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Biomedical subjects

K Takada

Publications and source records attributed to K Takada.

At least 253 records · Page 14Linked to original sources
PubMed1997

Cloning and sequencing of the gene encoding the cell surface glycoprotein of Haloarcula japonica strain TR-1.

The triangular disk-shaped halophilic archaeon Haloarcula japonica strain TR-1 has a glycoprotein on its cell surface. The complete gene encoding the cell surface glycoprotein (CSG) was cloned and sequenced. The gene has an open reading frame of 2586 bp, and a potential archaeal promoter sequence approximately 150 bp upstream of the ATG initiation codon. The mature CSG is composed of 828 amino acids and is preceded by a signal sequence of 34 amino acid residues. A hydropathy analysis showed a hydrophobic stretch at the C-terminus, that probably serves as a transmembrane domain. The amino acid sequence of the Ha. japonica CSG showed 52.1% and 43.2% identities to those from the Halobacterium halobium and Haloferax volcanii CSGs, respectively. Five potential N-glycosylation sites were found in the mature Ha. japonica CSG, sites that were distinctly different from those in Hb. halobium and Hf. volcanii. The Ha. japonica CSG gene was expressed in Escherichia coli.

Amino Acid Sequence↗
PubMed1997

Growth and differentiation of periodontal ligament-derived cells in serum-free defined culture.

We have developed a serum-free medium for the growth and differentiation of periodontal ligament-derived cells (PLC). In addition, the expression of both fibroblast growth factor (FGF) and FGF receptor (FGFR) in the PLC was investigated by immunohistochemical examination, heparin affinity chromatography (HAC), and reverse transcription-polymerase chain reaction (RT-PCR) analysis. Optimal growth of the cells was achieved in Iscove's modified Dulbecco's medium supplemented with insulin, transferrin, 2-mercaptoethanol, 2-ethanolamine, sodium selenite, and oleic acid in type-I collagen-coated dishes. Both FGF-1 and FGF-2 stimulated cell growth and inhibited differentiation as measured by inhibition of alkaline phosphatase activity of the cells. An immunohistochemical analysis of FGF-1 and FGF-2 revealed that immunoreactive FGF-1 and FGF-2 were detected predominantly in the cytoplasm of growing cells. In addition, perinuclear FGF-1 staining and nuclear FGF-2 staining were observed in the same growing cells. In contrast, a faint diffuse staining of FGF-1 and FGF-2 was detected in cytoplasm of the confluent differentiated cells. The 2.15 M NaCl eluate from HAC of the cell extracts exhibited growth-promoting activities for the PLC, and it also stimulated the growth of human umbilical vein-derived endothelial cells and inhibited binding of [125I]-FGF to its receptors, indicating the cells produced FGFs or FGF-like growth factors. RT-PCR analysis revealed that the cells expressed FGFR-1 mRNA but not mRNAs for FGFR-2, FGFR-3 and FGFR-4 mRNA. These results suggest that the FGF-FGFR-1 system plays an important role in the growth and differentiation of periodontal ligament-derived cells.

Alkaline Phosphatase↗
PubMed1997

Endoscopic and pathologic features of Epstein-Barr virus-associated gastric carcinoma.

BACKGROUND: Although the presence of Epstein-Barr virus has been documented in approximately 7% of patients with gastric carcinoma, the clinical features of Epstein-Barr virus-associated carcinoma have not been well documented. We studied the histologic and endoscopic characteristics of Epstein-Barr virus-associated gastric carcinoma. METHODS: We tested 124 gastric carcinomas from 117 patients using in situ hybridization for Epstein-Barr virus encoded small RNA1. The histologic and endoscopic findings in the Epstein-Barr virus-associated groups and the negative control groups were analyzed and compared. RESULTS: Twelve tumors (9.7%) were identified as Epstein-Barr virus associated. These lesions were located mainly in the upper part of the stomach (p < .05) and had a diffuse-type histology (p < .05) compared with those in the control group. Six of seven (85.7%) early Epstein-Barr virus-associated lesions were type 0 IIc (superficial depressed) or a combined type, and 42.9% were accompanied by submucosal nodules of carcinoma with lymphoid stroma. Four of five (80%) advanced Epstein-Barr virus-associated tumors were type 3 (ulcerated without definite limits), thought to be the advanced shape of superficial depressed lesions. CONCLUSIONS: Epstein-Barr virus-associated gastric carcinomas often appear as superficial depressed or ulcerated lesions in the upper part of the stomach and have a diffuse-type histology with lymphoid infiltration.

