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Biomedical subjects

H Fujihara

Publications and source records attributed to H Fujihara.

At least 37 records · Page 2Linked to original sources

Enhanced beta-receptor-mediated vasorelaxation in hypoxic porcine coronary artery.

To investigate the beta-adrenoceptor-mediated responses in hypoxic coronary arteries, we studied the effect of isoproterenol (Iso) on isolated porcine coronary arteries contracted with endothelin-1 in media aerated with 0, 5, 7.5, and 95% O(2). The concentration-response curve of Iso was significantly shifted to the left by hypoxia (0 and 5% O(2)). In oxygenated and hypoxic arteries, 3 x 10(-8), 10(-6), and 10(-5) M Iso significantly increased the contents of cAMP. However, there was no difference in the increases of cAMP content induced by 3 x 10(-8) M Iso between oxygenated and hypoxic arteries. The content of cAMP induced by high concentrations of Iso (10(-6) and 10(-5) M) was significantly larger in hypoxic than in oxygenated arteries. Furthermore, the potentiation by hypoxia of the Iso-induced vasorelaxation was inhibited by glibenclamide and depolarization by KCl, but not by removal of endothelium and indomethacin. The vasodilatory response to forskolin and dibutyryl cAMP was unaffected by hypoxia. We conclude that activation of the ATP-sensitive K(+) channel may account for the potentiation of the response to Iso in hypoxic coronary arteries.

Animals↗

[Anesthetic management for mitral valve replacement in a patient with mitral stenosis and dilated cardiomyopathy].

A 42-year-old man with dilated cardiomyopathy and rheumatic mitral stenosis underwent mitral valve replacement. Prior intravascular fluid administration and infusion of dopamine and dobutamine stabilized hemodynamics during the induction of anesthesia. High-dose fentanyl at pre-cardiopulmonary bypass period and circulatory assist with milrinone and intraaortic balloon pumping after the bypass enabled us to obtain stable hemodynamics. Preoperative dobutamine stress test provided us the effective information for circulatory management in this patient.

Adult↗

Inhibitory effect of 2,5-dimethylpyrazine on oxytocic agent-induced uterine hypercontraction of normal or pregnant female rats.

Intraperitoneal administration of 2,5-dimethylpyrazine (2,5-DMP) was found to inhibit oxytocin- and prostaglandin F2alpha-induced tetanic uterine contractions in normal or pregnant female rats. This suggests that 2,5-DMP may be used as a countercontraction agent or relaxant for preventing oxytocic agent-induced medical accident including uterine rupture or pressure death of the fetus due to uterine contractions.

Animals↗

Translocation of rhoA associated with Ca2+ sensitization of smooth muscle.

We determined the relationship between the localization of rhoA and Ca2+ sensitization of force in smooth muscle. In alpha-toxin-permeabilized rabbit portal vein at pCa 6.5, the particulate hydrophobic fraction of rhoA (10 +/- 1.6% of the total) was significantly increased by phenylephrine to 18 +/- 5.5% at 5 min, by AlF4- to 26 +/- 8.4% at 20 min, and dose-dependently up to 62 +/- 9.5% by guanosine 5'-O-(3-thiotriphosphate) (GTPgammaS; 0.3-50 microM). Translocation of rhoA was selective (Rac1 and Cdc42 were not translocated) and was quantitatively correlated (up to approximately 50%; r = 0.91, p < 0.05) with Ca2+ sensitization; high GTPgammaS concentrations (>/=10 microM) further increased translocation without increasing force. The initial recruitment of rhoA to the membrane paralleled the time course of contraction, but sensitization could be reversed without a decrease in particulate rhoA. High [Ca2+] (pCa 4.5) also increased particulate rhoA to 31 +/- 5.8%. Membrane-associated rhoA in unstimulated portal vein was a good substrate for in vitro ADP-ribosylation, whereas the large amount translocated by GTPgammaS was not. We conclude that 1) translocation of rhoA plays a causal role in Ca2+ sensitization, and 2) membrane-bound rhoA can exist in two or more states.

