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Biomedical subjects

M Aoyama

Publications and source records attributed to M Aoyama.

At least 73 records · Page 4Linked to original sources
PubMed1998

Interleukin 6 differentially potentiates the antitumor effects of taxol and vinblastine in U266 human myeloma cells.

Newer therapeutic strategies for the treatment of multiple myeloma have focused on antagonizing the growth-promoting functions of interleukin 6 (IL-6). In this study, we examined the antitumor effects of two mechanistically different microtubule poisons, Taxol and vinblastine, in U266 human myeloma cells and determined whether IL-6 altered these effects. Taxol and vinblastine led to a dose-dependent inhibition of [3H]thymidine incorporation and altered the DNA distribution pattern of U266 cells. Both drugs led to an increase in the proportion of cells in the sub-G1 fraction (<2N DNA). However, at the IC50 concentration, vinblastine, but not Taxol, increased the percentage of cells in the G2-M phase of the cell cycle. In the presence of IL-6, the DNA distribution pattern induced by Taxol or vinblastine was altered. Whereas IL-6 augmented the sub-G1 fraction and G2-M phase for Taxol-treated cells, only the G2-M phase was increased for vinblastine-treated cells. Furthermore, IL-6 enhanced the cytotoxicity of both drugs, which became evident only during recovery in cytokine-free and drug-free medium. However, the cytotoxicity of Taxol was augmented to a significantly greater extent than that of vinblastine (P < 0.001). Immunostaining with antibodies to alpha-tubulin and mitogen-activated protein kinase revealed colocalization of these two proteins within microtubule asters. In the presence of IL-6, the number of cells containing microtubule asters increased for Taxol treatment, but not for vinblastine treatment. These data indicate that IL-6 leads to differential modulation of the cytotoxicity of Taxol and vinblastine in U266 cells. Whereas recruitment of cells in the S phase of the cell cycle represents a major mechanism by which IL-6 potentiates the cytotoxicity of vinblastine, augmentation of the cytotoxicity of Taxol involves additional mechanisms. Furthermore, our data suggest that the microtubule-associated form of mitogen-activated protein kinase may play a role in IL-6-mediated enhancement of the cytotoxicity of Taxol. The clinical implications of these findings are discussed.

Antineoplastic Agents, Phytogenic↗
PubMed1998

OPC-41061, a highly potent human vasopressin V2-receptor antagonist: pharmacological profile and aquaretic effect by single and multiple oral dosing in rats.

The pharmacological profile and the acute and chronic aquaretic effects of OPC-41061, a novel nonpeptide human arginine vasopressin (AVP) V2-receptor antagonist, were respectively characterized in HeLa cells expressing cloned human AVP receptors and in conscious male rats. OPC-41061 antagonized [3H]-AVP binding to human V2-receptors (Ki = 0.43 +/- 0.06 nM) more potently than AVP (Ki = 0. 78 +/- 0.08 nM) or OPC-31260 (Ki = 9.42 +/- 0.90 nM). OPC-41061 also inhibited [3H]-AVP binding to human V1a-receptors (Ki = 12.3 +/- 0.8 nM) but not to human V1b-receptors, indicating that OPC-41061 was 29 times more selective for V2-receptors than for V1a-receptors. OPC-41061 inhibited cAMP production induced by AVP with no intrinsic agonist activity. In rats, OPC-41061 inhibited [3H]-AVP binding to V1a-receptors (Ki = 325 +/- 41 nM) and V2-receptors (Ki = 1.33 +/- 0. 30 nM), showing higher receptor selectivity (V1a/V2 = 244) than with human receptors. A single oral administration of OPC-41061 in rats clearly produced dose-dependent aquaresis. In treatment by multiple OPC-41061 dosing for 28 days at 1 and 10 mg/kg p.o. in rats, significant aquaretic effects were seen throughout the study period. As the result of aquaresis, hemoconcentration was seen at 4 hr postdosing although, no differences were seen in serum osmolality, sodium, creatinine and urea nitrogen concentrations at 24 hr postdosing. Furthermore, there was no difference in serum AVP concentration, pituitary AVP content or the number and affinity of AVP receptors in the kidney and liver at trough throughout the study period. These results demonstrate that OPC-41061 is a highly potent human AVP V2-receptor antagonist and produces clear aquaresis after single and multiple dosing, suggesting the usefulness in the treatment of various water retaining states.

