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Biomedical subjects

A Sakai

Publications and source records attributed to A Sakai.

At least 163 records · Page 9Linked to original sources
PubMed1996

Presence of poorly stained myocytes in acute myocarditis predicts improvement in cardiac function.

Histological findings in the acute phase of myocarditis were evaluated as a prediction of hemodynamic state in the chronic phase in 20 patients with clinical and pathological diagnoses of myocarditis who were followed up with echocardiography for at least 1 year. Endomyocardial biopsy samples were obtained from the left ventricle within 1 year of the onset of symptoms. Azan-Mallory staining was performed on the myocytes, which were categorized as either well stained or poorly stained. The point counting method was used to determine the fraction of each type. The improvement in ejection fraction within 1 year correlated significantly with the fraction of poorly stained myocytes (r = 0.46, p < 0.05). The ejection fraction at biopsy was negatively correlated with the volume fraction of well stained myocytes (r = -0.64, p < 0.01). The staining condition of myocytes may be useful in predicting the hemodynamic recovery of patients with myocarditis.

Acute Disease↗
PubMed1996

[A case report of a successful surgery for thoracoabdominal aortic aneurysm under partial cardiopulmonary bypass with selective perfusion of major abdominal branches].

A 69-year-old man showed gradually developing thoracoabdominal aortic aneurysm (TAAA) after coronary artery bypass grafting. The patient underwent graft replacement of TAAA uneventfully under partial cardiopulmonary bypass with selective perfusion of major abdominal branches. The major abdominal branches and two pairs of intercostal arteries were reconstructed. The patient showed no organ failure or spinal damage postoperatively. Partial cardiopulmonary bypass with selective perfusion of abdominal branches successfully protected both the visceral organs and the spinal cord from ischemia in a TAAA surgery.

Aged↗
PubMed1995

Tachykinins stimulate nitric oxide generation by canine cultured tracheal epithelium.

We studied the effects of tachykinins on the generation of nitric oxide (NO) from canine cultured tracheal epithelial cells using a specific amperometric sensor for this molecule. Immersion of the NO-selective electrode in the medium bathing the cells detected the baseline current of 30.5-61.7 pA, which corresponded to NO concentration ([NO]) at 44.0 +/- 7.6 nM (mean +/- S.E.M.). Substance P (SP, 10(-6) M) increased the current from 51.3 +/- 9.8 to 73.6 +/- 11.4 pA (P < 0.001), an effect that was not affected by NG-nitro-D-arginine methylester, but inhibited by NG-nitro-L-arginine methylester by 83 +/- 9% (P < 0.001), and this inhibition was restored by the subsequent addition of L-arginine, but not by D-arginine. SP and neurokinin A (NKA) increased [NO] in a dose-dependent manner, the maximal increases from the baseline level being 71.0 +/- 14.9 and 33.4 +/- 8.5 nM, respectively (P < 0.001 for each), whereas neurokinin B (NKB) had no effect. In the presence of phosphoramidon, the response of each tachykinin was augmented, but the rank order of potency was still NKA > SP >> NKB. These results suggest that NO is spontaneously released from airway epithelium and that tachykinins stimulate epithelial NO generation via NK2 receptors.

Animals↗
PubMed1995

Nitric oxide modulation of Ca2+ responses in cow tracheal epithelium.

Nitric oxide (NO) plays an important role in the regulation of Ca2+ -dependent airway epithelial function such as ciliary motility. In this experiment, the effect of NO on intracellular Ca2+ ([Ca2+]1) was studied in cultured cow tracheal epithelium by the fura-2 method. L-NG-nitroarginine methyl ester, an NO synthase inhibitor, per se did not significantly alter baseline [Ca2-]i, but bradykinin- and ATP-induced increases in [Ca2+]i were significantly reduced in the presence of L-NG-nitroarginine methyl ester. This inhibitory effect disappeared by a simultaneous addition of L-arginine. Sodium nitroprusside or dibutyryl cyclic GMP potentiated bradykinin- and ATP-induced increases in [Ca2+]i. Cytochemistry for NADPH diaphorase activity revealed the presence of NO synthase in the cultured epithelium. These results suggest that NO produced by NO synthase in airway epithelium modulates bradykinin- and ATP-induced [Ca2+]i responses, which may be dependent on cyclic GMP.

