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Biomedical subjects

R Alitalo

Publications and source records attributed to R Alitalo.

41 records · Page 3Linked to original sources
PubMed1987

Regulation of platelet-derived growth factor gene expression by transforming growth factor beta and phorbol ester in human leukemia cell lines.

We studied the expression of the genes encoding the A and B chains of platelet-derived growth factor (PDGF) in a number of human leukemia cell lines. Steady-state expression of the A-chain RNA was seen only in the promonocytic leukemia cell line U937 and in the T-cell leukemia cell line MOLT-4. It has previously been reported that both PDGF A and PDGF B genes are induced during megakaryoblastic differentiation of the K562 erythroleukemia cells and transiently during monocytic differentiation of the promyelocytic leukemia cell line HL-60 and U937 cells. In this study we show that PDGF A RNA expression was induced in HL-60 and Jurkat T-cell leukemia cells and increased in U937 and MOLT-4 cells after a 1- to 2-h stimulation with an 8 pM concentration of transforming growth factor beta (TGF-beta). PDGF A RNA remained at a constant, elevated level for at least 24 h in U937 cells, but returned to undetectable levels within 12 h in HL-60 cells. No PDGF A expression was induced by TGF-beta in K562 cells or in lung carcinoma cells (A549). Interestingly, essentially no PDGF B-chain (c-sis proto-oncogene) RNA was expressed simultaneously with PDGF A. In the presence of TGF-beta and protein synthesis inhibitors, PDGF A RNA was superinduced at least 20-fold in the U937 and HL-60 cells. PDGF A expression was accompanied by secretion of immunoprecipitable PDGF to the culture medium of HL-60 and U937 cells. The phorbol ester tumor promoter tetradecanoyl phorbol acetate also increased PDGF A expression with similar kinetics, but with a mechanism distinct from that of TGF-beta. These results suggest a role for TGF-beta in the differential regulation of expression of the PDGF genes.

Cell Differentiation↗
PubMed1985

Acute myelogenous leukaemia with c-myc amplification and double minute chromosomes.

Cytogenetic analysis of bone-marrow cells from a woman with preleukaemia showed numerous mitoses with trisomy 4 and double minute chromosomes. These abnormalities were later seen in blood cells during subsequent acute myeloid leukaemia (AML). Complete remission was achieved with three courses of doxorubicin, cytosine arabinoside, and prednisone. A further clonal abnormality, trisomy 6, was seen in leukaemic cells after the first relapse. Analyses of total DNA from the peripheral-blood cells during relapse showed that the c-myc oncogene was amplified about 30-fold in the leukaemic cells. The N-myc, c-mos, and c-myb oncogenes showed only single-copy signals. On average about two copies of c-myc resided on each dmin chromosome. The finding of amplification of a cellular oncogene (c-myc) in fresh AML cells containing double minute chromosomes suggests that clonal evolution of some leukaemia cell populations may involve selection for increased dosage of oncogenes.

Chromosome Aberrations↗
PubMed1985

Hypoprothrombinaemia and bleeding during administration of cefamandole and cefoperazone. Report of three cases.

Deficiency of vitamin K-dependent coagulation factors caused by the cephalosporin derivatives cefamandole, cefoperazone and moxalactam has been recently recognized. It has been suggested that this adverse reaction may result from vitamin K deficiency caused by eradication of the vitamin K producing intestinal bacteria or inhibition of action of vitamin K 1. Three patients are described in whom hypoprothrombinaemic bleeding developed during administration of cefamandole or cefoperazone. All patients were elderly, had previous malnutrition or had been on parenteral nutrition without vitamin K supplementation. One patient had renal failure. Bleeding manifested 5-14 days after the start of antibiotic treatment. Other causes of the bleeding were excluded. One case was fatal and in 2 cases the coagulopathy was corrected by administration of vitamin K 1 or fresh frozen plasma and cessation of the antibiotic. We recommend prophylactic administration of vitamin K 1 during cefamandole or cefoperazone treatment to patients at risk, i.e. elderly malnourished patients especially those with renal failure or on parenteral nutrition.

Aged↗