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Biomedical subjects

Y Sawada

Publications and source records attributed to Y Sawada.

At least 19 recordsLinked to original sources
PubMed1992

Comparison of coronary responses to intracoronary and intraaortic ergonovine and isosorbide dinitrate in patients with atypical chest pain.

Fifty patients with atypical chest pain were studied to compare coronary responses to intracoronary and intraaortic ergonovine. The diameters of the proximal, middle (1) and (2) (proximal segments of segments 2 and 3 [AHA classification], respectively), and distal segments of the right coronary artery were measured before and after intracoronary ergonovine (4 micrograms/minute over 4 minutes) and isosorbide dinitrate (ISDN) (2 mg) in 24 patients, and before and after intraaortic ergonovine (0.2 mg) and ISDN (5 mg) in 26. Mean vasoconstriction by intracoronary and intraaortic ergonovine were 13 +/- 1.5% and 9 +/- 0.8%, respectively (p < 0.02). Irrespective of the methods of administration, the responses to ergonovine were similar in the 4 segments. Mean vasodilation by intracoronary and intraaortic ISDN, which were used to quantify the degree of basal coronary tone, were 25 +/- 2.2% and 27 +/- 1.5%, respectively (p = not significant [NS]). There were significant negative linear correlations between the responses to ergonovine and ISDN in the middle (2) (r = -0.51; p < 0.05) and distal (r = -0.53; p < 0.01) segments in patients with intracoronary injection, and the proximal (r = -0.41; p < 0.05), middle (1) (r = -0.66; p < 0.01) and middle (2) (r = -0.69; p < 0.01) segments in patients with intraaortic injection. These observations indicate that low-dose administration of intracoronary ergonovine produces sufficient coronary vasoconstriction, similar to or slightly greater than that of intraaortic ergonovine in patients with atypical chest pain, but basal coronary tone may influence the vasoreactivity to ergonovine.

Aorta↗
PubMed1992

Existence of two pathways for the endocytosis of epidermal growth factor by rat liver: phenylarsine oxide-sensitive and -insensitive pathways.

The effect of phenylarsine oxide (PAO) on the internalization rate of epidermal growth factor (EGF) was investigated using perfused rat liver and isolated rat hepatocytes. In perfused liver, a tracer concentration of 125I-EGF alone or with excess unlabeled EGF (20 nM) was perfused and the internalization rate constants (kint) were measured. In the absence of PAO, kint values did not differ significantly for either dose condition. However, with the addition of PAO to the perfusate, the kint value dropped to 4% of that of the control at the low concentration of EGF, while dropping to only 40% of that of the control at the high concentration of EGF. These results suggest the existence of a PAO-insensitive internalization pathway having a kint value comparable with that of the other pathway. Similar EGF concentration-dependent inhibition of 125I-EGF internalization caused by PAO was ascertained using isolated rat hepatocytes. PAO also decreased the cellular ATP content in isolated hepatocytes. However, when we lowered the cellular ATP content with rotenone, the cell-surface binding and internalization of EGF were comparable with the control levels. We concluded that there exist dual pathways for the internalization of EGF and that excess doses of EGF lead to EGF internalization not only through a PAO-sensitive pathway but also through a PAO-insensitive pathway, whereas at a tracer dose of EGF, the internalization occurs mainly via the PAO-sensitive pathway.

Adenosine Triphosphate↗
PubMed1992

Analysis of the 5' flanking region of the rat proliferating cell nuclear antigen (PCNA) gene.

The proliferating cell nuclear antigen (PCNA), highly conserved among eukaryotes, is an auxiliary factor for DNA polymerase delta. In this report we sequenced 1560 nucleotides (nt) of the 5' flanking region of the rat PCNA gene and located the transcription initiation site. The sequence contains 1435 nt upstream of the cap site and promotes transcription of a linked heterologous reporter gene in rat, mouse and human cells. Transient expression assays using a series of 5' deletion mutants revealed that 240 nt of the upstream sequence are sufficient for full promoter activity. Three GC boxes and several other binding sites of transcription factors were observed, but neither a TATA nor a CCAAT sequence was found in this region. The results also suggested the existence of a negative regulatory element(s) between -968 and -691. Cotransfection with early region 1 (E1) genes of human adenoviruses activated the expression of the reporter gene, suggesting that an E1-responsive element is located at the proximal promoter region within 81 nt upstream of the transcription initiation site.

