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T Miyauchi

Publications and source records attributed to T Miyauchi.

At least 109 records · Page 6Linked to original sources
PubMed1996

Vasoconstriction by endothelin-1 in resistance and conduit portions of isolated human mesenteric arteries.

Although physiological processes related to vascular function differ greatly between resistance arteries and conduit arteries, it is not known whether the effects of endothelin-1 on these arteries differ in humans. In the present study, the conduit portion and the resistance portion of isolated human mesenteric arteries were suspended in a Krebs-Ringer solution. Norepinephrine and endothelin-1 produced concentration-dependent contractions in both portions. The EC50 value of norepinephrine in the resistance portion (3.7 x 10(-7) M, n = 8) did not differ from that in the conduit portion (3.4 x 10(-7) M, n = 7). However, the EC50 value of endothelin-1 in the resistance portion (3.0 x 10(-9) M, n = 8) was significantly lower than that in the conduit portion (1.1 x 10(-8) M, n = 7, P < 0.05). Although the maximum response to norepinephrine in the resistance portion (calculated as the percentage of 50 mM KCl-induced contraction) did not differ from that in the conduit portion, the maximum response to endothelin-1 in the resistance portion was significantly greater than that in the conduit portion. These results indicate that endothelin-1 induces more potent constriction in resistance portion than in conduit portion in isolated human mesenteric arteries.

Adult↗
PubMed1996

Endogenous endothelin-1 participates in the maintenance of cardiac function in rats with congestive heart failure. Marked increase in endothelin-1 production in the failing heart.

BACKGROUND: Although it was demonstrated that circulating endothelin-1 (ET-1) levels are elevated in congestive heart failure (CHF), the production and roles of ET-1 in the failing heart are not known. We investigated the production of ET-1 in the heart and the density of myocardial ET receptors in rats with CHF. We also investigated the effects of intravenously infused BQ-123, an endothelin(A) (ETA) receptor antagonist, on both heart and myocardial contractility in rats with CHF. METHODS AND RESULTS: We used the left coronary artery-ligated rat model of CHF (CHF rats). Three weeks after surgery, the rats developed CHF. Plasma ET-1 concentration was significantly higher in the CHF rats than in the sham-operated rats (P<.01). In the left ventricle, the expression prepro-ET-1 mRNA was markedly higher in the CHF rats than in the sham-operated rats. The peptide level of ET-1 in the left ventricle was also significantly higher in the CHF rats than in the sham-operated rats (500+/-41 versus 102+/-10 pg/g tissue, P<.01). Myocardial ET receptors were significantly higher in the CHF rats than in the sham-operated rats (243+/-20 versus 155+/-17 fmol/mg protein, P<.05). In the CHF rats, intravenous BQ-123 infusion (0.1 mg x kg(-1) x min(-1) for 120 minutes) significantly decreased both heart rate (P<.01) and LV+dP x dt(max) (P<.05) but not mean blood pressure. BQ-123 infusion did not affect these hemodynamic parameters in the sham-operated rats. CONCLUSIONS: In the present study, we demonstrated that the production of ET-1 in the heart is markedly increased and that the density of myocardial ET receptors is significantly elevated in the CHF rats. Intravenous BQ-123 infusion significantly reduced both heart rate and LV+dP/dt(max) in the CHF rats but not in the sham-operated rats. Therefore, the ET receptor-mediated signal transduction system in the heart appears to be markedly stimulated in the CHF rats, and endogenous ET-1 may be involved in the maintenance of the cardiac function in these rats.

Animals↗
PubMed1996

Regional 2-[18F]fluoro-2-deoxy-D-glucose uptake varies in normal lung.

