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Biomedical subjects

K Redmann

Publications and source records attributed to K Redmann.

At least 37 records · Page 2Linked to original sources

[Pretherapeutic testing of sensitivity to cytostatic drugs in primary cultures of selected urologic tumors].

In 30 patients with malignant urologic tumours (scrotal tumours, renal tumours, tumours of the urinary bladder) an in vitro cultivation of the primary tumor was tried. According to the technique of Tannenberger and Bacigalupo 21 primary cell cultures could be applied. This corresponds to an accession rate of 70%. After formation of a cell lawn and addition of cytostatics of the arbitrarily selected medicaments vinblastin, bleomycin, cis-DDP, actinomycin D the reaction of the cells on the drugs was judged light-microscopically and electrophysiologically by measuring the transmembrane potential 24 hours after the application of medicaments. Thus apart from a usual oncobiogram which has as its fundament the morphology of the cells an electrooncobiogram could be established. The authors dealt with the methodology of the TMP-measurement after Redmann as a relatively new method for the pretherapeutic sensitisation test of tumours. The reactions of the cells to the cytostatics mentioned were so multifarious in the 3 groups of tumours that no conclusions of general validity could be drawn. These different modes of reaction are to be regarded as an expression of the biological individuality of human tumours. Apart from answering theoretical questionings the TMP-measurements might be used in the pretherapeutic sensitisation test of cytostatics in malignant renal tumours.

Antineoplastic Agents

Membrane hyperpolarization following chronic exposure of FL-cells to low doses of ouabain.

The transmembrane potential (TMP) of FL-cells (monolayer cultures) in Eagle's medium with ouabain concentrations from 10(-4) to 10(-11) M was measured by means of glass microelectrodes over 96 h. High ouabain concentrations caused total depolarization of the cell membrane with subsequent cell death after 24 to 48 h. A level of 10(-7) M ouabain was tolerated by the cells over 96 h, and the TMP was decreased about 50% vs. controls in ouabain-free medium. Ouabain at concentrations from 10(-11) to 10(-8) M increases TMP by 20-40%, which decayed after 24 to 48 h. The low glycoside concentrations are assumed to cause, if only part of the glycoside receptors (Na+ pumps) is blocked, an activation of the still active pumps (turnover) and enhanced formation of transport enzymes and their incorporation into the membrane (replacement) so that the overall result is a stimulation of the cell membrane transport systems.

Cell Line

The expression of tumor-associated antigens in primary and metastatic human malignant melanoma.

Monoclonal antibodies were raised against cultured melanoma cells and selected for their reactivity with melanoma-associated antigens expressed on various melanoma lines. Of 34 monoclonal antibodies, which were all reacting with melanoma lines only 19 antibodies bound to fresh melanoma tissue. Of the 19 antibodies 10 displayed a broad cross-reactivity with normal cells and structures, whereas 9 had a restricted reactivity. Of these antibodies five types were defined, which detected antigens (nevocellular I, nevocellular II, neural, endothelial, basal cell), which were found on certain normal tissues and structures and on certain tumor phenotypes. On the basis of an extensive study on melanoma biopsies of different stages it became evident, that the endothelial, the basal cell and also HLA-DR antigens were significantly more expressed in high risk melanomas. The basal cell antigen was preferentially expressed in locoregional metastases. By immunization with fresh melanoma biopsies different specificities of monoclonal antibodies were obtained as compared to immunization with established cell lines.

Animals

[Measurements of ion concentrations with microelectrodes on vital tissue sections of human breast cancer].

The transmembrane potential (TMP) was described as a rapidly reacting and sensitive indicator for a great number of cell functions. The present paper reports on the measurement of ion concentration (IC) on vital microscopically controlled human mammary tissue slices. Satisfactory results have been achieved with changed on-light observation in comparison to other customary methods. Whereas a cytoxic effect has been observed with all treatments by means of 3H-thymidine uptake, IC-measurements showed only effects with Daunoblastin or distilled water in 4 out of 16 experiments. The effect of Daunoblastin measured by ion concentrations seems to be better visible if the tissue culture medium is exchanged by physiological NaCl-solution (0.9%). Nevertheless the described method cannot be recommended for drug sensitivity testing of human mammary carcinomas in organ culture.

