The effect of platelet homogenate fractions on megakaryocytopoiesis in the mouse.

Platelet homogenate suppresses megakaryocytopoiesis more effectively than intact platelets do. In mouse experiments mitochondrial, lysosomal, and microsome fractions separated by ultracentrifugation from platelet homogenate did not influence megakaryocytopoiesis, while the cytosol fraction inhibited it similarly as platelet homogenate. Besides thrombopoietin, the substance released from the platelets also takes part in the regulation of thrombocytopoiesis and this substance passes into the cytosol fraction on separation by ultracentrifugation.

Prognostic factors in dysmyelopoietic syndromes.

Dysmyelopoietic syndromes are characterized by cytopenia in peripheral blood and marrow maturation abnormalities. The condition has been studied in 33 patients with regard to the initial haematologic picture. A certain number of variables of prognostic value was observed: excess of marrow blasts, pancytopenia, and decreased growth of bone marrow cells in agar culture. The length of survival and the percentage of leukaemic transformation were different in patients with refractory anaemia and refractory anaemia with an excess of blasts.

[The role of splenectomy in the treatment of lymphomas of low malignancy]. / Die Rolle der Splenektomie in der Behandlung von Lymphomen niedriger Malignität.

The effect of splenectomy was studied in 30 patients with non-Hodgkin lymphoma of low malignancy. Severe bacterial infections occurred in 9 patients. Follow-up of the total group of 72 patients-years revealed one infection requiring hospitalization per eight patient-years. With chronic lymphatic leukaemia there was no difference in the incidence of severe infection between splenectomized and non-splenectomized patients. In 12 patients the splenectomy produced favourable results in that in some (8) cytostatic treatment was no longer required, while in others (4) the dose of cytostatic drugs could be reduced after several months without any medication. Survival rate was not influenced by splenectomy.

[In vitro study of bone marrow from leukemia patients and patients without hematologic disease]. / In-vitro-Untersuchung des Knochenmarkes von Leukämiekranken und Patienten ohne hämatologische Abweichungen.

The bone-marrow of 26 patients not affected with hematological diseases and 10 patients with untreated leukemia was investigated according to Dexter in long-term cultures. Survival time and cell content of those long-term cultures started with normal bone marrow were not influenced significantly, if reinoculation was made with autologeneic or allogeneic bone marrow. Even without repeated inoculation, leukemic cells grew for a longer time in long-term cultures than normal bone marrow cells. As far as the outcome of the disease is concerned, no conclusion can be drawn from the duration of cultivating leukemic cells growth.

Relationship between the age of platelets and their megakaryocytopoiesis-inhibiting effect.

Homogenate made from young platelets suppressed thrombocytopoiesis in mice more effectively than homogenate made from old platelets. To achieve the same suppressive effect as that of young platelets, homogenate made from twice as many old platelets were needed.

Effect of sera obtained from thrombocytopenic mice on syngeneic long-term bone marrow cultures.

BDF1 mice were rendered severely thrombocytopenic by antiplatelet serum and the effect of serum from these thrombocytopenic mice on early precursors of syngeneic bone marrow was studied in Dexter's long-term cultures. The CFUMega content had increased on the first day, reaching its maximum on the second and third days, and returned to its initial value by the seventh day. Repeated treatment prolonged the effect, and larger doses produced larger increases in CFUMega. Besides the increase in CFUMega content, the number of CFUS and of total cells also increased. The CFUC number did not change.

Effect of platelet homogenate on platelet production of bone-marrow-transplanted mice.