2-[18F]fluoro-2-deoxy-d-glucose positron emission tomography (FDG-PET) is a promising imaging procedure for detecting primary and metastatic cancer in the lungs. We have, however, failed to detect some small tumors in the lower lobes of the lungs. This study aimed to determine whether increase 18F background activity in the dependent lower lungs is present, which could make lesion detection more difficult. We measured the standardized uptake values (SUVs) for FDG of normal lung remote from the nodular lesion in 16 patients with newly diagnosed untreated lung lesions strongly suspected to represent non-small cell lung cancers. In addition, 15 patients with known or suspected primary breast cancers without pulmonary lesions were included as control subjects. After PET transmission images of the thorax were obtained, approximately 370 MBq of FDG was injected intravenously and imaging was immediately begun. Patients were supine throughout the study. SUVs were determined with images obtained 50-70 min after FDG injection. Regions of interest (ROIs) of 6x6 pixels were positioned over normal lung in anterior, mid, and posterior portions of upper, middle, and lower lung fields. Thus, as many as 18 ROIs were positioned in each patient. The SUVs of the posterior portion were significantly higher than those of the anterior and mid portions in the population of 31 cases (P <0.001). Also, the mean SUV of the lower lung field was significantly higher than the SUVs of the upper and middle lung fields in this population (P <0.01). This pattern was seen among the two groups of 16 patients suspected of having lung cancer and 15 control subjects. Background 18F activity was highest in posterior and lower lung in these patients. The maximum value of mean SUV observed in normal posterior lower lung was 0.804+/-0.230 (41% greater than the mean SUV in the anterior upper lung), which is in the range of the apparent SUV for a 5-mm lung lesion, with higher SUV, due to recovery coefficient issues. Thus this phenomenon could contribute to occasional false-negative lesions in those areas. Increased blood flow and FDG delivery and also scatter from heart and liver may contribute to the increased lower lung background activity. Regional differences in normal lung FDG uptake are significant and should be considered when interpreting pulmonary PET studies in patients with suspected primary or metastatic lung cancer.

Breast Neoplasms↗
PubMed1996

Plasma endothelin-1 level in athletes after exercise in a hot environment: exercise-induced dehydration contributes to increases in plasma endothelin-1.

We investigated whether dehydration due to exercise contributes to the increase in plasma endothelin-1 (ET-1) concentration. We measured the plasma concentration of ET-1 before and after exercise in a hot environment (about 30 degrees C). Five male intercollegiate Kendo (Japanese fencing) players entered the present study. Each athlete participated in 15 min of Kendo fighting, followed by 5 min of rest and another 15 min of Kendo fighting (i.e., total exercise 30 min), with or without oral intake of 700 ml of water. Body weight and left atrial diameter, a parameter that reflects changes in circulating plasma volume, were significantly decreased after exercise under both conditions. However, the decreases in both values were significantly greater after exercise without water intake than after exercise with water intake, indicating that dehydration and decreased circulating plasma volume were more marked after exercise without water intake. The extent of the increase in plasma ET-1 concentration appeared to be closely related to the extent of exercise-induced dehydration; the greater the dehydration, the greater the increase in plasma ET-1 concentration. These findings suggest that exercise-induced dehydration may contribute to increases in plasma ET-1 concentrations.

Adult↗
PubMed1996

Calcitonin gene-related peptide (CGRP) induces more potent vasorelaxation in the resistance portion than in the conduit portion of mesenteric arteries in humans.

Although physiological processes related to vascular function differ greatly between resistance arteries and conduit arteries, it is not known whether the effects of calcitonin gene-related peptide (CGRP), a vasodilator neuropeptide, on these arteries differ in humans. In the present study, the conduit portion and the resistance portion of isolated human mesenteric arteries were suspended in a Krebs-Ringer solution. CGRP produced vasorelaxations in both portions. The EC50 values were very low both in the resistance portion (2.4 x 10(-9) M, n = 7) and in the conduit portion (2.2 x 10(-9) M, n = 7). The maximum response to CGRP in the resistance portion was significantly greater than that in the conduit portion (94.6 +/- 4.0% vs. 64.1 +/- 2.6% relaxation of methoxamine-induced precontraction, both n = 7, p < 0.01). These data suggest that CGRP is one of the most potent endogenous vasodilators in both the resistance portion and the conduit portion of the human mesenteric arteries, and that CGRP induces more potent vasorelaxation in the resistance portion than in the conduit portion of these arteries.

Adult↗
PubMed1996

Behavioral effects of HT-90B, a putative novel anxiolytic agent with potent antidepressive activity.

