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Biomedical subjects

K Hirota

Publications and source records attributed to K Hirota.

At least 37 records · Page 2Linked to original sources
PubMed2002

Pupal commitment and its hormonal control in wing imaginal discs.

The timing of pupal commitment of the forewing imaginal discs of the silkworm, Bombyx mori, was determined by a transplantation assay using fourth instar larvae. The wing discs were not pupally committed at the time of ecdysis to the fifth instar. Pupal commitment began shortly after the ecdysis and was completed in 14 h. When the discs of newly molted larvae (0-h discs) were cultured in medium containing no hormone, they were pupally committed in 26 h. In vitro exposure of 0-h discs to 20-hydroxyecdysone accelerated the progression of pupal commitment. Methoprene, a juvenile hormone analog (JHA), did not suppress the change in commitment in vitro at physiological concentrations. Thus the wing discs at the time of the molt have lost their sensitivity to JH, and 20E is not a prerequisite for completion of pupal commitment. These results suggest that the change in commitment in the forewing discs may begin before the last larval molt.

Journal Article↗
PubMed2002

Ketamine and the inhibition of albumin extravasation in chemical peritonitis in rat.

BACKGROUND AND OBJECTIVE: It was previously reported that topical ketamine inhibits albumin extravasation in a rat chemical peritonitis model. Using the same model, the present study investigated whether intravenous ketamine inhibited this extravasation. METHODS: Twenty-four rats anaesthetized with pentobarbital (75 mg kg(-1)) were randomly assigned to two groups: ketamine and a 0.9% NaCl (saline) group (n = 12 each). Ketamine 1% or saline 0.1 mL kg(-1) min(-1) was given intravenously for 60 min to the respective group. After the abdomen had been opened, peritonitis was elicited by topically applying a filter paper containing 0.02 M HCl 0.07 mL onto the surface of the appendix or caecum for 5 min. Fifteen minutes after removal of the filter paper, Evans' blue dye (50 mg kg(-1)) was injected intravenously. The extravasated dye was colorimetrically quantified by a spectrophotometer at 620 nm. RESULTS: The infusion of ketamine significantly reduced Evans' blue extravasation: 5.26 (range 4.18-6.34) microg per 100 mg tissue compared with the saline group control: 6.81 (5.93-7.69) microg per 100 mg tissue (P < 0.05). CONCLUSIONS: It is suggested that ketamine anaesthesia may reduce albumin extravasation in inflammatory tissues.

Albumins↗
PubMed2002

Flurbiprofen does not change the bispectral index and 95% spectral edge frequency during total intravenous anaesthesia with propofol and fentanyl.

BACKGROUND AND OBJECTIVE: Previous studies have shown that general anaesthetic agents modulate the production of hypothalamic prostaglandins (PG) D2 and E2, which are mediators of sleep and wakefulness respectively. Although flurbiprofen, a cyclo-oxygenase inhibitor, is used clinically as a non-steroidal anti-inflammatory agent and postoperative analgesic, it reduces prostaglandin production. Thus, this agent may affect the depth of sedation during general anaesthesia. In this study, we examined if flurbiprofen affects the bispectral index, which correlates with sedation levels. METHODS: Fifteen patients who underwent elective surgery under total intravenous anaesthesia with propofol and fentanyl were studied. The sedation level was monitored using a bispectral index monitor. On attainment of stable haemodynamics and a bispectral index, patients were given flurbiprofen axetil 50 mg intravenously. A bispectral index and 95% spectral edge frequency were recorded before and 5, 10, 15, 20 and 30 min after flurbiprofen axetil intravenously. RESULTS: Bispectral indexes of 51.7 (95% CI: 47.3-56.8), 51.7 (47.1-56.3), 51.3 (46.3-56.3), 50.3 (45.8-54.2), 48.9 (43.6-54.1) and 50.3 (45.5-55.2) at 0, 5, 10, 15, 20, 30 min after flurbiprofen axetil intravenously were observed. There was no change in this or 95% spectral edge frequency. CONCLUSIONS: Clinical dose of flurbiprofen axetil does not alter the bispectral index and 95% spectral edge frequency under total intravenous anaesthesia with propofol and fentanyl.

Analysis of Variance↗
PubMed2002

Spasmolytic effects of colforsin daropate on serotonin-induced pulmonary hypertension and bronchoconstriction in dogs.

