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Biomedical subjects

W Horn

Publications and source records attributed to W Horn.

At least 19 recordsLinked to original sources
PubMed1991

General pharmacology, toxicology and future clinical development of HOE 077.

The prolylhydroxylase inhibitor HOE 077 which has proven to be liver-selective in animals was tested in general pharmacological and toxicological studies for unwanted effects and safety. The results of these studies permit clinical development. A single-dose study in healthy volunteers was performed which showed that kinetics and main metabolites in man were similar to those found in animals. Aspects of the future clinical development of HOE 077 are discussed.

Animals↗
PubMed1989

Paradoxical effects of retinal in neutrophil stimulation.

Retinal stimulates the activity of phospholipase C and superoxide (O2-) release in neutrophils. The latter response is comparable in magnitude to that observed when phorbol 12-myristate 13-acetate (PMA) is the stimulating agent. Cells treated with retinal, however, do not undergo degranulation, nor do they exhibit the formation of intracellular vesicles, as is commonly observed with other agents (e.g. Lochner, J. E., Badwey, J. A., Horn, W., and Karnovsky, M. L. (1986) Proc. Natl. Acad. Sci. U. S. A. 83, 7673-7677). Retinal promotes redistribution of the activity of protein kinase C from a soluble to a particulate fraction in neutrophils, and this redistribution precedes O2- release. Superoxide release stimulated with retinal, however, is largely insensitive to inhibitors of protein kinase C (1-(5-isoquinolinylsulfonyl)-2-methylpiperazine (H-7); staurosporine). These compounds substantially block both O2- release and the phosphorylation of two proteins with molecular masses of about 47 and 49 kDa when the stimulus is PMA. The data indicate that retinal and PMA elicit the formation of active protein kinase C complexes of different natures, or that the mechanism of stimulation of O2- release by retinal does not involve this kinase. The significance of these observations to the common use of retinoids as inhibitors of protein kinase C is discussed.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed1989

[Increase of oxygen partial pressure and acceleration of wound healing by tetrachlorodecaoxide].

63 transcutaneous measurements of oxygen pressure and 36 series of infrared thermograms in 9 hypoxic wounds showed that topical administration of tetrachlorine decaoxide (TCDO) results in increased oxygen supply of the wound. This effect is associated with improvement of the skin temperature and decrease of the pathological temperature difference between the wound and the surrounding tissue. TCDO can induce physiological wound healing, since it improves the mechanisms of the immune defence system, wound cleansing, granulation, and epithelialization in slow-healing wounds.

Adult↗
PubMed1988

Synergistic stimulation of neutrophils. Possible involvement of 5-hydroxy-6,8,11,14-eicosatetraenoate in superoxide release.

Neutrophils stimulated with optimal amounts of tumor-promoters that activate protein kinase C (e.g. mezerein, phorbol 12,13-dibutyrate) are known to release large quantities of superoxide: approximately 40-50 nmol O2-/min/10(7) cells. Previous studies have shown that treatment of neutrophils with the calcium ionophore A23187, or with 5-hydroxy-6,8,11,14-eicosatetraenonate (5-HETE), dramatically increased the ability of these cells to release O2- in response to suboptimal concentrations of the stimulants mentioned. In this manuscript, we provide data relevant to the basis of this augmentation of O2- release. The synergy with ionophore A23187 exhibited a partial requirement for extracellular Ca2+, whereas that with 5-HETE exhibited a near absolute requirement for that cation. Neutrophils stimulated with optimal amounts of tumor-promoters are known to exhibit a redistribution of protein kinase C activity from the soluble to a particulate fraction. A redistribution of kinase activity was not observed in cells stimulated synergistically. On the other hand, ionophore A23187 and 5-HETE increased the binding of a suboptimal amount of [3H] phorbol 12,13-dibutyrate to intact neutrophils by approximately 25 and 50%, respectively. Inhibitors of protein kinase C (i.e. sphingosine, 1-(5-isoquinolinylsulfonyl)-2-methylpiperazine) substantially blocked O-2 release from neutrophils stimulated either synergistically or with optimal levels of tumor-promoters. These data suggest a role for 5-HETE in modulating O-2 release by neutrophils and are discussed in relation to models of the interactions of protein kinase C with membranes.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed1988

Reduction of cytochrome c by oral mucosa of patients with oropharyngeal cancer.