Adult↗
PubMed1997

Assessment of the carcinogenicity of stevioside in F344 rats.

The carcinogenic potential of stevioside, a compound that is used as a sweetener for food and drink, was examined in F344 rats of both sexes. Stevioside was added to powdered diet at concentrations of 0 (control), 2.5 and 5%. The doses were selected on the basis of results from a 13-wk subchronic toxicity study and administered to groups of 50 male and 50 female rats ad lib. for 104 wk. All surviving rats were killed at wk 108. Body weight gains were slightly depressed in line with the dose of stevioside, in both sexes, and a significant decrease in the final survival rate was observed for the 5% treated males. Histopathologically, however, there was no significantly altered development of neoplastic or non-neoplastic lesions attributable to the stevioside treatment in any organ or tissue, except for a decreased incidence of mammary adenomas in females and a reduced severity of chronic nephropathy in males. It is concluded that stevioside is not carcinogenic in F344 rats under the experimental conditions described.

Administration, Oral↗
PubMed1997

Lack of carcinogenicity of medium-viscosity liquid paraffin given in the diet to F344 rats.

The carcinogenicity of medium-viscosity liquid paraffin was examined in Fischer 344 rats. Groups of 50 males and 50 females were given the material at dietary doses of 0 (control), 2.5 or 5% for 104 wk. Slight increases in food consumption and body weight were observed in both sexes of the 5% group. However, no significant differences between the control and treated groups were noted with regard to clinical signs, mortality and haematology findings. A variety of tumours developed in all groups, including the control group, but all the neoplastic lesions were histologically similar to those known to occur spontaneously in F344 rats, and no statistically significant increase in the incidence of any tumour type was found for either sex in the treated groups. Granulomatous inflammation in the mesenteric lymph nodes, considered to be a reaction to paraffin absorption, was observed with similar incidence and severity in both sexes of the 2.5 and 5% groups. Thus, it is concluded that under the present experimental conditions, the high dose, about 2000-200,000 times higher than the current temporary acceptable daily intake, does not have any carcinogenic potential in F344 rats. Furthermore, granulomatous inflammation observed in mesenteric lymph nodes were not associated with any development of neoplastic lesions.

Administration, Oral↗
PubMed1997

Changes in jaw movement and jaw closing muscle activity after orthodontic correction of incisor crossbite.

The possible influences of the direction of occlusal loading delivered to the incisors in the sagittal direction during chewing on jaw movement and jaw closing muscle activity were investigated. Ten healthy children with crossbite of one or two incisors on the right side were selected. Each subject chewed a piece of chewing gum on the right side, and jaw displacements and electromyographic signals from the posterior temporalis and superficial masseter muscles on the ipsilateral side were sampled simultaneously. After orthodontic correction of the incisor crossbite relationship, identical records were taken. The inclinations of the gliding contacts for each posterior tooth in the lateral jaw excursion position were consistent before and after the treatment. The posttreatment records showed broader jaw movement patterns in the frontal view and faster jaw movement velocity in the lateral direction at a level close to the habitual maximum intercuspation position, when compared with the pretreatment records (P < 0.05). The duration of the muscle activity and the incidence of the silent periods of the masseter muscle during chewing significantly decreased after the treatment (P < 0.05). The current results give a neurophysiologic rationale for explaining the significance of orthodontic treatment in improving lowered masticatory efficiency in the way that the change in direction of the occlusal load achieved by tooth movement influences on the periodontal sensory input, which, in turn, modifies the trigeminal motor output and thus, eventually, jaw muscle activities.

Bite Force↗
PubMed1997

Glutathione-doxorubicin conjugate expresses potent cytotoxicity by suppression of glutathione S-transferase activity: comparison between doxorubicin-sensitive and -resistant rat hepatoma cells.