Adenosine Triphosphate↗
PubMed1995

Role of nitric oxide in tachykinin-induced increase in potential difference of rabbit tracheal mucosa.

1. The effect of tachykinins on transepithelial potential difference (PD) of rabbit trachea and possible involvement of nitric oxide (NO) generation in vivo were investigated. 2. Perfusion of tracheal mucosa with neurokinin A (NKA) or substance P (SP) dose dependently increased PD in the presence of amiloride, with the potency being NKA > SP, but neurokinin B (NKB) had no effect. 3. Application of NG-nitro-L-arginine methylester (L-NAME, 10(-3) M) attenuated the NKA-induced increase in the amiloride-sensitive PD, causing a rightward displacement of the dose-response curve by approximately 1.0 log U, whereas NG-nitro-D-arginine methylester (D-NAME, 10(-3) M) did not. 4. The inhibitory effect of L-NAME was reversed by L-arginine (10(-2) M) but not by D-arginine (10(-2) M). 5. The release of NO was determined by a real-time measurement of NO concentration ([NO]) in the perfusate using specific amperometric sensors for this molecule. 6. NKA and SP increased [NO] in a dose-dependent manner, the maximal increase from the baseline value being 114 +/- 11 nM (mean +/- S.E.M., P < 0.001) and 54 +/- 6 nM (P < 0.01), respectively. 7. Histochemistry for NADPH diaphorase activity showed a strong staining within the epithelial cells. 8. We conclude firstly that tachykinins increase amiloride-sensitive PD in vivo, which probably reflects Cl- movement from the submucosa toward the respiratory lumen in tracheal mucosa, and secondly that NO generation by epithelial cells may be involved in this process.

Amiloride↗
PubMed1995

Effects of second intracellular loop mutations on signal transduction and internalization of the gonadotropin-releasing hormone receptor.

The gonadotropin-releasing hormone (GnRH) receptor belongs to the superfamily of heptahelical G protein coupled receptors, most of which have a highly conserved DRYXXV/IXXPL sequence in the second intracellular (2i) loop that has been implicated in G protein coupling. The predicted 2i loop of the GnRH receptor contains serine rather than tyrosine in the DRY sequence but retains the conserved hydrophobic Leu residue, which is required for G protein coupling and internalization of muscarinic receptors. The present study examined the effects of mutating the unique Ser140 to the conserved Tyr, and the conserved Leu147 to Ala or Asp, on agonist binding, internalization, and signal transduction. The S140Y mutant showed a 100% increase in agonist binding affinity, and its internalization was increased by 60% above that of the wild-type receptor. The binding characteristics of the Leu147 mutants were indistinguishable from those of the wild-type receptor, but their internalization was reduced by about 50%. The L147A and L147D mutants also showed significant impairment of GnRH-stimulated inositol phosphate production. These findings demonstrate that substitution of Ser140 by Tyr does not affect G protein coupling but significantly increases receptor affinity and internalization rate. In contrast, replacement of a conserved aliphatic residue (Leu147) impairs both G protein coupling and agonist-induced receptor internalization.

Amino Acid Sequence↗
PubMed1995

Effect of azelastine on airway hyperresponsiveness mediated by stimulated macrophages.