Superoxide radicals and other reactive oxygen products are likely to play a role in the development of mouth cancer since they are able to convert penultimate carcinogens present in cigarette smoke into ultimate carcinogens. Those radicals can be generated, e.g., by phagocytes infiltrating inflamed mucosa or by semiquinone radicals present in cigarette tar. We therefore measured the ability of oral mucosa of patients with oropharyngeal tumors to reduce cytochrome c. All patients were heavy smokers and drinkers. It was found that patient mucosa had by far more reducing power than control mucosa. Within the control group, smokers' mucosa was most active. When tested, the cytochrome c reduction was not inhibitable by superoxide dismutase or copper(II)3,5-diisopropylsalicylate. We hypothesize that reduction of cytochrome c by oral mucosa of smokers and patients with mouth cancer is primarily due to residues of cigarette tar containing conjugated quinones of mixed oxidative states which are strong reductants as well as producers of oxygen-centered radicals.

Cytochrome c Group↗
PubMed1987

[Resorption of progesterone through the intact skin of the breast in comparison with other body regions].

In healthy female volunteers the percutaneous absorption of progesterone from an ointment is studied comparing the absorption in the breast skin and that of other regions (thigh, abdomen). Before and certain times after the application progesterone serum levels are measured. A significant increase of mean serum levels (1 to 1.9 ng/ml) ist observed after application to the breast, while it is missing after application to other sites. Individual values of progesterone levels show a distinct peak after 30-120 min following application to the breast, while it lacks in three cases following other application. Serum peaks do not depend on the skin thickness as determined by ultrasound measurement. Percutaneous treatment with progesterone obviously is easier to perform using the breast skin than that of other regions.

Administration, Topical↗
PubMed1986

Features of the translocation of protein kinase C in neutrophils stimulated with the chemotactic peptide f-Met-Leu-Phe.

The effects of f-Met-Leu-Phe (fMLP) on neutrophils, i.e. elevation of the levels of cytoplasmic Ca2+ and intramembranous diacylglycerol, would be expected to be accompanied by translocation of protein kinase C (PKC) to the plasmalemma. However, fMLP-induced PKC translocation could hitherto be demonstrated only when cells were additionally treated with cytochalasin B. We show here that treatment of guinea pig neutrophils with fMLP alone does lead to a significant PKC translocation which can be inhibited by pertussis toxin. The translocation can be detected only if the incubation is terminated within 30 sec after addition of fMLP, the termination is rapid, e.g. by application of a freeze clamp-technique, and the concentration of Ca2+ chelators in the buffer used for lysing the cells is low.

Animals↗
PubMed1986

all-trans-Retinal stimulates superoxide release and phospholipase C activity in neutrophils without significantly blocking protein kinase C.

all-trans-Retinal was previously shown to stimulate high levels of superoxide release by guinea pig neutrophils. When the cells, previously labeled with [3H]inositol, are treated with all-trans-retinal, they exhibit a decrease in the levels of [3H]inositol phospholipids and an increase in the accumulation of [3H]inositol phosphates. The maximal accumulation of inositol phosphates and the optimal rate of superoxide release occurred together at approximately 7 min after stimulation. The levels of [3H]inositol phosphates accumulated were comparable to those observed when the cells were stimulated with a chemotactic peptide. In direct measurements, using concentrations that stimulate intact cells maximally, all-trans-retinal was found not to inhibit protein kinase C from the cytosol of neutrophils significantly. This contrasts with the situation with this kinase obtained from other sources. These observations represent additional effects of vitamin A on cells.

Free Radicals↗
PubMed1985

An improved fluorochrome microassay for the detection of living and non-living intracellular bacteria in human neutrophils.

Acridine orange fluorescence may be used to distinguish living from non-living intracellular bacteria in individual glass-adherent neutrophil granulocytes (PMN). An improvement of the original assay (Smith and Rommel, 1977; Pantazis and Kniker, 1979) is described which allows differentiation between ingested and cell-adherent bacteria. It is shown that this differentiation is impossible with the original method using wet-mounted preparations. With the improved method, however, using dry-mounted preparations, cell-adherent as well as extracellular bacteria lose their fluorescence. Moreover, the fluorescence of cell nuclei and granula is reduced to a minimum. Phagocytosis kinetics and selective inhibition of the myeloperoxidase of PMN show that living intracellular bacteria fluoresce green and non-living bacteria red in such dry-mounted preparations. The preparations can be stored and interpreted for at least 2 months. Application of this method requires 0.1 ml blood or cell-rich body fluid per preparation and is fast and inexpensive.

