On the mode of action of heterologous antileukemic sera. Growth of syngeneically transplanted leukemias in serum-treated sublethally irradiated mice (author's transl)]

Heterologous antisera against mouse leukemias prevented the outgrowth of syngeneically transplanted leukemia cells only in non irradiated but not in sublethally irradiated animals. Mice irradiated with 500 R and controls were subcutaneously injected with 50000 leukemia cells at the day following irradiation. They were given 5 injections each of 0,1 ml of heterologous antiserum. Whilst 22 out of 27 irradiated mice developed tumors non-irradiated controls were protected, only 2 out of 30 animals developed a tumor. Cytotoxicity tests with leukemia cells as targets and mouse serum as complement source showed that the complement activity of mouse serum had not been suppressed by the whole body irradiation. We suppose a cooperation between heterologous antiserum and a radiosensitive host cell as responsible for the antileukemic effect.     

Colonization of the mouse liver by transplanted virogenic leukemia cells. Electron microscopic investigations (author's transl)]

Cells of a virogenic, immature myelogenic leukemia were injected in i.p. in one week old mice, strain NMRI, each animal receiving 10(5), 10(6) or 13(7) cells respectively in 0.2 ml Hanks' BSS. Mice were sacrificed at different times between 10 hrs and 21 days p.i. and liver specimens were prepared for electronmicroscopic studies. 10 hrs p.i. the leukemic cells are found in the sinusoids of the liver and after 30 hrs in the periportal fields. The leukemia cells migrate into the Disse spaces from the sinusoids. The leukemic cells penetrate with cytoplasmic digitations between connected endothelial cells. There is no lytic disintegration of the endothelial cells. The leukemic cells multiply by mitotic division of the Disse spaces, thereby compressing the liver cells. The cell membranes of both cell-types remain intact. Electronmicroscopically no evidence is found of a secretion of enzymes from the leukemia cells that destroy liver cells. Destruction of the liver cells is the consequence of the growth-pressure exerted by the dividing leukemic cells. Within the liver of the recipients the leukemic cells produce RNA-viruses. In the cytoplasm - frequently in the area of the Golgi-field - groups of immature A-particles are formed. In the virus fields the ribosomes disappear. The immature A-particles consist of two concentric electron dense shells. On the surface of the liver cells budding particles and immature C-particles develop. Extracellular mature C-particles with a homogeneous nucleoid and an irregular outer shell may be seen. The formation of viruses is found to be independent of the stage of the leukemia.     

On the cytosic action of N-methyl-N-beta-chloraethyl-hydrazine and its benzaldehydhydrazone (author's transl)]

N-Methyl-N-beta-chloroethyl-hydrazine and its benzaldehydhydrazone are two new cytostatic methylhydrazines. Administered intraperitoneally, they are more effective in inhibiting the ascites tumor growth (Ehrlich's carcinoma in mice and Yoshida sarcoma in rats) than procarbazine in vitro as well as in vivo. The intraperitoneal administration of hydrazone shows a minor effect on the solid tumor. This may be explained by a different pharmacocinetical behaviour. Hydrazone is less toxic than procarbazine.     

Treatment of leukemia in the elderly (author's transl)]

The treatment of elderly patients, who suffer from leukemia must not be standardized. Impaired bone marrow function, cardiovascular disease and other organopathias require an individually adapted therapy. The aim of treatment should be a good quality of life and not a remission at any price. Aggressive therapy in cases of acute leukemia with little progress should be avoided in favour of symptomatic treatment. CLL are treated in the progressive state of disease. Haemolytic anaemia and recurrent infections may complicate the course of CLL. CML is not a disease of old age but when it occurs intermittent therapy with cautious dosage is preferable to a continuous therapy.     

On the carcinogenic action of N-nitroso-compounds. 5th Communication: acetoxymethyl-methyl-nitrosamine (author's transl)]

After oral application of 3.5 and 1.75 mg/kg Acetoxymethyl-Methyl-nitrosamine to Sprague-Dawley rats twice weekly, more than 80% of the animals developed squamous cell carcinomas of the forestomach after 6 months.     

On the cytostatic mechanism of action of N-methyl-N-beta-chloroethylhydrazine and its benzaldehydhydrazone (author's transl)]

N-Methyl-N-beta-chloroethyl-hydrazine and its bezaldehydhydrazone inhibit the synthesis of DNA and RNA in ascites cells in vitro faster and stronger than N,N-Dimethylhydrazine and procarbazina does. The benzaldehydhydrzone essentially inhibits influx and phosphorylation of nucleosides whereas N-Methyl-N-beta-chloroethylhydrazine acts directly on DNA synthesis.     

On the biophysical interpretation of ageing-factors (author's transl)]

The ageing-factor is a measure for the rate of ageing. In the model of vitality the error rate mu corresponds to the ageing-factor. The ageing-factors of several physical functions can be determined from the ascent of decrease of these functions. The standardized ageing-factors of the considered physiological functions range from 0.001 to 0.017 year--1 and are smaller than the ageing-factor of the whole organism. The date of the occurrence of pathological manifestations as a result of ageing-conditioned decrease of functions can be estimated by means of the ageing-factors.     

About the elimination of thromboagglutinins from anti-lymphocytic serum (author's transl)]

The possible utilization of the effect of immunological tolerance for inhibition of formation of thromboagglutinins was studied, which dependent of the kind of antigen employed for immunization more or less contaminate antilymphocyte sera (ALS) or globulins (ALG). In the sera of pigs weighing 80-90 kg, immunized with human thrombocytes the thromboagglutinin levels in a) animals tolerated in adult age with an i.v. dose of 2.2 X 10(9) thrombocytes though the complete inhibition of thromboagglutinin formation failed even in these conditions. The attempted induction of tolerance in adult animals, similarly as in newborn piglets obtaining a dose of 1 X 10(9) thrombocytes, was of little success. Good results were recorded in animals tolerated in the perinatal period with a dose of 5 X 10(9) thrombocytes though the complete inhibition of thromboagglutinin formation failed even in these conditions. The authors suggest that of all possible methods for thromboagglutinin elimination, for ALS production the above technique, i.e. the induction of tolerance during the perinatal period seems most feasible, both from the viewpoint of effectiveness and thrombocyte consumption as well.