BACKGROUND: We have previously found that agents increasing intracellular cAMP levels of smooth muscles, such as PDE3 inhibitors, aminophylline and prostaglandin E1, produce both bronchodilation and pulmonary vasodilation in serotonin-induced pulmonary hypertension and bronchoconstriction models. In the present study we have simultaneously evaluated the spasmolytic effects of colforsin daropate, a novel forskolin derivative, on serotonin-induced pulmonary hypertension and bronchoconstriction. METHODS: Ten mongrel dogs were anesthetized with pentobarbital. The pulmonary hypertension and bronchoconstriction were elicited with serotonin (10 microg/kg + 1 mg x kg(-1) x h(-1)) and assessed as percentage changes in pulmonary vascular resistance (PVR) and bronchial cross-sectional area (BCA) (basal = 100%). Initially, the relaxant effects of colforsin daropate (0-300 microg/kg) were determined. The PVR and BCA were assessed before and 30 min after serotonin infusion began and 5 min after each dose of colforsin daropate. To determine whether colforsin daropate-induced relaxation is independent of plasma catecholamine, propranolol 0.4 mg/kg was given following colforsin daropate 300 microg/kg i.v. RESULTS: Colforsin daropate reversed both pulmonary hypertension and bronchoconstriction dose-dependently: -logED50 (95% confidence intervals, mean ED50) for pulmonary hypertension and bronchoconstriction 5.44 (5.08-5.80, 3.6 microg/kg) and 4.90 (4.06-5.20, 12.5 microg/kg), respectively. However, colforsin daropate (>or= 30 microg/kg) produced a more pronounced systemic than pulmonary vasodilation. Although colforsin daropate (>or= 30 microg/kg) significantly increased plasma catecholamines, propranolol did not reverse the relaxant effects. CONCLUSIONS: Colforsin daropate may attenuate bronchoconstriction and pulmonary hypertension. In addition, as beta-blockade did not change the attenuation, the relaxant effects may be independent of plasma catecholamines.

Animals↗
PubMed2001

Reversible inhibition of hypoxia-inducible factor 1 activation by exposure of hypoxic cells to the volatile anesthetic halothane.

Volatile anesthetics modulate a variety of physiological and pathophysiological responses including hypoxic responses. Hypoxia-inducible factor 1 (HIF-1) is a transcription factor that mediates cellular and systemic homeostatic responses to reduced O(2) availability in mammals, including erythropoiesis, angiogenesis, and glycolysis. We demonstrate for the first time that the volatile anesthetic halothane blocks HIF-1 activity and downstream target gene expressions induced by hypoxia in the human hepatoma-derived cell line, Hep3B. Halothane reversibly blocks hypoxia-induced HIF-1alpha protein accumulation and transcriptional activity at clinically relevant doses.

Anaerobiosis↗
PubMed2001

FIH-1: a novel protein that interacts with HIF-1alpha and VHL to mediate repression of HIF-1 transcriptional activity.

Hypoxia-inducible factor 1 (HIF-1) is a master regulator of oxygen homeostasis that controls angiogenesis, erythropoiesis, and glycolysis via transcriptional activation of target genes under hypoxic conditions. O(2)-dependent binding of the von Hippel-Lindau (VHL) tumor suppressor protein targets the HIF-1alpha subunit for ubiquitination and proteasomal degradation. The activity of the HIF-1alpha transactivation domains is also O(2) regulated by a previously undefined mechanism. Here, we report the identification of factor inhibiting HIF-1 (FIH-1), a protein that binds to HIF-1alpha and inhibits its transactivation function. In addition, we demonstrate that FIH-1 binds to VHL and that VHL also functions as a transcriptional corepressor that inhibits HIF-1alpha transactivation function by recruiting histone deacetylases. Involvement of VHL in association with FIH-1 provides a unifying mechanism for the modulation of HIF-1alpha protein stabilization and transcriptional activation in response to changes in cellular O(2) concentration.

Amino Acid Sequence↗
PubMed2001

Study of the e(g) orbitals in the bilayer manganite La(2--2x)Sr(1+2x)Mn(2)O(7) by using magnetic Compton-profile measurement.

From the magnetic Compton-profile (MCP) measurement, we have directly differentiated for the first time the populations in two e(g)-type orbitals ( x(2) - y(2) and 3z(2) - r(2)) in a manganite. The experimental MCP's along the [001] direction for La(2--2x)Sr(1+2x)Mn(2)O(7) at x = 0.35 and 0.42 are fitted by the theoretical profiles obtained from the (MnO(6))(8-) ab initio calculations. The calculation confirms that the MCP clearly detects the oxygen hybridization in the e(g) orbitals. The e(g) state is dominated by the x(2) - y(2)-type orbital with almost constant population, while the population in the 3z(2) - r(2)-type orbital decreases with increasing the hole concentration x.