Acridine Orange↗
PubMed1985

Effect of phorone-induced glutathione depletion on the metabolism and hepatotoxicity of carbon tetrachloride and vinylidene chloride in rats.

Although the depletion of hepatic glutathione in male rats following treatment with phorone (diisopropylidene acetone) did not affect the xenobiotic-metabolizing microsomal enzyme system, the metabolic elimination of vinylidene chloride (VDC) from the atmosphere of a closed exposure system was inhibited. However, the hepatotoxicity of VDC was enhanced after GSH-depletion, although no enhancement of VDC-induced in vivo lipid peroxidation was observed. In contrast, GSH depletion had no influence on the metabolic elimination of carbon tetrachloride, but augmented both the hepatotoxic response to and the in vivo lipid peroxidation induced by CCl4. In the case of VDC GSH-depletion hepatoxicity was increased because of a change in the metabolic pathway, resulting in production of intermediates of greater toxicity: lack of GSH in CCl4 treated rats renders membrane phospholipids more susceptible to peroxidative damage.

Animals↗
PubMed1985

Effect of hypoxia on the metabolism and hepatotoxicity of carbon tetrachloride and vinylidene chloride in rats.

The metabolism of vinylidene chloride (VDC) and carbon tetrachloride (CCl4) was investigated by measuring the removal of the compounds from the atmosphere of a closed exposure system occupied with male rats. Hepatotoxicity was evidenced in the same rats by determining serum enzyme activities of the aminotransferases (GOT, GPT) and sorbitol dehydrogenase (SDH) before, at the end of the exposure time and 24 hrs later. Control rats exposed to VDC concentrations up to 2000 p.p.m. showed only slight increases of serum aminotransferase- and SDH-activities, which were not at all observed under hypoxic conditions. Hypoxia evoked a small, but significant reduction of the VDC metabolism at 500 p.p.m., but not at 2000 p.p.m. exposure concentration. In contrast to VDC CCl4-metabolism (150 p.p.m.) was increased under hypoxia and consequently hepatotoxicity was aggravated.

Animals↗
PubMed1979

[On the physiology of the growth of nail plate (author's transl)].

By following up histologically a localized storage of melanin in certain layers of the nail plate the differing theories on the cellular kinetics of the growth of human nail plate are checked up. Thus it turns out that the hitherto existing and even contradicting conceptions are not helpful to interpret uniquely the morphological phenomena of the concrete case. A plausible modification is presented.

Humans↗
PubMed1979

Peritoneal exudate T lymphocytes with specificity to sheep red blood cells. II. Inflammatory helper T cells and effector T cells in mice with delayed-type hypersensitivity and in suppressed mice.

Peritoneal exudate cells were induced in mice 4 days after immunization with SRBC. A low dose of SRBC (10(6) i.v.) caused T lymphocytes to appear in inflammatory exudates. These cells, not only transferred DTH reactions, but also functioned as helper T cells in antibody production after transfer to syngeneic nu/nu recipient mice. After a high dose of SRBC (10(9) i.v.), very few helper T cells and no DTH transferring T cells were found in inflammatory exudates, although they were present in the spleen. It is postulated that T cells mediating DTH reactions and helper T cells behave similarly as far as those dose dependency of appearance in inflammatory exudates is concerned. A high dose of sensitizing antigen causes retention of helper and effector T cells in the spleen, in this way favouring antibody formation; low doses of antigen allow them to leave the spleen, thus favouring mediation of DTH reactions in the periphery.

Animals↗
PubMed1979

[Juvenile melanoma; a clinical and histological study].

Investigations were carried out in 52 female and 18 male patients, aged between 2 and 49 years, with juvenile melanoma. The tumor occured as a solitary tumor in all cases except one. It was mainly localized on the head (54%), and the extremities, on the trunk in three cases only. In 35% the tumor could be diagnosed clinically. Light microscopy revealed in 37.1% spindle cells, in 17.1% epitheloid cells, and in 45.7% the juvenile melanoma was of the mixed type. A proliferation of the vascular endothelial cells (37.1%) as well as immature looking mast cells in the tumor region were prominent findings. A transepidermal elimination of tumor cell nests was noted in one case. The other results are in agreement with earlier descriptions of this tumor.

Adolescent↗