Animals↗

Structural studies of CV-70 polysaccharide.

The goal of this paper is the characterization of the chemical structure of the water-soluble polysaccharide, CV-70, produced by bacteria Beijerinckia sp. Beijerinckia sp. is a genus of gram-negative, aerobic bacteria, usually found in sugar cane root. The CV-70 polysaccharide was produced in a fermentation medium containing 5% sucrose as the carbon source, tryptose and salts, at 25 degrees C [1]. The polysaccharide was hydrolyzed with 2 N trifluoroacetic acid at 100 degrees C for 16 h, purified, and analyzed by HPLC. Index of refraction was used for the detection of sugars. For GC-MS analysis, the CV-70 polysaccharide was derivatized through methylation and acetylation. Together with the GC-MS data, periodate oxidation studies were used to determine the possible glucosidic linkages. Carbon-13 NMR studies were carried out with hydrolyzed and silylated samples. Glucose, galactose and fucose were identified as the components in the CV-70 polysaccharide, in a 3:1:3 ratio.

Bacteria↗

Inhibition of RhoA translocation and calcium sensitization by in vivo ADP-ribosylation with the chimeric toxin DC3B.

Pretreatment of intact rabbit portal vein smooth muscle with the chimeric toxin DC3B (10(-6) M, 48 h; ; ) ADP-ribosylated endogenous RhoA, including cytosolic RhoA complexed with rhoGDI, and inhibited the tonic phase of phenylephrine-induced contraction and the Ca2+-sensitization of force by phenylephrine, endothelin and guanosine triphosphate (GTP)gammaS, but did not inhibit Ca2+-sensitization by phorbol dibutyrate. DC3B also inhibited GTPgammaS-induced translocation of cytosolic RhoA () to the membrane fraction. In DC3B-treated muscles the small fraction of membrane-associated RhoA could be immunoprecipitated, even after exposure to GTPgammaS, which prevents immunoprecipitation of non-ADP-ribosylated RhoA. Dissociation of cytosolic RhoA-rhoGDI complexes with SDS restored the immunoprecipitability and ADP ribosylatability of RhoA, indicating that both the ADP-ribosylation site (Asn 41) and RhoA insert loop (Wei et al., 1997) are masked by rhoGDI and that the long axes of the two proteins are in parallel in the heterodimer. We conclude that RhoA plays a significant role in G-protein-, but not protein kinase C-mediated, Ca2+ sensitization and that ADP ribosylation inhibits in vivo the Ca2+-sensitizing effect of RhoA by interfering with its binding to a membrane-associated effector.

ADP Ribose Transferases↗

Down-regulation of G-protein-mediated Ca2+ sensitization in smooth muscle.

Prolonged treatment with guanosine 5'-[gamma-thio]triphosphate (GTP gamma S; 5-16 h, 50 microM) of smooth muscle permeabilized with Staphylococcus aureus alpha-toxin down-regulated (abolished) the acute Ca2+ sensitization of force by GTP gamma S, AIF-4, phenylephrine, and endothelin, but not the response to phorbol dibutyrate or a phosphatase inhibitor, tautomycin. Down-regulation also abolished the GTP gamma S-induced increase in myosin light chain phosphorylation at constant [Ca2+] and was associated with extensive translocation of p21rhoA to the particulate fraction, prevented its immunoprecipitation, and inhibited its ADP ribosylation without affecting the immunodetectable content of G-proteins (p21rhoA, p21ras, G alpha q/11, G alpha i3, and G beta) or protein kinase C (types alpha, beta 1, beta 2, delta, epsilon, eta, theta, and zeta). We conclude that the loss of GTP gamma S- and agonist-induced Ca2+ sensitization through prolonged treatment with GTP gamma S is not due to a decrease in the total content of either trimeric (G alpha q/11, G alpha i3, and G beta) or monomeric (p21rhoA and p21ras) G-protein or protein kinase C but may be related to a structural change of p21rhoA and/or to down-regulation of its (yet to be identified) effector.