Journal Article↗
PubMed2001

Expression pattern of a newt Notch homologue in regenerating newt retina.

We isolated part of a newt Notch homologue, N-Notch, from regenerating newt retina. The spatio-temporal pattern of N-Notch expression was studied by in situ hybridization at different stages of newt retinal regeneration. Proliferating cells were confirmed by the injection of bromodeoxyuridine (BrdU). In the early stage of regeneration, when the retina was one to two cells thick, all proliferating retinal progenitors expressed N-Notch. As the thickness of the retina increased with regeneration, N-Notch expression decreased in BrdU-positive cells on the vitreal side of the retina. Subsequently, presumptive retinal ganglion cells that were BrdU-negative cells appeared at the vitreal edge of the regenerating retina. These differentiating cells did not express N-Notch. Later, N-Notch expression decreased in the BrdU-positive cells on the scleral surface of the retina. Subsequently, presumptive photoreceptor cells that were BrdU-negative cells appeared in this region. These differentiating cells also did not express N-Notch. The proliferating retinal progenitors ceased expressing N-Notch and then stopped dividing during the differentiation of ganglion cells and photoreceptor cells. It was found that retinal regeneration involves the expression of an important developmental signaling molecule, Notch, in retinal progenitors and the expression of Notch ceased as cell differentiation proceeded during retinal regeneration.

Amino Acid Sequence↗
PubMed2001

Redox-sensitive transactivation of epidermal growth factor receptor by tumor necrosis factor confers the NF-kappa B activation.

Cross-communication between different signaling systems allows the integration of the great diversity of stimuli that a cell receives under varying physiological situations. In this paper we have explored the possibility that tumor necrosis factor (TNF) receptor signal cross-talks with epidermal growth factor (EGF) receptor signal on the nuclear factor-kappa B (NF-kappa B) activation pathway. We have demonstrated that overexpression of the EGF receptor (EGFR) in NIH3T3 cells significantly enhances TNF-induced NF-kappa B-dependent luciferase activity even without EGF, that EGF treatment has a synergistic effect on the induction of the reporter activity, and that this enhancement is suppressed by AG1478, EGFR-specific tyrosine kinase inhibitor. We also have shown that TNF induces tyrosine phosphorylation and internalization of the overexpressed EGFR in NIH3T3 cells and the endogenously expressed EGFR in A431 cells and that the transactivation by TNF is suppressed by N-acetyl-l-cysteine or overexpression of an endogenous reducing molecule, thioredoxin, but not by phosphatidylinositol 3-kinase inhibitors and protein kinase C inhibitor. Taken together, this evidence strongly suggests that EGFR transactivation by TNF, which is regulated in a redox-dependent manner, is playing a pivotal role in TNF-induced NF-kappa B activation.

Animals↗
PubMed2001

Rac1 activity is required for the activation of hypoxia-inducible factor 1.

Hypoxia-inducible factor 1 (HIF-1) is a transcription factor that mediates cellular and systemic homeostatic responses (including erythropoiesis, angiogenesis, and glycolysis) to reduced O(2) availability in mammals. Hypoxia induces both the protein expression and transcriptional activity of the HIF-1alpha subunit. However, the molecular mechanisms of sensing and signal transduction by which changes in O(2) concentration result in changes in HIF-1 activity are poorly understood. We report here that the small GTPase Rac1 is activated in response to hypoxia and is required for the induction of HIF-1alpha protein expression and transcriptional activity in hypoxic cells.

Animals↗
PubMed2001

Characterization of equine microsatellites and microsatellite-linked repetitive elements (eMLREs) by efficient cloning and genotyping methods.

We performed efficient cloning and genotyping methods for isolation of a large number of polymorphic microsatellites. The methods contain the time-efficient cloning method of constructing microsatellite-enriched libraries and the economic genotyping method of fluorescent labeling of PCR products. Eighty novel equine microsatellites cloned were efficiently isolated from the enrichment library and analyzed for genotype polymorphism. Of these, 72 microsatellites were analyzed with a good resolution. The average heterozygosity of all loci was 0.52, and the number of alleles ranged from one to 9 with an average of 4.5 alleles. The other eight loci showed multiple bands of PCR products, suggesting the occurrence of microsatellites in a repetitive element, in which the number of microsatellite repeats varies among different members of the repetitive element. We found five homologous groups at flanking regions in comparison with the flanking regions of microsatellites from DNA databases. One of them showed homology to equine repetitive element-2. In the other four homologous groups, the two groups were named equine microsatellite-linked repetitive element-1 (eMLRE-1) and equine microsatellite-linked repetitive element-2 (eMLRE-2) as novel equine repetitive elements identified from equine genome. These data should help the analysis of equine DNA sequences and the design of equine genome markers.

