Biomedical subjects

T Tateishi

Publications and source records attributed to T Tateishi.

At least 91 records · Page 5Linked to original sources

PubMed1997

Electrical stimulation on joint contracture: an experiment in rat model with direct current.

OBJECTIVE: To examine whether electrical stimulation could decrease the degree of joint stiffness in a rat lower extremity model. DESIGN: Rat knee joints were surgically immobilized in a flexed position for 3 weeks. Two groups of rats were stimulated with 20 microA and 50 microA constant direct current. Another group had surgical intervention and sham electrodes without electricity. The hind leg was extirpated and prepared for a sample with the femur-knee joint-tibia unit. Recording the knee flexion angle with extension torque, the degree of joint contracture was assessed biomechanically by measuring the bone-joint-bone sample as a cantilever. Measurement was performed with (1) spectral analysis of transfer function measurement using random mechanical noise with frequency range from 1 to 50Hz, and (2) dynamic stiffness and loss tangent with steady-state sinusoidal excitation (11 and 35Hz). RESULTS: The results showed that no significant difference or trend was found in vibration analysis among three groups. However, spectral analysis of transfer function measurement revealed more deformation against load, and more viscous nature in the stimulation groups, especially in low frequency band, than in the sham group. CONCLUSION: Electrical stimulation with constant direct current has a possibility of reducing the degree of joint contracture.

Animals↗

PubMed1997

A comparison of hepatic cytochrome P450 protein expression between infancy and postinfancy.

We immunochemically measured the contents of 9 different cytochrome P450 (CYP) isoenzymes expressed in the liver and compared them between two groups: one group of 6 infant and 4 perinatal patients and one group of 10 patients after infancy (over 1 year old). CYP protein expressed in human liver can be divided into three groups on the basis of expression pattern: (a) CYP2A6, 2C9, 2D6, 2E1, and 3A were present in all samples and no difference was observed between the two groups; (b) CYP1A2, 2B6, and 2C8 were expressed more after infancy than during infancy; and (c) CYP3A7, which has been considered a major CYP enzyme in fetal liver microsomes, was expressed in all infants as well as the four perinatal patients, whereas it was detected in only 2 patients after infancy. These results implied that CYP2A6, 2C9, 2D6, 2E1, and 3A are already expressed during perinatal and infant period, while CYP1A2, 2B6, and 2C8 are expressed highly in subjects over 1 year old, and CYP3A7 disappeared after infancy.

Adolescent↗

PubMed1997

The effects of streptozotocin-induced hypoinsulinemia on serum lipid levels in spontaneously hyperlipidemic rats.

We compared the effects of streptozotocin (STZ) treatment on serum cholesterol and lipoprotein levels in spontaneously hyperlipidemic rats (HLR), a hereditary hyperlipidemic model animal, with those in Sprague-Dawley rats (SDR). The body weight of control SDR and HLR were increased continuously for 30 days. Both SDR and HLR lost their body weight after STZ administration. Glucose levels of SDR and HLR were significantly increased by STZ treatment. Insulin levels were markedly decreased in HLR compared with those in SDR. Serum cholesterol and triglyceride levels of HLR treated with STZ were significantly higher than those of untreated HLR. The increment of both levels in HLR was much larger than that in SDR. The high density lipoprotein (HDL) cholesterol level of the STZ-treated HLR was significantly lower than that of untreated HLR. In the STZ-treated HLR the intensities of both bands of the very low density lipoprotein (VLDL) and the low density lipoprotein (LDL) were higher than those in untreated HLR, while the intensity of any lipoprotein band remained unchanged between STZ-treated and control SDR. The atherogenic index (the ratio of total cholesterol level minus HDL cholesterol level of HDL cholesterol level) in the STZ-treated HLR was significantly high compared with that in other groups. The STZ-treated HLR showed the extremely hyperlipidemic state and this animal might be useful in experiments for the development of atherosclerosis or the drug evaluation for the agents used in hyperlipidemia.

Animals↗

PubMed1997

Halothane inhalation inhibits the metabolism of chlorzoxazone, a substrate for CYP2E1, in rabbits.

