Biomedical subjects

K Terasawa

Publications and source records attributed to K Terasawa.

At least 55 records · Page 3Linked to original sources

PubMed2000

Enhanced expression of inducible nitric oxide synthase by Juzen-taiho-to in LPS-activated RAW264.7 cells, a murine macrophage cell line.

We have investigated the effect of Juzen-taiho-to (TJ-48) on inducible NO synthase (iNOS) expression and nitric oxide (NO) production in RAW264.7 cells, a murine macrophage cell line. TJ-48-lipopolysaccharide (LPS) combination induced iNOS mRNA expression earlier, stronger and remained longer that paralleled but with a higher NO production compared to LPS stimulation. TJ-48 itself showed no inducible effect either on NO production or iNOS mRNA expression. This phenomenon could be considered to contribute, at least in part, to the beneficial effects of TJ-48 through the iNOS-mediated activation of biodefense mechanism.

Animals↗

PubMed2000

Differential effect of antiallergic drugs on IgE-mediated cutaneous reaction in passively sensitized mice.

We investigated the effect of several antiallergic agents on murine IgE-mediated biphasic cutaneous reaction. Mice were passively sensitized by an intravenous injection of monoclonal anti-dinitrophenol (anti-DNP) IgE antibody. Skin reaction was elicited by an epicutaneous challenge of dinitrofluorobenzene (DNFB) and occurred biphasically with immediate-phase response (IPR) and late-phase response (LPR) at 1 and 24 h, respectively. Classical histamine H1 receptor antagonists and some chemical mediator-release inhibitors, such as diphenhydramine and terfenadine, inhibited IPR, but not LPR. In contrast, leukotriene B(4) (LTB(4)) receptor antagonist (ONO-4057) inhibited LPR only. Antagonists for LTC(4), D(4), E(4) receptor (ONO-1078) and platelet-activating factor (PAF) receptor (Y-24180) significantly inhibited both IPR and LPR, similarly to prednisolone. We recently found that a third-phase inflammatory reaction with marked infiltration of eosinophils (named very-late-phase response; vLPR), which is supposed to be a more important reaction in allergic diseases, was induced, peaking at day 8 following IPR and LPR in this model. The effect of these drugs on the triphasic skin reaction can be scored based on efficacy against IPR / LPR / vLPR; +/+/+ (prednisolone, a PAF receptor antagonist Y-24180, cyclosporin A and FK-506), +/-/- (diphenhydramine), +/+/- (azelastine and LT receptor antagonist ONO-1078), and -/+/+ (an LTB(4) receptor antagonist ONO-4057). Thus the inhibitory effect on vLPR as well as LPR may relate to the inhibition of eosinophil function mediated by LTB(4) and PAF and/or T cells. These findings may provide the basis for a treatment modality using various antiallergic agents in allergic disease.

Animals↗

PubMed1999

Inhibitory effect of Ephedrae herba, an oriental traditional medicine, on the growth of influenza A/PR/8 virus in MDCK cells.

Using several herbal extracts, we investigated whether certain Kampo medicines exert an inhibitory effect on the acidification of intracellular compartments such as endosomes and lysosomes (referred to as ELS), and thereby inhibit the growth of influenza A virus in Madin-Darby canine kidney cells. The vital fluorescence microscopic study showed that the extract of Ephedrae herba (EHext) among five herbal extracts inhibited acidification of endosomes and lysosomes in a concentration-dependent manner (100-400 microg/ml). Moreover the growth of influenza A/PR/8/34 (H1N1) (PR8) virus was inhibited when the cells were treated with EHext for 1 h immediately after infection, or treated as early as 5-10 min after infection. Conversely, virus growth resumed concomitantly with the reappearance of acidified ELS after removal of EHext. The fact that the inhibitory effect of EHext was completely or partially reversed by FeCl3, a tannin-reactive agent, strongly suggests that tannin is one of the active components in the extract.

Animals↗

PubMed1999

Effect of Shimotsu-to (a Kampo medicine, Si-Wu-Tang) and its constituents on triphasic skin reaction in passively sensitized mice.

