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Biomedical subjects

K Mizuno

Publications and source records attributed to K Mizuno.

At least 217 records · Page 12Linked to original sources
PubMed1999

Effects of zonisamide on K+ and Ca2+ evoked release of monoamine as well as K+ evoked intracellular Ca2+ mobilization in rat hippocampus.

To clarify the effects of zonisamide (ZNS) on neurotransmission and intracellular Ca2+ mobilization, both Ca2+ and K+ evoked hippocampal releases of dopamine (DA) and serotonin (5-HT) were determined by in vivo microdialysis, and K+ (25 and 50 mM) evoked elevation of intracellular Ca2+ level was determined by fluorescence microscopy in vitro. Therapeutic concentrations of ZNS had different effects on Ca2+ and K+ evoked release of monoamine. ZNS stimulated Ca2+ evoked monoamine release, while ZNS inhibited K+ evoked monoamine release. ZNS inhibited K+ evoked elevation of hippocampal intracellular Ca2+ levels in a concentration dependent manner. These results suggest that ZNS inhibits the depolarization induced by neuronal excitation, whereas ZNS might enhance the N-type Ca2+ channel activity or N-type Ca2+ channel related exocytosis mechanisms.

Animals↗
PubMed1999

Effects of body position on blood gases and lung mechanics of infants with chronic lung disease during tube feeding.

BACKGROUND: The effects of body position and feeding on lung mechanics and blood gases in very low birthweight infants with chronic lung disease (CLD) is not fully elucidated. METHODS: Seven very low birthweight infants who were being mechanically ventilated because of CLD were examined. They were enrolled in this study when their feeding volume exceeded 100 mL/kg per day. Each patient was kept on the same position (either prone or supine) during feeding. Feeding was given by a nasogastric tube for over 1 h every 3 h. Blood gases and lung mechanics were evaluated before, 20 min and 40 min after the initiation of the feeding and at the end of the feeding. RESULTS: The prone position resulted in a significant increase in arterial oxygen saturation during feeding. The tidal volume in the prone position was significantly larger than in the supine position only before feeding. There were no significant differences in minute ventilation between these positions during the study. Pulmonary resistance was not different in either position, but the static compliance and the work of breathing of spontaneous breaths were improved significantly when the infants were in the prone position. In the supine position, work of breathing increased and static compliance decreased significantly with time, while in the prone position, those values did not change significantly. CONCLUSION: The improvement in lung mechanics may partly explain better oxygenation obtained in the prone position. The prone position could decrease energy expenditure for spontaneous breathing and may shorten the period of ventilatory support for very low birthweight infants with CLD.

Analysis of Variance↗
PubMed1999

Differential effects of adenosine receptor subtypes on release and reuptake of hippocampal serotonin.

To clarify the effects of adenosine receptor subtypes (A1, A2 and A3) on hippocampal serotonin (5-HT) release and 5-HT reuptake activity, hippocampal extracellular 5-HT levels were determined in vivo by microdialysis in freely moving rats. Selective 5-HT reuptake inhibitor (SSRI) fluoxetine and DU24565 increased extracellular 5-HT levels. Adenosine and A1 receptor agonist, 2-chloro-N6-cyclopentyl-adenosine (CCPA), decreased extracellular 5-HT levels, whereas non-selective antagonist, caffeine, and A1 antagonist, 8-cyclopentyl-1,3-dimethylxanthine (CPT) increased them. When 5-HT reuptake activity was inhibited by DU24565 and fluoxetine, the effects of CPT and CCPA on 5-HT level were enhanced. A2A receptor agonist, CGS21680, A2 receptor agonist, PD125944, A2 receptor antagonist, 3,7-dimethyl-1-propargylxanthine (DMPX), and A3 receptor agonist, N6-2-(4-aminophenyl)ethyladenosine (APNEA) did not affect 5-HT levels; however, when A1 receptor was blocked by CPT, 5-HT levels were increased by adenosine, CGS21680 and PD125944, and decreased by DMPX and APNEA. Under conditions of A1 receptor blockade, pretreatment with DU24565 or fluoxetine, enhanced the stimulatory effects of CGS21680 and PD125944 as well as inhibitory effects of DMPX on 5-HT level, whereas the inhibitory effect of APNEA was abolished. These results indicate that the stimulatory effects of A2 receptor and inhibitory effects of A3 receptor on hippocampal extracellular 5-HT levels are masked or abolished by the inhibitory effects of A1 receptor. In addition, hippocampal serotonergic transmission might be modulated by hippocampal presynaptic adenosine receptor subtypes, and hippocampal 5-HT reuptake activity might be modulated by hippocampal A3 receptor.

