Depressive symptoms in hypercholesterolaemic patients treated with pravastatin.
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Adult↗
Biomedical subjects
G Konwalinka
Publications and source records attributed to G Konwalinka.
Inhibitory effect of 2-chlorodeoxyadenosine on granulocytic, erythroid, and T-lymphocytic colony growth.
Previous studies have shown that 2-chloro-2'-deoxyadenosine (CdA) is markedly toxic to normal and malignant human lymphocytes in vitro and in vivo. Recent clinical trials have shown that CdA is a very promising drug for the treatment of lymphoid malignancies. The present investigations were designed to test the effect of CdA on the in vitro clonal growth of both myeloid progenitors and T-lymphocyte colony-forming cells (CFU-TL) obtained from normal human bone marrow and peripheral blood. Cells were exposed to CdA in doses up to 1280 nmol/L. To reduce indirect effects of CdA mediated by accessory cells, monocyte- and T-lymphocyte-depleted bone marrow cells were used for our investigations. The results show a marked inhibition of myeloid progenitor and lymphocyte colony-forming cells in a dose-dependent manner, correlating with maturation stage in that the immature progenitor cells are more sensitive to this drug. Furthermore, our studies suggest that a sequence of metabolic events previously described for lymphocytes may be operative in myeloid progenitor cells because a minimal exposure time of 48 hours is required to obtain a marked inhibition. CdA toxicity was proposed to be linked with phosphorylation by deoxycytidine-kinase (E.C. 2.7.1.74), the levels of which have been found to be high in lymphocytes, but low in granulocytes. However, the marked inhibition of myeloid progenitor cells shown in these studies suggests that other factors such as modulation of the effect of CdA by the ambient levels of other deoxynucleosides might influence the apparent sensitivity of myeloid cells.
2-Chloroadenosine↗
[Bone marrow culture in aplastic anemia and preleukemias].
After incubation of bone marrow cells obtained from normal subjects and patients with pancytopenia in the double layer agar culture (Robinson-Pike), the clusters of different size and the colonies were counted on days 2, 3, 5, 7 and 10. Aplastic anemia and two types of preleukemia could be distinguished by a different growth pattern. A high incidence of small clusters (4-12 cells) was found in patients with aplastic anemia on days 2 and 3, whereas these aggregates were markedly reduced in preleukemia of type B. In preleukemia of type A an excessive number of small clusters was obtained. The morphology of cells in clusters and colonies was studied by cytochemical staining and electronmicroscopy. In preleukemia marked defects of maturation were demonstrable in the cells.
Anemia, Aplastic↗
[Aplastic anemias].
In the first part of this review diagnostic criteria and prognostic factors are summarized. The results of bone marrow culture with particular reference to the pathophysiology of this disease, are discussed. Finally, the conventional therapeutic approaches are summarized and recent developments in experimental treatment modalities are discussed.
Anemia, Aplastic↗
Detection of cytochemical and morphological anomalies in 'preleukemia'.
The present investigations confirm and extend previous reports on the occurrence of cytochemical anomalies among the hemopoietic cells in preleukemia. The cytochemical patterns of the hemopietic cells obtained from 19 patients suffering from a preleukemic disorder have been studied. The diagnostic value of the cytochemical examination using a panel of 10 different tests is emphasized. In a prospective study in 17 out of 25 patients, preleukemia had been correctly diagnosed. In 4 patients leukemia developed within 2-4 months from the diagnosis ('imminent leukemia'), in 13 patients leukemia or smouldering leukemia developed between 4 and 25 months after the diagnosis ('true preleukemia'). The cytochemical profiles of the hemopoietic cells of the latter have been compared with those of 14 patients suffering from aplastic anemia. In preleukemia the blasts did not exceed 3% of the nucleated bone marrow cells. The clinical value of the diagnosis 'preleukemia' is discussed as well as the prognosis and the possible therapeutic approaches.
Adult↗