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Biomedical subjects

W Lehmann

Publications and source records attributed to W Lehmann.

At least 127 records · Page 7Linked to original sources

Purification of a chalone-like inhibitor for Ehrlich ascites mammary carcinoma cells from bovine mammary gland.

A factor which inhibits the resumption of proliferation of stationary Ehrlich ascites mammary carcinoma (EAC) cells in vitro was isolated from the normal, lactating bovine mammary gland. After fractionation of the 50,000 g supernatant of the tissue homogenate by ammonium sulfate precipitation and gel filtration, it was further purified 2600-fold by ultrafiltration and lectin affinity chromatography. Polyacrylamide electrophoresis revealed one band containing all the activity. SDS gel electrophoresis showed a main band corresponding to a protein with a molecular weight of about 15,000 dalton. At this state of purity the factor concentration for half-maximal inhibition of proliferation was 12 ng/ml or 8 X 10(-10) M. The effects of factor concentrations of 4 X 10(-9) or 4 X 10(-8) M are abolished by 5 X 10(-9) M insulin almost completely or to 70%.

Animals↗

Aspects of chalone action.

The following aspects of action of a chalone-like factor for the Ehrlich ascites mammary carcinoma and of the granulocytic chalone are discussed: 1) Dependence on the state of proliferation. Rapidly growing cells respond poorly or not at all. 2) Antagonism with growth factors. The factor for the Ehrlich ascites mammary carcinoma is antagonized by physiological concentrations of insulin or by proinsulin. The granulocytic chalone is antagonized by colony stimulating factor. 3) Influence on cell cycle progression. Attempts and problems to analyse this influence for the factor for the Ehrlich ascites mammary carcinoma by flow cytometry are described.

Animals↗

[Deviations in the control of the monitor calibration of a circular accelerator].

The operation of an accelerator requires to perform at regular intervals a control measurement of the basic calibration. This measurement showed a deviation growing from week to week. Finally, the test measurements gave occasion to suppose a defect of the used ionizing chamber, but this was not confirmed by measurements at a gamma irradiation unit. When the chamber had been repaired by the manufacturer, there were no more deviations with respect to the basic measurement.

Particle Accelerators↗

[Mathematical methods in flow cytometry: the problem of evaluating DNA histograms of partially synchronous cell populations].

There is presented a procedure for determining the phase fractions in a cell population (i.e. the fractions of the G1-, S- and G2 + M-cells) from the corresponding DNA histogram obtained by flow cytometry. The evaluation procedure can regard arbitrary apriori information about the model parameters. It is based on a mathematical model of the DNA distribution for a growing cell population which contains the phase fractions and some further values as parameters. The parameter estimations rest on the Maximum-Likelihood-Principle by which the parameters of the theoretical model must be determined in such a way that the measured histogram corresponds to a maximum probability. As a consequence of the model flexibility especially the S-phase fraction which can be determined independently by labeling techniques, can be regarded as a fixed predetermined value. Such apriori information enhances the preciseness of the parameter estimation. The applications have shown that the determination of the S-phase fraction by means of flow cytometry can be very unprecise especially under partial synchronization. For the application of the evaluation programs (programming language ALGOL) the histograms must be free of cell detritus and clumping.

Animals↗

Combined chemotherapy of head and neck squamous cell carcinomas with methotrexate, bleomycin, and hydroxyurea.

Thirty-two patients with squamous cell carcinoma of head and neck not amenable to surgery or radiotherapy were treated with a combination of methotrexate 0.6 mg/kg IV weekly, bleomycin 15 mg IV weekly, and hydroxyurea 1,000 mg/m2 three oral doses weekly. Eleven complete responses and ten partial responses of more than 50% were observed. The mean duration was 43 weeks for complete responses and 35 weeks for partial responses. Toxicity consisted in leukopenia, thrombocytopenia, nausea, vomiting, stomatitis, and cutaneous alterations. Only one patient suffered reversible lung toxicity. These results suggest that a combination of three drugs in squamous cell head and neck cancer may be more effective than a combination of bleomycin and methotrexate only.

Antineoplastic Agents↗

Effect of temazepam and temazepam-ethanol on sleep.

The effects of temazepam 20 mg and temazepam 20 mg plus whisky 100 ml on sleep and performance were investigated in 5 healthy volunteers in comparison with placebo. In the sleep laboratory, after temazepam there was a trend for reduction of sleep latency, stage wake and stage 1 sleep, and for an increase in REM sleep. The addition of alcohol to the regimen reduced the sleep latency still further, and diminished REM sleep. In subjective assessments, temazepam received the highest score for quality of sleep and the temazepam/alcohol combination that for ease of falling asleep. None of the observed changes reached statistical significance. No morning hangover, as measured by effects on wakefulness, performance or affective state, was seen after the combined treatment. Its effect on blood pressure was negligible. It is concluded that the combined administration of temazepam and alcohol in the doses used here does not result in excessive additive, but in moderate pharmacological effects.

Adult↗

[Dopamine-induced secondary cardiomyopathy (author's transl)].

When myocardial fibre necrosis was produced experimentally in rats by high doses of dopamine, the main lesions were found in the left ventricular and septal myocardium. They could also be demonstrated in the left atrium. This report, which concerns clinical observations, is suggestive of a secondary cardiomyopathy in humans due to dopamine. The following pathogenetic mechanism is envisaged. The effects of dopamine are due to myocardial depletion of high energy phosphates following maximal stimulation and the increased, though inadequate adaptation of coronary resistance. The release of norepinephrine is also important. Aggravating factors may include the disturbed relationships of pulmonary ventilaltion to perfusion and the opening and dilatation of arterio-venous shunts in the lung, with subsequent hypoxaemia.

Animals↗

On a "chalone"-like factor for Ehrlich ascites mammary carcinoma.

In an aqueous ultrafiltrate (10 000--50 000) prepared from Ehrlich ascites mammary carcinoma (EAC) cells, ascites fluid and bovine mammary gland, a new factor was obtained which is involved in the growth regulating system of EAC cells as shown by the following facts: 1) It reversibly inhibits the proliferation of EAC cells in a 24 h suspension culture, depending on their proliferative state. Thus, stationary cells from the plateau phase of growth in vivo are prevented from resuming growth in vitro, while cells taken from the active phase of in vivo growth are not inhibited under the same conditions. Likewise, stationary cells do not respond when incubated in serum before the addition of the factor (depending on serum concentrations and time). The dose-response curve levels off at higher factor concentrations so that the maximal inhibition is about 50--65% (explained with different sensitivities of the cells in the assay system). The time course of the inhibition as well as preliminary data from flow cytophotometry and labeling with tritiated thymidine indicate an interference with the progression of G1-phase cells into the S-phase. 2) The activity of the factor is counteracted by insulin and proinsulin, both known as growth factors. The insulin concentration needed is dependent on the factor concentration; an almost maximal inhibition can be prevented by physiological concentrations of insulin. The activity can be destroyed by heat and trypsin and differs also in other properties from that of polyamines. The factor could not be detected in lung, liver, spleen, kidney, heart and L 1210 ascites fluid of the mouse or in bovine malignant lymph nodes, thymus, kidney or liver. The factor was purified from a homogenate of bovine mammary gland by ultrafiltration and affinity chromatography on sepharose-bound wheat lectin. Polyacrylamide electrophoresis showed about 5 bands of which one contained the activity (in some experiments overlapping with a second one). In this way a 800fold purification (starting from the ultrafiltrate) could be obtained. The overall purification (relative to the centrifuged homogenate) can be calculated to be more than 100 000 fold.

Animals↗