Search PubMed⌕ Search

Biomedical subjects

M Asano

Publications and source records attributed to M Asano.

At least 271 records · Page 15Linked to original sources
PubMed1993

Increased resting Ca2+ maintains the myogenic tone and activates K+ channels in arteries from young spontaneously hypertensive rats.

We examined whether the Ca2+ channel function in the resting state alters the resting tone in femoral and carotid arteries from spontaneously hypertensive rats (SHR) at early hypertensive stages (6 and 4 weeks of age), and data were compared with findings in age-matched normotensive Wistar-Kyoto rats (WKY). Strips of femoral and carotid arteries from 6-week-old SHR, but not from WKY, maintained a myogenic tone, that is, the resting tone decreased when 10(-7) M nifedipine was added. A similar myogenic tone was maintained in 4-week-old SHR. In strips of carotid arteries preloaded with fura-2, a fluorescent Ca2+ indicator, the decrease in cytoplasmic Ca2+ concentration following 0-Ca2+ solution or 5 x 10(-7) M nicardipine was significantly greater in SHR than in WKY. The basal 45Ca influx in femoral and carotid arteries from 6-week-old SHR was significantly increased when compared with WKY, and this increase in SHR was abolished by 10(-7) M nifedipine. The addition of charybdotoxin (a blocker of large conductance Ca(2+)-activated K+ channels) or of Bay k 8644 (an agonist of L-type voltage-dependent Ca2+ channels; VDCs), caused a concentration-dependent contraction, which was significantly greater in 6- and 4-week-old SHR than in WKY. These results suggest that the Ca2+ influx via L-type VDCs was increased in the resting state of femoral and carotid arteries from SHR at the early hypertensive stages, and therefore the myogenic tone was maintained and charybdotoxin-sensitive K+ channels were highly activated.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed1993

Proliferative and nonproliferative breast disease in atomic bomb survivors. Results of a histopathologic review of autopsy breast tissue.

BACKGROUND: The risk of female breast cancer in association with radiation dose is well established, on the basis of follow-up studies of the atomic bomb survivors and other exposed populations. This association is especially strong for women exposed before 20 years of age and appears to be much weaker among women exposed after 40 years of age. METHODS: Breast tissue samples from 88 high-dose and 225 low-dose autopsy cases from the Radiation Effects Research Foundation Life Span Study sample were examined in detail to determine whether nonproliferative and proliferative breast lesions are associated with radiation dose. RESULTS: Prevalence of proliferative disease in general and atypical hyperplasia in particular were positively associated with radiation dose. The associations were strongest for subjects who were between 40 and 49 years of age at the time of the bombing. CONCLUSIONS: It is hypothesized that the strongest association in women 40 to 49 years of age may be related to the age dependence of radiation-induced breast cancer, in that potential cancers induced in this age group by radiation exposure may receive too little hormonal promotion to progress to frank cancers.

Adolescent↗
PubMed1993

Significance of vascular endothelial growth factor/vascular permeability factor for solid tumor growth, and its inhibition by the antibody.

Angiogenesis is essential for successful tumor growth in vivo. There is a hypothesis that tumors secrete a putative tumor angiogenic factor (TAF) to facilitate blood vessel formations. Although several endothelial growth factors have been reported, it remains unclear whether these factors function as TAF in vivo. Vascular endothelial growth factor (VEGF)/vascular permeability factor (VPF) is a vascular endothelial mitogen that can increase blood vessel permeability. We have established a cell line (HeLa/v5), which secretes VEGF/VPF, by transfection of human VEGF/VPF cDNA. HeLa/v5 showed higher angiogenic activity, taken/planted ratio and tumor growth rate than the control transformant (HeLa/c), when they were implanted to nude mice. Administration of a polyclonal antibody, which neutralizes the mitogenic activity of VEGF/VPF in vitro, to the tumor implanted nude mice suppressed the in vivo growth of HeLa/v5. Furthermore, all 8 tumor cell lines we tested secrete VEGF/VPF into culture media. Our findings indicate that VEGF/VPF is a tumor angiogenic factor.

Animals↗
PubMed1993

Cleavage arrest in Xenopus embryos injected with a human c-myc gene.

The c-myc protein has been implicated in cell proliferation and differentiation of various cell lines, but its function in early embryos of Xenopus is obscure. We introduced the c-myc gene into embryos using a pcDL-SR alpha plasmid with an efficient promoter of the gene. It was found that fertilized eggs injected with the c-myc gene were arrested at the 4-cell stage within 1 h of the injection, when the plasmid that carried c-myc gene but not the plasmid that carried defective c-myc gene was injected. These results also suggest that Xenopus embryos already have the ability to transcribe an exogenously injected c-myc gene at the 4-cell stage.

