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Biomedical subjects

Y Sugiyama

Publications and source records attributed to Y Sugiyama.

At least 19 recordsLinked to original sources
PubMed1996

Morphological and functional factors predicting bladder deterioration after spinal cord injury.

PURPOSE: We investigated factors predictive of morphological and functional deterioration of the bladder in patients with spinal cord injury. MATERIALS AND METHODS: Urological evaluation, including excretory urography and urodynamic studies, was performed once a year in 66 patients. Bladder compliance was used as an index of bladder function. RESULTS: Mean age of the patients with worsening bladder form and function was significantly greater than that of those with no change. In patients with worsening bladder function intermittent catheterization was performed less frequently and mean catheterization volume was greater compared to those with improvement and no change. Catheterization was less frequent and at long intervals in patients with a high urethral closure pressure. CONCLUSIONS: High storage pressure due to a high urethral closure pressure is believed to cause deterioration of bladder form and function.

Adult↗
PubMed1995

Effect of oral ethanol intake on muscle sympathetic nerve activity and cardiovascular functions in humans.

The aim of the present study was to clarify the acute effect of alcohol drinking on muscle sympathetic nerve activity and other cardiovascular variables in young healthy human volunteers. Seven volunteers (25.0 +/- 4.7 years in age, weighing 59.9 +/- 5.9 kg) were instructed to lay down on a bed, and muscle sympathetic nerve activity (MSNA) was microneurographically recorded from the tibial nerve, simultaneously with an electrocardiogram, blood pressure with Finapres and autosphygmomanometer, cardiac output by impedance cardiography, and skin blood flow by laser Doppler flowmetry. After a 1-h rest, the subjects drank alcohol (0.6 g/kg) and were remained in resting position for 105 min. Blood ethanol levels indicated that they were moderately intoxicated. Heart rate constantly increased until 30 min after the ingestion, and maintained a peak level. MSNA was slightly but significantly suppressed just after the ingestion, and was gradually enhanced until the end of the experiment, showing a significant difference from the control level until 40 min in burst rate and until 25 min in total MSNA after the ingestion. Blood pressure showed an abrupt and transient increase at first, then gradual decrease until 30 min after the ingestion, and maintenance of the resting level until the end of the experiment. Cardiac output showed no constant tendency and no significant differences after the ingestion with wide interindividual variation. Skin blood flow increased 15 min after the ingestion.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗
PubMed1995

Systemic production of foreign peptides on the particle surface of tobacco mosaic virus.

By using a new tobacco mosaic virus (TMV) vector [Hamamoto, H., et al. (1993) Bio/Technology 11, 930-932], we have constructed TMV particles which present three different kinds of epitopes, two of them from influenza virus hemagglutinin (HA), and one from human immunodeficiency virus type I (HIV-I) envelope protein, on the surface of the particles. Each of these TMV particles reacted with each anti-peptide antiserum. These results suggest that this TMV vector can be used as an antigen presentation system.

Amino Acid Sequence↗
PubMed1995

Allelic losses in human chromosome 11 in lung cancers.

The relatively frequent loss of heterozygosity at loci on the short arm of chromosome 11 in human lung cancers has suggested the presence of a putative tumor suppressor gene. For location of the gene, a fine deletion map of human chromosome 11 was constructed by analysis of DNAs from 79 lung cancers with 31 sequence-tagged-site markers that dotted chromosome 11 and detected polymorphic changes in nucleotide sequences. The results showed that three regions, 11p12-p15, 11q12, and 11q14-q24, were commonly deleted in a considerable number of cancers, indicating the possible presence of more than one tumor suppressor gene. The range of deletion in the 11p15 region was estimated to be 4.5 megabases. That in the 11q24-q24 region was divided into two portions: one was 3 cM in length, and the other was longer and could not be specified because of lack of appropriate markers. The deletion in the 11q12 region was so short that two markers flanking the region could not be identified by genetic analysis.

Alleles↗
PubMed1995

Oscillatory phenomena in model membrane: electrical oscillation in lipid-impregnated membrane filter induced by alamethicin and controlled by bacteriorhodopsin.

