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H Yasuhara

Publications and source records attributed to H Yasuhara.

At least 19 recordsLinked to original sources
PubMed2003

Enhancement of 5-hydroxytryptamine-induced head-twitch response after olfactory bulbectomy.

5-Hydroxytryptamine(2A) receptor agonists evoke the head-twitch response in mice. The head-twitch response in olfactory bulbectomized mice elicited by the administration of 5-hydroxytryptamine (40 microgram/mouse, i.c.v.) was increased about threefold as compared with controls on the 14th day after the operation. The injection of ketanserin (1 mg/kg, i.p.), a 5-hydroxytryptamine(2A) receptor antagonist, inhibited this enhancement of 5-hydroxytryptamine-induced head-twitch response after olfactory bulbectomized. On the 14th day, the number of head-twitch response induced by 5-hydroxytryptophan (40, 80 and 160 mg/kg, i.p.), a precursor of 5-hydroxytryptamine, did not differ between olfactory bulbectomized and control mice. Monoamine oxidase-B activity in the forebrain of olfactory bulbectomized mice was higher than that in controls while monoamine oxidase-A activities were unchanged. The 5-hydroxytryptamine uptake into synaptosomes in the forebrain homogenates of olfactory bulbectomized mice was lower than that in controls. These findings indicate that olfactory bulbectomized causes the enhancement of head-twitch response by a supersensitivity of 5-hydroxytryptamine(2A) receptors in cerebral cortex derived from degeneration of neurons projecting from the olfactory bulb.

5-Hydroxytryptophan↗
PubMed2003

How useful is the "cocktail approach" for evaluating human hepatic drug metabolizing capacity using cytochrome P450 phenotyping probes in vivo?

Relatively selective in vivo substrate probes have been developed for several major CYP isoforms involved in oxidative drug metabolism. There are basically two in vivo methods for identifying the phenotype. One method, the selective (CYP-specific) phenotyping method, involves administering one single probe drug, whereas the other is a mixed phenotyping or "cocktail" method involving the simultaneous administration of multiple probe drugs, specific for the individual P450. At present, caffeine and chlorzoxazone are used most often as probe drugs for CYP1A2 and CYP2E1, respectively, but these are not necessarily the best probe drugs. Of the potential probe drugs for CYP2C9, CYP2C19, CYP2D6 and CYP3A4, none is really useful. Despite current limitations, the cocktail method for obtaining information about multiple CYP activities in a single experimental session is likely to be more widely used as a screening or phenotyping method for humans in the future.

Aryl Hydrocarbon Hydroxylases↗
PubMed2003

Involvement of cytochrome P450 2C9, 2E1 and 3A4 in trimethadione N-demethylation in human microsomes.

BACKGROUND AND OBJECTIVES: Trimethadione (TMO), an antiepileptic drug, may be used as a candidate for estimating hepatic drug-oxidizing activity. While TMO metabolism is mainly catalysed by CYP2C9, CYP2E1 and CYP3A4 the contribution of the different isoforms is unclear. In this study, we determined the percentage contribution of the three CYPs (CYP2C9, CYP2E1 and CYP3A4) to TMO N-demethylation. METHOD: We used human liver microsomes and human recombinant CYPs expressed in human B-lymphoblast cells and baculovirus-infected insect cells. RESULTS: The mean Km, Vmax and Vmax/Km values of TMO N-demethylation in human microsomes were 3.66 (mm), 503 (pmol/min/mg) and 2.61 (mL/h/mg), respectively. In the microsomes from human B-lymphoblast cells or baculovirus-infected insect cells, CYP 2C9, CYP 2E1 and CYP3A4 exhibited similar Km and higher Vmax in baculovirus-infected insect cells than B-lymphoblast cells. In baculovirus-infected insect cells, CYP2C9, CYP2E1 and CYP3A4 exhibited activities of 32, 286 and 77 pmol/min/pmol CYP, respectively. No CYP activity catalysed by CYP1A2 and 2D6 were detected in the two human cDNA expressed CYP isoforms. CONCLUSION: TMO is metabolized not only by CYP2E1 but also CYP3A4 and CYP2C9. The order of this metabolism is as follows: CYP2E1 >> CYP3A4 > CYP2C9.