Animals↗
PubMed2001

An endogenous redox molecule, thioredoxin, regulates transactivation of epidermal growth factor receptor and activation of NF-kappaB by lysophosphatidic acid.

Lysophosphatidic acid (LPA) is the smallest and simplest of all the glycerophospholipids that activates a specific GTP-binding protein coupled receptor to evoke multiple cellular responses. In this paper, we have demonstrated that LPA stimulates nuclear factor (NF)-kappaB-dependent gene induction in a neuronal cell line, NG108-15 and that this is under redox regulation by an endogenous molecule, thioredoxin. We also have shown that redox-sensitive transactivation of epidermal growth factor receptor by LPA confers NF-kappaB activation and small GTPase proteins are involved in this pathway.

Animals↗
PubMed2001

6-formylpterin, a xanthine oxidase inhibitor, intracellularly generates reactive oxygen species involved in apoptosis and cell proliferation.

The chemical property of 6-formylpterin and its biological functions were examined. Polarographic studies revealed that 6-formylpterin reacted with NAD(P)H and consumed oxygen. In contrast, other conjugated pterins, such as biopterin and neopterin, showed no consumption of oxygen. The production analysis using high-performance liquid chromatography documented that 6-formylpterin catalyzes the conversion from NADH to NAD. Electroparamagnetic resonance spin trapping experiments demonstrated that this reaction is accompanied with the generation of reactive oxygen species (ROS), superoxide anion and hydrogen peroxide. When 6-formylpterin was administered to HL-60 cells, intracellular ROS generation was observed and apoptosis was induced. In contrast, other conjugated pterins induced neither intracellular ROS generation nor apoptosis in HL-60 cells. The intracellular ROS generation by 6-formylpterin was observed in other cells, such as PanC-1 cells and Jurkat cells. 6-formylpterin suppressed cell proliferation in PanC-1 cells and inhibited Fas-mediated apoptosis in Jurkat cells. These findings indicate that, among conjugated pterins, 6-formylpterin has the unique property to transfer electron from NAD(P)H to oxygen and that the property brings about intracellular ROS generation, which exerts various biological functions such as induction of apoptosis, suppression of cell proliferation, and inhibition of Fas-mediated apoptosis.

Apoptosis↗
PubMed2001

Myristoleic acid, a cytotoxic component in the extract from Serenoa repens, induces apoptosis and necrosis in human prostatic LNCaP cells.

BACKGROUND: Prostatic tumors are well known to progress to hormonal therapy-resistant terminal states. At this stage, there are no chemotherapeutic agents to affect clinical outcome. An effective cell death inducer for these prostate cells may be a candidate as an attractive antitumor agent. The extracts from S. repens have been used to improve the state of prostatic diseases and we have attempted to identify the effective component from the extract. METHODS: Cell viability was examined in LNCaP cells, an in vitro model for hormonal therapy-resistant prostatic tumor. RESULTS: We found that exposure of the extract from S. repens resulted in cell death of LNCaP cells. We also identified myristoleic acid as one of the cytotoxic components in the extract. The cell death exhibited both apoptotic and necrotic nuclear morphology as determined by Hoechst 33342 staining. Cell death was also partially associated with caspase activation. CONCLUSIONS: It was demonstrated that the extract from S. repens and myristoleic acid induces mixed cell death of apoptosis and necrosis in LNCaP cells. These results suggest that the extract and myristoleic acid may develop attractive new tools for the treatment of prostate cancer.

Amino Acid Chloromethyl Ketones↗
PubMed2001

Surface hardness change of restorative filling materials stored in saliva.

OBJECTIVES: This study was to investigate the effect of saliva used as storage liquid and the length of storage effect on surface hardnesses of Fuji IX (GP) (FIX), Dyract (DR), Z-100 and Estio LC (ELC). METHODS: The materials were mixed according to the manufacturers' instructions and immersed in distilled water or human parotid saliva. Vickers hardness number (HVN) was measured 1, 7, 20 and 40 days after the materials were mixed. HVN was calculated from the indentation diameter after 100 or 300g loading on their surface for 15s. The two methods of characterization used in this work were X-ray photoelectron spectroscopy (XPS) for surface chemical composition and electron probe microanalysis (EPMA) for depth profile analysis. RESULTS: Only in FIX, did HVN increase with time at both storage conditions, distilled water and saliva. The increase rate of the value was higher when stored in saliva than distilled water. After 40 days storage in saliva, the HVN value of FIX increased by 39%. The increase for storage in saliva for DR was 22%, ELC 16%, and Z100 3%, compared to 1 day storage in distilled water. Ca and P peaks caused by saliva were detected by XPS and EPMA analysis, but these peaks did not exist in either composite resin or polyacid-modified composite resin by EPMA analysis. SIGNIFICANCE: Saliva has the remarkable effect of increasing surface hardness of Fuji IX (GP).

