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Biomedical subjects

T Tateishi

Publications and source records attributed to T Tateishi.

At least 37 records · Page 2Linked to original sources
PubMed2001

In vitro organization of biohybrid rat liver tissue incorporating growth factor- and hormone-releasing biodegradable polymer microcapsules.

To enhance the liver-specific functions of rat hepatocyte aggregates without the addition of exogenous growth factors, polylactic acid-polyglycolic acid (PLGA)/gelatin microcapsules that release insulin, dexamethasone, epidermal growth factors, and glucagon were prepared and incorporated into the hepatocyte aggregates in suspension culture. Precoating the capsules with fibronectin enhanced the incorporation of the microcapsules into the hepatocyte aggregates. In a growth factor- and hormone-free culture medium, these microcapsule-containing aggregates showed a sustained cell number and an ammonium detoxification capacity compared with two types of control culture. One was the culture of microcapsule-free aggregates with albumin-containing control capsules and the other was the culture of capsule-free aggregates that were supplied with the same factors and hormones from the culture medium at concentration levels expected from the release kinetics of the microcapsules. Our new methodology demonstrates that the performance and duration of bioartificial liver systems can be enhanced due to a more efficient maintenance of cell number by using such growth factor- and hormone-releasing microcapsules.

Ammonia↗
PubMed2000

CYP3A is responsible for N-dealkylation of haloperidol and bromperidol and oxidation of their reduced forms by human liver microsomes.

We studied the biotransformation of haloperidol, bromperidol and their reduced forms by human liver microsomes. Nifedipine oxidation (CYP3A) activity correlated significantly with N-dealkylation rates of haloperidol and bromperidol and oxidation rates of their reduced forms, while neither ethoxyresorufin O-deethylation (CYP1A2) activity nor dextromethorphan O-deethylation (CYP2D6) activity did. In chemical and immunoinhibition studies, only troleandomycin and anti-CYP3A4 serum inhibited both formation rates of 4-fluorobenzoylpropionic acid, a metabolite of haloperidol and bromperidol, and back oxidation rates. Among 10 recombinant isoforms examined, only CYP3A4 showed catalytic activity. The Vmax and Km values of N-dealkylation of bromperidol and reoxidation of reduced bromperidol were similar to those of haloperidol and reduced haloperidol, respectively. The present study indicates that CYP3A plays a major role in N-dealkylation of and oxidation back to bromperidol as well as haloperidol and suggests that modification of in vivo CYP3A activity by inhibition or induction may affect the pharmacokinetics and therapeutic effects of haloperidol and bromperidol.

Aryl Hydrocarbon Hydroxylases↗
PubMed2000

Involvement of tyrosine hydroxylase up regulation in dexamethasone-induced hypertension of rats.

We investigated the effect of dexamethasone (DEX) on tyrosine hydroxylase (TH) mRNA level, and TH activity and catecholamine levels in the adrenal medulla of the rat. DEX (1 mg/kg/day, s.c.) was administered for 2 days, and a control group was given corn oil. DEX significantly increased systolic blood pressure. TH mRNA level, TH activity, epinephrine level, and norepinephrine level in the adrenal medulla of DEX-treated rats were significantly higher than those of control rats. Also, epinephrine and norepinephrine levels in plasma were significantly higher in DEX-treated rats than in controls. alpha-Methyl-p-tyrosine prevented the DEX-induced blood pressure increase. These results suggest that the catecholamine synthetic pathway may be involved in DEX-induced hypertension.

Actins↗
PubMed2000

Effect of interferon-alpha on tyrosine hydroxylase and catecholamine levels in the brain of rats.

We investigated the effect of interferon on tyrosine hydroxylase (TH) and catecholamine levels in the brains of 12-week-old male Wistar rats. Interferon-alpha (300,000 IU/kg/day, s.c.) was administered to rats for 7 days. Locomotor activity of interferon-alpha-treated rats was significantly lower than that of control rats. Norepinephrine and dopamine levels and TH activities in the cerebral cortex, hypothalamus and medulla oblongata of interferon-alpha-treated rats were significantly higher than those of control rats. Norepinephrine and dopamine levels and TH activities in the thalamus and hippocampus were not different between interferon-alpha treated and control rats. These results suggest that interferon-alpha-induced depression may be related to change in the catecholamine synthetic pathway in the central nervous system.