Aluminum Compounds↗

Anti-chemotactic activity of capsular polysaccharide of Cryptococcus neoformans in vitro.

In this study, we demonstrated the anti-chemotactic activity of the capsular polysaccharides (CPSs) isolated from each of the heavily (H)- and weakly (W)-encapsulated strains of Cryptococcus neoformans in vitro. The capacity for activation of the alternative complement pathway (ACP) of cells of the two C. neoformans strains in fresh human sera was comparable to that of zymosan (insoluble control), whereas the capacity for generation of the chemotactic factor (CF) of the cells of the two strains in fresh murine sera was markedly lower in the order H- < W-strain than that of zymosan. Conversely, the capacities for ACP activation and CF generation of the CPSs were extremely lower than those of lipopolysaccharide (LPS, soluble control). When zymosan-activated murine serum was incubated with CPS, both CPSs inhibited CF activity dose dependently. When zymosan-activated serum was incubated with heat-killed cells of each strain of C. neoformans, H and W, the CF activity of the treated sera decreased significantly, suggesting that CPS per se did not affect the neutrophils directly, but CPS absorbed CF. On the other hand, both CPSs were shown to possess the O-acetyl groups in their molecules by 1H-nuclear magnetic resonance spectroscopy. The de-O-acetylation of both CPSs increased the capacity for ACP activation to a level similar to that of LPS, and the de-O-acetylated CPS of both strains exhibited a lower ability to inhibit CF than did native CPS. Collectively, these results suggest that the anti-chemotactic activity of CPS accounts for its ability to absorb the CF which was mostly generated at the sites around the cell wall of whole cells via the ACP, thus suppressing the inflammatory response by preventing dispersal of CF to the extracellular space; and also that the O-acetyl group is partly, if any, involved in the mechanism for incompetence in ACP activation as well as the inhibition of CF.

Acetylation↗

Somatosensory evoked potentials recorded from the posterior pharynx to stimulation of the median nerve and cauda equina.

Somatosensory evoked potentials (ppSEPs) in response to stimulation of the median nerve at the wrist and the cauda equina at the epidural space (the L4 level) were recorded from the posterior wall of the pharynx in 15 patients who underwent spinal surgery under general anesthesia, using disc electrodes attached to the endotracheal tube, and compared with segmental spinal cord potentials (seg-SCPs) that were recorded simultaneously from the posterior epidural space (PES). ppSEPs consisted of the initially positive spike (P9) followed by slow positive (P13) and negative (N22) waves. The P13 and N22 of ppSEPs had phase reversal relationship with the P2 and N2 recorded from the PES, respectively. The peak latencies of P9 (9.40 +/- 0.7 ms) (mean +/- SD), P13 (13.1 +/- 0.9 ms), and N22 (22.0 +/- 2.1 ms) of ppSEPs coincided with those of P1, N1 and P2 of seg-SCPs, respectively, ppSEPs were recorded more clearly with a reference electrode on the dorsal surface of the neck than with the reference electrode at the earlobe or back of the hand. The threshold and maximal stimulus intensities were also similar between the ppSEPs and seg-SCPs. Thus, the P9, P13, and N22 components of ppSEPs were thought to have the same origin as the P1, N1 and P2 of seg-SCPs, respectively. Therefore, the P9, P13 and N22 of ppSEPs may reflect incoming volleys through the root, synchronized activities of the interneurons and primary afferent depolarizations (PAD), respectively. ppSEPs in response to cauda equina stimulation showed that the latencies of the two initial components (4.6 +/- 0.4 and 6.4 +/- 0.6 ms) corresponded to those of the SCPs recorded from the PES (4.6 +/- 0.3 and 6.3 +/- 0.5 ms), suggesting that these potentials reflect impulses conducting through the spinal cord, similar to epidurally recorded SCPs.

Adult↗

The effects of halothane on arginine-vasopressin-induced Ca2+ mobilization from the intracellular stores and the receptor-mediated Ca2+ entry from the extracellular space in single cultured smooth muscle cells of rat aorta.