Animals↗
PubMed1993

Data on the CGG repeat at the fragile X site in the non-retarded Japanese population and family suggest the presence of a subgroup of normal alleles predisposing to mutate.

The fragile X mutation is the result of amplification in the repeat number of p(CGG)n in FMR-1; alleles with more than 52 repeats have been shown to be so unstable as to mutate in the repeat number in almost every transmission. To improve our understanding of mutations in normal alleles of FMR-1, the following studies were carried out in the Japanese population: a study on length variation in the repeat to determine the allele distribution of the repeat length in a non-retarded population, family studies to observe new mutations in normal allele, and haplotype analyses with microsatellite markers flanking the repeat to confirm estimated mutation rates and founder chromosomes in the fragile X syndrome. Analysis of the p(CGG)n in 370 unrelated males detected 24 distinct alleles with repeats of 18-44. A comparison with previously reported data suggests the presence of racial/ethnic differences in the allele distribution. No premutation allele was found in 824 unrelated X chromosomes examined by the polymerase chain reaction and Southern blot analysis. Family studies detected one new mutation in a total of 303 meioses. However, the mutation rate was not in accordance with the expected or observed heterozygosities in the population or with linkage disequilibrium observed between the repeat numbers and the haplotypes of the markers flanking the CGG. The haplotype in the chromosome in which the new mutation was found was the same as that frequently found in the Japanese fragile X chromosomes, and the variance in the CGG repeat number was wider in chromosomes with the haplotypes frequently found in the fragile X chromosome than in those with the other haplotypes. These observations suggest that a subgroup is present in normal alleles and that this subgroup is more liable to mutate than others.

Alleles↗
PubMed1993

A 5-lipoxygenase inhibitor, FR110302, inhibits ozone-induced airway hyperresponsiveness in guinea pigs and dogs.

Airway hyperresponsiveness is a key feature of asthma, and attenuating airway hyperresponsiveness is an important part of asthma therapy. In the present study we examined the inhibitory effect of a potent 5-lipoxygenase inhibitor, FR110302, on airway hyperresponsiveness induced by ozone exposure in guinea pigs and dogs. Respiratory resistance (Rrs) was measured by a forced oscillation method. Airway responsiveness was determined from the dose-response curve of Rrs to acetylcholine. Guinea pigs were exposed to 2.5 ppm ozone for 1 h. In a control group of guinea pigs, delta log PC100 (the index of the ozone-induced airway hyperresponsiveness) was 0.58 +/- 0.04 (log mg/ml). Treatment with FR110302 (10 or 100 mg/kg p.o.) significantly diminished delta log PC100 (10 mg/kg: 0.22 +/- 0.10; 100 mg/kg; 0.11 +/- 0.06). Dogs were exposed to 3 ppm ozone for 2 h. In a control group of dogs, delta log Dmin (another index of the ozone-induced airway hyperresponsiveness) was 1.24 +/- 0.15 (log unit). Treatment with FR110302 (1 or 3.2 mg/kg p.o.) significantly diminished delta log Dmin (1 mg/kg: 0.60 +/- 0.18; 3.2 mg/kg: 0.27 +/- 0.12). These results suggest that FR110302 may be a useful drug for attenuating airway hyperresponsiveness in asthmatic patients.

Acetylcholine↗
PubMed1993

Biodegradable poly(DL-lactic acid) formulations in a calcitonin delivery system.

A synthetic analogue of eel calcitonin, [Asu1, 7]-ECT, was incorporated into biodegradable poly(DL-lactic acids) with number-average molecular weights (Mn) of 1400-4400 by the melt-pressing technique. The in vitro release of drug from a parabolically degradable poly(DL-lactic acid) with Mn = 1400 showed an initial burst release and completed the release in 3 d from the start of the test. The drug release from a Mn = 4400 polymer with an S-type degradation pattern was kept at 14 +/- 5 units/d for an experimental period of 24 d.

Amino Acid Sequence↗
PubMed1993

Increased Ca2+ influx in the resting state maintains the myogenic tone and activates charybdotoxin-sensitive K+ channels in dog basilar artery.