Previous studies have reported that mice passively sensitized with anti-DNP (dinitrophenol) IgE antibody exhibited IgE-mediated skin reaction with an immediate phase response (IPR) at 1 h and a late phase response (LPR) at 24 h after the challenge of DNFB (dinitrofluorobenzene). We recently found that a third phase inflammatory reaction with intense and persisting infiltration of eosinophils, named very late phase response (vLPR), was induced by DNFB challenge peaking at 8 days. In this study, we examined the effects of a Kampo medicine, Shimotsu-to (Si-Wu-Tang), and its constituent crude drugs on triphasic skin reaction in passively sensitized mice. Shimotsu-to inhibited ear swelling in LPR and vLPR after DNFB challenge in a dose-dependent manner, and slightly diminished the scratching behavior considered to be associated with pruritus in IPR. The inhibitory effect on LPR and vLPR was partly due to Cnidii Rhizoma (Senkyu) in Shimotsu-to formulation, especially its fraction 5 containing cnidilide. On the other hand, Angelicae Radix (Toki) rather than Cnidii Rhizoma (Senkyu) in Shimotsu-to, inhibited the scratching behavior, although it did not inhibit the ear swelling in IPR. These findings indicate that the Shimotsu-to formulation is useful for the inhibition of cutaneous inflammatory diseases.

Animals↗

PubMed1999

Application of real-time radiation dosimetry using a new silicon LET sensor.

A new type of real-time radiation monitoring device, RRMD-III, consisting of three double-sided silicon strip detectors (DSSDs), has been developed and tested on-board the Space Shuttle mission STS-84. The test succeeded in measuring the linear energy transfer (LET) distribution over the range of 0.2 keV/micrometer to 600 keV/micrometer for 178 h. The Shuttle cruised at an altitude of 300 to 400 km and an inclination angle of 51.6 degrees for 221.3 h, which is equivalent to the International Space Station orbit. The LET distribution obtained for particles was investigated by separating it into galactic cosmic ray (GCR) particles and trapped particles in the South Atlantic Anomaly (SAA) region. The result shows that the contribution in dose-equivalent due to GCR particles is almost equal to that from trapped particles. The total absorbed dose rate during the mission was 0.611 mGy/day; the effective quality factor, 1.64; and the dose equivalent rate, 0.998 mSv/day. The average absorbed dose rates are 0.158 mGy/min for GCR particles and 3.67 mGy/min for trapped particles. The effective quality factors are 2.48 for GCR particles and 1.19 for trapped particles. The absorbed doses obtained by the RRMD-III and a conventional method using TLD (Mg(2)SiO(4)), which was placed around the RRMD-III were compared. It was found that the TLDs showed a lower efficiency, just 58% of absorbed dose registered by the RRMD-III.

Calibration↗

PubMed1999

Telomerase activity in malignant ovarian tumors with deregulation of cell cycle regulatory proteins.

Using a semiquantitative telomeric repeat amplification protocol assay, telomerase-positive frequencies and enzyme levels were measured. Out of 95% of 49 human ovarian tumors, the highest level of telomerase activity was observed in malignant tumors. Furthermore, by immunohistochemical staining of cell cycle regulatory proteins (pRB, p16, cyclin D1, cyclin E and p53) at the G1 checkpoint, we evaluated the relation between each protein alterations and the levels of telomerase activity. We could not demonstrate a clear relation with each molecule except for cyclin E, but suggesting that aberrant accumulation of these proteins was considered as a reason for telomerase deregulation, which may play an essential role in the pathway of telomerase regulation.

Adult↗

PubMed1999

Keishi-bukuryo-gan prevents the progression of atherosclerosis in cholesterol-fed rabbit.

In this study, we examined whether in vivo keishi-bukuryo-gan (a Kampo formulation) could prevent the progression of atherosclerosis in cholesterol-fed rabbits, an animal model for hypercholesterolaemia. Sixteen male Japanese white rabbits (2 kg body weight) were divided into two groups. Group A (n = 8) was fed standard rabbit chow containing 1% cholesterol for 8 weeks. Group B (n = 8) was fed standard rabbit chow containing 1% cholesterol and 1% keishi-bukuryo-gan for 8 weeks. At the end of the experiment, average plasma concentrations of total-cholesterol and IDL-cholesterol were 2055.9 +/- 201.8 mg/dL and 408.1 +/- 62.6 mg/dL in group A and 1950.5 +/- 126.3 mg/dL and 407.6 +/- 56.6 mg/dL in group B, respectively. The percentage of the surface area of the total thoracic aorta with visible plaque was significantly reduced by keishi-bukuryo-gan administration; group A was 33.2% +/- 5.3% and group B was 14.3% +/- 2.9%. beta-very low density lipoprotein (VLDL) and low density lipoprotein (LDL) isolated from cholesterol fed rabbits treated with keishi-bukuryo-gan (group B) were shown to be highly resistant to oxidative modification by cupric ion. Sera isolated from rabbits administered keishi-bukuryo-gan had reduced lipid peroxide formation compared with those from rabbits without keishi-bukuryo-gan. Thus, keishi-bukuryo-gan prevents the progression of atherosclerosis in cholesterol-fed rabbits in vivo by limiting oxidative LDL modification.

