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H Hirota

Publications and source records attributed to H Hirota.

At least 55 records · Page 3Linked to original sources
PubMed1995

Roles of stem cell factor in the in vitro growth of blast clonogenic cells from patients with acute myeloblastic leukemia.

We investigated the effects of stem cell factor (SCF) on the growth of blast clonogenic cells from 27 patients with acute myeloblastic leukemia (AML) and 3 patients with chronic myelocytic leukemia in myeloid crisis. SCF alone showed a significant stimulatory activity in 15 of 30 patients (50%). A marked reduction in the number of blast cell colonies supported by SCF alone was noted by the addition of neutralizing antibody (Ab) against granulocyte-macrophage colony-stimulating factor (GM-CSF). Ab against interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha) also moderately reduced the number of colonies, whereas Ab against granulocyte CSF (G-CSF) failed to do so. All four Ab together completely abolished the growth in 5 of 6 patients tested. c-kit antisense oligonucleotides reduced the colony formation supported by IL-3 or G-CSF or, in the absence of growth factor, in only 2 of 10 patients tested. SCF caused stimulation by acting synergistically with G-CSF, GM-CSF, IL-3, IL-6, IL-9, IL-11, and IL-12 in 20 of 27 (74%), 17 of 27 (63%), 14 of 28 (50%), 9 of 28 (32%), 1 of 15 (7%), 3 of 28 (11%), and 2 of 15 (13%) patients, respectively. Thus, SCF alone or in combination with some other factor stimulated the growth in 27 of 30 (90%) patients. Of 3 nonresponders, 2 were AML, M3 at presentation. G-CSF at the optimal concentration increased the sensitivity of blasts to SCF. Taken together, SCF acting in combination with other factors, but not alone, stimulates the growth of blast clonogenic cells. GM-CSF, IL-6, and TNF-alpha may be produced endogenously, whereas G-CSF and SCF may be supplied exogenously. Autocrine regulation of the growth of blasts seems to increase the responsiveness of the cells to any of these factors, allowing them to achieve a highly active growth state.

Base Sequence↗
PubMed1995

USF-19A, a new lipoxygenase inhibitor from Streptomyces sp.

USF-19A, a soybean lipoxygenase (SBL) and human 5-lipoxygenase (5-LO) inhibitor, was isolated from Streptomyces sp. USF-19 strain. Its chemical structure was determined by spectroscopic evidence to be a new member of the antimycin antibiotic family. The IC50 value of USF-19A against 5-LO was 28.0 microM.

Benzamides↗
PubMed1995

[Treatment of solid tumor by a small amount of direct current].

Solid tumor treatment was given in our animal laboratory to determine the mechanism of tumor disappearance by direct electric current, and clinical trials were done on 9 far advanced recurrent rectal cancers. Solid tumors of Yoshida sarcoma in Donryu rat were treated by 1 mA of constant direct current for 1 hour a day, for 4 days. The tumors disappeared in 13/16 within 21 days. Positive results of DNA Nick-end labeling and ladder patterns in the gel electrophoresis of DNA were observed in the regressing tumor specimen. It is considered that apoptosis is the one of the mechanisms of a disappearing tumor. As for the clinical trial concern, in 9 cases of rectal cancer, one CR and 5 PR were seen.

Aged↗
PubMed1995

[Optimal concentration of contrast medium in helical CT of the thorax].

In 99 examinations of 89 patients, we took CT images of the chest after administering one of three concentrations of contrast medium (iohexol 140 mgI/ml, 240 mgI/ml, 300 mgI/ml) to determine the optimal iodo-concentration for intravenous contrast enhancement in spiral CT. Attenuation values of the superior vena cava, ascending aorta, descending aorta, and pulmonary artery were measured to evaluate the degree of contrast enhancement. Five radiologists judged the image quality by scoring factors such as vascular opacification, delineation of the lung and chest wall, detectability of calcification, lymphadenopathy and pulmonary nodules, and the presence of artifacts. The relationships between the iodo-concentration and the scores were analyzed statistically. The higher the iodo-concentration of the contrast medium administered, the stronger the vascular structures were opacified. There was also a concurrent improvement in the detection of lymphadenopathy. However, artifacts appeared on the administration route as a result of the high-concentration contrast medium, and the image quality was degraded. Among the three groups, iohexol 240 mgI/ml exhibited the best performance, namely, good image quality, so that a high degree of contrast enhancement of the vasculature was obtained with few artifacts due to the contrast medium. However, we believe that iohexol 140 mgI/ml presents no significant problems in routine studies.