Haemopoiesis of mice was reconstituted with 1 X 10(6) bone marrow cells after 800 r total body irradiation. Then their megakaryocytopoiesis was inhibited by platelet homogenates given at different points of time on three subsequent days. The effect was measured by the peripheral platelet counts on the 14th day after transplantation when the platelet count of irradiated and marrow-transplanted CFLP animals was 410 X 10(9)/l, and that of CBA mice was 185 X 10(9)/1. Platelet homogenates prepared from 1-2.5 X 10(8) platelets daily given on days 1, 2 and 3 did not significantly reduce the peripheral platelet count estimated on the 14th day, while homogenates given on days 8, 9 and 10 reduced it markedly. Homogenates prepared from 0.7-1.0 X 10(6) white blood cells did not influence the 14th day platelet count. Thus, platelet homogenates exert their inhibitory effect at a late stage of platelet production, i.e. not by an inhibition of thrombopoietin or a thrombopoietin effect.

[Thrombopoietic activity induced by blood withdrawal and administration of antithrombocyte serum in nephrectomized rats. Role of kidneys in the production of thrombopoietin]. / Untersuchung der durch Blutentzug und Gaben von Antithrombozytenserum erzeugten thrombopoetischen Aktivität bei nephrektomierten Ratten. Zur Rolle der Niere bei der Erzeugung von Thrombopoetin.

The thrombopoietic serum activity was examined in rats during thrombocytopenia produced by bleeding or after treatment with antithrombocyte serum (ATS). 6 hours after both treatments the thrombopoietic activity of the serum, i.e. its content of thrombopoietin, is increased. After the ATS treatment of nephrectomized animals a similar increase of thrombopoietic activity as in normal animals could be achieved. In contrast to that, no similar increase of thrombopoietic activity was observed in nephrectomized animals after blood loss. According to the results of the authors the increase of thrombopoietic activity produced by different stimuli can be attributed to different mechanisms.

Specific thrombopoietic inhibition by syngeneic platelet homogenates.

Injections of 1 to 2.5 X 10(8) syngeneic, uninjured platelets did not diminish the circulating platelet count nor the bone marrow megakaryocyte content in mice, and did not influence the incorporation of 75selenomethionine into circulating platelets. However, platelet homogenates, prepared by repeated freezing and thawing of identical amounts of syngeneic paltelets induced a dose-dependent thrombocytopenia along with a diminution on bone marrow megakaryocyte content, and a decrease in 75 selenomethionine incorporation. Other circulating blood cell counts were not diminished after platelet homogenates, and three intravenous doses of homogenates prepared from 0.7 to 1 X 10(5) syngeneic buffy coat cells failed to influence circulating platelet count or 75 selenomethionine incorporation.

Effect of F-leurosine (formyl-leurosine) on platelet production in mice.

F-leurosine (formyl-leurosine) was found to exert a thrombocytopoietic effect in CFLP mice. The effect was most pronounced in a dose of 1.0 mg/kg. The increased activity of the megakaryocyte system was not due to thrombocytopenia. The preparation induced in the bone marrow an increasing megakaryocyte formation (increase of the megakaryocyte index, a shift to the left in the qualitative composition of the giant cells, increase of the 75Se-methionine incorporation). F-leurosine seems to exert its effect through a direct stimulation of the megakaryocyte system, which might be utilized in therapy.

Incorporation of H3-leucine in the mouse kidney in thrombocytopenia. Attempt to demonstrate thrombopoietin production.

Light and dark field autoradiography of semithin sections prepared 6 h after a treatment with APS showed that the incorporation of H3-leucine into the cells of the convoluted tubules of the kidney was increased in mice. There was no difference in the H3-leucine incorporation in the liver, either in thrombocytopenic or in untreated animals. The increased incorporation of leucine in the kidney in APS-induced thrombocytopenia showed coincidence with increased thrombopoietin production.

Erythropoietin level and thrombocytopoiesis in mice.

After administration of a single 1 IU dose of exogenous erythropoietin to mice or by stimulating endogenous erythropoietin production with androgen, the animals' thrombocytopoiesis, measured with selenomethionine incorporation, decreased. The suppression of endogenous erythropoietin level by hypertransfusion also caused a decrease of thrombocytopoiesis.