Halothane has a direct action on vascular smooth muscle cells and causes relaxation of these cells, yet neither the mechanism nor the site of its action is completely understood. Using digital imaging microscopy with the Ca2+ indicator fura-2, the effects of halothane on the intracellular [Ca2+] dynamics induced by arginine vasopressin (AVP) in the perinuclear region and cytosol in single cultured smooth muscle cells of rat aorta were studied. Changes in intracellular [Ca2+] were expressed as percent increases in the ratios of fluorescence intensity at 500 nm excited by 340 nm and 380 nm. AVP (10(-7) M) elicited an initial transient increase in [Ca2+] in the perinuclear region higher than that in the cytosol in Ca(2+)-containing solution (346% +/- 21% and 213% +/- 22%, respectively). Halothane, 0.5%, attenuated the [Ca2+] increase induced by AVP in the perinuclear region and cytosol, and halothane, 1.0% and 2.0%, abolished the differential increase. Under the continuous application of AVP (10(-7) M), Ca2+ restoration in the medium after perfusion with Ca(2+)-free solution increased the perinuclear [Ca2+] more than the cytosolic [Ca2+]. Both were significantly attenuated by 2.0% halothane, but not by nicardipine (10(-5) M) or ryanodine (10(-6) M). Our results suggest that halothane may attenuate the Ca2+ release from the intracellular Ca2+ stores more than the receptor-mediated Ca2+ entry from the extracellular space in the AVP-induced response in these cells.

Anesthetics, Inhalation↗

Relationship between tissue ischemia and venous endothelin-1 during abdominal aortic aneurysm surgery.

OBJECTIVES: Several substances may be released from ischemic tissues with the declamping shock that occurs during abdominal aortic aneurysm surgery. To clarify the relationship between tissue ischemia and venous endothelin-1 (ET-1) level in humans, plasma ET-1 and oxygen content in the iliac vein were measured before anesthesia, after the induction of anesthesia, after the release of the proximal and first distal clamps, after the release of the second distal clamp, and 1 hour after the second clamping. DESIGN: Prospective study. SETTING: A University hospital. PARTICIPANTS: Seven patients who underwent abdominal aneurysmectomy and replacement with bifurcated graft. INTERVENTIONS: A 20G catheter was inserted into the radial artery for the direct measurement of blood pressure and for collecting arterial blood. An 18G, 20-cm catheter was inserted into the femoral vein for collecting venous blood from the lower extremities. MEASUREMENTS AND MAIN RESULTS: The arterial and venous ET-1 levels did not change after the induction of anesthesia. Immediately after the initial release of the proximal and distal clamps, venous oxygen content dramatically decreased from 11.3 to 3.6 mL/dL (vol%) with significant increases in venous ET-1 concentration from 2.3 to 4.9 pg/mL. Concomitant with the decrease in venous oxygen content, venous plasma pH and base excess decreased with increase in PCO2, suggesting that ischemic changes in tissues distal to the cross-clamp may occur during aortic clamping. Venous ET-1 levels were significantly correlated with venous oxygen content, pH, PO2, oxygen saturation, base excess, blood sodium concentration, and potassium concentration. One hour after the second declamping, the venous ET-1 level remained high in comparison with the preanesthetic level, whereas the venous oxygen content returned to the preanesthetic level. There was no correlation between venous plasma ET-1 and venous plasma norepinephrine or epinephrine concentration. CONCLUSIONS: Tissue ischemia may increase venous ET-1 levels in humans. Factor(s) other than tissue ischemia may provoke the increase in venous ET-1 that occurs after the release of the second distal clamp.

Aged↗

Hypoxia modifies the vasodilatory effects of nitroglycerin, prostaglandin E1, and hydralazine on isolated porcine coronary arteries.