Breast Neoplasms

Effects of cytostatic drugs on the transmembrane potential and surface charge of cultured cells.

The transmembrane potential, the surface charge and the cell count were measured on cells cultured in vitro under the influence of various cytostatic substances. Lower concentrations of the agents induced an increase in membrane polarization. On the other hand membrane depolarization grew with both increasing exposure to cytostatic substances and rising content of the latter in the medium. The influence of higher doses was accompanied by morphological cell damage as well as a decrease in the surface charge of cells after a lengthy incubation time. Immediately after addition of chemotherapeutic substances to the cell cultures a damped oscillation of the TMP was observed. This clearly supports that the TMP is a rapidly reacting and very sensitive indicator for a great number of cell functions and an additional parameter in pretherapeutic sensitivity tests.

Antineoplastic Agents

Different changes in transmembrane potential of cultured cells after ouabain-inhibited active Na+/K+-transport.

The inhibition of (Na+/K+) activated membrane ATPase by cardiac glycosides is electrophysiologically detectable in terms of a reduction of the transmembrane potential (TMP) of cells. Two hours after incubation in medium with 10(-4) mole/l ouabain added, the TMP of cells were measured by means of glass microelectrodes. Compared with untreated controls, HeLa and FL-cells, human embryo cells, skin fibroblasts, leukocytes, and exudate macrophages without exception showed a TMP reduction typical of the particular cell kind. Primary cultures of human embryo cells and skin fibroblasts revealed the highest sensitivity (approx. 60% TMP reduction), while lesser and relatively low sensitivities were observed for permanent cells (approx. 30% TMP reduction) and white blood cells (approx. 20% TMP reduction), respectively. Unlike the above, the ovarian tumor cells showed inter-individually varied reactions within the range of TMP changes from - 55% to + 33%. The majority of malignant tumours, in particular, exhibited only a weak reaction in the ouabain test or no reaction at all. On the other hand, ovarian cysts or other clinically benign tumors showed the normal ouabain effect. The experimental results obtained for the ovarian tumors are believed to demonstrate a defect of one or several transport enzymes, which effect is associated with the malignancy of cells and may be used as a functional in vitro marker for malignancy in the field of cell physiology.

Animals

[In vitro electrophysiological determination of an individual ouabain sensitivity of human ovarian tumors].

In the standardized ouabain test (10(-4) mol/l, 2 h) 10 different cell cultures react with cell kind specific transmembrane potential (TMP) changes. Primary cultures of human embryo cells and skin transmembrane potential (TMP) changes. Primary cultures of human embryo cells and skin fibroblasts revealed the highest sensitivity (approx. 60-70% TMP reduction), while smaller and relatively low sensitivities were observed for permanent cells (approx. 30-40% TMP reduction) and white blood cells (approx. 20% TMP reduction), respectively. Unlike these cells, 36 human ovarian tumors showed interindividually varied reactions within the range of TMP changes from -55% to +33%. Especially, the majority of malignant tumors exhibited only a weak reaction in the ouabain test or no reaction at all. Ovarian cysts or clinically benign tumors showed a normal ouabain effect. The striking reactions of the ovarian tumor cells are believed to demonstrate a defect of one or several transport enzymes, especially of the (Na+/K+)-activated membrane ATPases. Possible correlations between the disturbed transport mechanisms of the cell membrane and the control of the cell growth and cell division are discussed.

Animals

Lyon phenomenon in ouabain-treated erythrocytes of Duchenne muscular dystrophy carriers as revealed by cell electrophoresis.

Using the cell-electrophoretic method, 0.1 mM ouabain/l Eagle MEM medium caused a moderate decrease in electrophoretic migration time (EMT) of erythrocytes in 19 out of 23 DMD-affected patients. In 8 out of 10 healthy boys, 0.1 mM ouabain induced an increase in erythrocyte EMT. Under the influence of 0.1 mM ouabain, the erythrocytes clearly showed a bimodal distribution of EMT in 9 out of 13 definite carriers and in 8 out of 17 possible carriers. In DMD patients, and in 10 healthy boys and 10 healthy women, no bimodal distribution of EMT was observed.