Adenosine↗
PubMed1999

Evaluation of apoptotic cells induced by ultraviolet light B radiation in epidermal sheets stained by the TUNEL technique.

Two major components of epidermal cells, keratinocytes and Langerhans cells, are injured by ultraviolet light B radiation, resulting in sunburn cell (apoptotic cell) formation, impaired function, and a reduced number of Langerhans cells. Quantitative analysis of Langerhans cell damage is usually performed using epidermal sheets, whereas that of keratinocytes has been performed by counting the number of sunburn cells in vertical tissue sections. In this study we assessed the influences of ultraviolet light B radiation on epidermal cells by apoptotic cell formation, using murine epidermal sheets stained by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling technique. Ten to 75 mJ per cm2 of ultraviolet light B radiation induced apoptotic cells in abdominal skin of C3H mice. The cells were induced in 6 h after 50 mJ per cm2 of ultraviolet light B irradiation with the peak in number in 24 h, 18.8 +/- 5.0 per mm2 and 97.7 +/- 7.4 per mm2, respectively. One week later, the apoptotic cells were not visualized. As C3H/He, BALB/C, and C57BL/6 mice showed almost the same frequency of apoptosis in epidermal sheets from 50 mJ per cm2 ultraviolet light B-irradiated skin, the induction of the cells by ultraviolet light B radiation did not depend on the genetic trait of the mouse. Xeroderma pigmentosum type A gene-deficient mice, however, showed a greater induction of apoptotic cells (216.9 +/- 25.2 per mm2) by ultraviolet light B radiation than xeroderma pigmentosum type A wild-type mice (89.5 +/- 13.6 per mm2) and conventional mice. Pretreatment with a SPF 60 sunscreen agent was quite effective in reducing the induction of apoptotic cells. Using confocal laser scanning microscopy and double staining, 1.5 +/- 2.7% of apoptotic cells were Ia-positive cells in 24 h after 50 mJ per cm2 of ultraviolet light B radiation. Apoptotic Ia-positive cells were not observed 48 h after the radiation. On the other hand, no apoptotic dendritic epidermal T cells were observed in up to 75 mJ per cm2 of ultraviolet light B radiated skin. Thus, nearly all apoptotic cells were keratinocytes, and Langerhans cells and dendritic epidermal T cells appeared resistant to ultraviolet light B-induced apoptosis. Compared with the assessment in vertical tissue sections, the terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling technique with epidermal sheets appeared to be a more physiologically relevant method for quantitative evaluation of apoptotic epidermal cells induced by ultraviolet light B radiation.

Animals↗
PubMed1999

Serum testosterone responses to continuous and intermittent exercise training in male rats.

Serum testosterone (T) were investigated at rest and following exercise during 6 weeks of continuous and intermittent swimming training in male rats, and the regulatory mechanisms of the changes were discussed by evaluating serum luteinizing hormone (LH), and conducting GnRH (gonadotropin releasing hormone, 1.5 microg/kg body weight) or hCG (human chorionic gonadotropin, 25 IU/kg body weight) challenge tests. Relative to the resting level, serum T increased after intermittent exercise (6.47 +/- 1.58 vs 3.08 +/- 2.85 nmol/l), which was followed with the same changes in LH (12.81 +/- 4.21 vs 5.70 +/- 1.56 nmol/l). Serum T was lower after continuous exercise compared to the resting level (2.02 +/- 0.53 vs 10.96 +/- 3.11 nmol/l), while LH level was higher than that in sedentary group (11.23 +/- 5.61 vs 5.00 +/- 1.61 nmol/l). No significant changes were observed in resting T during and after intermittent training. A lower resting T level was shown at the end of 3 weeks of continuous training as compared to the sedentary group (1.88 +/- 0.69 vs 12.36 +/- 2.10 nmol/l), but it increased after 6 weeks of training. Serum T increased significantly in the intermittent training group after hCG treatment as compared to the saline treatment (52.42 +/- 12.10 vs 6.81 +/- 6.22 nmol/l), but insignificantly in the continuous training group. The similar increases in serum LH were observed in all the groups after GnRH treatment.

