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Biomedical subjects

W Zschiesche

Publications and source records attributed to W Zschiesche.

At least 37 records · Page 2Linked to original sources

Members of the fatty acid binding protein family are differentiation factors for the mammary gland.

Mammary gland development is controlled by systemic hormones and by growth factors that might complement or mediate hormonal action. Peptides that locally signal growth cessation and stimulate differentiation of the developing epithelium have not been described. Here, we report that recombinant and wild-type forms of mammary-derived growth inhibitor (MDGI) and heart-fatty acid binding protein (FABP), which belong to the FABP family, specifically inhibit growth of normal mouse mammary epithelial cells (MEC), while growth of stromal cells is not suppressed. In mammary gland organ culture, inhibition of ductal growth is associated with the appearance of bulbous alveolar end buds and formation of fully developed lobuloalveolar structures. In parallel, MDGI stimulates its own expression and promotes milk protein synthesis. Selective inhibition of endogenous MDGI expression in MEC by antisense phosphorothioate oligonucleotides suppresses appearance of alveolar end buds and lowers the beta-casein level in organ cultures. Furthermore, MDGI suppresses the mitogenic effects of epidermal growth factor, and epidermal growth factor antagonizes the activities of MDGI. Finally, the regulatory properties of MDGI can be fully mimicked by an 11-amino acid sequence, represented in the COOH terminus of MDGI and a subfamily of structurally related FABPs. This peptide does not bind fatty acids. To our knowledge, this is the first report about a growth inhibitor promoting mammary gland differentiation.

Amino Acid Sequence↗

A new monoclonal antibody for detection of EGF-receptors in western blots and paraffin-embedded tissue sections.

The prognostic significance of the epidermal growth factor receptor status (EGF-R-status) for certain human tumors requires the development of antibodies useful for clinical application. We used purified receptor preparations to generate monoclonal antibodies immunoreactive with the EGF-R purified from placenta membranes and A431 tumors. Four of the hybridomas contained antibodies (R2, R3, R5, and R9) which recognized both antigens. Antibody R3 was shown to display the following properties: it binds with a KD value of about 10(-9)-10(-10) M to the receptor, a half maximal inhibition of EGF-binding is achieved at 5 x 10(-8) M, and in Western blots of cell membranes R3 specifically detects the EGF-R at 0.1 micrograms/ml. R3 inhibits EGF-dependent clonogenic growth of NRK cells and completely blocks EGF stimulated autophosphorylation of the receptor. Moreover, R3 also detects EGF-R in paraffin-embedded tissue sections taken from human salivary gland, term placenta, and adult skin and mammary carcinomas. Thus, R3 can be used in retrospective diagnostic clinical studies and might help to develop new immunotherapeutic intervention.

Animals↗

Exposure to soluble barium compounds: an interventional study in arc welders.

Soluble barium (Ba) compounds are well-known toxicants. Intoxications are mainly known in an acute form from casual or suicidal oral ingestion. No scientifically based data are available on possible health effects of inhalative exposure to soluble Ba salts at the workplace. Therefore, we investigated 18 welders in an interventional study over 1 week. They performed welding of Ba-containing stick electrodes and self-shielded flux cored wires under conditions similar to real working conditions. The welding fumes contained 31%-37% Ba, more than 90% of which was soluble in acids. Without appropriate preventive measures, a high rate of measurements exceeded the TLV values for total welding fumes of 5 mg/m3 and for soluble Ba of 0.5 mg/m3. The median fume concentrations were 13.2 mg/m3 in stick electrode welding and 12.3 mg/m3 in flux cored wire welding. The median Ba concentrations were 4.4 and 2.0 mg/m3 respectively. An integrated exhaust system built into the gun proved to be efficient in flux cored wire welding. The internal exposure to Ba reached median urine levels up to 101.7 micrograms/l (normal: below 20 micrograms/l) and median plasma concentrations of up to 24.7 micrograms/l (normal: below 8 micrograms/l). No health impact on the welders could be proven, but hypokalemia may have occurred as a result of the Ba exposure.

Air Pollutants, Occupational↗

[Medical ENT endoscopic studies in the iron and steel industry].

461 chromium- and nickel-exposed steelworkers were otolaryngologically examined by endoscopy. Besides chronic inflammatory diseases of the ear, nose and paranasal sinuses, the clinical diagnosis of leukoplakia and hyperplastic laryngitis was made for 30 workers. In no case a lesion suspicious of cancer was found. Office staff showing no such occupational risk factors served as the control group. It was found that in both groups smoking has to be assumed as the decisive factor for the development of chronic inflammation and precancerous changes in the oral cavity and the larynx.