We examined whether Ca2+ channel function in the resting state alters the resting tone and Ca(2+)-activated K+ (KCa) channel function in dog basilar artery: data were compared with findings in the mesenteric artery. Isolated dog basilar artery maintained a myogenic tone; that is, the resting tone decreased when either the Krebs solution was replaced with a Ca(2+)-free solution or nifedipine was added. The basal 45Ca influx in the resting state of the basilar artery was significantly increased compared with that in the mesenteric artery, and this increase in the basilar artery was reduced by nifedipine. The addition of charybdotoxin (ChTX), a blocker of large-conductance KCa channels, to the resting strips caused a concentration-dependent contraction in the basilar artery but not in the mesenteric artery. The ChTX-induced contraction in the basilar artery was abolished by nifedipine. In resting strips preloaded with 86Rb, the basal 86Rb efflux rate constant was significantly greater in the basilar artery than in the mesenteric artery. The addition of nifedipine to the resting strips decreased the basal 86Rb efflux rate constant only in the basilar artery. These results suggest that the transmembrane Ca2+ influx via L-type voltage-dependent Ca2+ channels was significantly increased in the resting state of the basilar artery and that the myogenic tone was therefore maintained and the ChTX-sensitive KCa channels were highly activated.

Animals↗
PubMed1993

Antianginal effects of YM-16151-4 in various experimental angina models.

The antianginal effects of YM-16151-4, a combined calcium entry blocking and beta 1-adrenoceptor blocking agent, were evaluated in various experimental angina models and compared with those of nifedipine and propranolol. In anesthetized dogs, YM-16151-4 (0.3 and 1 mg/kg intravenously, i.v.) increased coronary blood flow and reduced myocardial oxygen consumption (MVO2). In isolated dog coronary arteries, YM-16151-4 concentration-dependently inhibited 3,4-diaminopyridine-induced rhythmic contractions with an IC50 value of 91 nM. In anesthetized rats, YM-16151-4 also inhibited the ST-segment depression induced by vasopressin (0.5 U/kg i.v.) with an ED50 value of 29 mg/kg orally, (p.o.). Nifedipine was also effective in these models, but propranolol was not. In addition, YM-16151-4 (0.3 mg/kg i.v.) inhibited the ST-segment elevation in the epicardial ECG induced by coronary artery occlusion in anesthetized dogs. Propranolol (1 mg/kg i.v.) also inhibited this elevation, but nifedipine (0.003 mg/kg i.v.) did not. In anesthetized dogs, furthermore, the prolongation of PQ-interval induced by YM-16151-4 was almost the same as that induced by propranolol. These results demonstrate that YM-16151-4, in contrast to nifedipine and propranolol, is fully effective in these various types of angina models. Thus, YM-16151-4 is expected to prove a valuable antianginal agent in treatment of various types of angina pectoris, with these antianginal effects resulting from the sum of its calcium entry blocking and beta 1-adrenoceptor blocking activities.

4-Aminopyridine↗
PubMed1993

JICWELS' MCH training program in the Aiiku Institute: Asian MCH workshop.

Taking a form of Official Development Aid (ODA), the Japan International Cooperation of Welfare Services (JICWELS) and Imperial Gift Foundation, Boshi-Aiiku-Kai (Aiiku Association for Maternal and Child Health and Welfare) have extended a study program on maternal and child health (MCH) since 1989 on the commission of the Ministry of Health and Welfare. 'Community participation' is the key to the first international study program focused solely on MCH. The purpose of the program is to help to improve the planning and administration in the field of MCH. Through this, the information and experience attained in Japanese MCH activities are introduced especially by participation in community-level activities of 'Aiiku-Han' in which local citizens play a major role. The operation system of the Asian MCH Workshop, contents of the workshop, evaluation and future prospects are discussed.

Asia↗
PubMed1993

Charybdotoxin-sensitive K+ channels regulate the myogenic tone in the resting state of arteries from spontaneously hypertensive rats.