Analysis of Variance↗
PubMed1999

Inhibition of cAMP-mediated decidualization in human endometrial stromal cells by IL-1beta and laminin.

Both IL-1 and laminin are reported to inhibit progesterone receptor-mediated decidualization signals in endometrial stromal cells, but the effects of these two inhibitors on cAMP-mediated decidualization signals remain unknown. Furthermore, the interaction between IL-1-stimulated and laminin-stimulated signals has not been analyzed yet. In this study, interactions between these two decidualization-inhibitory signals and their effects on 8-Br-cAMP-mediated decidualization in human endometrial stromal cells were investigated. Prolactin release from decidualized stromal cells was measured by enzyme immunoassay in order to quantitate in vitro decidualization. Both IL-1beta and laminin were found to inhibit 8-Br-cAMP-induced decidualization in vitro in human endometrial stromal cells. IL-1beta dose-dependently inhibited decidualization of stromal cells cultured on both laminin-coated and collagen-coated dishes, while laminin inhibited the decidualization of stromal cells cultured both with and without IL-1beta. These results indicate that IL-1beta and laminin additively and mutually inhibit cAMP-mediated decidualization signals, and that they may inhibit these signals through different mechanisms.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed1999

Purification and characterization of caffeine synthase from tea leaves.

Caffeine synthase (CS), the S-adenosylmethionine-dependent N-methyltransferase involved in the last two steps of caffeine biosynthesis, was extracted from young tea (Camellia sinensis) leaves; the CS was purified 520-fold to apparent homogeneity and a final specific activity of 5.7 nkat mg-1 protein by ammonium sulfate fractionation and hydroxyapatite, anion-exchange, adenosine-agarose, and gel-filtration chromatography. The native enzyme was monomeric with an apparent molecular mass of 61 kD as estimated by gel-filtration chromatography and 41 kD as analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The enzyme displayed a sharp pH optimum of 8.5. The final preparation exhibited 3- and 1-N-methyltransferase activity with a broad substrate specificity, showing high activity toward paraxanthine, 7-methylxanthine, and theobromine and low activity with 3-methylxanthine and 1-methylxanthine. However, the enzyme had no 7-N-methyltransferase activity toward xanthosine and xanthosine 5'-monophosphate. The Km values of CS for paraxanthine, theobromine, 7-methylxanthine, and S-adenosylmethionine were 24, 186, 344, and 21 microM, respectively. The possible role and regulation of CS in purine alkaloid biosynthesis in tea leaves are discussed. The 20-amino acid N-terminal sequence for CS showed little homology with other methyltransferases.

Affinity Labels↗
PubMed1999

Prophylaxis of local vascular graft infection with levofloxacin incorporated into albumin-sealed dacron graft (LVFX-ALB Graft).

An animal model was used to assess the efficacy of levofloxacin (LVFX) incorporated into albumin (ALB)-sealed Dacron (LVFX-ALB) graft for the prevention of vascular graft infections caused by Staphylococcus aureus. Under general anesthetic, an interposition graft was placed into dog carotid artery. On completion of the operation, 0.1 ml of normal saline containing 10(7) colony-forming units (CFU) of a slime-producing S. aureus was inoculated directly onto the graft. After 1 day, the samples were sterilely harvested. The antibacterial activity of LVFX into the LVFX-ALB graft was evaluated by colony counting in bacterial cultures and by the fluorescent antibody method staining bacteria adhesion to the grafts. LVFX-ALB grafts had a lower infection rate than the control grafts (1/4, 10(2) CFU vs 4/4, 1.50 x 10(5)+/-1.38 x 10(5)CFU (mean+/-SE)). In an immunostaining study, LVFX-ALB grafts had small fluorescent areas showing S. aureus adhesion, while fluorescence was observed over the entire surface of the control grafts. Therefore, LVFX-ALB presumably had a bactericidal action and adhesive prevention against inoculated S. aureus. LVFX-ALB may be useful in preventing graft infections during and immediately after vascular reconstruction.

Albumins↗
PubMed1999

SCH 51344, an inhibitor of RAS/RAC-mediated cell morphology pathway.

