Masumi Baba

Cytotoxic effect of extracellular ATP on L1210 leukemic cells and normal hemopoietic stem cells

The cytotoxic effect of extracellular adenosine triphosphate (ATP) was examined on normal murine hemopoietic stem cells and a representative leukemic cell line (L1210). After L1210 cells were incubated with 4 mM ATP for 3 h, 3H-thymidine incorporation was almost completely inhibited. The number of viable L1210 cells was also significantly decreased and L1210 colony formation was suppressed to approximately 30% of the control level after treatment. The CFU-GM survival rate was reduced to 70%, however, CFU-S and marrow nucleated cell numbers were not changed after the same treatment with ATP. All mice that were injected with the untreated mixture of normal marrow cells (3.3 x 10(4)) and L1210 cells (3.3 x 10(3)) died of leukemia within 18 days. On the contrary, 85% of the recipients given ATP-treated grafts survived more than 70 days. These findings indicate that ATP extra vivo treatment is useful for purging the residual leukemic cells in autologous bone marrow transplantation.

Purging in autologous hematopoietic stem cell transplantation using adenosine triphosphate (ATP) and 4-hydroperoxycyclophosphamide (4-HC)

In this study, we show potent in vitro purging induced by adenosine triphosphate (ATP) for leukemic cells. The treatment of murine L1210 leukemic cells with 2mM of ATP in vitro for 3h was able to reduce the number of leukemic clonogenic cells by about one order of magnitude presumably by changing the permeability of the leukemic cell membrane. Furthermore, the incubation of L1210 cells with ATP (2mM) and low dose 4-hydroperoxycyclophosphamide (4-HC, 2 microg/ml) for 3h resulted in at least a four-log reduction of clonogenic L1210 cells. Only a slight degree of toxicity to pluripotent hematopoietic stem cells (CFU-S) was observed in both treatment protocols. To determine the efficacy of pharmacological purging by ATP, we designed a murine system to mimic the conditions expected in the clinical setting of autologous transplantation using simulated partial remission marrow (SPRM) which was prepared by mixing normal marrow cells and L1210 cells at a ratio of 9:1. After the SPRM cells were incubated in vitro at a concentration of 1 x 10(6)/ml with both ATP (2mM) and low dose 4-HC (2 microg/ml) for 3h, 5 x 10(4) of the cells were then injected into lethally irradiated 9 weeks male BDF1 mice. All the mice given untreated-SPRM died of leukemia by day 27, whereas none of the recipients transplanted treated-grafts had died by day 70, thus suggesting that the combination use of ATP and 4-HC may be a potentially effective way to purge leukemic cells in autologous stem cell transplantation. The mechanism of the selective killing of leukemic cells is assumed that 4-HC is effectively incorporated into leukemic cells by increasing the permeability of the cell membrane by ATP. Taken together, this simple and rapid procedure is able to purge leukemic cells from autologous bone marrow grafts.

Issues of day and night duty system at blood transfusion service to support emergency medicine.

救急医療の重要性と社会的要請の高まりの中で, 救急医療での当直体制を推進する大学病院に於いても医師, 看護婦を主体とした従来の方式による体制では大変困難な状況になっている. 従って, これからの救急医療を充実させるためには専門化し, 多様化されたコメディカル部門を有効に, しかも終日体制で整備して行く必要がある.このような背景の中で輸血業務に於ても当直体制への移行が広がりつつある. しかし, 各業務内容が専門化すればする程移行期に於ける問題が多い.そこで当院輸血室が1991年11月, 第3次救急医療を目的とした救命救急センター開設に伴い実施した輸血業務当直体制移行までの経緯, 方法, 内容および実施後の問題点, 今後の改善策などを検討したので報告する.

Abnormalities of serum transaminase activities in healthy blood donors.

The abnormalities of clinical labolatory tests were investigated among 17, 908 blood donors who came to the Department of Blood Transfusion, Nihon University Itabashi Hospital during the period from April 1, 1980 through March 31, 1983.The first check-up showed that abnormal rates of GOT and GPT activities over 40 mIU were 5.0% and that abnormal rate of GPT alone was 5.1 times more than that of GOT alone. Moreover, 10.5% of 270HBs antigen carriers had abnormal GOT and GPT activities.Of 102 patients with abnormal transaminase activities, clinical diagnosis in the secondary check-up included 65 patients (63.7%) with fatty liver associated with obesity and chronic alcoholic intake, 9 patients (8.8%) with chronic hepatitis and the remaining were required further examination for final diagnosis.These results suggest that the occurrence of post-transfusion non-A non-B hepatitis is not always associated with blood from about two third of apparently healthy donors with abnormal transaminase activities, because most of them have metabolic disoder of the liver, not infectious disease.