Thalidomide in advanced mastocytosis

Mastocytosis is an acquired orphan disease characterized by the abnormal accumulation of mast cells responsible for organ failure and systemic symptoms. Cytoreductive drugs have been shown to be effective, but have rarely resulted in complete or long-term remission. We report two patients with advanced systemic mastocytosis (SM) who were treated successfully with thalidomide, given at the maximal tolerated dosage. B and C-findings as well as clinical symptoms rapidly improved. After a follow-up of more than 1 year, the patients remained in partial remission. Thalidomide seems to be an active drug in advanced SM. However, clinical trials are warranted to define its efficacy and safety profiles.     

TGF-beta1 drives and accelerates erythroid differentiation in the epo-dependent UT-7 cell line even in the absence of erythropoietin

OBJECTIVE: TGF-beta1 is a powerful inhibitor of erythropoiesis. However, its mechanisms of action are not fully elucidated yet at the cellular level. In this work we have studied the effects of TGF-beta on UT-7 cell survival, proliferation and differentiation. MATERIALS AND METHODS: UT-7 cell line is strictly dependent on growth factors for cell survival, growth, and differentiation. Epo (2 U/mL) induces erythroid differentiation as assessed by up regulation of glycophorin A and the presence of 5%-10% benzidine positive cells (BPC). In contrast, even in the presence of Epo (2 U/mL), GM-CSF (1 ng/mL) inhibits erythroid differentiation. RESULTS: When UT-7 cells were switched from GM-CSF to Epo, TGF-beta1 (2 ng/mL) induced a rapid (3 days [Epo+TGF-beta1] vs 8 days [Epo]) and marked erythroid differentiation (80% [Epo+TGF-beta1] vs 10% [Epo] BPC) including Hemoglobin A synthesis (HbA/HbF ratio of 1 [Epo] vs 4 [Epo+TGF-beta1]). In the presence of GM-CSF, although to a lesser extent, TGF-beta1 induced erythroid differentiation (40% BPC). This effect was not a consequence of TGF-beta1-induced apoptosis because, in the presence of Epo or GM-CSF, apoptosis occurred only at day 8 or 10, respectively. Moreover, although SCF inhibited apoptotic effect of TGF-beta1, SCF+TGF-beta1+Epo was the best combination to give rise to the highest number of hemoglobinized cells. We further demonstrated that induction of erythroid differentiation by TGF-beta1 was not due to an autocrine loop involving Epo/Epo-R or to a prolongation of the G1 phase of the cell cycle. CONCLUSION: Taken together, these data suggest that TGF-beta1 is an inducer of erythroid differentiation, even stronger than Epo at the cellular level.     

Differential response of human basophils and mast cells to recombinant chemokines

Chemokines are proinflammatory peptides regulating the functions of various hematopoietic cells. We have analyzed the effects of seven recombinant human (rh) chemokines (MCAF, RANTES, MIP-1, MIP-1, IL-8, GRO, and IP-10) on the growth and function of human basophils and mast cells. We found that MCAF, but not RANTES, MlP-la, MIP-1, IL-8, GRO, or IP-10, causes direct and dose-dependent histamine release from basophils (MCAF, 5 g/ml: 26.9 ± 3.4%; other chemokines: < 5% of total histamine). An increased (2.1 to 3.5-fold) response to MCAF was obtained when basophils were preincubated with rh interleukin-3 (100 units/ml). Moreover, IL-3-primed basophils became responsive to physiologic concentrations (< 1 g/ml) of MCAF, IL-8, and RANTES. None of the chemokines tested was able to induce histamine secretion in mast cells obtained from lung (n=2), skin (n=1), uterus (n=3), or tonsils (n=3), even when cells had been preincubated with the mast cell agonist SCF. The chemokines also failed to modulate the expression of activation antigens (CD11b/C3biR, CD25/IL-2R, CD63, IL-3R, CD117/c-kit) on the mast cell line HMC-1 or the basophil cell line KU-812 and were unable to induce differentiation of basophils or mast cells in culture. Together, our results show that basophils respond to rhIL-8, rhMCAF, and rhRANTES and that, unlike human basophils, human mast cells are unresponsive to recombinant chemokines.This work was supported by FWF Austria, grant P-9359, and by Sandoz, Vienna     

The real superdonors

Before frequency and age limits were established for blood donations, certain individuals were exceptional in the frequency and the number of blood donations over their life. We call them “superdonors” and describe their common characteristics through some examples. The physiologic characteristics allowing these individuals to give blood several hundred times without developing an anemia are unknown.     

Über den Entaktivator,ein biologisch wirksames Oxydationsprodukt des Ergosterins

Ohne ZusammenfassungMit 21 Textabbildungen.Mit Unterstützung der Deutschen Forschungsgemeinschaft.     

Beiträge zur Chemie des Carcinoms

Ohne ZusammenfassungMit 1 Textabbildung.     

Über Respirationsversuche bei Infusion von isotonischen Kochsalzlösungen

Ohne Zusammenfassung