1. To determine the possible role of Ca(2+)-activated K+ (KCa) channels in the regulation of resting tone of arteries from spontaneously hypertensive rats (SHR), the effects of agents which interact with these channels on tension and 86Rb efflux were compared in endothelium-denuded strips of carotid, femoral and mesenteric arteries from SHR and normotensive Wistar-Kyoto rats (WKY). 2. Strips of carotid, femoral and mesenteric arteries from SHR exhibited a myogenic tone; that is, the resting tone decreased when either the Krebs solution was changed to a 0-Ca2+ solution or 10(-7) M nifedipine was added. 3. The addition of charybdotoxin (ChTX, 10(-9)-10(-7) M), a blocker of large conductance KCa channels, to the resting strips of these arteries produced a concentration-dependent contraction, which was significantly greater in SHR than in WKY. Relatively low concentrations of tetraethylammonium (0.05-5 mM) produced a concentration-dependent contraction which was similar to the ChTX-induced contraction in these strips. 4. The ChTX-induced contractions in SHR were greatly attenuated by 10(-7) M nifedipine and by 3 x 10(-6) M cromakalim, a K+ channel opener. Cromakalim alone abolished the myogenic tone in SHR. 5. The addition of apamin (a blocker of small conductance KCa channels, up to 10(-6) M), or of glibenclamide (a blocker of ATP-sensitive K+ channels, up to 5 x 10(-6) M), to the resting strips failed to produce a contraction. 6. In resting strips of carotid, femoral and mesenteric arteries preloaded with 86Rb, the basal 86Rb efflux rate constants were significantly greater in SHR than in WKY. The addition of 10-7 M nifedipine to the resting strips decreased the basal 86Rb efflux rate constants only in SHR.7. The cellular Ca2+ uptake in the resting state of carotid and femoral arteries from SHR was significantly increased when compared to WKY, and this increase in SHR was significantly reduced by 10-7M nifedipine.8. These results suggest that the ChTX-sensitive KCa channels were highly activated to regulate the myogenic tone in the resting state of carotid, femoral and mesenteric arteries from SHR. The increased Kca channel functions in SHR arteries appeared to be secondary to the increased Ca2' influx via L-type voltage-dependent Ca2+ channels in the resting state of these arteries.

Animals↗
PubMed1993

Modification by charybdotoxin and apamin of spontaneous electrical and mechanical activity of the circular smooth muscle of the guinea-pig stomach.

1. The effects of charybdotoxin and apamin, putative blockers of Ca(2+)-activated K+ channels, on spontaneous electrical and mechanical activity of circular smooth muscle of the guinea-pig stomach antrum were examined in the presence of 1 microM tetrodotoxin and 1 microM atropine. 2. Both charybdotoxin (> 3 nM) and apamin (> 3 nM) dose-dependently increased the amplitude of spontaneous contractions without altering their frequency. The maximum effect of charybdotoxin was much greater than that of apamin. Both toxins increased the amplitude of intracellular Ca2+ oscillations measured with fura-2. 3. When the extracellular Ca2+ concentration was lowered to 1.5 mM or less, apamin did not significantly potentiate the contractions whereas charybdotoxin still potentiated them but with less potency. 4. Charybdotoxin (30 nM) increased the amplitude of spikes and slow waves, and slightly decreased the resting membrane potential. On the other hand, apamin (100 nM) preferentially increased the slow wave amplitude with no effect on the resting membrane potential. 5. These results suggest that both toxins affect the spontaneous contraction by modifying the electrical activity and that charybdotoxin-sensitive K+ channels and apamin-sensitive ones are differently involved in the spontaneous electrical activity.

Acetylcholine↗
PubMed1993

An anti-CD3 monoclonal antibody protects mice against a lethal infection with Listeria monocytogenes through induction of endogenous cytokines.

Mice were protected against a lethal infection with Listeria monocytogenes when treated with low doses of an anti-CD3 monoclonal antibody (MAb). Injection of anti-CD3 MAb induced rapid production of endogenous tumor necrosis factor (TNF) in the spleens and endogenous gamma interferon (IFN-gamma) in the bloodstreams and spleens of mice. Administration of anti-Thy1.2 MAb or a combination of anti-CD4 MAb and anti-CD8 MAb resulted in suppression of anti-CD3 MAb-induced endogenous cytokine production and antilisterial resistance. Alternatively, in vivo depletion of anti-CD3 MAb-induced TNF and IFN-gamma by the simultaneous administration of antibodies against TNF and IFN-gamma suppressed anti-CD3 MAb-induced antilisterial resistance. Moreover, injection of anti-complement receptor type 3 (Mac-1, CD11b) resulted in inhibition of anti-CD3 MAb-induced antilisterial resistance. These results suggest that the preventive effect of anti-CD3 MAb might be due to activation of phagocytes by TNF and IFN-gamma induced by stimulating CD4+ T cells and CD8+ T cells with the MAb. Furthermore, treatment with anti-CD3 MAb did not inhibit establishment of acquired resistance against secondary infection with L. monocytogenes.

Animals↗
PubMed1993

Endogenous gamma interferon is essential in granuloma formation induced by glycolipid-containing mycolic acid in mice.