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

Propentofylline administered by microdialysis attenuates ischemia-induced hippocampal damage but not excitatory amino acid release in gerbils.

Systemic administration of propentofylline (PPF), an adenosine uptake inhibitor, has been demonstrated to protect CA1 pyramidal cells from death following transient cerebral ischemia in gerbils. In order to examine the direct effects of this inhibitor, we tested whether or not PPF administered into the hippocampus in situ through a microdialysis probe could attenuate ischemia-induced excitatory amino acid (EAA) release and prevent subsequent death of CA1 pyramidal cells in the gerbil. The EAA release and death of CA1 pyramidal cells observed in the hippocampus were compared with those in the contralateral hippocampus of the same animal into which vehicle alone was administered. The results indicated that pre- as well as post-treatments with PPF inhibited the death of CA1 pyramidal cells after 5-min ischemia in a dose-dependent manner, but did not significantly alter the EAA release during ischemia and reperfusion in the same animals. While the neuroprotective effect of PPF against ischemic damage has commonly been ascribed to attenuation of EAA release during ischemia, other actions of adenosine such as those influencing the synaptic responses, neuronal excitation, and local cerebral circulation, or as yet unidentified actions may be involved in the observed neuroprotective effects of PPF.

Amino Acids↗
PubMed1994

Different effect of thymidine kinase loss on TTP pools; comparison among human leukemia cell lines.

Thymidine kinase (TK)-deficient cells were established from six human leukemia cell lines to evaluate the role of TK in maintaining intracellular TTP pools. The residual TK activities in mutant cells were less than 3% of those of wild-type strains, except for a B-lymphoid cell line, Ball-1 (8.7%). In a promyelocytic leukemia cell line (HL-60), a splenic B cell line (WI-L2) and Ball-1, a mutational loss of TK resulted in a decrease of TTP pools by 80%, 33% and 54%, respectively. On the other hand, in the T cell lines, Molt-3, Molt-4 and CEM, TTP did not show any significant differences between parent and TK-deficient cells. TK-deficient HL-60 cells had, however, comparable levels of dATP, dGTP and dCTP with wild-type cells. An analysis of growth characteristics showed that the decrease of TTP was not due to the change of the cell cycle distribution. These results indicate that TK plays a different role in maintaining TTP pools among human leukemia cell lines.

B-Lymphocytes↗
PubMed1994

Different mode of cell death induced by calcium ionophore in human leukemia cell lines: possible role of constitutive endonuclease.

The mechanism of cell death induced by calcium ionophore, A23187, was investigated in six human leukemia cell lines. Following exposure to 1 microM A23187, the myelogenous cell lines (HL-60, U-937, KG-1) underwent apoptosis within 3 h as determined by their morphology and DNA fragmentation assay. In contrast, T-lymphoblastic leukemia cell lines (Molt-4, Molt-3, CEM) revealed necrotic cell death after 24 h of incubation. However, an initial rise of intracellular free calcium concentrations and growth inhibition after treatment with A23187 were similar in the two cell types. We further showed that an endonuclease capable of mediating internucleosomal DNA fragmentation was constitutively expressed in the cytosol but not in the nuclei of the myelogenous cell lines, although this endonuclease was not detected in either the nuclei or the cytosol of the T-lymphoblastic cell lines. The activation of the endonuclease in myelogenous cells is calcium-independent and has an optimal pH of 7.5-9. It is inhibited by 1 mM zinc ion or 300 microM aurintricarboxylic acid. We propose that this constitutive endonuclease may be related to the susceptibility of myelogenous leukemia cell lines to apoptotic cell death.

Apoptosis↗
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

Cytochrome oxidase and hexokinase activities in an infusion edema model with preserved blood flow.

Despite numerous investigations, the mechanisms underlying the neurological deficits observed in association with interstitial edema remain unclear. A recent study has demonstrated that the cerebral blood flow (CBF) in edematous white matter is unchanged if the blood flow values are corrected for dilution. In contrast, the cerebral glucose metabolism (CMRgl) has been found to be increased. In order to examine the effects of interstitial edema on the oxidative metabolism, we measured the cytochrome oxidase (CYO) activity, a marker of mitochondrial respiration, and the hexokinase (HK) activity, a marker of glycolysis, together with CBF and CMRgl employing the iodoantipyrine and deoxyglucose autoradiography in an infusion edema model in rats. In agreement with the previous study, CBF was not significantly changed in the edematous hemisphere. No significant alterations in CMRgl and HK activity were noted. In contrast, there was a significant decrease in CYO activity in the edematous hemisphere (-17%; p < 0.01), which was correlated to the edema. These findings suggest that interstitial edema causes a decreased mitochondrial respiratory function despite a maintained circulation. This may be explained by postulating a decreased oxygen delivery and/or accumulation of lactate, both of which have been shown to interfere with mitochondrial respiratory function.