RAS interacts with multiple targets in the cell and controls at least two signaling pathways, one regulating extracellular signal-regulated kinase (ERK) activation and the other controlling membrane ruffling formation. These two pathways appear to act synergistically to cause transformation. Human smooth muscle alpha-actin promoter is repressed in RAS-transformed cells and derepressed in revertant cell lines, suggesting that it is a sensitive marker to follow phenotypic changes in fibroblast cells. SCH 51344 is a pyrazoloquinoline derivative identified on the basis of its ability to derepress alpha-actin promoter in RAS-transformed cells. Previous studies have shown that SCH 51344 is a potent inhibitor of RAS transformation. However, SCH 51344 had very little effect on the activities of proteins in the ERK pathway, suggesting that it inhibits RAS transformation by a novel mechanism. Recently, we have demonstrated that SCH 51344 specifically blocks membrane ruffling induced by activated forms of H-RAS, K-RAS, N-RAS, and RAC. Treatment of fibroblast cells with this compound had very little effect on RAS-mediated activation of ERK and JUN kinase activities. SCH 51344 was effective in inhibiting the anchorage-independent growth of Rat-2 fibroblast cells transformed by the three forms of oncogenic RAS and RAC V12. These results indicate that SCH 51344 inhibits a critical component of the membrane ruffling pathway downstream from RAC and suggest that targeting this pathway may be an effective approach to inhibiting transformation by RAS and other oncogenes.

Actins↗
PubMed1999

Increased natural killer cell activities in patients treated with gonadotropin releasing hormone agonist.

Natural killer (NK) cell activity in patients treated with gonadotropin-releasing hormone agonists (GnRH-a) was studied. The subjects were 8 patients with endometriosis (6 with ovarian endometrial cyst, 2 with adenomyosis) and 3 patients with uterine leiomyoma. Changes in serum estradiol (E2) concentration and NK cell activity in peripheral blood were analyzed before and after GnRH-a treatment (buserelin 900 microg/day for 4-5 months). NK cell activity was determined by 51Cr release assay and E2 by radioimmunoassay. NK cell activity before GnRH-a treatment was 37.7 +/- 19.0%, and after therapy activity increased significantly to 50. 8 +/- 18.2%. However, no significant correlation between the increase in NK cell activity and the decrease in E2 concentration was found. Results indicate that the standard GnRH-a treatment for endometriosis and uterine leiomyoma might increase NK cell activity. The etiology of the increase of NK activity with GnRH-a treatment is likely related to factors other than E2 concentration.

Adult↗
PubMed1999

Prevalence of GB virus C/hepatitis G virus ribonucleic acid and anti-hepatitis G virus-E2 antibodies among Japanese children with histories of transfusions or with liver diseases.

To clarify the prevalence of Japanese children thought to be at a risk for infection with GB virus-C (GBV-C)/hepatitis G virus (HGV), we investigated the detection rates of serum GBV-C/ HGV ribonucleic acid (RNA) by reverse transcription-seminested PCR and serum anti-HGV-E2 antibody by ELISA in 162 children with histories of blood or plasma product transfusions or with liver diseases and performed phylogenetic analysis of the 5' noncoding region sequences of GBV-C/HGV genomes. Children with histories of transfusions were divided into those who had been treated with antineoplastic agents for malignant diseases (malignant group) and those who had received transfusions for nonmalignant diseases (nonmalignant group). Children with liver diseases were divided into hepatitis B (HBV), hepatitis C (HCV), and non-A-C hepatitis groups. We detected GBV-C/ HGV RNA in 11 of 33 (33.3%) and anti-HGV-E2 in 1 of 27 (3.7%) children in the malignant group and in 3 of 56 (5.4%) and 1 of 53 (1.9%) children, respectively, in the nonmalignant group. Neither GBV-C/HGV RNA nor anti-HGV-E2 was detected in the HBV and non-A-C hepatitis groups. GBV-C/HGV RNA and anti-HGV-E2 were detected in 7 of 23 (30.4%) and in 1 of 18 (5.6%) children, respectively, in the HCV group. All children positive for either GBV-C/HGV RNA or anti-HGV-E2, except one whose route of GBV-C/HGV infection suggested mother-to-infant transmission, had histories of transfusions. The phylogenetic analysis showed that all isolates in this study were divisible into three groups and that most of them were clustered into group 3 (Asian group).