The effect of the anti-allergic drug azelastine, 4-(p-chlorobenzyl)-2-(hexahydro-1-methyl-1H-azepine-4-yl)-1-(2H)-phth alazione), on airway hyperresponsiveness induced by immunologically stimulated pulmonary alveolar macrophages was investigated in canine bronchial segments under isometric conditions in vitro. Macrophages stimulated with anti-dinitrophenyl immunoglobulin E (IgE) antibody and dinitrophenyl-human serum albumin potentiated the contractile responses to electrical field stimulation at all frequencies, an effect that was abolished by azelastine (3 x 10(-5) M). In contrast, azelastine had no effect on the potentiation of the contractile responses to electrical stimulation by U46619, a thromboxane A2 mimetic. The IgE-mediated release of thromboxane A2 from macrophages was inhibited by azelastine in a concentration-dependent fashion, the maximal decrease and the concentration required to produce a half-maximal effect being 84 +/- 6% (P < 0.001) and 16 microM, respectively. These results suggest that azelastine may attenuate macrophage-induced parasympathetic airway hyperresponsiveness through an inhibition of the release of thromboxane A2.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed1995

Lung cyclic nucleotides in exercise-trained rats attenuate hypoxic pulmonary vasoconstriction.

We examined the effects of exercise training on pulmonary arterial blood pressure (Ppa) and on adenosine 3',5'-cyclic monophosphate (cAMP) and guanosine 3',5'-cyclic monophosphate (GMP) concentrations in lung tissue at rest and during exercise under hypoxic conditions in catheter-implanted rats. Male Wistar rats were divided into an exercise-trained group (ET, n = 32) and nonexercised control group (control, n = 32). ET rats exercised 40 min/day 6 days/week for 6 weeks, at an altitude of 610 m on a treadmill. The mean Ppa levels of the ET were significantly lower than those of controls at rest and during exercise at 610- and 2500-m altitudes. The exercise-induced mean Ppa increase in the ET was less than that in controls at both 610- and 2500-m altitudes. Resting lung cAMP increased more in the ET than in controls at both 610- and 2500-m altitudes. In ET, cGMP was significantly greater at the 2500-m altitude than at the 610-m altitude at rest and just after exercise. Hypoxic exercise in ET was accompanied by a preferential increase in cGMP but not in cAMP. These results suggest that the intracellular augmentation of cAMP and cGMP in ET plays an important role in attenuating hypoxic pulmonary vasoconstriction (HPV) and exercise-induced increases in Ppa.

Animals↗
PubMed1995

Cardiopulmonary function in bicycle racing over mountainous terrain at moderate altitude.

To examine cardiopulmonary function during exercise in a mountainous region at moderate altitude, we measured cardiac frequency, oxygen consumption (VO2), and percentage arterial hemoglobin oxygen saturation (%SaO2) before and after a bicycle race with a starting point at 638 m and finishing point at 1980 m. The time required to ascend an elevation of 10 m was prolonged with increasing altitude, and heart rate also increased with altitude. The %SaO2 at the starting point and at the finishing point differed significantly (P < 0.01). Faster cyclists exhibited higher %SaO2 and lower VO2, while slower cyclists exhibited a reduction in %SaO2 and an increase in VO2 immediately after the race. The %SaO2 recovery time was significantly correlated with the racing time (r = 0.54, P < 0.001). Therefore, the faster cyclists' oxygen debt upon completion of the race may be small and recovery of cardiopulmonary function may be fast, while the slower cyclists' oxygen debt may be large and recovery of cardiopulmonary function may be slow.

Adult↗
PubMed1995

Cardio-pulmonary function of cyclists competing on an ascending mountain course between altitudes of 1400 m and 2800 m.