Animals↗
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↗
PubMed1994

In vivo administration of granulocyte colony-stimulating factor promotes neutrophil survival in vitro.

We recently showed that recombinant human granulocyte-colony stimulating factor (rhG-CSF) maintained the viability of human neutrophils in incubation for up to 72 hours. However, it is not known whether rhG-CSF can enhance neutrophil survival in in vivo situations. To clarify this issue, we investigated neutrophil survival in vitro following in vivo injection of rhG-CSF. Neutrophils were obtained from 4 pediatric patients with malignancies and healthy adult volunteers before and after rhG-CSF administration. Neutrophils obtained before rhG-CSF treatment started to undergo apoptosis after 24 h of incubation. In contrast, the survival of neutrophils drawn after rhG-CSF administration increased by approximately 24 h. Concomitantly, the appearance of typical ladder-like DNA fragmentation was delayed. Such an increase in neutrophil survival was inhibited by co-incubation with either H 7 (10 mumol/l) or H 8 (20 mumol/l), which worked as protein kinase C inhibitors. Although our study did not measure neutrophil survival in vivo directly, it provides us with further evidence that rhG-CSF may function to prolong neutrophil life expectancy in vivo.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed1994

Induction of apoptosis in childhood acute leukemia by chemotherapeutic agents: failure to detect evidence of apoptosis in vivo.

This study is designed to investigate whether apoptosis occurs in vivo in pediatric patients with acute leukemia during induction therapy. When patients with common acute lymphoblastic leukemia (cALL) and acute myeloblastic leukemia (AML) were treated with prednisolone (60 mg/m2/day, p.o. or i.v.) and etoposide (150 mg/m2/day, i.v.), respectively, the blast cell counts fell to below 30% and 5%, respectively, in 1 week. However, during this cytoreduction phase, neither morphologically apoptotic cells nor fragmentation of DNA derived from peripheral blast cells were detected at any preparations. On the other hand, cALL but not AML cells spontaneously undergo apoptosis following their culture in vitro. The addition of autologous serum instead of fetal calf serum substantially prevented apoptosis from occurring spontaneously in cALL cells. When cALL and AML cells freshly obtained from patients before therapy were treated in vitro with 10 mumol/l prednisolone and 20 micrograms/ml etoposide, respectively, these cells underwent apoptosis within 6 hours, as determined by a morphological and DNA fragmentation assay. These in vivo and in vitro findings suggest that, although anticancer drugs may induce apoptosis in vivo, these apoptotic cells cannot be detected due to their rapid removal from the circulation.

Adolescent↗
PubMed1994

Myelodysplastic syndrome with t(9;11)(p22;q23) after treatment for B-cell acute lymphoblastic leukemia without epipodophyllotoxins.

Secondary myelodysplastic syndrome (MDS) with t(9;11)(p22;q23) developed in a child after intensive treatment for B-cell acute lymphoblastic leukemia diagnosed 12 months earlier. His chemotherapy had consisted mainly of cyclophosphamide and methotrexate, but no epipodophyllotoxins. The combination of MDS, the cytogenetic anomaly involving bands at 11q23 and no previous exposure to epipodophyllotoxins represents a unique case of therapy-related leukemia.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1994

Noninvasive quantitative evaluation of the morphology of the major pulmonary artery branches in cyanotic congenital heart disease. Angiocardiographic and echocardiographic correlative study.

BACKGROUND: Precise noninvasive evaluation of pulmonary artery (PA) morphology is extremely important for medical and surgical management of patients with cyanotic heart disease. In this study, the accuracy of two-dimensional echocardiography combined with color Doppler flow mapping to assess the size, stenosis, and atresia of the major PA branches was examined using a new parasternal approach. METHODS AND RESULTS: With the use of right and left high parasternal windows, we visualized each of the major portions along the right (R-PA) and left (L-PA) pulmonary arteries in 45 of the 47 examinations (96%) in 38 patients with cyanotic heart disease. The patients were between 13 days and 20 years old (mean age, 2.9 years). The internal diameters of the major PA branches were measured at three points along the R-PA (the proximal, mid, and distal portions) and at the proximal and distal portions on the L-PA in systole by both two-dimensional echocardiography and angiography. In addition, the diameter of the stenosis in the PA branch was measured. These PA values as determined by two-dimensional echocardiography correlated well with those obtained by angiography (r = .95 to .97). By two-dimensional echocardiography with color Doppler flow mapping, 17 of 19 lesions with stenoses or atresia of the major PA branches were predicted as defined by angiography (sensitivity, 89.5%; specificity, 100%). Differences between the distal parts of the L-PA and R-PA of > 30% in diameter were determined by angiography in 15 examinations and by two-dimensional echocardiography in 12 examinations (sensitivity, 80%; specificity, 97.4%). CONCLUSIONS: Our technique permits noninvasive evaluation of the size, stenoses, and atresia of the major portions of the PA branches in patients with cyanotic heart disease both before and after surgery.