Animals↗

PubMed1999

Effect of Choto-san, a kampo medicine, on impairment of passive avoidance performance in mice.

In mice with procephalic ischaemia loading, disrupted passive avoidance retention performance was dose-dependently improved by Choto-san, but this effect was antagonized by NAN-190, a serotonin1A receptor antagonist. In mice with decreased intracerebral serotonin concentration, Choto-san prevented disturbance in acquiring a passive avoidance response after scopolamine administration, but did not influence the decreased serotonin concentration. These results suggested that Choto-san showed the anti-amnestic effect based on the stimulation of serotonin1A receptors.

Animals↗

PubMed1999

Effect of extract prepared from the roots of Paeonia lactiflora on endothelium-dependent relaxation and antioxidant enzyme activity in rats administered high-fat diet.

This study examined the effect of Paeoniae Radix (PR) on endothelial function and the activity of superoxide dismutase (SOD) of erythrocytes in rats administered a high-fat diet. Administration of the extract of PR increased the endothelium-dependent relaxation and the activities of SOD compared with high the cholesterol diet group significantly. Hypercholesterolaemia induced an increase of endothelial superoxide anion and endothelial dysfunction. Paeoniae Radix is suggested to have a protective effect on endothelial cells and their function.

Animals↗

PubMed1999

Efficacy of Choto-san on vascular dementia and the protective effect of the hooks and stems of Uncaria sinensis on glutamate-induced neuronal death.

Two different multicenter studies on the efficacy of Choto-san on patients with vascular dementia, one a well-controlled but non-double blind (60 patients), the other a double-blind controlled study (139 patients), were performed. In the well-controlled study, Choto-san was superior in global improvement rating, utility rating and improvement of subjective symptoms, psychiatric symptoms and disturbance in daily living activities. In the double-blind study, with more objective criteria than the well-controlled study, Choto-san was also superior in global improvement rating, utility rating and improvement of subjective symptoms, psychiatric symptoms and disturbance in daily living activities. These results suggest that Choto-san is effective in the treatment of vascular dementia. Uncaria sinensis (OLIV.) HAVIL. (US) is the main medicinal plant composing Choto-san. Glutamate-induced cell death of cultured cerebellar granule cells was protected by the application of water extract of US in a dose-dependent manner, and concentrations of 10(-5) to 10(-4) g/ml had a significant effect compared to exposure to glutamate only. Further, the increase of 45Ca2+ influx into cells by glutamate was also blocked by the water extract in a dose-dependent manner. These results suggest that US has a protective effect on glutamate-induced neuronal death in cultured cerebellar granule cells through the inhibition of Ca2+ influx.

Activities of Daily Living↗

PubMed1999

Killer-cell inhibitory receptors, CD158a/b, are upregulated by interleukin-2, but not interferon-gamma or interleukin-4.

Although it is now accepted that killer-cell inhibitory receptors (KIRs), which were molecularly cloned in 1995, deliver negative signals to natural killer (NK) cells regarding the recognition of target cells, it is still unclear how the expression of these receptors on lymphocytes is regulated. Therefore, we investigated the regulation of expression of representative KIRs, CD158a and CD158b, by cytokines such as interleukin-2 (IL-2), IL-4 and interferon-gamma (IFN-gamma). Neither IL-4 nor IFN-gamma affected the expression of CD158a/b, but incubation for 48 h with IL-2, which enhances the killer activity of NK cells, upregulated the expression of the KIRs. This upregulation by IL-2 was also observed in CD16-positive cells sorted from total lymphocytes. In contrast, IL-4, which is a down-regulator of IL-2-induced killer responses, did not change the level of CD158a/b expression when added after the IL-2 treatment. These findings suggest that IL-2 plays an important role in the regulation of CD158a/b expression, and might be involved in controlling NK activity via regulating expression of these molecules.

Cells, Cultured↗

PubMed1999

Inhibitory effect of ferulic acid and isoferulic acid on the production of macrophage inflammatory protein-2 in response to respiratory syncytial virus infection in RAW264.7 cells.

