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Biomedical subjects

R Bessho

Publications and source records attributed to R Bessho.

28 records · Page 2Linked to original sources
PubMed1995

Selection and partial characterization of calcium ionophore (A23187) resistant cells.

We have selected calcium ionophore (A23187)-resistant cells (AR-7) in a human promyelocytic leukemia cell line, HL-60. AR-7 showed approximately 8.5-fold resistance to A23187 compared with the wild type cells after continuous exposure for 3 days. AR-7 had cross resistance to ionomycin (4.6-fold) and thapsigargin (340-fold) which can also increase intracellular Ca++. Similar magnitude of resistance to apoptosis, as defined by characteristic morphology and internucleosomal DNA fragmentation, induced by these agents was observed after 4 hr of incubation. However, both the elevation of intracellular Ca++ following stimulation with various concentrations of A23187 and the sensitivity to anti-cancer agents including etoposide, 1-beta-D arabinofuranosylcytosine, and hydroxyurea were comparable between the two cell types. This cell line is considered to be useful for exploring the mechanism(s) of cell death, especially apoptosis, induced by calcium ionophore.

Antineoplastic Agents↗
PubMed1995

Association of high molecular weight DNA fragmentation with apoptotic or non-apoptotic cell death induced by calcium ionophore.

Calcium ionophore (A23187)-induced high molecular weight (HMW) and internucleosomal DNA fragmentation were investigated in human leukemia cell lines. An apoptosis-sensitive cell line, HL-60, showed HMW, internucleosomal DNA fragmentation and morphological changes of apoptosis by A23187. MOLT-4, which is resistant to apoptosis, exhibited only HMW DNA fragmentation and died of necrosis under the same conditions. Autodigestion experiments suggested the endonucleolytic activity to cause HMW fragmentation in the cytoplasm of both cell lines. The activity was more dependent on Mg2+ than Ca2+ in HL-60, whereas it was Ca(2+)-dependent in MOLT-4. These results suggest that HMW DNA fragmentation is not specific to apoptosis.

Apoptosis↗
PubMed1995

Augmentation by aphidicolin of 1-beta-D-arabinofuranosylcytosine-induced c-jun and NF-kappa B activation in a human myeloid leukemia cell line: correlation with apoptosis.

1-beta-D-arabinofuranosylcytosine (ara-C) (2 microM) can induce apoptosis in a human myeloid leukemia cell line, U937, after 4 h of incubation. Pretreatment of cells with aphidicolin (2 microM) augments ara-C-induced apoptosis, since it was first observed at 0.4 microM ara-C and became more intense at 2 and 10 microM. Although aphidicolin itself had a marginal effect on c-jun expression, it significantly augmented ara-C induced c-jun upregulation by shortening the lag time and lowering ara-C concentrations necessary for the induction of detectable c-jun transcripts. Aphidicolin and ara-C acted synergistically to increase NF-kappa B DNA binding activity as determined by an electrophoretic mobility shift assay. Expression of c-myc was slightly increased through the DNA degradative phase, and was then downregulated. Thus, the activation of NF-kappa B and c-jun expression seems to be well correlated with the potentiation by aphidicolin of ara-C-induced apoptosis.

Antimetabolites, Antineoplastic↗
PubMed1995

[Serum ECP level of infants of atopic dermatitis].

Forty-seven infants with atopic dermatitis (AD) were examined for ECP (eosinophil cationic protein) levels in sera at 3 to 4, 6 to 7, 12 and 18 months after birth. ECP levels in AD were significantly higher than those of control infants at every examination. The levels of ECP in AD were significantly correlated with the severity of dermatitis judged by a slightly modified version of the method of Businco et al. We concluded that ECP levels in sera are a useful marker for the severity of dermatitis in infants with AD.

Biomarkers↗
PubMed1995

[Sequential coronary artery bypass grafting utilizing the internal thoracic and gastroepiploic artery as in situ grafts].

36 consecutive patients (male:female = 33:3, mean age 57.3) underwent sequential coronary artery bypass grafting (CABG) utilizing the left internal thoracic artery (LITA, n = 30), right gastroepiploic artery (RGEA, n = 8) as in situ grafts. Two patients received sequential bypass grafting with both grafts simultaneously. No right internal thoracic arteries were used except for one as a free nonsequential graft. Taking into account the adjunctive venous anastomoses and the arterial nonsequential anastomoses, there were 3.5 anastomoses per patients. Proxymal side-to-side anastomosis of LITAs were all constructed on the diagonal branches except for one on the proxymal Left Anterior Descending Coronary Artery (LAD), whereas that of the RGEAs were on the proxymal Right Coronary Artery (RCA) (2), distal RCA (6) or distal circumflex (1). Distal end-to-side anastomoses of LITAs were all on the LAD, and those of the RGEAs were on the distal RCA (3) or distal circumflex artery (5). Proxymal side-to-side anastomoses were always performed first, allowing us to assess the distal flow through the graft before we anastomose it to the distal branch. We routinely obtain a preoperative angiogram of the arterial grafts, which enable us to fully assess the suitability of the arteries as in situ grafts. There were no perioperative deaths, nor perioperative myocardial infarctions, however, two patients died of extracardiac causes at 42 and 68 days after operation respectively. For the thirty four survivors, followup was complete (4-49 months, average 12.3 months). One still had angina of Canadian Cardiovascular Society Classification (CCSC) class 2, and 33 were free of angina.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Pyrrolidine dithiocarbamate, a potent inhibitor of nuclear factor kappa B (NF-kappa B) activation, prevents apoptosis in human promyelocytic leukemia HL-60 cells and thymocytes.