Angiocardiography↗
PubMed1994

Regional blood flow distribution and left ventricular output during early neonatal life: a quantitative ultrasonographic assessment.

To examine the serial changes of left ventricular output and regional blood flow distribution during the early neonatal period, we measured blood flow volume in the ascending aorta, middle cerebral artery, celiac artery, superior mesenteric artery, and renal artery in 23 normal term infants at 1, 4-8, 24, and 96 h after birth. The blood flow volume in each vessel was measured by the pulsed Doppler technique. In the middle cerebral artery, celiac artery, and superior mesenteric artery, the blood flow volume at 1 and 4-8 h of age was significantly lower than after 24 h of age. In contrast, renal artery blood flow volume did not change significantly throughout the study period. The reduced organ blood flow volume soon after birth was related to a low diastolic blood flow in the major vessels, and the percent diastolic integral of blood flow velocity in each vessel showed an inverse linear correlation with the diameter of the ductus arteriosus. The left ventricular output 1 h after birth was 365 +/- 69 mL/kg/min, which was significantly higher than after 4-8 h of age. Left ventricular output gradually declined to 301 +/- 63 mL/kg/min at 4-8 h of age (p < 0.05 versus 96 h), 272 +/- 48 mL/kg/min at 24 h, and 258 +/- 54 mL/kg/min at 96 h. There was a significant positive correlation between left ventricular output and the ductus arteriosus diameter.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Flow Velocity↗
PubMed1994

Antiarrhythmic effects of eicosapentaenoic acid during myocardial infarction--enhanced cardiac microsomal (Ca(2+)-Mg2+)-ATPase activity.

The effects of dietary supplementation with eicosapentaenoic acid (EPA) on ventricular arrhythmias during myocardial infarction were examined in a canine model. EPA was incorporated into cellular membranes after ingestion of EPA-ester (100 mg/kg body weight/day) for 8 weeks. The ratio of EPA to arachidonic acid (AA) in platelet cell membranes and myocardial microsomes was significantly increased (7% to 37% in platelet cell membranes; p < 0.01, 3% to 12% in non-infarcted cardiac microsomes; p < 0.01, and from 2% to 8% in infarcted cardiac microsomes; p < 0.01). Dietary supplementation with EPA significantly reduced the incidence and severity of arrhythmias during coronary artery occlusion. Immediately after coronary artery occlusion, all of the animals in the control group that were given a toxic dose of digitalis developed ventricular tachycardia (VT) or ventricular fibrillation (Vf), whereas none of the animals in the EPA-supplement group developed VT or Vf within 15 min after administration of digitalis. Regardless of the presence of an infarcted area, the specific activity of the Ca(2+)-pump enzyme ((Ca(2+)-Mg2+)-ATPase) within the myocardial microsomal fraction of the EPA-supplemented group was significantly higher than in that of the control group (Vmax: 140.5 +/- 19.1 vs 94.8 +/- 28.9 nmol/mg/min in non-infarcted cardiac microsomes, p < 0.01, 130.9 +/- 18.4 vs 90.2 +/- 26.4 nmol/mg/min in infarcted cardiac microsomes, p < 0.01, EPA vs control group, respectively). The specific activities of the Na(+)-pump enzyme ((Na(+)-K+)-ATPase) and NADPH-dependent cytochrome C reductase in infarcted and non-infarcted cardiac microsomes did not differ between these groups. These results indicate that EPA supplementation increases the (Ca(2+)-Mg2+)-ATPase activity within myocardial membranes that is involved in Ca2+ metabolism in myocardial cells by increasing the ratio of EPA to AA within cellular membranes. These cellular alterations are likely to reduce the severity of ventricular arrhythmias by inhibiting the rapid accumulation of intracellular Ca2+ following ischemia.

Animals↗