Adolescent↗
PubMed1999

Synthesis and antitumor activities of water-soluble benzoylphenylureas.

Water-soluble benzoylphenylurea derivatives were synthesized as candidate prodrugs and their antitumor activities were examined in vivo against P388 leukemia. Some of the prodrugs were highly soluble in water and showed good antitumor activities against P388 leukemia cells in mice when injected intravenously.

Animals↗
PubMed1999

Mechanism of inhibitory effect of warfarin on mesangial cell proliferation.

Because proliferation of mesangial cells is a hallmark of glomerular diseases, understanding the regulatory mechanism of mesangial proliferation is important for the treatment. Warfarin has long been used to treat glomerular diseases, although its mechanism of effect on mesangial proliferation has remained unknown. Therefore, this study was conducted to examine whether warfarin can inhibit mouse mesangial cell proliferation by focusing on Gas6, which has been shown to be activated by vitamin K-dependent gamma-carboxylation. In mesangial cells, Gas6 and its receptor Axl were expressed. In addition, exogenous Gas6 phosphorylated Axl, activated extracellular signal-regulated kinase, and stimulated [3H]-thymidine incorporation in mouse mesangial cells. This study also examined whether endogenous Gas6 stimulates mesangial proliferation. Conditioned medium (CM) from serum-starved mesangial cells could stimulate [3H]-thymidine incorporation and phosphorylate extracellular signal-regulated kinase, whereas CM in the presence of warfarin could not. Simultaneous administration of vitamin K could cancel the inhibitory effect of warfarin. These results suggest that vitamin K-dependent growth factors in the CM are critical for mesangial proliferation. Addition of the extracellular domain of Axl to the CM inhibited its mitogenic effect on mesangial cells, suggesting that this vitamin K-dependent growth factor is Gas6. It is concluded that Gas6 is an endogenous mitogen in mesangial cells, and warfarin inhibits mesangial proliferation possibly by inhibiting gamma-carboxylation of Gas6. This study sheds light on the regulation of mesangial proliferation and may lead to a new therapeutic strategy for glomerular diseases.

Animals↗
PubMed1999

Formulation of glutaraldehyde disinfectant for alginate impressions.

The effect of buffer agents incorporated in glutaraldehyde disinfectants on the surface quality of dental models was examined by the measurement of surface roughness, X-ray diffraction analysis and SEM observation. Seven experimental glutaraldehyde disinfectants were prepared using two buffer agents, potassium acetate alone or potassium acetate and sodium hydrogen carbonate in combination. Four kinds of sulfate--zinc, calcium, potassium and magnesium sulfate--were added to these disinfectants in order to accelerate the hydration of calcium sulfate hemihydrate. The impressions treated with the experimental disinfectants for 1 h produced stone surfaces which had significantly lower surface roughness values than those treated with the commercial disinfectants (p < 0.05). The X-ray diffraction analysis and SEM observation showed that these superior surfaces were produced as a result of significant reductions in the amount of residual calcium sulfate hemihydrate. Replacement of buffer agents in commercial glutaraldehyde disinfectants with chemicals such as those studied in the present study will improve the surface quality of dental stone.

Alginates↗
PubMed1999

[Methods of sleep induction for EEG recordings: comparison between three hypnotics and natural sleep].

We compared the effects of three oral hypnotics, monosodium trichloroethyl phosphate (MTP), chloral hydrate (CH), and pentobarbital calcium (PTB), to those of non-medication on wake-sleep states and sleep activation of epileptic seizure discharges. The subjects consisted of 410 epileptics and 171 non-epileptic outpatients (mean age: 12.5 years) of the Department of Pediatrics, Nagoya City University Hospital. Complete EEG records including awake and sleep states were obtained in 230/241 (95%) of patients with MTP, 20/22 (91%) of those with CH, 72/85 (85%) of those with PTB, and 225/233 (97%) of those without any hypnotics. There were no statistically significant differences in the effect of sleep induction among the four groups. Sleep activation effects were observed in 25% of patients with natural sleep and 35% of those with induced sleep. There was no statistical difference (p > 0.05). These results suggested MTP, CH, and PTB are useful hypnotics for sleep EEG recordings.

Adolescent↗