We demonstrated the inhibitory effect of halothane (HAL) inhalation on the metabolism of chlorzoxazone (CZZ), a substrate for CYP2E1, in a bolus and a continuous injection study in rabbits receiving artificial ventilation. In a bolus injection study, the inhalation of 1.0% HAL significantly increased the half-life and the area under the curve and decreased the clearance of CZZ compared with those variables in midazolam administration. In a continuous injection study, the effect of various concentrations of inhaled HAL on plasma CZZ concentration at steady state was compared. Systolic and diastolic arterial blood pressure were decreased dose-dependently after 0.5%, 1.0%, or 2.0% HAL was inhaled. Although the plasma concentration of CZZ was increased 2.5-fold after 3 h of HAL inhalation, there was no significant difference in mean plasma concentrations among the groups treated with 0.5%, 1.0%, or 2.0% HAL. In contrast, the plasma concentration of lidocaine, a substrate for CYP3A, remained unchanged after 1.0% HAL was inhaled. These results suggest that general anesthesia obtained with HAL inhalation will affect the metabolism of drugs administered concomitantly when the drug is a substrate for CYP2E1.

Anesthesia, Inhalation↗

PubMed1997

Effects of ovariectomy and estrogen replacement on aorta angiotensin-converting enzyme activity in rats.

We investigated the possibility that physiological doses of estrogen protect against atherosclerotic change produced by changes in vascular angiotensin-converting enzyme (ACE) activity. Rats were ovariectomized, and after 14 days, treated with estradiol-17 beta (0.2 microgram/rat) for 14 weeks. Aorta ACE activity significantly increased in the ovariectomized rats, and decreased following estradiol-17 beta administration to a level not different from proestrous control rats. These results suggest that the lack of estrogenic action increases atherosclerotic change associated with changes in aorta ACE activity and that estrogen replacement therapy reduces the risk of atherosclerotic change associated with the decrease of aorta ACE activity.

Administration, Oral↗

PubMed1997

Increases in hematopoietic responses caused by beta-glucans in mice.

The effects of various (1-->3)-beta-D-glucans on hematopoietic responses of mice were investigated by measuring colony stimulating activity in sera and ascites of the mice administered glucan. We have demonstrated that the hematopoietic response was increased by various structures of (1-->3)-beta-D-glucans, i.e. soluble glucans (linear, branched, single helix, triple helix) and particulate glucans. From the viewpoint of structure and activity relationships, we found several characteristic features: i) hematopoietic response induced by the particulate glucan disappeared faster than that by the soluble glucans, ii) conformation of the glucans, single vs. triple helix, are relatively independent of the response, iii) linear glucan had a weaker response, and iv) there is a strong strain-dependency of the response. These results corresponded well with the fact that branched (1-->3)-beta-D-glucans, but not linear and not particulate, are often used as biological response modifiers for cancer patients.

Animals↗

PubMed1997

Enhancement of the affinity of androgen receptor in the adrenal medulla of spontaneously hypertensive rats.

We investigated the alteration of tyrosine hydroxylase (TH) mRNA expression and androgen receptor in the adrenal medulla of spontaneously hypertensive rats (SHR). The TH mRNA expression in the adrenal medulla of SHR was higher than that of Wistar Kyoto rats (WKY). The testosterone increased the TH mRNA expression of SHR, but not WKY. The affinity of androgen receptor in the adrenal medulla of SHR was higher than that of WKY; however, the number of androgen receptor was not different. These results suggested that the increased binding affinity of the androgen receptor of SHR may be related to TH gene transcription in the adrenal medulla.

Adrenal Medulla↗

PubMed1997

Rigix plate system for anterior fixation of thoracolumbar vertebrae.

Only a few plate systems are available for anterior fixation of thoracolumbar vertebrae because of the difficulty in fastening a screw and a plate together. If the fixation is inadequate, the screws will become loose. The Rigix plate system consists of screws made of titanium alloy and a plate made of pure titanium. All screws used for internal fixation are screwed into the plate. This system permits the use of anchor screws, which facilitate exertion of force to compress the vertebral bodies together or to distract them from each other. In this study, Rigix plates were used in 24 patients (20 with burst fractures and 4 with metastatic tumors). In the 20 patients with fracture, internal fixation with a graft and a Rigix plate was performed after anterior decompression. In the four patients with malignant tumors, total spondylectomy was performed anteriorly and posteriorly, followed by implantation of a vertebral prosthesis, and then internal fixation with a Rigix plate combined posterior instrumentation with Diapson (Stryker Co., Tokyo, Japan) pedicular screws. Bone union was achieved in all patients. Neither breakage of instruments nor loosening of connections occurred in any case. In patients treated for bone metastases, the reconstructed spinal structure was able to be maintained for a long period. Of the screws used, five (5%) were not able to remain fixed as intended because they were inserted at inappropriate angles into the plate, but the fixation itself was excellent. Because of the low profile, ease of manipulation (mean instrumentation time was 25 min), and compatibility with magnetic resonance imaging, the Rigix plate is useful for anterior fixation of thoracolumbar vertebrae.