The cytotoxic mechanism of a conjugate of doxorubicin (DXR) and glutathione (GSH) via glutaraldehyde (GSH-DXR) was investigated using DXR-sensitive (AH66P) and -resistant (AH66DR) rat hepatoma cells. GSH-DXR accumulated in AH66DR cells as well as in AH66P cells without efflux by P-gp and exhibited the potent cytocidal activity against both cells compared with DXR. To examine whether thiol from GSH-DXR affected the expression of cytotoxicity, two conjugates of DXR, with modified peptides containing alanine or serine substituted for cysteine in GSH were prepared and their cytotoxicities determined. Substitution of these amino acids for cysteine resulted in an approximately two- to fourfold reduction in cytotoxic activity against both cell lines compared with the effect of GSH-DXR. Depletion of intracellular GSH by treatment of both cells with buthionine sulphoximine did not change the cytotoxic activity of DXR, BSA-DXR or GSH-DXR. By co-treating the cells with tributyltin acetate, an inhibitor of glutathione S-transferase (GST), and either DXR, BSA-DXR or GSH-DXR, the cytotoxicity was markedly increased. Interestingly, GSH-DXR showed non-competitive inhibition of GST activity and its IC50 value was 1.3 microM. These results suggested that the inhibition of GST activity by GSH-DXR must be an important contribution to the expression of potent cytotoxicity of the drug.

Animals↗
PubMed1997

The involvement of pertussis toxin-sensitive G proteins in the post receptor mechanism of central I1-imidazoline receptors.

1. To elucidate the possible involvement of pertussis toxin (PTX)-sensitive G proteins in the post receptor mechanism of alpha 2-adrenoceptors and imidazoline receptors, we examined the effect of pretreatment of the central nervous system with PTX on the antidysrhythmic effect of dexmedetomidine, a selective alpha 2-adrenoceptor agonist, and rilmenidine, a selective I1-imidazoline receptor agonist on halothane-adrenaline dysrhythmias in rats. 2. Dexmedetomidine (0, 1.0, 2.0, 5.0 micrograms kg-1 min-1.i.v.) and rilmenidine (0, 1.0, 3.0, 10, 20 micrograms kg-1, i.v.) prevented the genesis of halothane-adrenaline dysrhythmias in a dose-dependent fashion. Both idazoxan (10, 20 micrograms kg-1, intracerebroventricularly (i.c.v.)), an alpha 2-adrenoceptor antagonist with high affinity for imidazoline receptors, and rauwolscine, (40 micrograms kg-1, i.c.v.), an alpha 2-adrenoceptor antagonist with low affinity for imidazoline receptors inhibited the action of dexmedetomidine (5.0 micrograms kg-1, min-1, i.v.), but the inhibitory potency of idazoxan was much greater than that of rauwolscine. While the pretreatment with PTX (0.1, 0.5, 1.0 micrograms kg-1, i.c.v.) did not change the dysrhythmogenecity of adrenaline, this treatment completely blocked the antidysrhythmic property of rilmenidine (20 micrograms kg-1, i.v.) as well as dexmedetomidine (5.0 micrograms kg-1 min-1, i.v.). 3. It is suggested that central I1-imidazoline receptors as well as alpha 2-adrenoceptors may be functionally coupled to PTX-sensitive G proteins.

Adrenergic alpha-2 Receptor Agonists↗
PubMed1997

Case report: dentofacial orthopedic and surgical orthodontic treatment in hemifacial microsomia.

The patient showed bilateral agenesis of the mandibular condyle and glenoid fossa, rare features of hemifacial microsomia. The patient was treated with functional appliances to modify mandibular growth during active facial growth. After the pubertal growth spurt, treatment included rotational advancement of the mandible combined with alloplastic reconstruction of the condylar process and glenoid fossa.

Child↗
PubMed1997

Pain and other cardinal TMJ dysfunction symptoms: a longitudinal survey of Japanese female adolescents.

