Shingo Aikawa

Comparison of erythropoietic response to androgen in young and old senescence accelerated mice.

In this study, to clarify whether the functional capacity of hemopoietic progenitor cells and the micro-environment of aged mice are identical with those of the young, we investigated the changes in the number of hemopoietic progenitor cells and the production of regulatory cytokines from splenic cells as well as changes in the serum levels of cytokine in senescence-accelerated mice (SAM) after administration of 19-nandrolone decanoate (19-ND), a synthetic androgenic anabolic steroid. 19-ND induced an increase in erythroid colony-forming units (CFU-E), erythroid burst-forming units (BFU-E), and granulocytic-macrophage committed progenitor cells (CFU-GM) in bone marrow and spleen; especially remarkable increases were observed in the splenic CFU-E in both young and old mice. Antigen expression analysis of hemopoietic organs revealed that total TER-119+ cells per spleen of young and old mice with androgen treatment rose 2.6- and 3.2-fold over their respective control values. The responsiveness of hemopoietic progenitor cells to androgen did not change with age. Injection of 19-ND into young and old mice markedly enhanced the erythropoietin levels but not IL3 and GM-CSF levels in the serum of both groups. Cytokine production assessed by pokeweed mitogen-stimulated spleen condition medium showed an age-related decline. Androgen treatment could not influence IL-3 and GM-CSF production of spleen. These findings suggest that the spleen of both old and young mice served as the major site of regenerative repopulation of hemopoietic progenitors, especially the late erythroid progenitors in 19-ND-treated mice. The proliferative reserve of erythropoiesis with androgen treatment in aged mice was not reduced more than that in treated-young mice.

Treatment of high-risk peripheral T-cell lymphomas other than anaplastic large-cell lymphoma with a dose-intensified CHOP regimen followed by high-dose chemotherapy. A single institution study.

We investigated the efficacy of a dose-intensified double-CHOP regimen followed by high-dose chemotherapy with or without peripheral blood stem cell transplantation (PBSCT) in 11 patients with four types of peripheral T-cell lymphoma (PTCL). Three of the 4 patients with unspecified PTCL (PTCLu) achieved complete response (CR); 1 patient relapsed and 1 died of secondary leukemia after consolidation therapy. All angioimmunoblastic T-cell lymphoma (AILT) and subcutaneous panniculitis-like T-cell lymphoma (SPTCL) patients achieved CR; 5 of 6 have remained disease free for more than 3 years. The patient with hepatosplenic lymphoma did not achieve CR even after PBSCT and underwent allogenic bone marrow transplantation (allo-BMT). Thus, our regimen appears to be effective for high-risk AILT and SPTCL. However, allo-BMT should be considered for high-risk of PTCLu and hepatosplenic T-cell lymphoma.

Age-related changes in myelopoietic response to lipopolysaccharide in senescence-accelerated (SAM) mice.

The effects of in vivo lipopolysaccharide (LPS) administration on myelopoiesis were examined in senescence-accelerated (SAM) mice. Young mice injected with LPS exhibited: (a) increased femoral proliferative pool size; (b) transient reduction in femoral non-proliferative pool size and number of femoral colony forming unit-granulocyte macrophages (CFU-GMs); (c) marked increase in splenic CFU-GMs; and (d) transient increase in S-phase of femoral CFU-GMs. The responses of old mice after LPS administration differed from those of young mice in the following points: (a) no recovery of the femoral non-proliferative pool or femoral CFU-GMs, (b) less significant augmentation of the femoral proliferative pool and splenic CFU-GMs, and (c) prolonged reduction in S-phase of femoral CFU-GM. Injection of LPS into mice resulted in a hyperproduction of colony-stimulating activity (CSA) in bone followed by production of colony-inhibitory activity (CIA) in young mice and in contrast, an excessive CIA secretion from bone without an increase in CSA levels in old mice. These imbalances in the regulatory factors derived from non-hemopoietic cells in the bones may lead to an inappropriate response of myelopoiesis in aged SAM mice after LPS administration, which may play a key role in infections.