Adult↗

PubMed1996

The activity of dihydropyrimidine dehydrogenase from rat liver was not affected by any of five 5-hydroxytryptamine antagonists.

We estimate the influence of five 5-hydroxytryptamine receptor (5-HT3) antagonists on the activity of dihydropyrimidine dehydrogenase (DPDase), the rate-limiting enzyme in 5-fluorouracil (5FU) metabolism. The activity of DPDase from the rat liver was compared in the cytosol mixture of 5FU incubated with or without each of five 5-HT3 antagonists. DPDase activity was not altered in the presence of any 5-HT3 antagonist studied here. It may be inferred from these results that the any 5-HT3 receptor antagonist examined in this study has little or no effect on fluorouracil catabolism.

Animals↗

PubMed1996

Preliminary examination of the influence of incubation time or cytosolic protein concentration on dihydropyrimidine dehydrogenase activity.

We examined the influence of incubation time or cytosolic protein concentration on the metabolite production of 5-fluorouracil (5FU). Although the activity of dihydropyrimidine dehydrogenase (DPDase) from rat liver is considered to be retained for up to 60 min, the production rate of 5FU metabolites was reduced, probably due to depletion of the substrate in 40 mumol/l and lower concentration of 5FU. Since the ratio of the metabolite production rate to the cytosolic protein became smaller in higher concentrations of cytosolic protein, the DPDase activity should be compared in the same concentration of cytosolic protein. The production rate of 5FU metabolites was considered to be linear up to 40 mumol/l 5FU incubated with 500 micrograms cytosolic protein. The rate of the metabolite production calculated by one-point sampling significantly correlated with the enzyme activity by the multi-point sampling method. Minimizing sampling points to determine the DPDase activity would save time and expense.

Animals↗

PubMed1996

Metabolism of 5-methylchrysene and 6-methylchrysene by human hepatic and pulmonary cytochrome P450 enzymes.

The metabolism of environmentally occurring methylated polynuclear aromatic hydrocarbons by human cytochrome P450 (P450) enzymes has not been examined previously. We compared the metabolism of the tobacco smoke constituents 5-methylchrysene (5-MeC), a strong carcinogen, and 6-MeC, a weak carcinogen, in 18 hepatic and 11 pulmonary human microsomes. Major metabolites of 5-MeC were its proximate carcinogen trans-1,2-dihydroxy-1,2-dihydro-5-methylchrysene (5-MeC-1,2-diol), as well as 5-MeC-7,8-diol, bay region dihydrodiols, and phenols. 5-MeC-1,2-diol and 5-MeC-7,8-diol were formed stereoselectively, with the R,R enantiomers predominating. Major metabolites of 6-MeC were 6-MeC-1,2-diol, bay region dihydrodiols, phenols, and 6-(hydroxymethyl)chrysene. 6-MeC-1,2-diol was also formed stereoselectively in the 1R,2R configuration. All human liver samples formed the proximate carcinogenic 1,2-diols (0.2-2.3 pmol/mg protein/min for 5-MeC and 0.3-3.1 pmol/mg protein/min for 6-MeC). Comparable results were obtained in pulmonary microsomes, but the extent of metabolism was less than in the hepatic samples, and only 4 of 11 samples showed activity. Catalytic activities known to be associated with specific P450s were analyzed in each hepatic sample and correlated with levels of 5-MeC and 6-MeC metabolites in the same samples. The results of the correlation analysis indicated that P450s 1A1 and 1A2 were active in the formation of 5-MeC-1,2-diol and 6-MeC-1,2-diol, as well as several other metabolites resulting from ring oxidation. The formation of the hydroxymethyl metabolites was catalyzed by P450 3A4 (for 5-MeC) or P450s 3A4 and 1A2 (for 6-MeC). Experiments with chemical inhibitors and antibodies supported these results. The metabolism of 5-MeC and 6-MeC was also investigated using purified recombinant human P450s 1A1, 1A2, 2C10, 2D6, 2E1, 3A4, and 3A5. P450s 1A1, 1A2, and 2C10 had higher activities than the other enzymes for ring oxidation of 5-MeC and 6-MeC, whereas P450s 1A2 and 3A4 were more active than the other enzymes for methyl hydroxylation of 6-MeC. Only P450 3A4 showed substantial catalytic activity for methyl hydroxylation of 5-MeC. Collectively, the results of these studies demonstrate that P450s 1A2 and 2C10 are important catalysts of the metabolic activation of 5-MeC and 6-MeC in human liver, whereas P450 1A1 plays a major role in the metabolic activation of these compounds in human lung.

Antibodies↗

PubMed1996

Elevated tyrosine hydroxylase mRNA levels in medulla oblongata of spontaneously hypertensive rats.