Longitudinal data were obtained for 4 years from 361 Japanese high school girls between the ages of 12 and 16. The data were analysed for the occurrence of pain and its associations with the occurrence of other cardinal TMJ dysfunction symptoms and occlusal states. It was determined that even if pain or noise or jaw-deviation symptoms appeared, those symptoms did not necessarily last thereafter. The symptoms were not persistent but rather appeared and disappeared repetitively. Those who exhibited noise during at least one of the surveys of the 4-year survey period showed a significantly higher prevalence of pain than those who did not exhibit noise at all (P < 0.05). Those who exhibited noise by the age of 13 showed a significantly higher prevalence of pain than those who exhibited noise after age 14 (P < 0.1). The temporal occurrence of pain depended upon the appearance of noise and the age at which noise first appeared. On the other hand, the occurrence of pain symptoms was not necessarily related to specific types of malocclusions, which suggests the significance of multifactorial contributions in understanding the aetiology of pain rather than the occlusal factor.

Adolescent↗
PubMed1997

Drug conjugate of doxorubicin with glutathione is a potent reverser of multidrug resistance in rat hepatoma cells.

A recent study has suggested that degraded adducts smaller than 2 kDa in molecular weight of bovine serum albumin (BSA)-conjugated doxorubicin (DXR) (BSA-DXR) might exhibit cytotoxicity against multidrug resistant (MDR) cells. To investigate this notion further, intracellular accumulation and cytotoxicity of DXR coupled to several small peptides, such as glycylglycine (diGly), glycylglycylglycine (triGly), reduced glutathione (GSH) and oxidized glutathione (GSSG), were investigated using DXR-sensitive (AH66P) and DXR-resistant (AH66DR) rat hepatoma cell lines. Against both AH66P and AH66DR cells, diGly-conjugated DXR (diGly-DXR) and triGly-conjugated DXR (triGly-DXR) demonstrated the same cytotoxic activity as DXR, and the accumulation of both conjugates in the two cell lines was almost similar to that of DXR. After treatment of AH66DR cells with 5 microM verapamil [an inhibitor of P-glycoprotein (Pgp)], the intracellular levels of diGly-DXR and triGly-DXR were markedly increased and consequent cytotoxicity was improved. On the other hand, GSH-conjugated DXR (GSH-DXR) showed 9- and 7.5-fold more cytotoxic activity than BSA-DXR against AH66P and AH66DR cells, respectively. GSH-DXR accumulated rapidly in AH66DR cells, probably by the same mechanism as in AH66P cells, because the treatment of AH66DR cells with verapamil did not cause a significant increase in the intracellular drug level as compared with that in cells treated without verapamil. The levels of cytotoxicity and accumulation of GSSG-DXR were the same as those of BSA-DXR for both cell lines. These results indicate that GSH-DXR exerts potent cytotoxicity against both cell lines among the peptide DXR conjugates examined because of the rapid uptake and high accumulation of GSH-DXR similar to that of DXR without efflux.

Animals↗
PubMed1997

Immunohistochemical localization of fibroblast growth factor-1 (FGF-1), FGF-2 and fibroblast growth factor receptor-1 (FGFR-1) in pleomorphic adenoma of the salivary glands.

Fibroblast growth factor-1 (FGF-1) and FGF-2 are heparin-binding polypeptides that are potent mitogens for neoplastic cells. In this study, fibroblast growth factor-1 (FGF-1), FGF-2, and fibroblast growth factor receptor-1 (FGFR-1) were immunohistochemically analyzed in 10 patients with pleomorphic adenoma of the salivary gland by using specific monoclonal antibodies. The tumor tissues were histopathologically classified as: tubular, solid, myxoid or chondroid. Both FGF-1 and FGF-2 were immunohistochemically identified in the tumor cells of all histological types. In addition, immunoreactive FGF-2 was also found in the basement membrane of tubular type tumor cells. Conversely, FGFR-1-positive tumor cells were essentially confined to the tubular and solid areas of tumors. Tumor cells in the myxoid and chondroid areas were FGFR-1 immunonegative. These results suggest that the co-expression of FGF and its receptor appears to be related to the proliferative activity of tumor cells in the tubular and solid areas, whereas loss of FGF receptor expression may be associated with the differentiation of tumor cells into myxoid and chondroid tissue types.

