymes (phase II of biotransformation) remains unaffected. A similar situation exists in cholestatic patients in which drug elimination is altered. In vitro studies with human liver homogenate, microsomes, and liver slices confirm the animal experiments by showing that cytochrome P-450 as well as the metabolism of hypnotics are reduced in cholestasis.

Animals↗