The present study has investigated the expression of tyrosine hydroxylase (TH) mRNA and its activity in medulla oblongata of spontaneously hypertensive rats (SHR) and Wistar Kyoto rats (WKY). The TH mRNA levels were determined by Northern blot and dot blot analyses. The TH activity and the expression of TH mRNA in medulla oblongata of SHR were significantly higher than those of WKY. These results suggest that the hypertension of SHR may be related to the high activity of TH due to the high level of TH mRNA which increases norepinephrine levels in the medulla oblongata.

Animals↗

PubMed1996

Karyotyping by PFGE of clinical isolates of Sporothrix schenckii.

From October 1991 to December 1992 we had eight patients with sporotrichosis at Tsukuba University Hospital in Japan. With 8 strains isolated from these patients, PFGE (pulsed-field gel electrophoresis) analyses were carried out to examine whether the karyotype of S. schenckii is distinguished by our method and whether this molecular approach is a useful means of biotyping of S. schenckii strains. Chromosomes were separated by contour-clamped homogeneous electric field (CHEF) gel electrophoresis. The strains had six to eight chromosomes and a total genome size was approx. 28 Mbp. Although these karyotypes of all the isolates looked closely similar to each other, they were grouped into three types.

Electrophoresis, Gel, Pulsed-Field↗

PubMed1996

Identification of human liver cytochrome P-450 3A4 as the enzyme responsible for fentanyl and sufentanil N-dealkylation.

Alfentanil, sufentanil, and fentanyl are synthetic opioids that are metabolized by oxidative N-dealkylation in the liver. We have previously shown that cytochrome P-450 3A4 (CYP3A4) contributes significantly to human liver microsomal alfentanil oxidation. Since identification of specific drug-metabolizing enzymes allows prediction of the variables affecting drug metabolism, the purpose of the present study was to identify the P-450 enzymes responsible for sufentanil and fentanyl metabolism in human liver microsomes. Microsomal preparations fortified with a reduced nicotinamide-adenine dinucleotide phosphate-generating system were incubated with 0.25 microM 3H-fentanyl or 3H-sufentanil. Rates of N-dealkylated metabolite formation significantly correlated with nifedipine oxidation activity (a marker of CYP3A4 activity) for fentanyl and sufentanil (r = 0.93 and 0.87, n = 18, respectively), but not with the oxidation activity for ethoxyresorufin (CYP1A2), S-mephenytoin (CYP2C19), bufuralol (CYP2D6), or chlorzoxazone (CYP2E1). Gestodene and troleandomycin (chemical inhibitors of CYP3A4) and antibody to CYP3A4 inhibited N-dealkylation of fentanyl and sufentanil. Chemical inhibitors of CYP2C, 2E1, and 2D6 did not inhibit N-dealkylation of fentanyl and sufentanil. Recombinant CYP3A4 expressed in Escherichia coli showed N-dealkylation activity of fentanyl and sufentanil, while expressed CYP1A2, 2C10, and 2E1 enzymes did not. We conclude that CYP3A4 is responsible for fentanyl and sufentanil N-dealkylation in vitro.

Analgesics, Opioid↗

PubMed1996

A quantitative visualization study of flow in a scaled-up model of a centrifugal blood pump.

A quantitative flow visualization study of a scaled-up model of a centrifugal blood pump was performed. Since the size of the scaled-up model was three times as large as the original pump under development, and the kinematic viscosity of the saline solution used as the working fluid was approximately one-third that of the blood, we obtained a similar flow at one twenty-seventh the angular velocity of the original pump. The flow was visualized by seeding the saline solution with neutrally buoyant particles and by illuminating the model with a laser light sheet. Since the gap flow behind the impeller is important for thrombus formation, it was recorded by a high-speed video camera, and the velocity field was evaluated automatically by particle tracking velocimetry. It was shown that in the gap behind the impeller there existed a region where the velocity profile was almost flat which can be called a core region. The results indicated the effectiveness of the present visualization technique for centrifugal blood pumps.

Biomechanical Phenomena↗

PubMed1996

Effect of Ti, Al, and V ions on the relative growth rate of fibroblasts (L929) and osteoblasts (MC3T3-E1) cells.