We examined the effect of pyrrolidine dithiocarbamate (PDTC), which potently blocks the activation of nuclear factor kappa B (NF-kappa B), on the induction of apoptosis by a variety of agents. Treatment of a human promyelocytic leukemia cell line, HL-60, with 10 micrograms/mL etoposide or 2 microM 1-beta-D-arabinofuranosylcytosine induced NF-kappa B activation within 1 hr and subsequently caused apoptosis within 3-4 hr. The simultaneous addition of 50-500 microM PDTC with these agents blocked NF-kappa B activation and completely abrogated both morphologically apoptotic changes and internucleosomal DNA fragmentation for up to 6 hr. However, PDTC failed to inhibit the endonuclease activity contained in the whole cell lysates. The inhibitory effect of PDTC was also observed in etoposide- and dexamethasone-induced apoptosis in human thymocytes at a concentration of 1-10 microM. Since PDTC has both antioxidant and metal-ion chelating activities, we tested the effects of N-acetyl-L-cysteine (NAC) (antioxidant) or o-phenanthroline (OP) (metal-ion chelator) on the induction of apoptosis. Pretreatment of HL-60 cells or thymocytes with 100-500 microM OP for 2 hr, but not 10-60 mM NAC, suppressed subsequent occurrence of apoptosis induced by etoposide. These results suggest that the activation of NF-kappa B plays an important role in the apoptotic process of human hematopoietic cells.

Acetylcysteine↗
PubMed1994

Variable susceptibility to apoptosis induced by calcium ionophore in hybridomas between HL-60 promyelocytic and CEM T-lymphoblastic leukemia cell lines: relationship to constitutive Mg(2+)-dependent endonuclease.

We recently reported that treatment with calcium ionophore, A23187, induces apoptosis in human myelogenous leukemia cells but causes necrotic cell death in T-lymphoblastic leukemia cells. To better understand the underlying mechanisms of such different modes of cell death, we established hybridomas between HL-60 promyelocytic and CEM T-lymphoblastic leukemia cells. The resulting hybridomas were divided into three groups in terms of their susceptibility to apoptosis following exposure to A23187: (1) hybridomas highly sensitive to apoptosis, (2) hybridomas with intermediate sensitivity to apoptosis which occurs later and to a lesser extent, and (3) hybridomas resistant to apoptosis. However, growth inhibition after 72 h of incubation and an initial rise in intracellular free calcium concentrations induced by A23187 were similar in the three groups. Expression of Ca(2+)-independent/Mg(2+)-dependent endonuclease, which had an optimal pH of 7.5-8.5 and was inhibited by Zn2+, was correlated with the susceptibility of the hybridomas to A23187-induced apoptosis. Thus, this endonuclease may play, at least in part, an important role in the induction of apoptosis in leukemia cell lines. Analysis of hybridomas between apoptosis-sensitive and apoptosis-resistant cells is useful in the elucidation of genetic factors which regulate cell death.

Apoptosis↗
PubMed1994

Somatic mutations at T-cell antigen receptor and glycophorin A loci in pediatric leukemia patients following chemotherapy: comparison with HPRT locus mutation.

Frequencies of somatic mutations in pediatric patients with leukemia were evaluated following intensive treatment at three different loci: the hypoxanthine-guanine phosphoribosyl transferase (HPRT), T-cell antigen receptor (TCR), and glycophorin A (GPA) gene. Thirty-two children with acute lymphoblastic leukemia (ALL), nine children with acute myelogenous leukemia (AML), and 20 age-matched healthy controls were included in the study of mutant frequencies (Mfs) at the HPRT and TCR loci. Among these patients and controls, individuals with heterozygous MN blood type, i.e., 14 children with ALL, three children with AML, and nine healthy controls, served for the further assessment of variant frequency (Vf) at the GPA locus. In ALL patients, geometric mean Mfs and Vfs at these loci were significantly higher than in healthy controls. The high Mf value at the HPRT locus persisted for up to 8 years after the end of chemotherapy. On the other hand, the Mf values at the TCR locus and Vf values at the GPA locus declined gradually with time. In AML patients, on the other hand, the geometric mean Mf only at the TCR locus was significantly higher than in the controls, albeit to a lesser degree than in ALL patients. These data suggest that anti-cancer therapy induces somatic mutations at various loci and that ALL patients are more susceptible to mutagenic intervention than are AML patients.

Adolescent↗