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Biomedical subjects

U Fuhrmann

Publications and source records attributed to U Fuhrmann.

10 recordsLinked to original sources
PubMed1992

Stable transfection of androgen receptor and MMTV-CAT into mammalian cells: inhibition of cat expression by anti-androgens.

A hormone-inducible transcriptional system has been established, based on the stable transfection of the rat androgen receptor (rAR) and a reporter plasmid containing the mouse mammary tumour virus promoter linked to the chloramphenicol acetyltransferase gene (pMMTV-CAT) into steroid receptor-negative CV-1 cells. First, the rAR was stably introduced into CV-1 cells. Single clones were tested for stable expression of functionally active AR by analysing the effect of dihydrotestosterone on induction of transiently transfected pMMTV-CAT. Stable transfection and the expression of AR was confirmed by steroid-binding assays. In a second step, a clone expressing physiological amounts of AR protein (30 fmol/mg protein) was stably transfected with pMMTV-CAT to yield a permanent cell line that stably expresses functional AR and MMTV-CAT sequences. This cell line provides a powerful tool for the efficient and accurate determination and quantification of the effects of androgens and anti-androgens on reporter gene transcription. This was demonstrated by investigating the action of the three anti-androgens hydroxyflutamide, casodex and cyproterone acetate. The three compounds were shown to reverse the effects of the androgen R1881 on gene expression but were themselves devoid of agonistic activity.

Androgen Antagonists↗
PubMed1990

The v-erb A oncogene causes repression of erythrocyte-specific genes and an immature, aberrant differentiation phenotype in normal erythroid progenitors.

We have compared the effects of the v-erb A oncogene on proliferation and differentiation of normal erythroid progenitors with those of tyrosine kinase oncogenes, e.g. v-sea. For this, a v-erb A retrovirus containing the neomycin resistance gene as a selectable marker or, alternatively, a v-erb A-ts v-sea retrovirus were used to infect normal bone marrow cells. V-erb A induced the outgrowth of immature, erythropoietin(EPO)-dependent erythroid cells from infected bone marrow which ceased to proliferate and disintegrated after 9 to 18 divisions. In contrast, ts-v-sea erythroblasts grew for the expected 25 to 40 population doublings in the absence of EPO. Transcription of the erythrocyte genes carbonic anhydrase II and erythrocyte anion transporter was significantly inhibited in v-erb A infected erythroblasts, indicating that v-erb A alone was sufficient for the repression of the erythrocyte-specific genes observed in AEV-transformed leukemic cells. A detailed analysis of the differentiation phenotype induced by v-erb A in erythroblasts (in the presence or absence of a temperature-inactivated ts sea oncogene) indicates that v-erb A-erythroblasts express a partially mature, aberrant phenotype characterized by the coexpression of mature and immature differentiation antigens. This phenotype clearly differs from that induced by tyrosine kinase oncogenes in erythroid cells.

Animals↗
PubMed1989

Gangliosides mediate inhibitory effects of tetanus and botulinum A neurotoxins on exocytosis in chromaffin cells.

Bovine chromaffin cells in monolayer culture were preloaded with 3H-NA (noradrenaline) and subsequently stimulated with carbachol. Botulinum A neurotoxin partially inhibited the evoked release of 3H-NA and the basal efflux of the hormone. The inhibition of evoked release did not exceed 40%, although the cells were exposed to 10 micrograms/ml of toxin for 6 days. The inhibitory effect of botulinum A neurotoxin was neutralized by its antibodies. In contrast to botulinum A neurotoxin, tetanus toxin at even higher concentrations did not influence evoked release. This difference in sensitivity could be explained by the ganglioside pattern of chromaffin cells. Ganglioside GD1a, a putative receptor for botulinum A neurotoxin, could be identified in lipophilic extracts, whereas the tetanus toxin binding gangliosides GT1b and GD1b could not be detected by means of thin-layer chromatography. Treatment of the cells with neuraminidase abolished both, GD1a and the inhibitory effect of botulinum A neurotoxin. Incubation of chromaffin cells with a mixture of gangliosides (21% GM1, 44% GD1a, 15% GD1b, 20% GT1b) not only increased the efficacy of botulinum A neurotoxin but also made the cells sensitive towards tetanus toxin. The concentration-response curve of botulinum A neurotoxin was shifted to the left about five-fold and the maximum inhibition of evoked release was increased up to 60%, even though the cells were exposed to the toxin for 3 days only. In contrast, the maximum inhibition that could be achieved by tetanus toxin was 40%. The results indicate that polysialogangliosides are important for the intracellular accumulation of these clostridial neurotoxins.

Adrenal Medulla↗
PubMed1989

The mutated, myeloid cell-specific growth factor receptor v-fms transforms avian erythroid but not myeloid cells.

In avian hematopoietic cells, transformation by tyrosine kinase oncogenes is restricted to the erythroid lineage. To study the mechanism of this striking target cell specificity, we constructed an avian retrovirus correctly expressing the feline v-fms protein, an oncogenic version of the myeloid-specific CSF-1 receptor. Similar to other tyrosine kinase oncogenes (erbB, src, fps, sea), the v-fms oncogene induced progenitor cells to self-renew in an erythropoietin-independent manner. Spontaneous differentiation of the transformed cells was arrested by v-erbA. v-fms failed to induce transformation of myeloid cells but caused myeloid cells transformed by the v-myb oncogene, as well as normal macrophages, to proliferate independent of cMGF (chicken myelomonocytic growth factor). Unlike the other tyrosine kinases, v-fms did not induce cMGF secretion in myb-myeloblasts, suggesting a nonautocrine mechanism of growth factor independence.

Alpharetrovirus↗
PubMed1979

[Nephroblastoma].

Explore the source record for details and available documents.

Bone Neoplasms↗
PubMed1979

[Nephroblastoma, partly appearing as a sarcoma botryoides of the renal pelvis (author's transl)].

A renal tumour in a 4-year old girl morphologically appeared as both a nephroblastoma and, in parts, as a sarcoma botryoides of the renal pelvis. The histogenesis of this dysontogenetic tumour is most probably due to a disturbance of growth and differentiation both of the metanephrogenic blastema as well as partly of the urethral bud. This type of dysontogenetic tumour is extremely rare. Problems of diagnosis and operative therapy and the possibility of postoperative radiation therapy and cystostatic treatment are discussed.

Child, Preschool↗
PubMed1978

[Cardiotoxicity in long term treatment with cytostatics (author's transl)].

During cytostatic combination treatment with five different anti-tumor agents two female patients suffered from cardiac failure which proved fatal. This was mainly due to doxorubicine (adriamycin) and daunorubicine. In an 8-year-old patient the cumulative dose was reached after 14 months of treatment (total dose of adriamycin 420 mg/m2, of daunorubicine 280 mg/m2) and in a 7-year-old patient after 16 months (total dose of adriamycin 480 mg/m2, of daunorubicine 280 mg/m2). Cardiac failure which occurred 12 months after the onset of treatment in a 12-year-old girl (total dose of adriamycin 310 mg/m2 and of daunorubicine 280 mg/m2) could be brought under control. The cumulative dose of adriamycin should be limited to 500 mg/m2 in children without risk factors.

Bone Neoplasms↗