3T3 Cells↗
PubMed1992

Detection of human papillomavirus DNA sequences in tongue squamous-cell carcinoma utilizing the polymerase chain reaction method.

Twenty-four cases of tongue squamous-cell carcinoma (SCC) were analyzed for human papillomavirus (HPV) DNAs by the polymerase chain reaction (PCR) method and the dot-blot hybridization technique. HPV DNAs were detected in 8 cases. One specimen histopathologically diagnosed as poorly differentiated grade-III SCC contained both HPV-16 and HPV-18 DNA, and 7 other cases contained HPV-16 DNA.

Adult↗
PubMed1992

Effect of basic drugs on the hepatic uptake of ouabain by sinusoidal plasma membrane vesicles isolated from rat liver.

Although antiarrhythmic drugs are used to treat digitalis-induced cardiac disorders, some of these drugs have been reported to increase the serum digoxin concentration in patients, causing the severe side-effects. We have previously shown that many basic drugs including antiarrhythmic drugs inhibited the hepatic uptake of cardiac glycosides into isolated rat hepatocytes, which could be a cause for the increased serum digoxin concentration. The present study was designed to examine the mechanism of this inhibition using isolated rat sinusoidal plasma membrane vesicles. The effect of nine basic drugs (dipyridamole, nifedipine, verapamil, chlorpromazine, lidocaine, quinidine, ajmaline, disopyramide, and propranolol) on the uptake of ouabain was studied. Quinidine reduced the initial uptake rate of ouabain (30 s) while it did not change the uptake of ouabain in an equilibrium condition (30 min). Other basic drugs, such as verapamil, dipyridamole, and nifedipine also significantly reduced the initial uptake rate of ouabain. These basic drugs had no effect on the membrane fluidity. The inhibitory effects on the vesicular uptake were significantly correlated with the inhibitory effects on ouabain uptake by the isolated rat hepatocytes. These findings may suggest that the mechanism of the inhibition involves the inhibition of the transport process via the sinusoidal plasma membrane.

Animals↗
PubMed1992

Nonlinear pharmacokinetics of hepatobiliary transport of rose bengal in rats after i.v. bolus administration with varying doses.

To investigate the nonlinear kinetics in the hepatobiliary transport of rose bengal (RB), the time profiles of plasma concentration and biliary excretion rate after its i.v. administration at various doses were measured in rats. The total body clearance decreased remarkably with increased dose. The hepatic uptake clearance also showed a similar dose dependency, and saturation of hepatic uptake at least partly accounts for the dose-dependent change in total body clearance. The peak biliary excretion rate approached the transport maximum (approximately 150 nmol min-1 kg-1) with increased dose. To further clarify which process in RB hepatobiliary transport has nonlinearity, we analysed thus obtained data based on a three-compartment model. The hepatic uptake and sequestration rate constants decreased remarkably with increased dose. The initial hepatic uptake rates assessed from the plasma disappearance rate during the early phase fit well to the Michaelis-Menten equation with a saturable and a nonsaturable component. The maximum uptake velocity and Michaelis constant were 4.7 mumol min-1 kg-1 and 360 microM, respectively. That hepatic uptake has a much higher capacity (about 30 fold) than biliary excretion suggests that biliary excretion can be a rate-determining process in the overall hepatobiliary transport of RB. We conclude that the saturation of both hepatic uptake and biliary excretion could be the main causes for the nonlinear pharmacokinetics of hepatobiliary transport of RB.

Animals↗
PubMed1992

Pharmacokinetic profile of glycyrrhizin in healthy volunteers by a new high-performance liquid chromatographic method.

An improved high-performance liquid chromatographic method was developed for the quantification of glycyrrhizin and its metabolites in human plasma. The improved method was selective and made it possible to determine precisely glycyrrhizin at levels as low as 500 ng/mL. The pharmacokinetic behavior of glycyrrhizin and its metabolites after oral and intravenous administration of glycyrrhizin to normal subjects was investigated. After oral administration of glycyrrhizin (100 mg) to three normal subjects, the major metabolite of glycyrrhizin (glycyrrhetic acid) appeared in plasma (less than 200 ng/mL), but glycyrrhizin was not found. On the other hand, glycyrrhizin was found in urine, and the amount excreted was 1.1-2.5% of the dose. This finding suggests that glycyrrhizin is partly absorbed in the intact form from the gastrointestinal tract. The concentration of glycyrrhizin in plasma after intravenous administration of glycyrrhizin (40, 80, and 120 mg) showed biexponential profiles during the 24-h period after administration of each dose. The glycyrrhizin metabolites, glycyrrhetic acid and glycyrrhetic acid-3-O-glucuronide, were not detected in either plasma or urine. The terminal half-life of glycyrrhizin, the apparent volume of the central compartment, the steady-state distribution volume, and the total body clearance in three dosing experiments were 2.7-4.8 h, 37-64 mL/kg, 59-98 mL/kg, and 16-25 mL/kg/h, respectively. Glycyrrhizin was not detected in plasma after oral administration of the usual therapeutic dose of glycyrrhizin, and no dose dependency of the drug was observed in the dose range of 40-120 mg.