Cell Movement

Effect of 5-fluorouracil and thymidine on the transmembrane potential and zeta potential of HeLa cells.

The main result of the experiments reported in this paper is the observation that HeLa cells, when treated with 5-fluorouracil (5-FU), show a damped oscillatory response in the transmembrane potential. This effect is counteracted by thymidine. Damped oscillation in the transmembrane potential occurs within the first hr after addition of 5-FU, commencing with an initial hypopolarization. At low concentrations (10(-8) through 10(-7) M), hyperpolarization of the cell membrane is observed after lengthy incubation time (24 to 96 hr). Membrane depolarization is enhanced at higher concentrations (10(-6) through 10(-4) M) and with increasing exposure to the cytostatic substance. The surface charge or zeta potential of HeLa cells is altered to a lesser extent by 5-FU than is the transmembrane potential. Distinct effects can be observed as late as after 72 and 96 hr. When thymidine (2 x 10(-5) M) is added along with 5-FU, the depolarizing action of the antimetabolite can be abolished. Thymidine itself, at the concentration used, causes almost no change in membrane polarization. The results suggest that the effect of 5-FU on the cell membrane is related to the influence of the antimetabolite on cell growth. Moreover, this membrane effect might be the primary cause for the cytostatic action.

Cell Membrane

[The effect of roentgen rays on the transmembrane potential and on the electrophoretic mobility of polymorphonuclear granulocytes and FL-cells (author's transl)].

Two hours after X-irradiation at 37 degrees C in vitro at doses ranging from 50 rad to 20 krad the transmembrane potential and the surface charge of polymorphonuclear granulocytes and FL-cells showed a dose-dependent decrease. However, between two and four days after irradiation at 10 krad FL-cells revealed an increase in both transmembrane potential and surface charge. Small doses of ionizing radiation (e.g. 10 rad) resulted in aperiodically damped oszillations of membrane polarisation in leucocytes.

Cell Line

[Membrane effect of potassium rhodanide and methotrexate].

In HeLa cells and macrophages rhodanide ions cause biological hyperpolarization of the cell membranes, while methotrexate hyperpolarizes the membranes as an antimetabolite. Cell physiologically, rhodanide has a general stimulating effect within the physiological control range of the cell. This membrane effect could be related to the physiological and therapeutic action of rhodanide in processes involving immunological events.

Animals

[Influence of ouabain on the electrophoretic mobility of erythrocytes in 7 patients with Duchenne's muscular dystrophy].

Measurements of electrophoretic mobility of erythrocytes under the influence of ouabain were carried out on seven patients suffering from progressive Duchenne's muscular dystrophy. While ouabain-treated erythrocytes of healthy controls showed a significant decrease (alpha = 0.001) in electrophoretic mobility, an increase was found in five of the patients, and two patients revealed a slight drop in electrophoretic mobility. A significant difference (alpha = 0.001) was obtained in comparing the control group of patients. Initial trial measurements suggested that such a difference is also true for some other forms of muscular dystrophy and Werdnig-Hoffmann's spinal muscular atrophy.

Child

[Macrophage membrane potential test: an electrophysiological modification of the Field-Caspary test in melanoma patients].

In modification of the cytopherometric test according to FIELD and CASPARY [3] were studied the influence of the cell-free supernatant (lymphokine) of the lymphocyte antigen reaction on the transmembrane potential of macrophages obtained from guinea pigs (peritoneal exsudate cells PEC). Macrophage membrane potential (MMP) was determined by glass microelectrode technique. In agreement with histological and clinical findings in malignant melanoma and Dubreuilh's disease with malignatization we observed a depolarization of the macrophage membrane up to 40% as compared with controls. A depolarization up to 60% was obtained in patients having undergone BCG vaccination, if the antigen used was PPD. In control persons and in non-malignant pigmentary tumors (such as foreign body granuloma) we found no variation of MMP. The results indicate that cell mediated immunity is closely correlated with membrane permeabilities, ion gradients and cell metabolism.

Clinical Trials as Topic