The present study examined the role of endogenous gamma interferon (IFN-gamma) in the formation of granulomas in mice which had been given a single intravenous injection of glycolipid-containing mycolic acid (trehalose 2,3,6'-trimycolate) purified from cell walls of Rhodococcus aurantiacus (Gordona aurantiaca) (GaGM) in the form of liposome. The histological status of granuloma formation in the livers, spleens, and lungs of GaGM-injected mice was studied at weeks 1 through 5, and the titers of endogenous IFN-gamma in all of these organ extracts and in the sera were determined by enzyme-linked immunosorbent assay. The granulomas, composed of epithelioid cells, developed until 3 weeks postinjection, and thereafter the granulomas regressed. The production of endogenous IFN-gamma was biphasic, with an early phase detected at days 1 through 3 and a late phase detected at weeks 1 through 5. The latter peak of endogenous IFN-gamma production proceeded in parallel with granuloma formation. Both the areas of granulomas and titers of IFN-gamma in these organs were dependent on the doses of GaGM used for injection. The cells which produce endogenous IFN-gamma in the spleens appear within the granulomas. To study the role of endogenous IFN-gamma in granuloma formation, the in vivo administration of rat anti-mouse IFN-gamma monoclonal antibody was carried out. Anti-mouse IFN-gamma monoclonal antibody neutralized endogenous IFN-gamma and resulted in the suppression of the number of granulomas and the size of each granuloma. These findings suggest that biphasic production of endogenous IFN-gamma in the local lesions may be crucial to the formation and development of the granulomas.

Animals↗
PubMed1993

Functional role of Ca(2+)-activated K+ channels in resting state of carotid arteries from SHR.

Carotid arteries from spontaneously hypertensive rats (SHR) exhibited an active tone when exposed to a physiological salt solution; that is, the tension decreased when nifedipine was added. To determine the possible role of Ca(2+)-activated K+ (KCa) channels in the resting state of these arteries, the effects of agents that interact with these channels on tension and 86Rb efflux were compared in endothelium-denuded strips of carotid arteries from SHR and normotensive Wistar-Kyoto rats (WKY). The addition of charybdotoxin, a blocker of high-conductance KCa channels, to the resting strips produced a concentration-dependent contraction in SHR but not in WKY. In resting strips preloaded with 86Rb, the basal 86Rb efflux rate constant was significantly greater in SHR than in WKY. The addition of nifedipine to the resting strips decreased the basal 86Rb efflux rate constant only in SHR. The effect of nifedipine on tension and 86Rb efflux in 25.9 mM K(+)-contracted strips of WKY was comparable to the effect of this blocker in the resting strips of SHR. The basal 45Ca influx in resting strips of SHR was significantly increased when compared with WKY, and this increase in SHR was abolished by nifedipine. These results suggest that the transmembrane Ca2+ influx via L-type voltage-dependent Ca2+ channels was significantly increased in the resting state of carotid arteries from SHR and that the KCa channels were highly activated.

Animals↗
PubMed1993

Adjuvant effect of interleukin-1 on the development of late asthmatic response in guinea pigs.

The adjuvant effect of silica and IL-1 in the development of late asthmatic responses (LARs) in guinea pigs was studied. Different doses of silica or recombinant human (rh) IL-1 (1 microgram) with Ascaris suum were used for the immunization. The serum IL-1 concentration was measured after the immunization. One week after the immunization, antigen was challenged and respiratory resistance (Rrs) was measured. Rrs increased silica dose dependently in the late phase, and the increment of Rrs in the late phase was significantly correlated with the serum IL-1 concentration (p < 0.05). In addition, rhIL-1 administration showed an increase in Rrs at the late phase. Antigen-specific IgE and IgG1 were also measured and were increased in guinea pigs immunized both with silica and rhIL-1.

Adjuvants, Immunologic↗
PubMed1993

Development of a model membrane system using stratum corneum lipids for estimation of drug skin permeability.

Several model membrane systems have been reported to predict the skin permeability of drugs, but model membranes using stratum corneum (SC) lipids have never been reported. Thus, we developed a model membrane system for drug permeation study by fixing liposomes composed of SC lipids (ceramides, palmitic acid, cholesterol, and cholesterol-3-sulfate) onto a supporting filter, Biodyne B. The permeability of several drugs with different lipophilicities was investigated. Permeability increased with drug lipophilicity, estimated from the octanol/buffer solubility ratio of the drug. For relatively polar drugs, however, the permeability was almost constant, and very close to the value of a K+ ion, suggesting the membrane has both lipidic and aqueous pathways. Drug permeability through our system was compared with that through guinea pig skin. A good correlation (r = 0.880) was observed, although the former was one order of magnitude greater than the latter. Our model system will be useful not only for practical application, but also for basic studies, such as the elucidation of the relationships between SC lipid composition and drug permeability.

Animals↗