Physiological changes were investigated in the cardio-respiratory function of competitors in a bicycle race which involved not a flat course but ascending a mountain, from 1400 m to 2800 m. Heart rate throughout the race, arterial oxygen saturation and pulmonary function before and after the race of well trained competitors were measured. The individual's maximal heart rate during the race was designated as HRmax for the calculations. (1) There were significant correlations between the age and the mean %HRmax during the race, between mean %HRmax and time, and between age and time (n = 15); the mean %HRmax had a 3.90 times greater effect on time than did age. (2) The individuals who performed best had lower values of oxygen saturation just after finishing the race (n = 51). (3) At 1 min after reaching the finishing line, oxygen saturation levels had recovered to the value of 20 min after finishing the race, whereas the heart rate was still in the process of recovery (n = 18). (4) Maximum expiratory flow at 50% vital capacity measured 30 min after reaching the finishing line was significantly higher than at the starting point. The intensity of the load on the cardiac system produced by completion of this course was estimated to be almost the same as that of a full marathon on a flat course. The time depended on both the youth of the cyclist and on his ability to maintain a high value of %HRmax during the race.

Adolescent↗
PubMed1995

Nucleosides and nucleotides--CXXXVII. Antitumor phospholipids with 5-fluorouridine as a cytotoxic polar-head: synthesis of 5'-phosphatidyl-5-fluorouridines by phospholipase D-catalyzed transphosphatidylation.

5'-Phosphatidyl-5-fluorouridines, with the same backbone structure as that of natural phospholipids, in which a polar-head group of usual phospholipids is replaced by 5-fluorouridine, were designed to be potent antitumor agents. 5'-Phosphatidyl-5-fluorouridines with a variety of diacyl or dialkyl residues in the glycerol moiety, were synthesized by phospholipase D-catalyzed transphosphatidylation from the corresponding phosphatidylcholine and 5-fluorouridine. These new compounds were evaluated in mice with experimental tumors by ip and po administration. Dipalmitoyl and distearoyl derivatives 1b and 1c had the greatest antitumor activity against both P388 leukemia and Meth A fibrosarcoma in mice.

Animals↗
PubMed1995

Effects of macrolide antibiotics on neurally mediated contraction of human isolated bronchus.

BACKGROUND: Long-term administration of macrolide antibiotic substances is an alternative therapy used in the treatment of asthma and airway hyperresponsiveness, but neither its mechanism of action nor whether this substance exerts an immediate action in the airways is known. METHODS: Contractile responses of human isolated bronchial strips to electrical field stimulation (EFS) and acetylcholine were assessed under isometric conditions in the absence and presence of erythromycin, roxithromycin, or clarithromycin. RESULTS: Incubation of tissues with erythromycin (3 x 10(-5) mol/L) attenuated the contractile responses to EFS so that the stimulus frequency required to produce 50% of the maximal contraction increased from 4.1 +/- 0.5 to 10.1 +/- 0.7 Hz (mean +/- SE; p < 0.001). In contrast, contractile responses to acetylcholine were not changed. Erythromycin reduced the EFS-induced contraction in a concentration-dependent fashion; the maximal decrease from the baseline response was 92.8% +/- 3.6% (p < 0.001). This inhibitory effect was not altered by propranolol, indomethacin, ouabain, charybdotoxin, or mechanical removal of the epithelium. Roxithromycin and clarithromycin likewise inhibited neurally mediated contraction. CONCLUSIONS: These results suggest that macrolides may inhibit cholinergic neuroeffector transmission in the human airway smooth muscle, probably by reducing exocytotic release of acetylcholine from the nerve terminals.

Acetylcholine↗
PubMed1995

Initiating activity of quinones in the two-stage transformation of BALB/3T3 cells.