We investigated the effect of ferulic acid (FA) and isoferulic acid (IFA), which are the main active components of the rhizoma of Cimicifuga heracleifolia (CH), an anti-inflammatory drug used frequently in Japanese traditional medicine, on the production of macrophage inflammatory protein-2 (MIR-2) in a murine macrophage cell line, RAW264.7, in response to respiratory syncytial virus (RSV) infection. Following the exposure of cells to RSV for 20h, the MIP-2 level in condition medium was increased to about 20 ng/ml, although this level in mock-infected cells was negligible. In the presence of either FA or IFA, RSV-infected cells reduced MIP-2 production in a dose-dependent manner. These data suggest that FA and IFA might be responsible, at least in part, for the anti-inflammatory drug effect of CH extract through the inhibition of MIP-2 production.

Animals↗

PubMed1999

Mutational analysis of beta-catenin gene in Japanese ovarian carcinomas: frequent mutations in endometrioid carcinomas.

To investigate the contribution of the beta-catenin gene to the development of ovarian carcinomas, mutational analysis of exon 3 of the beta-catenin gene was conducted. We analyzed 61 primary ovarian carcinomas, consisting of 49 non-endometrioid-type and 12 endometrioid-type tumors, for genetic alteration of the beta-catenin gene. Five carcinomas showed beta-catenin mutations (S37C, T41I, T41A), including 4 (33%) of 12 endometrioid-type tumors and 1 (14%) of 7 mucinous-type tumors. All of these mutations altered at the serine/threonine residues that are potential sites of GSK3-beta phosphorylation. We detected no carcinomas with interstitial deletion involving exon 3 of beta-catenin. Furthermore, we immunohistochemically studied 27 of the 61 ovarian carcinomas. Both nuclear and cytoplasmic beta-catenin expressions were demonstrated in 4 of the 27 ovarian carcinomas for which tissue samples were available for examination. All 4 cases exhibited mutations in exon 3 of beta-catenin, including a mucinous carcinoma. Our results suggested that beta-catenin gene mutation at potential GSK3-beta phosphorylation sites results in accumulation of beta-catenin protein within the cells and its translocation to nuclei. Accumulated beta-catenin protein may be involved in the development of endometrioid-type ovarian carcinomas, and some mucinous-type ovarian carcinomas.

Adult↗

PubMed1999

Mutational analysis of STK11 gene in ovarian carcinomas.

Recently STK11, the causative gene of Peutz-Jeghers syndrome (PJS) was identified on chromosome 19p13.3. PJS is often accompanied by several malignancies, including breast tumor, adenoma malignum of the uterine cervix, and ovarian tumor. To investigate the involvement of STK11 gene in the development of ovarian carcinomas, we analyzed 30 ovarian carcinomas for loss of heterozygosity (LOH) and STK11 gene mutations. We found one missense mutation (codon 281, Pro to Leu) with heterozygous and somatic status. This mutation occurred at codon 281, which lies within the mutational hot spot (codon 279-281) of STK11 gene previously reported in PJS. We also detected LOH in 2 (11%) of 19 informative ovarian carcinomas. Our results suggest that mutations of the STK11 gene may play a limited role in the development of ovarian carcinomas.

AMP-Activated Protein Kinase Kinases↗

PubMed1999

Effect of Uncariae ramulus et Uncus on endothelium in spontaneously hypertensive rats.

The protective effect of the extract of Uncariae ramulus et Uncus (URE) against endothelium disorder due to hypertension was investigated. We administered low (150 mg/kg/day) and high (450 mg/kg/day) doses of URE orally to spontaneously hypertensive rats for 8 weeks. Endothelium dependent vasodilatation by acetylcholine increased significantly in the high URE group compared with the control group. Endothelium dependent vasocontraction by xanthine oxidase decreased significantly in the high URE group compared with the control group. Serum NO2-/NO3- were tended to increase in the high URE group. It is suggested that URE may have a protective effect for the endothelium against the influence of hypertension.

Acetylcholine↗

PubMed1999

Evaluation of the protective effects of alkaloids isolated from the hooks and stems of Uncaria sinensis on glutamate-induced neuronal death in cultured cerebellar granule cells from rats.

