Effect of vincristine, adriamycin and glucocorticoids on myeloma cells in vitro.

The effect of in vitro exposure to vincristine, Adriamycin, and glucocorticoids was studied in 4 human myeloma cell lines. The drug concentrations tested approximated the steady-state plasma level achievable clinically. Marked growth inhibition was seen in all 4 cell lines with vincristine, but in only 2 with Adriamycin. Glucocorticoids were only minimally inhibitory. The inhibition by glucocorticoids was reversible after drug removal, but that by vincristine and Adriamycin was sustained except the vincristine inhibition of ARH-77 cells. The degree of cell growth inhibition paralleled the reduction in tumor cell 3H-thymidine uptake. Cell cycle distribution analysis showed an arrest of myeloma cells at M/G2 phase by vincristine and Adriamycin and an inhibition of myeloma cells from entering into S phase by dexamethasone. Dose-response analysis with ARH-77 cells, a cell line that appeared the most chemoresistant, showed that the growth-inhibitory effect of Adriamycin and vincristine was roughly proportional to the product of drug concentration and exposure time. However, in contrast to Adriamycin, an effective vincristine concentration and exposure time that totally inhibited cell growth was unable to prevent cell regrowth after drug removal. A higher vincristine concentration appeared to be more effective in preventing cell regrowth.

[Possibilities for increasing the elimination rate of Bonnecor]. / Möglichkeiten zur Beschleunigung der Elimination von Bonnecor.

Bonnecor is excreted in rats both via urine (3/4) and bile (1/4). It was the aim of this study to find out suitable methods for detoxication of a poisoning with this antiarrhytmic drug. In vivo methods intended to enhance the renal excretion of Bonnecor (forced diuresis, changes in urinary pH-values, peritoneal dialysis) are not qualified for therapeutically relevant increase of Bonnecor elimination. Relating to this Bonnecor is quite comparable with other antiarrhythmic drugs or dibenzazepine derivatives. The hemoperfusion can be recommended for the therapy of a Bonnecor overdosage as a propping up of symptomatic methods of intensive care, which are precendentally indicated. Therefore the therapy of a Bonnecor poisoning seems to be more promising compared to intoxications with other antiarrhythmics. Among the adsorbents tested, the resin Wofatit UH91 is most suitable to remove Bonnecor from the organism. If hemoperfusion equipments are not available, hemodialysis can also be used for acceleration of Bonnecor elimination, although its effectivity is only one third of that of hemoperfusion.

Assessment of the quality of life of patients with advanced cancer.

Four methods of assessment of the quality of life were compared in 100 patients with advanced cancer. All showed highly significant correlations with each other. In particular, a single-item linear analogue self-assessment (LASA) which indicated the patients' general feeling of well-being showed a highly significant correlation with multiple item measures of the quality of life (interviewer-administered and self-administered versions of a 5-item quality of life index, and a 21-item LASA). The LASA indicating well-being was compared in a further 30 patients with a similar single-item LASA in which the term 'quality of life' was used. This comparison again showed a highly significant correlation. It is concluded that a single-item LASA asking the direct question "How would you rate your quality of life today?" is a valid and reliable indicator of the quality of life of patients with cancer.

The absorbance coefficient of beef heart cytochrome c1.

Isolated cytochrome c1 contains endogenous reducing equivalents. They can be removed by treating the protein with sodium dithionite followed by chromatography. This treatment has no effect on the reaction with cytochrome c, nor does it alter the optical spectrum, or the polypeptide or amino acid composition of the protein. Both the titration of dithionite-treated ferrocytochrome c1 with potassium ferricyanide and the anaerobic titration of dithionite-treated ferricytochrome c1 with NADH in the presence of phenazine methosulphate lead to the same value for the absorbance coefficient of cytochrome c1: 19.2 mM-1 . cm-1 at 552.4 nm for the reduced-minus-oxidised form. This value was also obtained when the haem content was determined by comparing the spectra of the reduced pyridine haemochromes of cytochrome c and cytochrome c1. Comparison of the optical spectra of cytochrome c and cytochrome c1 by integration shows equal transition moments for the transitions in the porphyrin systems of both proteins. A set of equations with which the concentration of the cytochromes aa3, b, c and c1 can be calculated from one reduced-minus-oxidised difference spectrum of a mixture of these proteins.

The isolation and purification of cytochrome c1 from bovine heart.

A large-scale isolation method for cytochrome c1 from beef heart is presented, based in principle on the procedure of Yu et al. (Yu, C.A., Yu, L. and King, T.E. (1972) J. Biol. Chem. 247, 1012--1019). Optimal solubilization of cytochrome c1 from succinate-cytochrome c oxidoreductase was achieved with 15% beta-mercaptoethanol, 1.5% cholate, 0.5% deoxycholate in 8% saturated ammoniun sulphate. The protein is purfied to a higher degree by chromatography on DEAE-cellulose and Ultrogel AcA 44. The method is reproducible and gives highly purified cytochrome c1 with a yield from succinate-cytochrome c oxidoreductase of 40%. The purified cytochrome c1 contains 32 nmol of heme/mg protein and has a spectral heme-to-protein ratio (Ared417nm/Ax276nm) of 2.7. Reduced cytochrome c1 is oxidized very rapidly by ferricytochrome c (k = 3 . 10(7) M-1 . S-1 at 10 degrees C, 100 mM potassium phosphate (pH 7.0) and 1% Tween 20). Polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulphate shows that the isolated protein consists of one peptide, with a molecular weight of 31 000, carrying the chromophore. In the presence of 1% sodium cholate or 1% Tween 80, cytochrome c1 is in the monomeric state, whereas at lower concentrations of detergent the protein aggregates. The aggregation of cytochrome c1 is found to be reversible.