A lipid-impregnated membrane filter was able to show reproducibly of an electrical oscillation under constant current stimulation when alamethicin and protamine were present in the chamber whose salt concentration was higher than the other and the membrane was left for about 12 h. In addition, bacteriorhodopsin, which is a light-activated proton pump, was found to control the oscillation. The oscillatory phenomenon was considered to be driven by the alternating change in the ion-selectivity of the membrane between cation and anion. Impedance measurement indicated the existence of lipid rearrangement which might prepare an environment for both alamethicin and protamine to cause the oscillation.

Alamethicin↗
PubMed1995

Receptor-mediated clearance of G-CSF derivative nartograstim in bone marrow of rats.

To clarify the role of the granulocyte colony-stimulating factor (G-CSF) receptor in the nonlinear elimination of a recombinant human G-CSF derivative, nartograstim (NTG), the accompanying changes in the in vivo NTG total body clearance at steady state (CLss) or the early-phase tissue uptake clearance (CLuptake) in rats were compared with the change in the number of G-CSF receptors in bone marrow. The infusion rate-dependent decrease in CLss in control rats confirmed the existence of a saturable elimination mechanism for NTG. The Michaelis-Menten constant (Km) and maximal velocity for this saturable process were estimated to be 107 pM and 15.5 pmol.h-1.kg-1, respectively. The Km for this saturable process was comparable with the dissociation constant (Kd) for the specific binding of NTG to bone marrow cells. After administration of excess NTG, the CLuptake of tracer amounts of 1251-NTG by bone marrow and spleen, which corresponds to the receptor density in the tissues, was reduced at 2 h but gradually recovered. This change in CLuptake corresponds well to the change in the in vitro NTG-binding capacity in each isolated cell. This reduction in CLuptake might be due to the downregulation of G-CSF receptors on the cell surface. On the other hand, the saturable CLss in cyclophosphamide-treated rats was 17% of that in control rats, whereas the saturable CLss in rats given NTG repeatedly was twofold greater than in controls, which is associated with the upregulation of G-CSF receptors.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

Change in hepatic handling of hepatocyte growth factor during liver regeneration in rats.

The change in the hepatic uptake clearance of hepatocyte growth factor (HGF) during liver regeneration in rats was examined. The hepatic uptake clearance per gram liver of 125I-labeled HGF in vivo decreased to a minimum level only 15 min after partial hepatectomy (PH). In the perfused liver, in which the effect of endogenous substances can be ignored, the hepatic uptake clearance of 125I-HGF did not change until at least 3 h after PH, suggesting that the decrease in the clearance in vivo is caused by some endogenous inhibitors. Such a decrease in the clearance cannot be explained only by the elevated endogenous HGF concentration in plasma. In addition, at 48 h after PH the decrease in hepatic uptake clearance was comparable for in vivo and perfused liver (approximately 50 and 60% reduction, respectively), suggesting that the decreased hepatic clearance in vivo at that time was caused mainly by reduction in the binding and/or uptake by the liver itself. In addition, the hepatic uptake clearance of 125I-HGF at that time in the presence of an excess (135 pM) of unlabeled HGF was comparable with that of the control, indicating that only the saturable portion of hepatic uptake clearance is reduced. The internalization rate constant representing the probability of cell surface-bound 125I-HGF being internalized per unit time increased to three times that of the control at 15 min after PH, demonstrating that the internalization of HGF is enhanced immediately after the start of liver regeneration.

Animals↗
PubMed1995

Transient increase in human muscle sympathetic nerve activity during manual acupuncture.

To clarify the effects of manual acupuncture on the autonomic nervous system, we measured efferent muscle sympathetic nerve activity (MSNA) from the right peroneal nerve while simultaneously recording blood pressure and heart rate both during the resting period and after manual acupuncture applied to the Tsusanli acupoint of the same limb. The needle was rotated intermittently for 30 s at 5-min intervals. MSNA increased transiently with the suppression of heart rate during rotation of the acupuncture needle. No consistent change in blood pressure was found throughout the acupuncture session. After removal of the needle, both the MSNA and heart rate returned to the initial control values, and the mean blood pressure showed an increase over the resting value. MSNA showed a negative correlation with heart rate in four out of five subjects who received acupuncture. These results suggest that the coactivation of cardiac vagal and muscle sympathetic nerves is evoked by the acupuncture maneuver.