Administration, Oral↗
PubMed1992

The effect of continuous topical application of heparin on flap survival.

To evaluate the beneficial effects of heparin on flap survival area, an experimental study was carried out on dorsal flaps in rats. Topical applications of heparin, released from a silicone gel sheet onto the critical area (which generally necrosed without treatment), resulted in an increase in the flap survival area and rate as compared to controls (p < 0.01). When heparin was applied topically but solely to an area proximal to the critical area however, no increase in the survival area resulted.

Administration, Topical↗
PubMed1992

Patterning in hydra cell aggregates without the sorting of cells from different axial origins.

Aggregates of Hydra cells were studied to find out how the primary centers that form new heads are generated in a system of cells in which the original pattern has been destroyed. Since cells that originate near the heads (apical cells) temporarily maintain a high level of head activation potential during aggregate formation and may contribute to pattern formation, their distribution in the aggregates was investigated. The mutual distances between labeled epithelial cells were followed by vitally staining apical cells with DAPI. The distribution was random during early regeneration stages (3, 6, 24 hr). These results show that epithelial cells originating from apical regions do not sort. That is, dynamic cell movement to generate rudiments of new heads is not necessary for head formation in aggregates. A possible explanation of the mechanism is discussed.

Animals↗
PubMed1992

Effect of a novel class I antiarrhythmic agent, TYB-3823, on the calcium current in single guinea pig ventricular myocytes.

The effect of TYB-3823 on Ca2+ current (ICa) of guinea pig ventricular myocytes was investigated by means of whole-cell patch-clamp technique. TYB-3823 (100-1,000 microM) caused a concentration-dependent decrease in ICa. Furthermore, a reduction of ICa induced by TYB-3823 (1,000 microM) was progressively accentuated by repetitive membrane depolarization, indicating a rate-dependent block of ICa. However, the inhibitory potency on ICa was approximately 1/1000 of a Ca2+ antagonistic agent, verapamil hydrochloride. Considering evidence that 3-30 microM TYB-3823 decreased the maximum upstroke velocity of the action potential of guinea pig ventricular muscles, it is indicated that the drug does not show its Ca2+ antagonistic property in the usual concentration range as a class I antiarrhythmic agent.

Animals↗
PubMed1992

A technique of haemostasis of the extremities after debridement of burn wounds.

A technique used to achieve prompt haemostasis in burned wounds of the extremities is described. After tangential debridement using a tourniquet, thrombin solution (1000 units in 1 ml of saline solution) is applied on the entire wound. Immediately after removing the tourniquet; the wound is tightly wrapped with a thin plastic film and a pressure bandage over the entire wound. The pressure bandage is kept on for approximately 10 min after removing the tourniquet. With this procedure, haemostasis of the capillary oozing can be promptly and completely achieved. Furthermore, arterial and venous haemostasis can also be achieved, with clots present at the arterial and venous haemorrhagic points. As these clots can be removed easily, ligation or electrocoagulation is necessary. This technique is especially useful for haemostasis in a wound of the extremity after tangential excision leading to decreasing blood loss.

Adolescent↗
PubMed1992

Benefits of silicone cream occlusive dressing for treatment of meshed skin grafts.

A side-by-side evaluation of a silicone cream occlusive dressing technique for grafted meshed skin on the extremities of 10 patients is described. The site treated by silicone cream showed less congestion in the interstices of the mesh, less visible diamond pattern, and less hardness of the skin in all patients compared with the control site, which was treated by application of petroleum jelly ointment. The general appearance of the silicone cream-treated site showed better cosmetic results when compared with the control site.

Adolescent↗
PubMed1992

Prevention of dressing slippage under an elastic bandage.

A technique is described to prevent the shift in position of dressing materials by applying a double-sided adhesive tape between the skin and the elastic bandage. This technique also prevents a shift in position of a pressure garment, especially when applied around joints on the extremities.