2-tert-Butyl-1,4-benzoquinone (BQ), a metabolite of the rodent carcinogen 3-tert-butyl-4-hydroxyanisole (3-BHA), has been shown previously to have initiating activity for cell transformation. In this paper, we examined the initiating activity of quinones in a two-stage transformation assay using BALB/3T3 cells. Cells were treated first with a quinone and then with the tumor promoter 12-O-tetra-decanoylphorbol-13-acetate (TPA). The quinones tested were 1,4-benzoquinone (pQ), phenyl-1,4-benzoquinone (PhQ), menadione and 2,5-di-tert-butyl-1,4-benzoquinone (DBQ) in addition to BQ. pQ is a metabolite of benzene and phenacetin, and PhQ is a metabolite of o-phenylphenol (OPP) and sodium o-phenylphenate (OPP-Na). All of the tested quinones induced transformation in the presence of TPA but not in its absence. The extent of transformation caused by quinones followed by TPA was weak but statistically significant. Thus these quinones were shown to act as initiators in the transformation of BALB/3T3 cells. This result suggests that BQ, pQ and PhQ may be involved in carcinogenesis by 3-BHA, benzene, phenacetin, OPP and OPP-Na in vivo. Menadione has been reported to cause cytotoxic effects and mutations through active oxygen generation from semiquinone radicals. DBQ has two bulky substitutes which interfere with covalent bonds with DNA. Menadione and DBQ exhibited initiating activity in the present study. This result suggests that active oxygens generated from semiquinone radicals may play a role in the initiation of cell transformation.

3T3 Cells↗
PubMed1995

Intramuscular myxoma with fibrous dysplasia: a report of two cases with a review of the literature.

Two cases are reported of a rare association of intramuscular myxoma with fibrous dysplasia in a 70 and 40 year old Japanese woman, respectively. One of them had a solitary intramuscular myxoma, and the other patient suffered from two intramuscular tumors that had been initially misdiagnosed as myxoid liposarcoma. Only 24 cases of this kind of association have been recorded in the literature. This association should be taken into consideration to avoid inappropriate treatment, when cases of myxoid soft tissue tumor with a bone lesion are encountered.

Adult↗
PubMed1995

Effect of BQ123 on vasoconstriction as a result of either hypoxia or endothelin-1 in perfused rat lungs.

A possible role of endothelin (ET)-1 in mediating hypoxic pulmonary vasoconstriction (HPV) was examined by comparing haemodynamic differences between ET-1-induced vasoconstriction and HPV in isolated perfused rat lungs. An ETA receptor antagonist (BQ123) was also employed to assess the effects of ET-1. The pulmonary arterial pressure (Ppa) was significantly increased by alveolar hypoxia (3% O2) and by ET-1 (5 nM). The pulmonary microvascular pressure was not changed by hypoxia, but increased more than two-fold by ET-1 (P < 0.01). Hypoxia significantly increased pulmonary arterial resistance (P < 0.01) while ET-1 significantly increased pulmonary venous resistance (P < 0.01), and slightly increased arterial resistance. Lung weight was increased by ET-1 and decreased by hypoxia, accompanied by similar Ppa responses in both cases. BQ123 (10(-6) M and 10(-5) M) did not influence the changes in Ppa and lung weight induced by hypoxia or angiotensin II (0.3 micrograms). BQ123 did, however, suppress (P < 0.05) the increase in Ppa and lung weight induced by 5 nM ET-1. Thus, it appears unlikely that ET-1 is involved in changes in pulmonary vascular tone during acute HPV.

Animals↗
PubMed1995

Effects of exercise-training on hypoxia and angiotensin II-induced pulmonary vasoconstrictions.

The present study was undertaken to determine whether exercise-training for 6 weeks would inhibit pulmonary vasoconstriction induced by hypoxia in isolated, blood-perfused rat lungs. Hypoxic pulmonary vasoconstriction (HPV) and angiotensin II (AII)-induced pulmonary vasoconstriction were significantly less in the exercise-trained (ET) group than in the control (cont) group with all challenges. Normoxic pulmonary arterial and capillary pressures in the ET group were significantly lower than those in the cont group and capillary pressor response to hypoxia was less in the ET group than in the cont group. In conclusion, it appears that HPV and AII-induced vasoconstrictions can be reduced by exercise-training, because it would seem that exercise-training repeated responses to increased shear-stress resulting from elevated blood flow in pulmonary vessels.

Angiotensin II↗