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Biomedical subjects

M Sasada

Publications and source records attributed to M Sasada.

At least 73 records · Page 4Linked to original sources
PubMed1986

Pharmacokinetics of aclarubicin and its metabolites in humans and their disposition in blood cells.

The pharmacokinetics of aclarubicin, a new anthracycline antibiotic, was studied in five patients with acute leukemia or in L1210 cell suspension. Aclarubicin disappeared very rapidly from plasma and whole blood after administration at a dose of 20 mg per patient by iv bolus injection. The concentration of active metabolite M1, on the other hand, increased for up to 2 or 4 hrs after administration and exceeded that of aclarubicin, and then remained at much higher concentrations than aclarubicin for up to 24 hrs after administration. In addition, the levels of aclarubicin and its metabolites in whole blood were much higher than the corresponding plasma levels in four of the patients. The drug concentrations in blood cells of 11 patients determined 4 hrs after administration showed a significant positive correlation with leukocyte counts. Moreover, the concentration of aclarubicin and its metabolites was found to be much higher in the leukocyte fraction than in the erythrocyte fraction in vivo and in vitro. These findings indicate that aclarubicin and its metabolites in blood cells were mainly accumulated in leukocytes. In the study of intracellular drug distribution in L1210 cells, the largest amount of aclarubicin was incorporated into the nuclear fraction. This suggests a close relationship between the pronounced drug accumulation in leukocytes and the high affinity of aclarubicin for DNA.

Aclarubicin↗
PubMed1986

Establishment of a novel acute monoblastic leukemia cell line (YK-M2) having a near-triploid karyotype.

The YK-M2 cell line was established from the peripheral blood of a patient with acute monoblastic leukemia in whom an anterior mediastinal tumor preceded the peripheral blood manifestation. The established cells grew in a single cell suspension with a doubling time of 60 h and consisted of primitive monoblastic cells. The cells were 52% positive for peroxidase staining and manifested strongly positive activity of alpha-naphthyl acetate esterase, which was completely inhibited by sodium fluoride. The cells showed strong expression of Fc gamma receptors and phagocytosed sensitized ox erythrocytes. When the cells were incubated with 1 alpha,25-dihydroxy-vitamin D3, they were induced to differentiate into mature monocyte-macrophage-like cells, which reduced the nitroblue tetrazolium dye and released a small amount of the superoxide anion. Cytogenetic studies revealed that the cells had a near-triploid karyotype with a modal chromosome number of 68, and the short arm of one No. 17 chromosome was deleted [del(17)(p11)]. The YK-M2 cell line is particularly unique in that the cells retained the polyploid karyotype that may be an initial cytogenetic change in the malignant transformation of the parent leukemia cells.

Adult↗
PubMed1984

Defective bactericidal activity and absence of specific granules in neutrophils from a patient with recurrent bacterial infections.

Recent studies have suggested that specific granules and/or their contents may have a role in neutrophil adherence, oxidative metabolism, and other aspects of cell function. In the current report, we studied neutrophil function in a 13-year-old female with recurrent pyogenic infections and absent specific granules previously documented by electron microscopy. Levels of cobalamin (vitamin B12)-binding protein and lactoferrin were markedly decreased in this patient's neutrophils. Bactericidal activity against Escherichia coli was decreased at 60 and 120 min (percentage organisms killed: patient neutrophils, 48 and 33%; control neutrophils, 90 and 99%, respectively). Defective killing of Staphylococcus aureus was also documented. Degranulation and adherence were normal. Levels of lactoferrin and cobalamin-binding protein were decreased in plasma but normal in saliva, indicating that the defect was specific for hematopoietic tissue. Superoxide anion production was normal in the patient, while hydroxyl radical generation was decreased in response to opsonized zymosan. The data support the concept that specific granules and their contents are important for oxidative metabolism and other neutrophil functions.

Adolescent↗
PubMed1984

Acute leukemia with two cell populations of lymphoblasts and monoblasts.

A 46-year-old man had acute leukemia with two cell populations of lymphoblasts and monoblasts (L1 and M5-b in FAB classification, respectively), which were characterized by morphological, cytochemical and cell marker studies. At the time of diagnosis about 80% blasts were terminal deoxynucleotidyl transferase (TdT) positive lymphoid cells, while the rest were TdT negative monocytoid cells. After induction chemotherapy of vindesine and prednisolone for 15 days, almost all blasts were TdT negative monocytoid cells. Therefore, an additional course of the chemotherapy with the protocol for acute nonlymphocytic leukemia was given and one month later the patient achieved complete remission.

Antigens, Surface↗
PubMed1983

Activation of mouse peritoneal macrophages by lipopolysaccharide alters the kinetic parameters of the superoxide-producing NADPH oxidase.

Macrophages activated by infection or elicited by injection of lipopolysaccharide (LPS), when stimulated with phorbol myristate acetate, release greater amounts of superoxide anion (O-2) than do normal resident macrophages. This enhanced production of O-2 and of other oxygen metabolites derived from O-2 is responsible, at least in part, for the enhanced microbicidal activity of these cells. To investigate the molecular basis for the enhanced oxygen metabolite response, the kinetic parameters of the enzyme responsible for NADPH-dependent production of O-2 (NADPH oxidase) were compared in LPS-elicited and resident mouse peritoneal macrophages. Resident and LPS-elicited macrophages were stimulated with phorbol myristate acetate, disrupted by sonication, assayed for their content of NADPH, and fractionated by centrifugation. The distribution of NADPH oxidase activity among the fractions was similar in both types of macrophage. A membrane-rich 27,000 X g pellet, which had the highest specific activity for the oxidase among the various fractions, was utilized to study the kinetic parameters of the oxidase from normal and LPS macrophages. The oxidase from LPS-elicited macrophages displayed a higher Vmax and a lower Km for NADPH than did the oxidase from normal cells. LPS-elicited cells also had a higher intracellular concentration of NADPH than did normal cells. The altered Km and Vmax, combined with the higher concentration of NADPH, resulted in a 2.2- to 3.5-fold increase in the calculated velocity of the oxidase from LPS-elicited macrophages compared with that from resident macrophages. These results suggest that the enhanced oxygen metabolite response of activated macrophages is due, in part, to modification of the enzyme responsible for the production of O-2.

Animals↗
PubMed1983

[Phase II study with methyl-6[[[2-chloroethyl) nitrosoamino] carbonyl] amino]-6-deoxy-alpha-D-glucopyranoside (MCNU) in hematological malignancies].

A total of 117 cases with hematological malignancies were treated with MCNU at doses of 70-100 mg/m2. Following are the results obtained. 1. MCNU showed a marked depression of cells in the cases with CML, polycythemia vera and thrombocythemia. The low level of cells was maintained for 2 to 7 months. 2. A good response was observed in several cases with blastic crises of CML. 3. No response was observed in two cases with acute leukemia. 4. Although a fair response was observed in several cases with malignant lymphoma or multiple myeloma, moderate bone marrow suppression was observed in a majority of the cases.

Adult↗