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Biomedical subjects

E Vellenga

Publications and source records attributed to E Vellenga.

220 records · Page 13Linked to original sources

Platelet activation, fibrinolytic activity and circulating immune complexes in Raynaud's phenomenon.

Circulating immune complexes (CIC), platelet activation and fibrinolytic activity were assessed in 133 patients with Raynaud's phenomenon (RP), 41 with primary RP, 73 with secondary RP and 19 with RP and minor symptoms of connective tissue disease (suspected secondary RP). Increased levels of CIC were found in secondary and suspected secondary RP. In those groups spontaneous platelet aggregation also was found, a percentage of which correlated with levels of CIC. In all groups elevated levels of beta-thromboglobulin, a platelet specific protein released during platelet activation, and decreased levels of alpha 2-antiplasmin, the main inhibitor of fibrinolysis, were found, together with hyperfibrinogenemia.

Adult↗

The additive effect of peripheral blood stem cells, harvested with low-dose cyclophosphamide, to autologous bone marrow reinfusion on hematopoietic reconstitution after ablative chemotherapy in breast cancer patients with localized disease.

The additive effect of peripheral blood stem cells (PBSCs) to autologous bone marrow transplantation (ABMT) on haematopoietic reconstitution, after ablative chemotherapy in patients with locally advanced breast cancer, was evaluated. Patients were treated with induction chemotherapy, followed by ablative chemotherapy consisting of mitoxantrone and thiotepa. Group I (n = 14) received ABMT and granulocyte macrophage-colony stimulating factor (GM-CSF), group II (n = 11) received ABMT, PBSCs and granulocyte-colony stimulating factor (G- CSF). PBSCs were harvested after a low-dose cyclophosphamide (750 mg/m2), followed by G-CSF. Stem cell harvest was routinely started 12 days after cyclophosphamide. Compared to group I, group II showed a significant reduction in the median number of days for leukocytes < 0.5 x 10(9)/L 4.5 days, leukocytes < 1.0 x 10(9) / l 5.5 days, platelets < 20 x 10(9)/ l 9 days and platelets < 40 x 10(9) / l 12.5 days. The median number of transfusions of platelets fell from 11.5 to 7 and of red blood cells from 8.5 to 6. The median hospitalisation duration declined from 40.5 to 30 days, fever above 38 degrees C with 7.5 days, fever above 38.5 degrees C with 4 days and antibiotic treatment with 8.5 days in group I versus group II. Improvement of haematological recovery, duration of fever and hospitalisation was observed by the addition of PBSCs, obtained after a relatively low-dose cyclophosphamide and G-CSF and stem cell pheresis on fixed days, to autologous bone marrow and growth factor in the period after ablative chemotherapy.

Adult↗

Divergent effects of IL-10 and IL-4 on the proliferation and growth factor secretion by acute myeloblastic leukemic cells.

The effects of interleukin-10 (IL-10) and IL-4 were studied on the spontaneous and IL-1, IL-3, and Granulocyte-Colony Stimulating Factor (G-CSF) supported proliferation of acute myeloid leukemic cells. IL-10 inhibited the spontaneous proliferation in 1 out of 12 (1/12) cases while the IL-1 stimulated the tritiated thymidine (3H-TdR) uptake was suppressed in 2/12 cases as a result of IL-10 administration. In the presence of G-CSF, IL-10 affected 3H-TdR uptake in 2/12 and no distinct changes were observed in the presence of IL-3. In contrast IL-4 alone stimulated (3H-TdR) uptake with a factor two or more in 7/12 cases. In the presence of IL-1 and G-CSF a further enhancement was noted in 2 and 5 cases respectively. In 2/12 cases IL-4 inhibited the spontaneous or IL-1 and G-CSF supported proliferation. To study whether the changes in 3H-TdR uptake are related to the endogenous secretion of G-CSF and GM-CSF, AML blast cells (n = 5) were cultured in medium supplemented with IL-1 or IL-3 in the absence and presence of IL-10 and IL-4. IL-10 did not inhibit the spontaneous secretion of G-CSF or GM-CSF but suppressed the IL-1 induced GM-CSF secretion in 2/5 cases. These moderate effects were observed despite the strong inhibition of IL-10 on the IL-6 secretion by human activated monocytes. In contrast to IL-10, IL-4 also inhibited the spontaneous (3/5) and cytokine induced (5/5) secretion of G-CSF and GM-CSF (4/5) protein in the cases in which an enhancement of the 3H-TdR uptake was noticed. In summary the data indicate that the proliferative effects of IL-4 are in some cases uncoupled from the endogenous secretion of cytokines. In addition IL-10 affects the AML cells in a limited number of cases despite the similarity in effects between IL-4 and IL-10 in suppressing cytokine secretion from activated human monocytes.

Adult↗

Mutual interactions between p53 and growth factors in cancer.

The function of p53 tumour suppressor protein is determined by various intrinsic properties of the protein. The effect of p53 DNA-binding, and protein-protein interactions are determined by the conformation of the protein. Thus, p53 fulfils its role in cell cycle control and the onset of apoptotic cell death, which is altered when the wild-type p53 (wt-p53) conformation is changed due to mutation. This review focuses on the communal interactions of wt- and mutant p53 (m-p53) with growth factors and shows that m-p53 affects different cell biological functions that determine the malignant behaviour of cells. P53, for instance, affects the response of cells to growth factors and growth factor-withdrawal. Furthermore, p53 is involved in the expression of several growth factor- and growth factor receptor genes. These data suggest that restoration of the wt-p53 phenotype in tumour cells with m-53 might not only affect cell cycle control and apoptotic mechanisms but could also reduce autocrine growth and restore sensitivity to physiological growth inhibitors.

Animals↗