We have previously shown that an aqueous extract of the hooks and stems of Uncaria sinensis (Oliv.) Havil., Uncariae Uncus Cum Ramulusis, protects against glutamate-induced neuronal death in cultured cerebellar granule cells by inhibition of Ca2+ influx. Because it is not known which components of Uncaria sinensis are active, in this study we have evaluated, by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide (MTT) staining, the neuroprotective effects of the oxyindole alkaloids corynoxeine, rhynchophylline, isorhynchophylline and isocorynoxeine, and the indole alkaloids geissoschizine methyl ether, hirsuteine and hirsutine, isolated from the hooks and stems of Uncaria sinensis, on glutamate-induced cell death. We also investigated the inhibitory effects of the compounds on 45Ca2+ influx in cultured rat cerebellar granule cells. Cell viability evaluated by the MTT assay was significantly increased by application of rhynchophylline (10(-3) M), isorhynchophylline (10(-4)-10(-3) M), isocorynoxeine (10(-4)-10(-3) M), hirsuteine (10(-4)-3 x 10(-4) M) or hirsutine (10(-4)-3 x 10(-4) M) compared with exposure to glutamate only, with the effect of isorhynchophylline being the strongest. The increased 45Ca2+ influx into cells induced by glutamate was significantly inhibited by administration of rhynchophylline (10(-3) M), isorhynchophylline (3 x 10(-4)-10(-3) M), isocorynoxeine (3 x 10(-4)-10(-3) M), geissoschizine methyl ether (10(-3) M), hirsuteine (3 x 10(-4)-10(-3) M) or hirsutine (3 x 10(-4)-10(-3) M). These results suggest that oxyindole alkaloids such as isorhynchophylline, isocorynoxeine and rhynchophylline and indole alkaloids such as hirsuteine and hirsutine are the active components of the hooks and stems of Uncaria sinensis which protect against glutamate-induced neuronal death in cultured cerebellar granule cells by inhibition of Ca2+ influx.

Alkaloids↗

PubMed1999

Effects of green tea tannin on cisplatin-induced nephropathy in LLC-PK1 cells and rats.

A study was conducted to clarify whether green tea tannin ameliorated cisplatin-induced renal injury in terms of lactate dehydrogenase and malondialdehyde leakage from a renal epithelial cell line, swine-derived LLC-PK1 cells in culture. Green tea tannin was shown to suppress the cytotoxicity of cisplatin, the suppressive effect increasing with the dose of green tea tannin. The effect of cisplatin was then investigated in rats given green tea tannin for 40 days before cisplatin administration and in control rats given no green tea tannin. In control rats, blood, urinary and renal parameters and the activities of antioxidative enzymes in renal tissue deviated from the normal range, indicating dysfunction of the kidneys. In contrast, rats given green tea tannin showed decreased blood levels of urea nitrogen and creatinine, and decreased urinary levels of protein and glucose, reflecting less damage to the kidney. In this group, the activity of catalase in the renal tissue was increased, while the level of malondialdehyde was decreased, suggesting the involvement of radicals in the normalizing of kidney function. Based on the evidence available it appeared that green tea tannin eliminated oxidative stress and was beneficial to renal function.

Animals↗

PubMed1999

Physiological changes in Pachinko players; beta-endorphin, catecholamines, immune system substances and heart rate.

Pachinko is a popular form of recreation in Japan. However, in recent years, along with Pachinko's popularity, "Pachinko dependence" has become topical news. The purpose of this study was to investigate beta-endorphin, catecholamines, immune system responses and heart rate during the playing of Pachinko. The following significant results were observed. (1) Plasma concentration of beta-endorphin increased before playing Pachinko and while in the Pachinko-center (p < 0.05). (2) Beta-endorphin and norepinephrine increased when the player began to win (i.e. at "Fever-start") compared to baseline (p < 0.05). (3) Beta-endorphin, norepinephrine and dopamine increased when the winning streak finished (i.e. at "Fever-end") compared to baseline (p < 0.05-0.01). (4) Norepinephrine increased past 30 minutes after "Fever-end" compared to baseline (p < 0.05). (5) Heart rate increased before "Fever-start" compared to baseline, peaked at "Fever-start" and rapidly decreased to match rates measured at rest. But the increase was observed from 200 seconds after "Fever-start" (p < 0.05-0.001). (6) There was a positive correlation between the number of hours subjects played Pachinko in a week and the differences between beta-endorphin levels at "Fever-start" and those at rest (p < 0.05). (7) The number of T-cells decreased while the number of NK cells increased at "Fever-start" compared to baseline (p < .05). These results suggest that intracerebral substances such as beta-endorphin and dopamine are involved in the habit-forming behavior associated with Pachinko.

Adult↗