Animals↗
PubMed1997

The fifth allele of the human deoxyribonuclease I (DNase I) polymorphism.

The fifth allele, DNASE1*5, of human deoxyribonuclease I (DNase I) has been discovered. Polymerase chain reaction fragments containing exon 5 of the DNase I gene were screened for DNA polymorphism using single-strand conformation polymorphism (SSCP) analysis. DNAs from 114 unrelated Japanese and 81 German individuals were tested and a new variant was detected. By DNA sequencing analysis, this variant was found to be caused by a heterozygous G-A transition at nucleotide position 1227 that results in a Val to Met substitution at amino acid position 92 of the mature enzyme. The nucleotide substitution was also confirmed by mismatched polymerase chain reaction (PCR)-restriction fragment length polymorphism (RFLP) analysis. Genotyping of the variant could be carried out by three independent reactions based on PCR amplification, and phenotyping by isoelectric focusing followed by immunostaining. The results supported the presence of the fifth codominant allele, DNASE1*5, which generates a new isozyme.

Alleles↗
PubMed1997

DYS19 marker in Japanese populations.

Allele frequencies of the Y chromosome-specific short tandem repeat system DYS19 (Y-27H39) were determined from blood samples obtained from 251 unrelated Japanese in Fukui and Gunma Prefectures. Five alleles that contained 10, 11, 12, 13 and 14 repeats of GATA were detected. Allele frequency distributions in Japanese populations were different from those in other Asian and Caucasian populations.

Alleles↗
PubMed1997

Suppression of ischemic edema in mice by manganese-hyaluronate conjugate.

Manganese-hyaluronate conjugate (Mn-HA) was synthesized from a diethylenetriaminepenta-acetic acid derivative of hyaluronic acid and manganese ion. The conjugate markedly scavenged super-oxide anion in vitro and exhibited much higher anti-inflammatory activity than superoxide dismutase in suppressing paw edema in mice when intravenously injected 30 min before the initiation of ischemia.

Animals↗
PubMed1997

Rapid changes in pial arterial diameter and cerebral blood flow caused by ipsilateral carotid artery occlusion in rats.

We investigated rapid changes in pial arterial diameter and in cerebral blood flow (CBF) caused by transient ipsilateral common carotid artery occlusion (CCA-O) in anesthetized rats in order to elucidate how the cerebral circulation reacts to acute stem artery occlusion. In separate groups of rats, pial arterial diameter was recorded through a closed cranial window and CBF was recorded by laser-Doppler flowmetry. CCA-O was performed for 5 minutes under normotension and normocapnia (control) and under graded hypotension, hypercapnia and hypocapnia. In the control condition, pial arterial diameter increased rapidly, triggered by CCA-O. It took 12 +/- 3 s to reach the maximum of 204 +/- 42% of the value before CCA-O, and 60 +/- 24 s to become stable at 131 +/- 11%. CBF decreased rapidly to 66 +/- 11%, then increased reactively to 135 +/- 9%, and again decreased to 91 +/- 3%. The reactive increase in CBF caused by CCA-O decreased in parallel with the degree of hypotension, and also became barely detectable under hypercapnia. Our data suggest that active vascular dilation in the territory of the occluded artery is important for inducing collateral circulation.

Animals↗
PubMed1997

[Mitral valve replacement and closure of ventricular septal defect in the first two months of life].

A 2-month-old female infant weighing 4.2 kg was admitted with severe congestive heart failure and respiratory distress. The patient was operated upon under a diagnosis of severe congenital mitral regurgitation and ventricular septal defect. There was thickening of the anterior leaflet and short thickened chordae. The valve was judged not amenable to repair and it was replaced with a 17 mm St. Jude Medical valve. She was extubated on the 5th postoperative day. Post operative anti-coagulant therapy was initiated with warfarin potassium, dipyridamole and ticlopidine hydrochloride. The postoperative course was uneventful and the patient is doing well 9 months after the operation.