Acupuncture Therapy↗
PubMed1995

Saturable uptake of a recombinant human granulocyte colony-stimulating factor derivative, nartograstim, by the bone marrow and spleen of rats in vivo.

Kinetic analysis of the in vivo tissue distribution of the recombinant human granulocyte colony-stimulating factor (rhG-CSF) derivative, nartograstim (NTG; nartograstim is an international nonproprietary name of KW-2228, Kyowa Hakko Kogyo, Tokyo, Japan) was studied in rats to determine the mechanism of the growth factor's nonlinear pharmacokinetic properties. The early-phase tissue uptake clearance (CL(uptake)) by each tissue was determined within 5 min after the i.v. administration of 125I-NTG. Coadministration of various amounts (0.6-150 microgram/kg) of unlabeled NTG did not produce any significant change in CL(uptake) by kidneys and liver. The hepatic and renal extraction ratios of NTG were low, 0.10 to 0.15, which suggests that there is no saturable uptake system in either of these organs. CL(uptake) by the kidneys was comparable to the glomerular filtration rate of unbound NTG. By contrast, a dose-dependent reduction in CL(uptake) by bone marrow and spleen was clearly observed with increasing doses of unlabeled NTG, i.e., at the maximal dose, these values were 14% and 20%, respectively, of those after a tracer dose. A saturable process was, therefore, involved in the tissue uptake of 125I-NTG by bone marrow and spleen. The intrinsic clearance (Vmax/Km) of this saturable uptake by bone marrow, 1.4 ml min-1 kg-1, was greater than that by the spleen, 0.09 ml min-1 kg-1. The sum of the intrinsic clearances of the saturable process was comparable with the value for the clearance of the saturable elimination process of NTG obtained previously by nonlinear pharmacokinetic analysis.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

Different biliary excretion systems for glucuronide and sulfate of a model compound; study using Eisai hyperbilirubinemic rats.

The disposition of conjugated metabolites (sulfate and glucuronide) was investigated in Eisai hyperbilirubinemic rats (EHBR) and normal Sprague-Dawley (SD) rats by in vivo and liver perfusion methods. EHBR are mutant rats that have conjugated hyperbilirubinemia as an autosomal recessive trait inheritance, and they show impaired excretion of organic anions into the bile. 6-Hydroxy-5,7-dimethyl-2-methylamino-4-(3-pyridylmethyl) benzothiazole (E3040), a novel dual inhibitor of 5-lipoxygenase and thromboxane A2 synthetase, was used as a model compound, because the major metabolites of E3040 are glucuronide and sulfate. After the i.v. injection of [14C]E3040 to EHBR and SD rats, the plasma AUC for glucuronide was greater in EHBR than in SD rats. The cumulative biliary excretion of the glucuronide was impaired to a great extent in EHBR, and the urinary excretion was enhanced. There was no significant difference in the cumulative biliary and urinary excretion of sulfate between EHBR and SD rats. The influx, efflux and sequestration rates of E3040, measured by a multiple indicator dilution method in the perfused rat liver, were similar in EHBR and SD rats. The biliary excretion of the glucuronide formed in the liver, measured by the liver perfusion method, was also severely impaired in EHBR, so the recovery of the glucuronide in the outflow specimens was markedly enhanced. The disposition of the sulfate did not change in either type of rat.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Nonlinear pharmacokinetics of a recombinant human granulocyte colony-stimulating factor derivative (nartograstim): species differences among rats, monkeys and humans.