Compomers↗
PubMed2001

Effect of diltiazem on cardiac function assessed by echocardiography and neurohumoral factors after reperfused myocardial infarction without congestive heart failure.

The purpose of this study was to examine the effect of diltiazem on cardiac function and neurohumoral factors (BNP, epinephrine, norepinephrine) after reperfused myocardial infarction without congestive heart failure (Killip class I). On the first day after myocardial infarction following reperfusion therapy patients were randomly assigned to diltiazem treatment (group 1, n=33) or no treatment (group 2, n=39). We then performed echocardiographic examinations on the patients and measured heart rate, mean blood pressure and neurohormones (BNP, epinephrine and norepinephrine). Follow-up evaluations of echocardiography were performed at 4 and 12 weeks and of neurohormones at 1 and 4 weeks after acute myocardial infarction. The highest peaks of plasma BNP, epinephrine, and norepinephrine levels were observed before treatment and decreased with time in both groups. After 4 weeks the level of plasma BNP in the diltiazem treatment group was lower than in the no treatment group [55+/-3 pg/mL vs 85+/-5 pg/mL (P < 0.05)]. Other neurohormones did not differ between groups. Fractional shortening (FS) and ejection fraction (EF)improved after myocardial infarction in both groups, but significantly more in the diltiazem group (P < 0.05) after 12 weeks of treatment. Changes in BNP correlated significantly with changes in left ventricular end systolic volumes, FS and EF. In this study, diltiazem significantly improved systolic function and reduced the level of plasma BNP after myocardial infarction, which suggest that diltiazem may have a beneficial effect on myocardial infarction without congestive heart failure.

Aged↗
PubMed2001

Spasmolytic effect of magnesium sulfate on serotonin-induced pulmonary hypertension and bronchoconstriction in dogs.

BACKGROUND: Magnesium (Mg2+) has relaxant effects on histamine-induced bronchoconstriction. In addition, Mg2+ has been reported to reduce vascular smooth muscle tone and be clinically useful for treatment of persistent pulmonary hypertension of the newborn. In this study, we evaluated the relaxant effect of Mg2+ on serotonin (5HT)-induced bronchoconstriction and pulmonary hypertension. METHODS: Seven mongrel dogs were anesthetized with pentobarbital (30 mg x kg(-1) + 2 mg x kg(-1) x h(-1)) and paralyzed by pancuronium (0.2 mg x kg(-1) x h(-1)). Bronchoconstriction and pulmonary hypertension were elicited with 5HT (10 microg x kg(-1) + 1 mg x kg(-1) x h(-1)). Airway caliber was evaluated by changes in bronchial cross-sectional area (BCA) of the 3rd bronchial bifurcation measured by a fiberoptic bronchoscope method as previously reported. Pulmonary hypertension was assessed by changes in pulmonary vascular resistance (PVR). The BCA and PVR were expressed as per cent of the basal level. Thirty minutes after start of 5HT infusion, magnesium sulfate (MgSO4): 0 (saline), 1, 10, 100 and 1000 micromol x kg(-1) was given i.v.. Arterial blood was also collected to measure plasma level of Mg2+ and catecholamines. RESULTS: 5HT increased %PVR to 163+/-25% and decreased % BCA by 39.2+/-4.5%. Plasma level of Mg2+ following MgSO4 1000 micromol x kg(-1) i.v. exceeded its toxic level. The ED50s of MgSO4 (dose producing 50% relaxation of maximal constriction) was 47.8 micromol x kg(-1) and 1.09 mmol x kg(-1) for pulmonary hypertension and bronchoconstriction, respectively. The ratio of %PVR to %SVR was about 1.0 after MgSO4 0-100 micromol x kg(-1) i.v., although the ratio significantly increased after 1000 micromol x kg(-1) i.v.. CONCLUSION: In dogs, 5HT-induced pulmonary hypertension but not bronchoconstriction was significantly reduced by an iv bolus of MgSO4, resulting in a plasma concentration within the assumed therapeutic level.

Animals↗