Chromium↗

Differentiation-promoting effects of mammary-derived growth inhibitor (MDGI) on pluripotent mouse embryonic stem cells.

Pluripotent embryonic stem cells (line BLC6), when cultivated in vitro as embryoid bodies and injected subcutaneously into syngeneic mice, form teratocarcinomas consisting of embryonal carcinoma cells and differentiated tissues of all three primary germ layers. In order to study the possible effects of the mammary-derived growth inhibitor (MDGI) on the differentiation pattern of the tumors developing in the mice, BLC6 cell-derived embryoid bodies were treated in vitro for 4 days with either MDGI or a synthetic peptide composed of the C-terminal 11 amino acids of MDGI. In those tumors, significantly more differentiated neural tissue and lesser proportions of undifferentiated embryonic carcinoma cells (ECC) were found in the MDGI- and peptide-treated groups, compared with controls. The results are discussed with respect to a possible differentiation-promoting capacity of MDGI.

Animals↗

Tellurium-intoxication.

Tellurium is one of the rarest elements on earth. Intoxications are rare and almost exclusively occupationally exposed workers are affected. Only a few cases of non-occupational poisoning have been reported so far. Severe poisoning results in respiratory depression and circulatory collapse. After occupational exposure main symptoms and signs include loss of appetite, dryness of the mouth, suppression of sweating, a metallic taste in the mouth, and most notable, a sharp garlic odor of the breath, sweat and urine. We report our findings in a 37 year old, non-occupationally exposed woman with tellurium intoxication.

Adult↗

Immunohistochemical characterization of spontaneous amyloidosis in captive birds as AA-type, using monoclonal and polyclonal anti-AA antibodies against mammalian amyloid.

Spontaneous amyloid diagnosed by means of Congo red and polarization microscopy in 3 flamingos, 1 crowned crane, 1 red-breasted goose, and 1 common golden-eye was studied using immunohistochemical techniques. The avian amyloid cross-reacted with a number of monoclonal and polyclonal anti-AA antibodies directed against mammalian amyloid fibril proteins. This confirmed that both "secondary" and "idiopathic" avian amyloid is of the AA-type. The results demonstrate the possibility to successfully using cross-reactive anti-AA antibodies for the diagnosis of non-mammalian amyloidosis.

Amyloidosis↗

Retardation of growth and epithelial differentiation in suckling mice by anti-EGF antisera.

Anti-EGF serum administered to newborn mice led to an increasing rate of growth retardation and body weight gain during the following period up to 5 weeks after birth, but sometimes to an effect found reversible after 3-4 weeks. In addition, striking delay of differentiation of skin epidermis and appendages and of intestinal Paneth's cells was ascertained about 4 weeks after birth. The findings point to neutralization of EGF or abolition of its effects by anti-EGF serum and, thus, substantiate the suggestion that EGF plays a physiological role during the early postnatal growth and differentiation.

Animals↗

Effects of anti-EGF serum on newborn mice.

Administration of anti-EGF serum to newborn mice led to delay of eyelid opening and incisor tooth eruption, acceleration of hair growth and delay of weight gain. These results indicate that in the first week after birth EGF still has a physiological function, which can be abrogated by anti-EGF serum.

Animals↗

Interaction of Lotus-tetragonolobus Lectin (LTL) and an MIF-like factor with guinea-pig macrophages. I. Effects on macrophage migration inhibition and receptor-binding studies.

Purified Lotus-tetragonolobus lectin (LTL) was studied for its interaction with guinea-pig peritoneal macrophages in the migration-inhibition and spreading-inhibition assay. LTL was found capable of inhibiting macrophage migration in a dose-response relationship similar to that of an MIF-life factor present in rat Zajdela-hepatoma ascites, whereas macrophage spreading was less affected. Mitogenic activity of the fucolectin could be excluded. Both the LTL and MIF-like factor seem to come into action by means of alpha-L-fucopyranosyl residues-containing macrophage surface receptors. Both substances act synergistically in inhibiting migration of macrophages. Since binding studies with 125I-LTL demonstrated competition with the MIF-like factor, it is suggested that the latter and LTL share a common surface receptor, and that optimal occupation densities are required for the realization of the inhibitory effect. Possibly, LTL acts in a monomeric form in the migration inhibition assay.