Animals↗
PubMed2000

C1-C2 intra-articular screw fixation for atlantoaxial posterior stabilization.

STUDY DESIGN: A trial of a new posterior stabilization technique for atlantoaxial instability and a report of preliminary results. OBJECTIVES: To describe a new posterior stabilization technique for atlantoxial instability. SUMMARY OF BACKGROUND DATA: Magerl's transarticular screw fixation is an accepted technique for rigid atlantoaxial stabilization, which reportedly has yielded many good clinical results. However, the technique is technically demanding and poses a risk of injury to the nerves and veins. METHODS: Eleven patients who had been treated with intra-articular screw fixation in combination with Halifax interlaminar clamp (OSTEONICS, Allendale, NJ) for atlantoaxial instability were observed. Results of their clinical examinations and biomechanical studies using resinous bones of a cervical spine model were reviewed. RESULTS: In all patients, occipital pain, neck pain, and neural deficit improved, and bony fusion with no correction loss was shown on radiography. To date, no vascular or neural complications have been found, and no instrumentation failures have occurred. In the biomechanical study, the Halifax with transarticular screw fixation had significantly greater flexion stiffness than the Halifax only or the Halifax with intra-articular screw fixation, but the torsion stiffness of the Halifax with intra-articular screw fixation was significantly greater than that of the other Halifax combinations. CONCLUSION: The preliminary results showed that this technique was effective in strengthening the rotational stability of the atlantoaxial fixation and was considered useful for atlantoaxial posterior stabilization.

Adult↗
PubMed2000

Preparation, solubility, and cytocompatibility of zinc-releasing calcium phosphate ceramics.

Zinc is an essential trace element with stimulatory effects on bone formation. Therefore, zinc was doped into beta-tricalcium phosphate to develop zinc-releasing biomaterials to promote bone formation. The zinc-doped beta-tricalcium phosphate, beta-tricalcium phosphate, and hydroxyapatite powders were mixed at a (Ca+Zn)/P molar ratio of 1.60, followed by sintering into a dense body at 1100 degrees C for 1 h. The sintered body was a composite ceramic consisting of zinc-doped beta-tricalcium phosphate and hydroxyapatite phases. The composite ceramic contained zinc oxide when the zinc content was higher than 1.20 wt %. The composite ceramic released zinc under pseudophysiological conditions. However, the release of calcium and phosphate decreased with an increase in zinc content in a range higher than 0.12 wt % owing to a decrease in solubility of the zinc-doped beta-tricalcium phosphate phase. Proliferation of osteoblastic MC3T3-E1 cells was significantly increased on the composite ceramic with a zinc content from 0.6 to 1.20 wt %, compared with those without zinc. When the zinc content was higher than 1.20 wt %, release of zinc from the zinc oxide caused cytotoxicity. Therefore, the zinc content of the composite ceramic must be <1.20 wt %.

Animals↗
PubMed2000

Stimulatory effect of zinc-releasing calcium phosphate implant on bone formation in rabbit femora.

Although hydroxyapatite (HAP) and tricalcium phosphate (TCP) are currently used as bone graft substitutes or coatings on metallic prostheses because of their excellent biocompatibility and osteoconductivity, they do not stimulate bone formation or inhibit bone resorption. Zinc, an essential trace element in many animals, has a direct specific proliferative effect on osteoblastic cells and has a potent and selective inhibitory effect on osteoclastic bone resorption in vitro. Therefore, zinc-containing beta-tricalcium phosphate (ZnTCP) ceramics and composite ceramics of ZnTCP and HAP (ZnTCP/HAP) were implanted in the femora of New Zealand White rabbits for 4 weeks to promote bone formation. The implants were sintered ceramics with zinc contents of 0 (control), 0.063, 0.316 and 0.633 wt %. Histological and histomorphometrical investigation of the undecalcified sections revealed an increase by 51% (p =.0509) in the area of newly formed bone around the ZnTCP/HAP implants of 0. 316 Zn wt % compared with the control. Plasma zinc concentration was unchanged. An increased bone resorption on the endosteal surface was observed when ZnTCP and ZnTCP/HAP of 0.633 Zn wt % were implanted. To promote bone formation, the optimum zinc content of the calcium phosphate ceramics was therefore 0.316 wt %.

Animals↗
PubMed2000

A biodegradable hybrid sponge nested with collagen microsponges.