Adenoma, Pleomorphic↗
PubMed1997

Biodistribution of cyclosporin encapsulated in liposomes modified with bioadhesive polymer.

The purpose of this investigation was to study the possibility of renewing the immunosuppressive activity of cyclosporin by formulating the compound in liposomes modified with bioadhesive polymers. The liposomes prepared were evaluated both pharmacokinetically and pharmacodynamically. Tissue distribution and plasma pharmacokinetics of cyclosporin and model dye, sudan black, which is as hydrophobic as cyclosporin, were studied in rats after intravenous infusion (10 mg kg-1). The immunosuppressive efficacy of liposomal cyclosporin preparations was studied in the allogenic rat-heart-transplantation model, where cyclosporin therapy (10 mg kg-1) continued for one week. The entrapment of sudan black in liposomes modified with bioadhesive polymers resulted in higher sudan black delivery to the spleen and the liver than with standard sudan-black-loaded liposomes. Among the modified liposomes, those modified with carbopol 941 showed the most remarkable enhancing effect on the delivery of sudan black to these organs and total plasma clearance of sudan black decreased to 38.6 +/- 7.8 mL h-1 kg-1 (standard liposomes, 58.9 +/- 6.4 mL h-1 kg-1). Delivery of cyclosporin to the spleen and the liver was increased approximately twofold by modifying the liposomes with carbopol 941. In the preliminary study on the allogenic rat-heart-transplantation model, the mean survival days of the graft were 18.8 +/- 2.9 days for the group receiving cyclosporin liposomes modified with carbopol 941, 14.2 +/- 4.4 days for the group receiving standard cyclosporin liposomes and 7.6 +/- 0.5 days for the group receiving cyclosporin solution. The encapsulation of cyclosporin in liposomes modified with bioadhesive polymer enhanced the residence time of cyclosporin in the systemic circulation, resulting in approximately twofold greater delivery of cyclosporin to the spleen and liver. However, in the allogenic rat-heart-transplantation model no significant difference was detected between the immunosuppressive efficacy of cyclosporin encapsulated in bioadhesive polymer-modified liposomes and that encapsulated in standard liposomes.

Acrylic Resins↗
PubMed1997

Oral sustained-release cisplatin preparation for rats and mice.

A new oral sustained-release solid-dispersion preparation of cisplatin (cis-diamminedichloroplatinum(II): cisplatin) has been developed for administration to small experimental animals such as mice. This preparation was obtained by formulating cisplatin with the water-insoluble polymer ethylcellulose and with stearic acid in different ratios. In-vitro dissolution studies showed that cisplatin release characteristics were zero-order for the formulation cisplatin-ethylcellulose-stearic acid (1:10:5) and levels equilibrated 7 h after the start of the experiment. The availability of cisplatin from this preparation was evaluated both in rats and mice. The cisplatin preparation (20 mg kg-1) was administered orally to rats and the resulting curve of serum cisplatin levels against time was compared with that obtained after intravenous infusion (20 mg kg-1) to rats. By comparing the areas under serum concentration-time curves (AUCs), the bioavailability of cisplatin was estimated to be 31%. The mean residence time (MRT) of cisplatin solid dispersion was 6.13 +/- 0.43 h, whereas the MRT of cisplatin administered by intravenous infusion was 3.89 +/- 0.05 h. Serum cisplatin levels were maintained above 0.3 mg mL-1 (believed from our clinical studies to be the minimum effective concentration) for 24 h. The curve of serum cisplatin level against time suggested that cisplatin was released from the solid dispersion preparation in a sustained-release fashion. Similar levels were also maintained in mice for 24 h. The MRT of the cisplatin preparation was 10-16 h in mice, which is longer than that obtained after oral administration of the physical mixture. The serum free-cisplatin concentration was determined to be 0.10 mg mL-1 in mice serum in which the total cisplatin concentration was 0.30 mg mL-1. The free fraction of cisplatin in mice serum was the same as that in human patient serum. Pathological examination showed that this new sustained-release oral cisplatin preparation did not have any side effects on the gastrointestinal tract. These results suggest usefulness of this new solid-dispersion preparation for oral cisplatin therapy in lung cancer patients.