NTG is a human G-CSF derivative produced by Escherichia coli using gene-engineering techniques. The dose dependency of NTG pharmacokinetics in rats and monkeys was examined and compared with that previously reported for humans. In all species, the total clearance decreased and the mean residence time was prolonged as the intravenously administered dose of NTG was increased. At higher doses, the clearance in each species approached a constant value. This suggests that both saturable and nonsaturable processes are involved in NTG elimination. At the lowest dose, the saturable process accounted for 57% to 76% of total clearance. The plasma concentration-time profiles of NTG in rats and monkeys were analyzed by nonlinear pharmacokinetic models which contained both linear and Michaelis-Menten type elimination from the central compartment. The Km and Vmax values in rat, about 240 pM and 40 pmol/hr/kg, respectively, were comparable to those in the monkey. On the other hand, the values in humans were smaller, about 17% and 7%, respectively, than those in experimental animals. Therefore, the intrinsic clearance of saturable process (Vmax/Km) in humans was about one-half that in monkeys. To clarify the mechanism of the saturable clearance of NTG, the in vitro metabolic activities in rat bone marrow, spleen cells and peripheral leukocytes, which possess the G-CSF receptor, were determined. The metabolic activity of bone marrow cells was five-fold greater than that of the other cells. The in vitro metabolic and binding studies with bone marrow cells, demonstrated that the Im in NTG metabolism and Kd for NTG binding were 94 and 142 pM, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

In vitro measurement of chemosensitivity of human small cell lung and gastric cancer cell lines toward cell cycle phase-nonspecific agents under the clinically equivalent area under the curve.

BACKGROUND: Based on the previous finding that cell killing effects of cell cycle phase-nonspecific agents depend on the concentration-time product (C x T) or the area under the curve (AUC), the authors investigated in vitro cytotoxic effects of nimustine hydrochloride (ACNU) and mitomycin C (MMC) under an experimental condition in which the assay AUC was equivalent to their clinically achievable AUC. METHODS: The cytotoxic effects of these agents on human cancer cell lines, consisting of 9 small cell lung carcinomas (SCLC) and 10 gastric cancers, were measured by a tetrazolium-based colorimetric assay (MTT assay). RESULTS: These cell lines individually responded to ACNU and MMC in this assay condition. When the authors considered 60% or greater cell kill to be effective, the in vitro response rates of SCLC to ACNU and MMC were 22% (two of nine carcinomas) and 67% (six of nine carcinomas), respectively. The response rates of gastric cancer to ACNU and MMC were 10% (1 of 10 carcinomas) and 40% (4 of 10 carcinomas), respectively. Except for the response of SCLC to ACNU, these in vitro response rates corresponded well to the clinical rates (SCLC to ACNU and MMC, 47% [14 of 30 carcinomas] and 50% [17 of 34 carcinomas], respectively; gastric cancer to ACNU and MMC, 11% [4 of 37 carcinomas] and 30% [63 of 211 carcinomas], respectively). CONCLUSIONS: These results suggest that the introduction of the clinically equivalent AUC to the in vitro chemosensitivity test for cell cycle phase-nonspecific agents may improve its clinical predictability.

Carcinoma, Small Cell↗
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

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

Photophosphorylation elements in halobacteria: an A-type ATP synthase and bacterial rhodopsins.

Photophosphorylation in halobacteria is carried out by two rather simple elements: an A-type ATP synthase and light-driven ion-pumping bacterial rhodopsins. The unique features of halobacterial ATP synthase, mostly common to archaebacteria (A-type), and of new members of the bacteriorhodopsin family are introduced along with studies performed in the authors' laboratory. This is the story of how we found that the A-type ATP synthase is close to V-type ATPase but far from F-type ATPase, although all three ATPases are believed to have the same ancestor. Archaerhodopsins, the new members of the proton-pumping retinal proteins, were found in Australian halobacteria and have been used in a comparative study of bacterial rhodopsins.

Adenosine Triphosphatases↗
PubMed1992

Enhanced muscle sympathetic nerve activity during sleep apnea in the elderly.

To examine how muscle sympathetic nerve activity (MSNA) becomes modified during sleep apnea in the elderly, we analyzed polysomnographic recording simultaneously with microneurographically recorded MSNA. Subjects were three healthy elderly males aged 72, 75, and 76. MSNA was suppressed with deeper non-REM sleep stages in these elderly subjects. In all three subjects, sleep apnea for 10 s or longer was observed during sleep of 00:00-06:00. During sleep apnea, MSNA was enhanced concomitantly with a blood pressure fall and a reduction in saturation rate of oxyhemoglobin. With the termination of sleep apnea, MSNA was maximally enhanced with a transient elevation of blood pressure. We conclude that sleep apnea induces an enhancement of MSNA, which may be responsible for hypertensive episodes during sleep.

Aged↗