To evaluate the potency of vasodilatory drugs in hypoxia, we studied the effects of nitroglycerin (NTG), prostaglandin E1 (PGE1), and hydralazine on porcine coronary artery constricted with endothelin-1 (ET-1) in both oxygenated and hypoxic conditions. Removal of endothelium potentiated NTG-induced relaxation in oxygenated conditions. Hypoxia potentiated relaxation of endothelium-intact arteries induced by NTG, but not relaxation of endothelium-denuded arteries. These findings suggest that hypoxia may modify endothelial function in NTG-induced relaxation. The relaxation of endothelium-intact and -denuded arteries induced by PGE1 in hypoxia was significantly greater than that in the oxygenated condition. PGE1 significantly increased the content of cyclic AMP in the hypoxic condition; it was much greater than that in the oxygenated condition, suggesting that hypoxia may enhance PGE1-induced relaxation by increasing cyclic AMP levels. Hypoxia attenuated hydralazine-induced relaxation in both endothelium-intact and denuded arteries. Indomethacin and aspirin attenuated hydralazine-induced relaxation in the oxygenated condition, suggesting that cyclooxygenase-related eicosanoid(s) may be involved in hydralazine-induced relaxation. However, indomethacin did not alter relaxation of hypoxic arteries induced by hydralazine. These findings suggest that hypoxia may inactivate cyclooxygenase in hydralazine-induced relaxation. Hypoxia may greatly modify the action of vasodilators on porcine coronary smooth muscle.

Alprostadil↗

Pharmacokinetics, safety, and pharmacologic effects of OPC-21268, a nonpeptide orally active vasopressin V1 receptor antagonist, in humans.

The pharmacokinetics, safety, and pharmacologic effects of OPC-21268, a nonpeptide orally active vasopressin V1 receptor antagonist, have been investigated in 33 healthy subjects. First, 24 subjects were randomly divided into 3 groups of 8, 6 of whom were given 2 ascending single oral doses out of 6 (10, 50, 150, 300, 450, and 600 mg) of OPC-21268 after an overnight fast. The remaining two subjects in each group received placebo as control at each dosing. Additionally, after this procedure, the 6 subjects who received 50-mg single doses were given the same dose in a nonfasting condition. After the single-dose study was completed and the safety and tolerability were ascertained, the remaining 9 subjects, including 3 controls, were given 300 mg of the drug 3 times daily for 7 days (days 3-9) and were given single 100-mg oral doses before (day 1) and after (day 10) this repeated-dose study. OPC-21268 plasma concentrations declined in a monoexponential or biexponential pattern after reaching the maximum plasma concentrations (Cmax). The mean (+/- standard error of the mean) plasma half-life (t1/2) of the alpha phase ranged from 1.31 +/- 0.11 to 1.78 +/- 0.15 hours, and the mean t1/2 of the beta phase ranged from 4.31 +/- 0.28 to 6.28 +/- 0.59 hours. The area under the concentration (AUC0-infinity) and Cmax were proportional to the dose (P < .001).(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗

Modification by CO2 of endothelin-1-induced contraction of isolated guinea pig trachea.

To investigate the effect of changes in CO2 tension on airway smooth muscle tone induced by various agonists, contractile responses to acetylcholine, histamine and endothelin-1 (ET-1) were studied in isolated guinea pig tracheae at very low PCO2 (16 +/- 0 mmHg, n = 38), moderately low PCO2 (28 +/- 0 mmHg, n = 23), normal PCO2 (38 +/- 1 mmHg, n = 70) or high PCO2 (94 +/- 1 mmHg, n = 32). The minimum concentration of ET-1 (10(-10) M) needed to induce contractions was lower than that of acetylcholine (10(-7) M) and histamine (10(-7) M) at normal PCO2. Changes in PCO2 did not significantly affect acetylcholine- or histamine-induced contractions. In contrast, very low and moderately low PCO2 attenuated the contractions induced by ET-1, but high PCO2 potentiated those induced by a high concentration of ET-1. Very low PCO2 with normal pH and with high pH attenuated the contractions caused by ET-1, whereas normal PCO2 with high pH did not. These results suggest that ET-1-induced airway smooth muscle contraction can be modified by PCO2 per se. Aspirin and indomethacin potentiated the responses to ET-1 at very low PCO2 more than at normal PCO2, but attenuated the responses to low concentration of ET-1 at high PCO2. These results also suggest that cyclooxygenase-related eicosanoids are involved in the effects of PCO2 on ET-1-induced contractions.