The effect of Ti, V and Al ions on the relative growth rate of L929 cells and MC3T3-E1 cells was investigated by a cell culture method with metallic powders. These powders were sterilized under a U.V. lamp for 6 h, suspended in the medium and extracted for 48 h, 72 h and 96 h in the incubator. After filtering with a 0.2 microns filter, 3.0 x 10(4) L929 cells and 5 x 10(4) MC3T3-E1 cells were seeded in these filtrates of the medium with and without (control) the presence of the metallic powder. The number of cells was counted using a coulter counter from 1 to 7 days. The number of L929 cells after 4 days of incubation was almost similar for Ti and the control, whereas in the case of A1 and V extraction the number of cells was too low as compared to that of the control. The relative growth rate of L929 cells for Ti, A1 and V after 4 days of incubation was about 1, 0.2 and 0.02, respectively. A similar trend was also observed for MC3T3-E1 cells. The effect of the relative growth rate of L929 cells at different extraction times of 48 h, 72 h and 96 h was examined. It was found that the relative growth rate of L929 cells for Ti, A1 and V extraction was almost the same at all three extraction times. A number of 2.0-5.0 x 10(4) cells was seeded in the medium of A1 extraction. The effect of this initial number of cells on the relative growth rate of L929 cells was investigated. The relative growth rate of L929 cells decreased as the initial number of L929 cells increased. Moreover, dilutions from 1 to 10 times in the case of A1 and from 1 to 4000 times in the case of V were made. The relative growth rate became equal to 1 at 5 times dilution for A1 and at 4000 times dilution for V, for both L929 and MC3T3-E1 cells. From the measures of the concentration of the released A1 and V ions on the relative growth rate of L929 cells, it could be seen that there was a marked decrease in the concentrations of A1 and V ions from 0.3 ppm to 0.1 ppm.

Aluminum↗

PubMed1996

Microsomal codeine N-demethylation: cosegregation with cytochrome P4503A4 activity.

Codeine is metabolized by glucuronidation, by O-demethylation to morphine, and by N-demethylation to norcodeine. The enzyme responsible for the O-demethylation to morphine has been identified as cytochrome P4502D6 (CYP2D6). The purpose of the present study was to identify the specific P450 enzyme responsible for codeine N-demethylation. Microsomal preparations (250 pmol of P450) obtained from 12 human liver donors were incubated with 20 microM codeine and analyzed for norcodeine formation. Codeine N-demethylation activity was linearly correlated with nifedipine oxidation activity (r = 0.90, p < 0.001), a marker of CYP3A4, but not with codeine O-demethylation, a marker of CYP2D6. Preincubation with troleandomycin (50 microM), or gestodene (50 microM) inhibitors of CYP3A4, decreased the rate of production of norcodeine by 60 and 45% compared to control values, respectively. Similarly, ketoconazole (10 microM) and erythromycin (10 microM) inhibited codeine N-demethylation by 75 and 35%, respectively. In contrast, the presence of quinidine, sulfaphenazole, or diethyldithiocarbamate in the incubation mixture had no effect on norcodeine formation. Preincubation with antibodies raised to CYP3A4 (5 mg lgG/nmol P450) caused 96% inhibition of norcodeine production, whereas preimmune IgG or antibodies raised to CYP2A6 and CYP2C had no effect. Additionally, significant norcodeine production was observed with purified CYP3A4 derived from human liver microsomes. In conclusion, codeine N-demethylation activity cosegregates with CYP3A4 activity. Coadministration of codeine with selective inhibitors of CYP3A4 may result in increased morphine production and enhanced pharmacodynamic effects due to shunting down the CYP2D6 pathway.

Aryl Hydrocarbon Hydroxylases↗

PubMed1995

Biotransformation of tritiated fentanyl in human liver microsomes. Monitoring metabolism using phenylacetic acid and 2-phenylethanol.

Norfentanyl has been identified previously as a urinary metabolite of fentanyl. However, at clinically relevant concentrations, norfentanyl are below the limits of detection. The use of labeled drug in metabolic studies is a standard approach to overcome the limitations imposed by metabolite concentrations that are below detection limits. Unfortunately, the available tritium-labeled fentanyl yields unlabeled norfentanyl following N-dealkylation. Thus, we have developed a technique to monitor the N-dealkylation of fentanyl using the other products of N-dealkylation. The biotransformation of fentanyl was studied in human liver microsomes. After incubation with human liver microsomes for 20 min, almost 50% of a 0.03 microM concentration of [3H]-fentanyl was metabolized to the [3H]N-dealkylated metabolite phenylacetaldehyde, which was then converted principally to [3H]2-phenylethanol and to a smaller extent to [3H]phenylacetic acid in microsomal incubates. The apparent Km,app and Vmax,app for norfentanyl formation were 82 +/- 21 microM and 4.7 +/- 0.4 nmol product formed/min/nmol cytochrome P450, respectively. Thus, this study defined methodology that can be used to evaluate the metabolism of fentanyl, both in vivo and in vitro, at clinically relevant concentrations.

Analgesics, Opioid↗