1. HT-90B,((-)-N-[2-(8-methyl-1,4-benzodioxane-2-ylmethyl)am in o]ethyl]tricyclo[3,3,1,1(3,7)] decane-1-carboxamide), is a novel serotonin 5-HT(1A) full agonist with serotonin 5-HT(2) antagonistic action. 2. In a water licking conflict test, HT-90B (3-30 mg/kg, po) was more effective than buspirone in abolishing response suppression. 3. In a forced swim test, HT-90B (3-30 mg/kg, po) reduced the duration of immobility after a single oral dose, which contrasts with the requirement of multiple doses for desipramine (as a standard antidepressant) to produce the effect. 4. These two behavioral effects of HT-90B (20 mg/kg,po) were still evident even 4 hr after oral administration. And no tolerance was observed for these behavioral effects after repeated oral administration (10 mg/kg, b.i.d., 2 weeks). 5. HT-90B hardly produced any diazepam- or buspirone-like side effects. 6. In conclusion, it is suggested HT-90B is a potent anti-depressive anxiolytic with minimal side effects.

Adamantane↗
PubMed1996

Computerized electroencephalogram in untreated schizophrenics: a comparison between disorganized and paranoid types.

Computerized electroencephalogram (CEEG) data were obtained from 30 patients with the disorganized type and 20 patients with the paranoid type of acute untreated schizophrenia and compared with data from age- and sex-matched controls. All patients with acute untreated schizophrenia exhibited more pronounced delta, theta, alpha 1 and beta 1 activity and less prominent alpha 2 activity than the control subjects. These findings support previous studies, and indicate the coexistence of cerebral hypofunction and excitability in acute schizophrenic patients. Compared with the controls, patients with disorganized type schizophrenia had significant increases in theta and beta 1 and decreases in alpha 2 activities; but a significant increase in delta and alpha 1 activities in the posterior regions and beta 2 activity in the frontal regions of the brain. Patients with paranoid type schizophrenia showed significantly increased delta activity in the posterior regions, increased alpha 1 activity in the anterior regions and decreased alpha 2 activity in both these regions. In the paranoid type, however, there was no significant finding for the theta, beta 1 and beta 2 activities. Disorganized type schizophrenics exhibited more increased theta and decreased alpha 2 activity than patients with paranoid type schizophrenia. The CEEG differences between the disorganized and the paranoid types appear to reflect different clinical entities and may help to differentiate both schizophrenias.

Adult↗
PubMed1996

Necessity of dual blockade of endothelin ETA and ETB receptor subtypes for antagonism of endothelin-1-induced contraction in human bronchi.

1. Endothelin (ET)-1 has been postulated to be involved in the development of obstructive airway diseases in man. In the present study, we attempted to characterize ET receptor subtypes mediating ET-1-induced contraction in human isolated bronchi. The ET receptor antagonists used in the present study were BQ-123 (ETA receptor-selective), BQ-788 (ETB receptor-selective) and BQ-928 (ETA/ETB dual). Sarafotoxin S6c (S6c) was also used as an ETB receptor-selective agonist. 2. In human bronchi, ET-1 and S6c (10(-12)M to 10(-7) M) produced concentration-dependent contraction with almost equal potency (pD2: 8.88 +/- 0.16 for ET-1 and 9.42 +/- 0.15 for S6c). The contraction induced by S6c was competitively antagonized by BQ-788 alone (1 and 10 microM) with a pKB value of 7.49 +/- 0.21, suggesting that the stimulation of ETB receptors causes a contraction of human bronchi. However, contrary to expectation, the concentration-response curves for ET-1 were not affected by BQ-788. The ET-1- and S6c-induced contractions were not affected by BQ-123 (10 microM). Thus, ET-1-induced contraction of human bronchi is not antagonized by BQ-123 alone or by BQ-788 alone. 3. Combined treatment with 10 microM BQ-123 and 10 microM BQ-788 significantly antagonized the contraction induced by ET-1 with a dose-ratio of 11. BQ-928 also significantly antagonized ET-1-induced contraction with a pKB value of 6.32 +/- 0.24. 4. The specific binding of [125I]-ET-1 to human bronchial membrane preparations was inhibited by BQ-123 (100 pM to 1 microM) by approximately 40%. Combination treatment with BQ-788 (100 pM to 1 microM) completely inhibited the BQ-123-resistant component of [125I]-ET-1 specific binding. 5. In conclusion, the present study demonstrates that BQ-788 alone cannot inhibit ET-1-induced contractions in human bronchi, although human bronchial ETB receptors are BQ-788-sensitive. Furthermore, it was shown that blockade of both receptor subtypes antagonizes ET-1-induced contraction, and that both receptor subtypes co-exist in human bronchial smooth muscles. These findings suggest that ETA receptors as well as ETB receptors are involved in ET-1-induced contraction in human bronchi. If ET-1 is involved in human airway diseases, dual blockade of ETA and ETB receptors may be necessary to treat the diseases.