Adhesives↗
PubMed1992

'Albumin-mediated transport phenomenon' observed for ligands with high membrane permeability. Effect of the unstirred water layer in the Disse's space of rat liver.

In this paper, we offer experimental evidence of the rate-limiting diffusion of ligands through the unstirred water layer (UWL) as an explanation for the so-called albumin-mediated transport phenomenon. The relative membrane permeability of various ligands was first evaluated using isolated rat hepatocytes. Then, the effect of albumin on the uptake of ligands of a wide range of membrane permeabilities was examined using the perfused rat liver. The results were similar to those expected from the UWL model: ligands with high membrane permeability (warfarin, diazepam and taurocholate) clearly exhibited albumin-mediated transport, those with medium membrane permeability (tolbutamide and salicylate) showed less albumin-mediated transport, and ligand with low membrane permeability (cefodizime) did not show albumin-mediated transport. These results were explained by simulation studies of two separate cases based on the UWL model; one assuming the rapid equilibrium of ligand binding with albumin, and the other considering the slow dissociation of ligands from albumin. In light of these findings, we suggest that the rate-limiting diffusion through the UWL plays an important role in the so-called albumin-mediated transport phenomenon.

Animals↗
PubMed1992

Kinetic analysis of hepatobiliary transport of vincristine in perfused rat liver. Possible roles of P-glycoprotein in biliary excretion of vincristine.

Recent studies using bile canalicular membrane vesicles have suggested that P-glycoprotein may play a role in excreting some anticancer drugs from the liver to the bile. At steady state after a continuous single-pass perfusion of a tracer concentration of [3H]vincristine in the rat liver, the extraction ratio was approximately 0.6, and 70% of the extracted drug was excreted into the bile mostly in unchanged form. The liver/perfusate and bile/liver unbound concentration ratios obtained after correction for intracellular binding and the inside-negative membrane potentials and/or pH difference between the inside and outside of the cells, were approximately 2-3 and 160-280, respectively, suggesting a highly concentrated biliary excretion process. We also examined the effects of verapamil, a P-glycoprotein-related transport inhibitor in cancer cells, on the hepatobiliary transport of [3H]vincristine. Verapamil 50 microM in the perfusate caused a decrease in the biliary excretion rate of [3H]vincristine, whereas [14C]taurocholate (reference compound) remained constant. In contrast, the hepatic uptake rate of [3H]vincristine exhibited minimum reduction, suggesting that verapamil selectively inhibited the biliary excretion of [3H]vincristine at the canalicular membrane. The fact that verapamil had little effect on the initial velocity of [3H]vincristine uptake by isolated hepatocytes also supports the above findings. Since the effect of 150 microM verapamil in the perfusate was not selective for vincristine, the biliary excretion rates of both compounds ([3H]vincristine, [14C]taurocholate) were reduced by this concentration of verapamil. In conclusion, the concentrative excretion of vincristine into the bile and its selective inhibition by a moderate concentration of verapamil provide indirect evidence for the contribution of P-glycoprotein to the biliary excretion of vincristine in a perfused rat liver system.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1992

A nasal vestibular flap for reconstruction of the upper lip.

A technique to reconstruct the hair-bearing upper lip by means of a hair-loaded nasal vestibular flap is described. This flap is elevated from the nasal vestibular area, and does not result in nasal deformity. This flap is especially suitable to reconstruct the medial portion of the hair-bearing upper lip in adult males.

Hair↗
PubMed1992

Kinetic modeling of ouabain tissue distribution based on slow and saturable binding to Na,K-ATPase.

The significance of the binding to Na,K-ATPase in the tissue distribution of ouabain was previously documented (Harashima et al., Pharm. Res. 9:474-479, 1992). The purpose of this study was to obtain a kinetic model of ouabain tissue distribution. In most tissues, the ouabain concentration continued to rise after the termination of infusion (5 min), with the peak tissue concentration at approximately 20 min. This delay could not be explained by the rapid equilibrium model (RE model), nor could the kinetics of ouabain be explained by an RE model modified for saturable binding. Since ouabain binding to Na,K-ATPase is slow, the association and dissociation processes were incorporated into a model that can accurately fit the observed time courses of ouabain. The obtained binding parameters corresponded well with the observed values in the in vitro binding experiments, except for muscle. These results quantitatively support the role of the slow and saturable binding of ouabain to Na,K-ATPase in its tissue distribution.

Animals↗