Animals↗

Production of interferon and other lymphokines during murine tumour growth. III. Characterization of microbial growth inhibitory activity in cell-free supernatants of rat Zajdela ascites hepatoma.

A microbial growth inhibitory factor (MGIF) detected in the cell-free fluid of Zajdela ascites hepatoma of the rat was characterized by means of gel filtration, ion exchange chromatography and isoelectric focusing. It was shown that MGIF is a nondialysable protein with a molecular weight of about 19,000 to 25,000. Charge heterogeneity was revealed by isoelectric focusing which demonstrated pI of 3.8--4.5 and 5.0--6.0. MGIF seems to differ from tumour cell-derived MIF detected in the same ascitic fluids.

Ammonium Sulfate↗

Characterization of tilorone-induced mouse migration inhibitory factor by affinity chromatography and isoelectric focusing.

Administration of tilorone to mice highly reproducibly induces a nontoxic serum migration inhibitory factor (MIFt) which was previously shown to originate from macrophages. The inhibitory activity could partially be purified by affinity chromatography on alpha-L-fucose-Sepharose 6B columns. Isoelectric focusing demonstrated two separable chemical entities with IEPs of about 4.0 and 5.9. While the first constitutes the inducible MIFt, the latter apparently represents migration inhibitory serum factor being found also in normal mouse serum.

Animals↗

A nonspecific inhibitor of macrophage migration in cell-free ascites of rat Zajdela hepatoma. I. Biological studies on inhibitor formation.

Wistar rats were inoculated with Zajdela ascites hepatoma. A nonspecific inhibitor of macrophage migration was detected in the cell-free ascitic fluid during the early phase of tumor growth (at day 4-8). Dose-response curves of cell-free ascitic fluids revealed peak migration inhibitory activity at dilutions up to 1:640. The migration inhibitory activity presents a nondialyzable protein, unaffected by freezing, lyophilization, incubation at 60 degrees C for 30 min or pH 2 treatment. In all probability, the presumed factor is produced by the tumor cells as revealed by studies in vitro.

Animals↗

A nonspecific inhibitor of macrophage migration in cell-free ascites of rat Zajdela hepatoma. II. Biochemical characterization and purificaton.

Macrophage migration inhibitory activity from Zajdela hepatoma ascites (AH-MIF) was characterized by ion exchange chromatography, gel filtration and isoelectric focusing. The data obtained indicate molecular heterogeneity according to net charge as revealed by chromatography on DEAE-Sephadex A-50. Furthermore, molecular sieve chromatography with Sephadex G-100 demonstrated the existence of subfractions with molecular weights of about 45,000, 20,000 and 10,000 - 15,000 respectively. Isoelectric focusing revealed further heterogeneity of a subfraction (10,000 - 15,000) eluting at 0.17 - 0.25 M NaCl by ion exchange chromatography. The migration inhibitory factor(s) from Zajdela hepatoma ascites were shown to adsorb to alpha-L-fucose-Sepharose 6B columns. The relationships of AH-MIF to functionally similar tumor-derived factors and to lymphocyte-derived conventional MIF ar discussed.

Animals↗

Production of interferon and other lymphokines during murine tumour growth. I. Lymphokines in cell--free fluid of rat Zajdela ascites hepatoma.

Cell-free ascites of rat Zajdela hepatoma was assayed for the presence of lymphokine-like factors. Macrophage migration inhibitory and microbial growth inhibitory cytokines were detected with peak activities at day 4-8 and 10-11 after tumour inoculation, respectively. Occasionally, skin reactive activity was found, whereas only borderline titres of an interferon-like substance were demonstrated. Preliminary studies indicated that both migration inhibitory and microbial growth inhibitory factors are proteins resembling the corresponding lymphocyte-derived lymphokines. The cellular site of formation of these factors remains to be determined.

Animals↗

Production of interferon and other lymphokines during murine tumour growth. II. Induction of an interferon by Ehrlich ascites cells in outbred mice.

A viral inhibitor produced in the peritoneal cavity of outbred Swiss mice inoculated with allogeneic Ehrlich ascites cells was identified as an interferon. It was antigenically related to viral interferons of type 1 and seems to be produced by macrophages. The interferon activity in the peritoneum reached maximal levels at 24 hr after tumour challenge. Interferon induction by Ehrlich ascites cells was not inhibited in lipopolysaccharide-hyporeactive mice. In addition, cell growth inhibition, enhanced interferon production after priming with small doses of this interferon, and increased susceptibility of cells treated with this interferon to the toxic effect of double-stranded RNA was demonstrated.

Animals↗