Administration, Oral↗
PubMed1997

Spontaneous establishment of an Epstein-Barr virus-infected fibroblast line from the synovial tissue of a rheumatoid arthritis patient.

An Epstein-Barr virus (EBV)-infected fibroblast line, designated DSEK, was spontaneously established from synovial tissue of a patient with rheumatoid arthritis (RA). DSEK cells expressed EBV nuclear antigens EBNA-1 and EBNA-2 and latent membrane protein LMP-1. Cell surface markers of DSEK cells were similar to those of EBV-negative fibroblast clones derived from synoviocytes and were negative for lymphocyte and macrophage markers. DSEK cells expressed CD44, CD58, and HLA-DR antigens and spontaneously produced interleukin-10 basic fibroblast growth factor and transforming growth factor beta1. These results indicate that rheumatoid synoviocytes can be a target for EBV infection and suggest that EBV may play a role in the pathogenesis of RA.

Arthritis, Rheumatoid↗
PubMed1997

Epstein-Barr virus infection of human gastric carcinoma cells: implication of the existence of a new virus receptor different from CD21.

Recombinant Epstein-Barr virus (EBV) with a selectable marker successfully infected the human gastric carcinoma cell lines AGS, MKN28, and MKN74. Following incubation in selective media, drug-resistant cell clones were isolated and proved to be infected with EBV. All gastric carcinoma cell clones were positive for EBNA 1 but negative for EBNA 2. LMP 1 expression was negative in most clones, but there were a few exceptions. Gastric carcinoma cells were negative for the EBV receptor CD21, and infection was not inhibited by pretreatment of cells with the anti-CD21 monoclonal antibody OKB7. The results indicate that gastric carcinoma cells are susceptible to EBV infection and that infection is mediated via a new receptor different from CD21.

Cell Line↗
PubMed1997

Regulation of masticatory force during cortically induced rhythmic jaw movements in the anesthetized rabbit.

To examine the relationships between masticatory force, electromyogram (EMG) of masticatory muscles, and jaw movement pattern, we quantitatively evaluated the effects of changing hardness of a chewing substance on these three variables. Cortically induced rhythmic jaw movements of a crescent-shaped pattern were induced by electrical stimulation of the cerebral cortical masticatory area in the anesthetized rabbit. The axially directed masticatory force was recorded with a small force-displacement transducer mounted on the ground surface of the lower molars. EMGs were recorded from the masseter and digastric muscles simultaneously with jaw movements. Five test strips of polyurethane foam of different hardness were prepared and inserted between the upper molar and the transducer during the movements. The peak, impulse, and buildup speed of the masticatory force increased with strip hardness, whereas duration of the exerted force did not vary with strip hardness. The integrated activity and duration of the masseteric EMG bursts also increased with strip hardness. The integrated EMG activity of the digastric bursts was weakly related to strip hardness, whereas the duration was not. The minimum gape increased with strip hardness, but the maximum gape did not. The horizontal excursion of the jaw did not vary in a hardness-dependent manner, although it was greater in the cycles with strip application than in the cycles without strip application. Deprivation of periodontal sensation by cutting the nerves to the teeth reduced the buildup speed of the force, maximum gape, net gape, and horizontal jaw movements. The denervation also elongated the force duration and that of masseteric EMG bursts. However, the rate of the hardness-dependent changes in the above parameters did not alter after denervation. The latency of the masseteric EMG response to strip application was evaluated before and after denervation. In both conditions, it was > or = 6 ms in approximately 70% of the cycles and <6 ms in the remaining approximately 30%, which cannot be explained by a simple reflex mechanism. On the basis of the analysis of correlation coefficients, the masseteric integrated EMG seemed to be a good indicator of the peak and impulse of the masticatory force both before and after denervation. We conclude that periodontal afferents would be responsible for a quick buildup of masticatory force and that afferents other than those from periodontal tissue would contribute to the hardness-dependent change of masticatory force during cortically induced rhythmic jaw movements.

Animals↗