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Biomedical subjects

Sveinn Gudmundsson

Publications and source records attributed to Sveinn Gudmundsson.

4 recordsLinked to original sources

Sulphasalazine inhibits human antigen-specific immune responses in vivo.

OBJECTIVE: To study the effects of the antirheumatic drug sulphasalazine (SASP) on the immune system by analysing systemic and gut-associated immune responses. METHODS: A total of 23 healthy volunteers were treated with either SASP or placebo for 5 weeks in a double-blind fashion and immunised 2 weeks after the initiation of treatment. Specific immune responses were triggered by subcutaneous immunisation with tetanus toxoid and by peroral immunisation with inactivated influenza vaccine. The effects of treatment on specific immunity to tetanus and influenza were evaluated by enzyme-linked immunospot assay quantifying the number of circulating specific and total antibody-producing cells (spot-forming cells (SFC)) at 6, 8 and 10 days after immunisation. RESULTS: An immunosuppressive effect of SASP on systemic immune response was observed with a decrease in the total number of IgG-SFC, IgG anti-tetanus SFC and IgG anti-tetanus antibody levels in serum. SASP also exerted an immunosuppressive effect on the mucosa-associated immune system as seen from its down-regulating effect on the total number of circulating IgA SFC. CONCLUSIONS: These data show firstly that SASP exerts an immunosuppressive effect on defined immune responses to immunisation in vivo, and secondly that both mucosa-associated and systemic immunity are affected by SASP treatment.

Adolescent↗

Flt3/Flk-2 ligand in combination with thrombopoietin decreases apoptosis in megakaryocyte development.

The growth factors thrombopoietin (TPO) and Flt3/Flk-2-ligand (FL), either independently or in combination, modulate megakaryocyte development. Our results show that bone marrow CD34+ cells cultured with TPO and FL differentiate at a slower rate into CD41+ cells and are delayed in apoptosis at the later stages of the cultures compared to cells cultured with TPO alone. Our data also show that FL in synergy with TPO may inhibit apoptosis in megakaryocyte development by up-regulating bcl-2 and inducing conformational changes of p53, in MK progenitors. FL in combination with TPO slows down maturation and consequently delays apoptosis of MK progenitor cells.

Apoptosis↗

An age-associated decrease in the frequency of C4B*Q0 indicates that null alleles of complement may affect health or survival.

We studied the distribution of complement C4, C3, and factor B allotypes in 423 healthy Icelandic subjects from 17 to 89 years of age. A marked decrease was observed in the carrier frequency of variant alleles of complement C4B (C4B(*)Q0) and C3 (C3(*)F). These results confirm our previous observations on Hungarian subjects and suggest a negative effect of C4B(*)Q0 on health or survival.

Adolescent↗

Flt3/Flk-2-ligand in synergy with thrombopoietin delays megakaryocyte development and increases the numbers of megakaryocyte progenitor cells in serum-free cultures initiated with CD34+ cells.

Megakaryocytopoiesis involves proliferation and maturation of committed precursors that increase their size by polyploidy, a process that is believed to be critical for the efficient production and release of platelets. Thrombopoietin has been shown to act on proliferation, maturation, and survival pathways in megakaryocytopoiesis. Less is known about the role of Flt3/Flk-2-ligand in this development. Apoptosis has an important role in hematopoiesis in general. It has been shown to have an effect on senescent megakaryocytes but not megakaryocyte progenitor cells. In this study, a serum-free culture model was developed, differentiating bone marrow CD34(+) hematopoietic stem cells into megakaryocytes, using thrombopoietin and Flt3/Flk-2-ligand. The model was used to study the effect of these growth factors on expansion of megakaryocyte progenitor cells, differentiation of megakaryocytes, and ploidy. Our results demonstrate that bone marrow CD34(+) cells cultured with thrombopoietin and Flt3/Flk-2-ligand show a lower developmental rate into MK cells compared to cells cultured with thrombopoietin alone. Cells cultured with thrombopoietin and Flt3/Flk-2-ligand expressed less CD41, the ploidy level was lower, and they appeared less mature. On the other hand, the cells showed up to 10-fold increase in cell numbers compared to five-fold increase when cultured with thrombopoietin alone. These results suggest that Flt3/Flk-2-ligand in synergy with thrombopoietin may slow down megakaryocyte development by causing increased proliferation of megakaryocyte progenitor cells.

Antigens, CD34↗