Female↗
PubMed1997

[Prognostic implication of DNA contents on long-term outcome of childhood acute lymphoblastic leukemia].

Prognostic value of cellular DNA content was evaluated in 189 children with acute lymphoblastic leukemia. Treatment outcome of the three different DNA index (DI) groups (Group A, DI = 1.0 vs. Group B, DI 1.01-1.15 vs. Group C, DI > or = 1.16) was compared between the two treatment risk groups (standard-risk and high-risk groups) stratified by the initial leukocyte count and age. In the standard-risk group, these groups had 10-year event free survival (EFS) rate (SE) of 62% (6%), 40% (21%) and 87% (6%), respectively (p < 0.05). In the high risk group, they had 10-year EFS rate of 30% (5%), 33% (27%) and 60% (19%), respectively (p < 0.01). Use of the DI, leukocyte count and age may be sufficient to distinguish the patients with an extremely low risk of failing to the standard ALL therapy from the patients with a relatively high-risk of treatment failure.

Child↗
PubMed1997

[Hemodynamic effects of amrinone in children during cardiopulmonary bypass and postoperative 12 hours].

Hemodynamic effects of amrinone in children during cardiopulmonary bypass (CPB) and postoperative 12 hours were studied. In 10 patients undergoing open heart surgery, 1 mg/kg of amrinone was infused as the initial CPB dose and 5 - 10 micrograms/kg/min of amrinone was continuously administered as the maintenance dose during CPB and postoperative 12 hours. Amrinone levels ranged from 0.9 to 1.4 micrograms/ml during CPB and postoperative 12 hours. After infusion of amrinone, mean arterial blood pressure decreased significantly, but other parameters did not show remarkable change. The administration of amrinone during CPB showed enough vasodilating effect and decreased the need of conventionally used other vasodilators (nitroglycerin or prostaglandin E1). The postoperative course of 10 patients was clinically uneventful. The administration of amrinone in 10 patients did not produce thrombocytopenia compared with the control group (5 patients) in the postoperative period. In conclusion, the administration of amrinone during CPB and postoperative 12 hours in children was useful in producing enough vasodilating effect without major side effect.

Amrinone↗
PubMed1997

[Effects of aprotinin on blood loss reduction in children undergoing repair of tetralogy of Fallot].

The effect of aprotinin on the blood loss reduction was studied in children undergoing repair of tetralogy of Fallot. We administered aprotinin to consecutive 21 patients during the repair of tetralogy of Fallot and examined the blood loss and operative time in comparison with that in a control group of 20 patients. 30,000 KIU/kg of aprotinin was infused as the initial cardiopulmonary bypass (CPB) dose and 10,000 KIU/kg/hr was continuously administered as the maintenance dose during CPB. There was no resternotomy case due to bleeding and no operative death in both groups. Blood loss after CPB during operation and total blood loss during operation were significantly lower in aprotinin group than in control group. There were no differences between two groups in the volume of chest tube drainage in the postoperative 24 hours and the duration of chest tube drainage. Time from cessation of CPB to skin closure and total operative time were significantly shorter in aprotinin group than in control group. In conclusion, aprotinin was effective on the reduction of blood loss and the shortening of operative time in children undergoing repair of tetralogy of Fallot.

Aprotinin↗
PubMed1996

Growth stimulatory effect of thrombopoietin on the blast cells of acute myelogenous leukaemia.

Thrombopoietin stimulated blast colony formation in 11/20 acute myelogenous leukaemia (AML) patients studied. The FAB subtypes of the blasts responding to thrombopoietin were not restricted to those of the megakaryocyte lineage, but also included M1-M5 AML blasts. The morphology of colony cells produced by megakaryocytic blasts showed megakaryocytoid features, whereas colony cells produced by M1-M5 AML blasts remained myeloblasts. An increase in CD41 was observed in the cells of colonies produced by blasts from the megakaryocyte lineage involving leukaemia and chronic myeloid leukaemia in blastic crisis. Thrombopoietin receptor was observed on leukaemic blasts which formed colonies following incubation with thrombopoietin.