Acetylcholine↗

Potent aquaretic agent. A novel nonpeptide selective vasopressin 2 antagonist (OPC-31260) in men.

Solute-free water diuretics (aquaretics) by antagonizing hydrosmotic vasopressin receptors (V2) may be useful in treating water-retaining diseases. The effects of intravenous administration of a newly developed nonpeptide, selective V2 antagonist, OPC-31260, at doses ranging from 0.017 to 1.0 mg/kg to groups of healthy, normally hydrated men were compared with those of 0.33 mg/kg furosemide and placebo. OPC-31260 increased the hypotonic urine volume dose dependently for the first 4 h, while furosemide induced sodium diuresis for 2 h. The absolute increase in the cumulative response in the urine to the highest doses of OPC-31260 was not significantly different from that to furosemide. The higher doses of OPC-31260 rapidly lowered urine osmolality for 2 h, particularly between minutes 15 and 45 (e.g., 1.0-mg/kg dose: 63 +/- 2 mOsm/kg in urine collected between minutes 30 and 45). In a marked hypotonic diuresis, mean free water clearance of the 4-h urine increased dose proportionally into the positive range, reaching 1.80 +/- 0.21 ml/min at 1.0 mg/kg. Whereas furosemide induced marked Na and K diuresis, OPC-31260 increased urinary Na excretion only slightly. At 4 h, 0.75 and 1.0 mg/kg of OPC-31260 almost doubled the plasma arginine vasopressin; and the higher doses increased plasma osmolality and plasma Na slightly, but did not alter plasma K, blood pressure, or heart rate. OPC-31260 thus safely induced a potent aquaretic effect in men.

Adult↗

[Anesthetic management of a neonate with critical pulmonary valve stenosis for balloon pulmonary valvuloplasty].

We administered general anesthesia for balloon pulmonary valvuloplasty (BPV) to a 19 day-old male infant, weighing 2,789g, with critical pulmonary stenosis. The patient had severe cyanosis and mild right heart failure. Atropine (0.01 mg.kg-1) was administered intravenously immediately before induction of anesthesia. Pancuronium (0.4 mg) was used to facilitate endotracheal intubation and for the subsequent control of ventilation. Anesthesia was maintained with oxygen and enflurane (0.25 approximately 0.5%) supplemented with intravenous administration of fentanyl (1.5 micrograms.kg-1). During catheterization for balloon pulmonary valvuloplasty, SpO2 and blood pressure decreased temporarily to 35% and 50 mmHg, respectively. Several side effects of balloon inflation have been reported, such as bradycardia, arrhythmia, and the decrease in systemic blood pressure and arterial oxygen saturation, mainly due to the occlusion of pulmonary blood flow. Therefore, it might be recommended that BPV should be performed under stable state of general anesthesia with continuous monitorings of especially ECG, arterial blood pressure, central temperature, SpO2, ETCO2 and urine output.

Anesthesia, General↗

SPECT demonstration of splenosis.

Splenosis is defined as the heterotopic autotransplantation of splenic tissue. The main cause of splenosis is splenic rupture following abdominal trauma, in which fragments of splenic tissue are seeded throughout the peritoneal cavity. Demonstration of splenosis by scintigraphy or CT imaging has been reported, but there is no previous report of simultaneous demonstration by SPECT and CT imaging. Autotransplantation of splenic tissue in the abdominal cavity forms a solid tumor-like image on CT and is difficult to differentiate from other abdominal masses. In such cases, SPECT demonstration of splenosis is very important for identification of its exact site. A case report of splenosis is presented, in which simultaneous demonstration by SPECT and CT was performed. This was confirmed at laparotomy for gastrectomy.

Abdominal Neoplasms↗