Adult↗
PubMed1996

Relationship between intracoronary thrombolysis and fibrino-coagulation--special reference to TAT/PIC and FPA/PIC.

To clarify the relationship between the results of intracoronary thrombolytic therapy (ICT) and fibrino-coagulation in patients with acute myocardial infarction (AMI), the thrombin-antithrombin III complex (TAT) and fibrinopeptide A (FPA), as indices of accelerated coagulation, and the plasmin- alpha 2-plasmin inhibitor complex (PIC), as an index of accelerated fibrinolysis in peripheral blood, were measured just before and after heparin injection (5,000 U), and immediately after ICT. Twenty-four patients with AMI were divided into 2 groups according to the results of ICT; successful ICT (group S) and unsuccessful ICT (group F). As a control group (group C), 14 age-matched normal volunteers were also studied. The levels of TAT and FPA before ICT were significantly higher in groups S and F than in group C (p < 0.01). The TAT level before ICT in group F was higher than that in group S (p = 0.07), however, the TAT, FPA and PIC levels showed no significant differences between groups S and F at each sampling time. TAT/PIC before ICT was significantly higher in group F than in group S (F: 0.026 +/- 0.020 vs S: 0.008 +/- 0.004, p < 0.05), whereas there was no remarkable difference in FPA/PIC between groups S and F. These results indicate that hyper-coagulation had occurred in the AMI cases and that coagulation had been more accelerated in group F. TAT/PIC might be an index of the equilibrium of the fibrino-coagulating system. Therefore, TAT/PIC measurement before thrombolytic therapy may be more useful than TAT measurement alone for evaluating recanalization in ICT.

Aged↗
PubMed1996

Anaphylactic IgE and IgG1 production for hapten can be enhanced by contrast media.

Various side effects have been associated with the clinical use of contrast media. Immunological mechanisms have been proposed but there have been very few experimental studies with animal models. We have attempted to develop murine models to determine whether or not anaphylactic antibodies such as IgE and IgG1 against hapten (DNP) were enhanced with contrast medium (iopamidol) as an adjuvant or if the contrast medium itself produced antibodies of the IgE class. The results showed that anti-hapten IgE and IgG1 production was greatly enhanced with immunogen plus contrast medium. Anti-contrast medium antibodies of the IgE class could not be detected by PCA reactions. The enhancement of IgE and IgG1 production for hapten was associated with IL-4 release by the neutralization test used by monoclonal anti-IL-4 antibodies. This is the first observation to show that contrast media may have a strong adjuvant effect for the production of IgE and IgG1. This murine model demonstrates a possible immunological function of contrast media in vivo.

Anaphylaxis↗
PubMed1996

[MASS phenotype].

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Aortic Diseases↗
PubMed1995

The neuroprotective effect of a potent and selective inhibitor of type I NOS (L-MIN) in a rat model of focal cerebral ischaemia.

Our newly synthesized delta-(S-methylisothioureido)-L-norvaline (L-MIN) was shown to have potent inhibitory effects on Ca(2+)-dependent and constitutively expressed neuronal nitric oxide synthase (type I NOS) when compared to other commonly recognized NOS inhibitors and produced an IC50 value of 5.7 nM. By contrast, this compound exhibited more than 40-fold weaker inhibitory effects on the other NOS isoforms. Administration of L-MIN (0.1, 0.3 and 1 mg kg-1, i.p.) to rats immediately after 2 h middle cerebral artery occlusion and 2 h reperfusion reduced infarct size in a dose-dependent manner. These results suggest that type I NOS activation has a crucial role in the pathogenic cellular mechanisms underlying cerebral ischaemia.

