Kaori Shiraishi

Surface phenotype analysis of CD16+ monocytes from leukapheresis collections for peripheral blood progenitors

In peripheral blood progenitor cell (PBPC) collections from patients with solid tumour or haematological malignancy, monocytes were separated into two subpopulations. The majority of monocytes expressed CD14 at a high density without CD16 antigen (the CD14+CD16− monocytes). The remaining monocytes co‐expressed CD14 and CD16 (the CD14+CD16+ monocytes). These CD14+CD16+ monocytes amounted to 20.6 ± 15.8%, while those in peripheral blood (PB) obtained from healthy volunteers were 7.3 ± 3.1% (P < 0.05). When subdividing the CD14+CD16+ monocytes into CD14brightCD16dim and CD14dimCD16bright cells, both populations were found to be increased in PBPC collections. Since typical CD14+CD16+ monocytes are the CD14dimCD16bright population, we compared the additional surface antigens on CD14dimCD16bright monocytes with those of CD14+CD16−monocytes. In PBPC collections, the CD14dimCD16bright monocytes exhibited lower levels of CD11b, CD15, CD33 and CD38 expression and higher levels of CD4, CD11a, CD11c and MHC class II, and also revealed a higher percentage of CD4+ cells and a lower percentage of CD15+ cells and CD38+ cells, compared with the CD14+CD16− monocytes. When compared with the CD14dimCD16bright monocytes in PB, those in PBPC collections exhibited higher expression of CD4 and lower expression of CD11b, and also showed higher percentages of CD4+ cells and CD38+ cells and a lower percentage of CD11b+ cells. These results suggest that PBPC collections may be rich in the CD14+CD16+ monocytes in which the proportion of the immature population is increased. It is likely that these monocytes participate in the haematological and immune recovery after PBPC transplantation.

Stavudine, Lamivudine, Indinavir による治療中に重篤な乳酸アシドーシスを発症したAIDS

Recently, several class-related adverse events have been recognized with antiretroviral drugs. For nucleoside analogue reverse transcriptase inhibitors. (NRTI), lactic acidosis with hepatomegaly and hepatic steatosis have been reported. These appear to occur at a low frequency, but with a high fatality rate. We report a case of fatal lactic acidosis in a patient with acquired immunodeficiency syndrome (AIDS) treated with stavudine (d4T), lamivudine (3TC) and indinavir (IDV). A 48-year-old male AIDS patient was admitted with complaints of general fatigue and dyspnea. His medications at presentation included d4T, 3TC and IDV. Physical examination demonstrated icteric sclerae and abdominal tenderness with hepatomegaly. Laboratory data demonstrated a severe metabolic acidosis with an anion gap due to lactate accumulation. Despite intensive treatment, cardiorespiratory arrest occurred and this could not be resuscitated.

Effect of Heat-Pretreatment on Interleukin-2-Activated Killer Cells for in vitro Purging

Objective: Lymphokine-activated killer activity is effective in purging residual malignant cells from autologous bone marrow (BM) or leukapheresis collections for peripheral blood progenitor cells (PBPC). In this study, the effect of additional heat pretreatment on IL-2-activated cytotoxicity was examined. Methods: Nonadherent mononuclear cells from peripheral blood (PB), PBPC collections or BM were exposed to the desired temperature for 1 h, and successively cultured for 7 days in the presence of 1,000 units/ml of recombinant human interleukin-2 (IL-2). Cytotoxicity of IL-2-activated cells was determined by flow cytometry, using PKH-26-labelled K-562 or Raji target cells, and the cell surface antigens were also analyzed. Results: IL-2-activated cells from all specimens showed a distinct generation of cytotoxic activities. The activities were significantly decreased by heat at 42°C, but not changed by heat pretreatment at 40°C. In the surface expression of IL-2-activated cells, the increase of CD56+ cells from PB, PBPC collections and the decrease of CD28 cells from PBPC collections were shown to be significant (p < 0.05), but these changes were not found when the cells were heat-pretreated at 42°C. Discussion: These results suggested that a tumor-killing therapeutic temperature (≧42°C) may lead to a disadvantage in posttransplantation immunity, and that this reduction of IL-2-activated cytotoxicity may partly be due to a lack of the enhancement of CD56+ cells or the reduction of CD28+ cells.