Cell Division↗
PubMed1996

The ultrastructural localization of NADPH-diaphorase in the cerebral arteries of rats.

The ultrastructural localization of nicotinamide adenine dinucleotide phosphate-diaphorase (NADPH-d), which has been considered to be a neuronal nitric oxide synthase (NOS), was explored in the vascular endothelial cells and perivascular nerves of the cerebral arteries in the rat. In order to detect NADPH-d activity, 2-(2'-benzothiazolyl)-5-styryl-3-4-(4'-phthalhydrazidyl) tetrazolium chloride was utilized as a substrate for NADPH-d histochemistry at the electron microscopic level. In vascular endothelial cells, NADPH-d positive deposits were observed on the nuclear envelope and the endoplasmic reticulum (smooth or rough surfaced). Positive deposits were seen on distinct membrane portions of the endoplasmic recticulum (ER) in the perivascular nerves (axons), but no positive materials were observed either in the cytoplasm of the endothelial cells or in the axoplasm of the perivascular nerves. It was concluded that NOS is located on the membranes of the ER and the nuclear envelope, and that NOS may play substantial roles in the regulation of the cerebral vessels.

Animals↗
PubMed1996

[Acute myelogenous leukemia with ins(21;8) expressing AML-1-MTG8 fusion transcript].

Here we report a case of acute myelogenous leukemia (M2, FAB classification) presenting with cytogenetic abnormalities of ins(21;8), +del(8) without t(8;21). A 8;21 chromosome translocation is frequently found in acute myelogenous leukemia, especially in the M2 subtype. The translocation results in a fusion transcript between AML1 and MTG8 (ETO), assigned on chromosomes 21 and 8, respectively. Among patients with a t(8;21) abnormality, solid leukemic tumor deposits outside the marrow or good response to chemotherapy are observed frequently. Decrease in neutrophil alkaline phosphatase score and positive rate, and eosinophilia in bone marrow or the blast cells with Auer rods expressing CD19, CD56 antigens occur at a relatively high rate. Although our case lacked these clinical, cytological and cytochemical features, expression of chimeric AML1-MTG8 mRNA was detected. AML1-MTG8 fusion transcript may play a critical role in leukemogenesis of AML M2. Studies on this case may help to reveal the oncogenic function of the AML1-MTG8 fusion gene in AML M2.

Adult↗
PubMed1995

Cell cycle kinetics in childhood acute leukemia studied with in vitro bromodeoxyuridine labeling, Ki67-reactivity, and flow cytometry.

Cell cycle kinetics of childhood acute leukemia were determined by the in vitro labeling of marrow blast cells with bromodeoxyuridine (BrdUrd) and subsequent flow cytometry of BrdUrd/DNA and Ki67/DNA in 18 patients with acute lymphocytic leukemia (ALL) and eight patients with acute nonlymphocytic leukemia (ANLL). The BrdUrd-labeling index (BrdUrd-LI) and the duration of S phase (Ts) were calculated from the slope of the regression line obtained by plotting the serial labeling indices against the labeling time. The Ts and potential doubling time (DTpot) of marrow leukemia cells varied from 6.1 to 34.3 h (median 14.3 h) and 1.1 to 20.7 days (median, 7.3 days), respectively. The duration of the total cell cycle time (Tc) which was determined by the Ki-67-derived growth fraction (Ki-67-GF) varied from 14.0 to 112.5 h (median 43.2 h). BrdUrd-LI, DTpot, Ki-67-GF and Tc were significantly correlated with the subtypes (early B-ALL, T/B- ALL and ANLL) of the disease. The median values of LI and GF were much lower in ANLL than in ALL. However, the low proliferative activity of ANLL was not accompanied by a prolonged duration of the total cell cycle time. The longest median duration of Tc was noted in early B-ALL (75.2 h) and the median Tc in ANLL (36.7 h) was close to that in T/B-ALL (34 h). Ts appeared to be rather independent of subtypes of the disease. These results show that there are distinct in vitro growth characteristics in relation to the subtypes of childhood acute leukemia.

Bone Marrow↗