Analysis of Variance↗
PubMed1995

Increase in choroidal blood flow in rabbits with endothelin-1 induced transient complete obstruction of retinal vessels.

BACKGROUND: In a previous paper, we reported that retinal blood flow (RBF) ceased immediately after injection of 1 nmol endothelin-1 (ET-1) and no recovery of RBF was detected for at least 50 min. In this study, we confirmed the same duration of RBF cessation and measured choroidal blood flow (CBF) for 180 min. METHODS: We measured CBF in a rabbit model of transient complete obstruction of retinal vessels induced by intravitreal injection of a high dose of ET-1, using the hydrogen clearance method. We also investigated the effects of intravitreal injection of ET-1 on intraocular pressure (IOP), blood pressure, pulse rate and blood gases. RESULTS: CBF was significantly greater in the ET-1-injected eyes than in the control eyes 40-130 min after injection of ET-1 (P < 0.05). The maximal CBF ratio in the ET-1-injected eyes was 128 +/- 7.4% at 40 min. CBF decreased to the pre-injection level at 140 min after the injection of ET-1. There was no significant change in blood pressure, pulse rate and blood gases throughout this experiment, and there was no significant difference in IOP between ET-1-injected eyes and control eyes. CONCLUSION: It seems likely that the increase in CBF resulted from some local mechanisms of control that compensated for the decrease in RBF induced by intravitreal injection of ET-1. This model may be useful for investigation of the regulatory system of intraocular circulation, including endothelin receptors.

Animals↗
PubMed1995

Pharmacological profile of (-)HT-90B, a novel 5-HT1A receptor agonist/5-HT2 receptor antagonist.

1. HT-90B ((-)-N-([2-(8-methyl-l, 4-benzodioxane-2-ylmethyl)amino]ethyl) tricyclo[3,3,1,1(3.7)] decane-1-carboxamide) had high affinities for the 5-HT1A (Ki = 0.18 nM) and 5-HT2 (Ki = 9.2 nM) receptors. 2. HT-90B inhibited forskolin activated adenylate cyclase in rat hippocampal membranes as a 5-HT1A full agonist (IC50 = 2 nM), and the potency of the drug was higher than that of 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT), a standard 5-HT1A agonist. 3. In the serotonin syndrome test, HT-90B behaved as a weak partial 5-HT1A agonist in reserpinized rats. 4. 5-HT2 receptor-mediated potentiation of rabbit platelet aggregation by serotonin (5-HT) was reduced by HT-90B (IC50 = 1.73 microM). 5. Head twitch response induced by 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI), a 5-HT2 agonist, was inhibited by HT-90B in mice. 6. It is concluded that HT-90B has potent 5-HT1A receptor agonist as well as 5-HT2 receptor antagonist properties in vitro and in vivo.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1995

Structure of the mouse basigin gene, a unique member of the immunoglobulin superfamily.

Basigin is a membrane glycoprotein belonging to the immunoglobulin superfamily. The mouse basigin gene was isolated from a genomic DNA library of the BALB/c mouse, and the structure of the gene and its flanking region (11.8 kb) was completely determined. The mouse basigin gene consists of seven exons and six introns spanning 7.5 kb. The distance between the first and second exons is 5.1 kb. The first immunoglobulin-like domain of the basigin molecule is encoded by the second and third exons, and the second immunoglobulin-like domain by the fourth and fifth exons. The fifth exon encodes not only the C proximal portion of the second immunoglobulin-like domain, but also the transmembrane domain and a small portion of the cytoplasmic domain. Thus, the organization of the basigin gene is unique. The 5' upstream sequence of the basigin gene contains no TATA box or CAAT box, but has a CpG-rich island. The BALB/c genomic sequence of all seven exons is consistent with the cDNA sequences of the 129/SV and Swiss mice except several minor substitutions in the 3'-terminal sequence of the 3'-noncoding region. No protein polymorphism has so far been found in basigin of different mouse strains.

Amino Acid Sequence↗