A biodegradable hybrid sponge of poly(DL-lactic-co-glycolic acid) (PLGA) and collagen was fabricated by forming microsponges of collagen in the pores of PLGA sponge. Observation of the PLGA-collagen hybrid sponge by scanning electron microscopy (SEM) showed that microsponges of collagen with interconnected pore structures were formed in the pores of PLGA sponge. The hybrid structure further was confirmed by scanning electron microscopy-electron probe microanalysis (SEM-EPMA), and elemental nitrogen was detected in the microsponges of collagen and on the pore surfaces of PLGA, but not in cross-sections of PLGA regions. The formation of collagen microsponges was dependent on collagen concentration, the effective range of which was from 0.1 to 1.5 (w/v) %. The mechanical strength of the hybrid sponge was higher than that of either PLGA or collagen sponges, in both dry and wet states. The wettability with water was improved by hybridization with collagen, which facilitated cell seeding in the hybrid sponge. Mouse fibroblast L929 cells attached well and spread on the surfaces of the microsponges of collagen in the hybrid sponge. The distribution of cells was spatially uniform throughout the hybrid sponge. Use of the PLGA sponge as a skeleton facilitated formation of the hybrid sponge into desired shapes with high mechanical strength while collagen microsponges contributed good cell interaction and hydrophilicity.

Animals↗
PubMed2000

Pemphigoid nodularis with IgA autoantibodies against the intracellular domain of desmoglein 1.

Pemphigoid nodularis is a rare variant of bullous pemphigoid. We report a 49-year-old Japanese male with clinical and histopathological features of pemphigoid nodularis including circulating and in vivo-bound IgG antibasement membrane zone antibodies and IgA anti-intercellular antibodies. Although the precise molecular target of the IgG autoantibodies could not be determined, intriguingly, immunoblotting showed that the IgA in the patient's serum reacted with the intracellular domain of desmoglein 1, the target antigen in cases of pemphigus foliaceus. However, the IgA did not react with the extracellular domain of desmoglein 1 in sensitive enzyme-linked immunosorbent assay studies using a baculovirus system. These results suggest therefore that these IgA antibodies may possibly not be pathogenic. The mechanism for the production of different autoantibodies is unknown, but this case provides further illustration of the atypical skin immunoreactants often seen in this unusual subtype of bullous pemphigoid.

Anti-Inflammatory Agents↗
PubMed2000

Structural characterization of a new variant of the CYP2A6 gene (CYP2A6*1B) apparently diagnosed as heterozygotes of CYP2A6*1A and CYP2A6*4C.

During the course of investigating the frequency of a CYP2A6 whole deletion-type polymorphism (CYP2A6*4C) in Japanese, an unexpectedly large population of heterozygotes for CYP2A6*4C and the wild-type (CYP2A6*1A) was found. Cloning of a cDNA encoding CYP2A6 from the liver of individuals judged as heterozygotes for CYP2A6*4C and the CYP2A6*1A was carried out to identify the causal allele(s) responsible for a possible overestimation. A clone isolated from the liver cDNA library possessed 58 bp sequences in the 3'-untranslated region, which was replaced with the corresponding region of the CYP2A7 gene. The same gene conversion existed in the genomic DNA, indicating that the replacement was not a cloning artifact. Based on the gene structure of the allele (CYP2A6*1B), this variant was thought to be one of the causal alleles responsible for overestimation of heterozygotes for CYP2A6*4C and CYP2A6* A. To investigate this further, we developed a genotyping method which could distinguish the CYP2A6*A, CYP2A6*1B and CYP2A6*4C alleles from each other. The results clearly showed that CYP2A6*1B was the sole allele responsible for the overestimation. We conclude that the new genotyping method allows determination of six genotypes of the CYP2A6 gene, simultaneously and precisely, in both Oriental and Caucasian populations.

3' Untranslated Regions↗
PubMed2000

Higher incidence of elevated body temperature or increased C-reactive protein level in asthmatic children showing transient reduction of theophylline metabolism.

The authors investigated whether theophylline metabolism is decreased in asthmatic patients and what condition may be related to its reduction. Fifty-two children with asthma were given 15 mg/kg/day aminophylline intravenously at a constant rate. Blood and spot urine samples were collected at 24 hours, 48 hours, and 72 hours after beginning infusion. The ratio of plasma theophylline concentration at 72 hours to that at 24 hours (C72h/C24h) varied from 0.42 to 1.51 (average 0.894). Plasma theophylline concentration of patients with lower C72h/C24h than average reduced significantly, while the concentration of those with higher C72h/C24h remained unchanged. The urinary ratio of the sum of the metabolites to theophylline was significantly increased in the patients with the lower ratio. Among the demographic characteristics examined, significant difference was found only in the incidence of patients with C-reactive protein (CRP) of 0.5 mg/dl or greater or patients with a fever of 37.5 degrees C or greater when admitted. Acute febrile illness accompanied by increased CRP level may affect theophylline metabolism.

Adolescent↗
PubMed1999

Multiple cytochrome P-450 subfamilies are co-induced with P-glycoprotein by both phenothiazine and 2-acetylaminofluorene in rats.

We studied the effects of two P-glycoprotein (P-gp) inducers, 2-acetylaminofluorene (2-AAF) and phenothiazine (PTZ), administered intraperitoneally, on the activities and content of hepatic cytochrome P-450 (CYP) subfamilies in hepatic microsomes of Sprague-Dawley rats. After 4-day administration of 2-AAF or PTZ, the P-gp content was increased. The total CYP content after PTZ treatment was significantly increased compared with that of controls. The CYP1A, CYP2B and CYP3A2 contents were induced, while the CYP2C6, CYP2C11 and CYP2E1 contents remained unaffected. A marked increase in CYP1A1 was found after administration of each compound. Ethoxyresorufin O-deethylase, pentoxyresorufin O-deethylase, and testosterone 6beta hydroxylation activities showed a significant increase after both 2-AAF and PTZ treatments. In particular, ethoxyresorufin O-deethylase exhibited more than ten times greater activity than that of the controls after the treatments. These results suggest that P-gp inducers affect several CYP subfamilies in addition to CYP3A, which is reported to be up-regulated coordinately with P-gp by a CYP3A inducer.

2-Acetylaminofluorene↗
PubMed1999

No ethnic difference between Caucasian and Japanese hepatic samples in the expression frequency of CYP3A5 and CYP3A7 proteins.

Ethnic differences in the pharmacokinetics of nifedipine, a substrate of CYP3A, and in CYP3A7 expression have been reported. The aim of the present study was to measure the protein levels of CYP3A4, CYP3A5, and CYP3A7 and nifedipine oxidation activity in hepatic microsomes from 15 Caucasian and 15 Japanese patients for comparison between the two ethnic groups. Nifedipine oxidation activity and CYP3A4 protein level were well correlated. No significant difference between Caucasian and Japanese microsomal samples was found in nifedipine oxidation activity or in the CYP3A4 protein level. CYP3A5 was detected in 6 of 15 Caucasian samples and in 5 of 15 Japanese samples, but no ethnic difference was found in either the frequency of expression or its protein level. CYP3A7 was found in 10 of 15 Caucasian samples and in 14 of 15 Japanese samples. Although the estimated CYP3A7 protein level was higher in the Japanese than in the Caucasian samples, its protein level was much lower than that of CYP3A4. These results imply that the contribution of CYP3A5 or CYP3A7 to the purported Caucasian-Japanese ethnic difference in the overall CYP3A activity seems to be small.

Adolescent↗
PubMed1999

Carbamazepine induces multiple cytochrome P450 subfamilies in rats.

We compared the effect of three different doses (30, 60, and 100 mg/kg) of carbamazepine (CBZ) administered intraperitoneally for 1, 3, and 7 days on the activity and protein content of hepatic cytochrome P450 (CYP) subfamilies in Sprague-Dawley rats. After 3-day- and 7-day administration with CBZ, the total CYP content had increased in a dose-dependent fashion. Among six enzyme activities examined, only aniline hydroxylase activity remained unchanged after 7-day treatment with CBZ. Pentoxyresorufin O-deethylase activity showed the most significant increase and was induced up to 7 days in a time-dependent fashion. Pretreatment of rats with cycloheximide significantly suppressed the pentoxyresorufin O-deethylase induction by one dose of 100 mg/day CBZ. Immunoblot analysis showed a significant correlation between the protein content of each isoenzyme examined and its activity except CYP2E1 after 7-day treatment with CBZ. Similar results were obtained in the mRNA levels of CYP subfamilies. These results suggested that CBZ may induce multiple CYP subfamilies, except CYP2E1, and the activity and the protein content of CYP2B showed the greatest increase with increased CYP2B mRNA.

Analgesics, Non-Narcotic↗