Anticonvulsants↗
PubMed2002

Inhibition of growth of human breast cancer cells in culture by neutron capture using liposomes containing 10B.

Cell destruction in boron neutron capture therapy is effected by nuclear reaction between 10B and thermal neutrons with the release of alpha-particles (4He) and lithium-7 ions (7Li). 4He kills cells within 10 microm of the site of 4He generation, therefore it is theoretically possible to destroy tumour cells without affecting adjacent healthy tissue, given selective delivery of compounds containing 10B. Liposomes wore prepared by vortex dispersion of solutions containing 10B compounds with dried lipid films and the effects of those compounds on human breast cancer cells in culture were examined after thermal neutral irradiation. [3H]-TdR incorporation by MRKnu/nu-1 cells treated with 10B-containing liposomes showed 40% suppression compared with liposomes without 10B, at 2 x 1012 n/cm2 thermal neutron fluence. Inhibition of tumour cell growth with liposomes prepared with 100 mm 10B-compound was as significant as with those made with 500 ppm 10B solution. The concentration of 10B in liposomes was 76.5 +/- 3.4 microg/mL. Boronated liposomes can thus deliver sufficient 10B atoms to this line of breast cancer cells in culture to effect cytotoxicity and suppression of growth after thermal neutron irradiation.

Boron↗
PubMed2002

Leukotriene receptor antagonist, montelukast, can reduce the need for inhaled steroid while maintaining the clinical stability of asthmatic patients.

BACKGROUND: Oral leukotriene receptor antagonists have been shown to have efficacy in chronic asthma. OBJECTIVE: To determine whether the addition of montelukast could lead to a reduction in inhaled corticosteroid dose without a significant decrease in peak expiratory flow rate (PEFR). METHODS: After a 4-week run-in period, 191 moderate-to-severe asthmatic patients whose asthma had been well controlled with daily inhaled corticosteroid therapy (beclometasone dipropionate 800 to 1600 micro g/day), were randomly assigned to one of two treatments - placebo (n = 98) or montelukast 10 mg once daily (n = 93) - for a 24-week, multicentre, double-blind, treatment period. At the beginning of the active treatment period, the daily dose of inhaled corticosteroid was halved in all of the patients. In addition, the inhaled corticosteroid dose was subsequently titrated every 8 weeks, based on PEFR, asthma symptoms and beta-agonist use. RESULTS: After 8 weeks of a 50% reduction in inhaled corticosteroid use, morning PEFR increased by 5.3 +/- 32.3 L/min from baseline in patients receiving montelukast and significantly decreased by 6.9 +/- 29.0 L/min in those receiving placebo (P = 0.035). In addition, evening PEFR significantly decreased by 9.8 +/- 28.5 L/min (P = 0.003) in the placebo group, but was maintained in the montelukast group. In spite of a subsequent 50% reduction in the inhaled corticosteroid dose every 8 weeks, morning and evening PEFRs were maintained over the 24-week treatment period in the montelukast group; PEFR significantly decreased in the placebo group. There was a significant difference between the two groups with regard to morning PEFR, therapy score and asthmatic score at weeks 8, 16 and 24, as well as evening PEFR at week 8. However, the symptom scores were not significantly different between the two groups or within each group. CONCLUSION: These data suggest that montelukast reduces the need for inhaled corticosteroids while maintaining asthma control over a 24-week period. Therefore, montelukast may be useful for long-term treatment in patients with asthma who require high doses of inhaled corticosteroids.

Acetates↗
PubMed2001

Antinociceptive effect following dietary-induced thiamine deficiency in mice: involvement of substance P and somatostatin.

We produced thiamine deficiency by treating mice with a thiamine deficient (TD) diet, but not with pyrithiamine, a thiamine antagonist. Twenty days after TD feeding, a significant antinociceptive effect was observed in the formalin test. A single injection of thiamine HCl (50 mg/kg, s.c.) on the 19th day after TD feeding (on the late TD stage) failed to reverse the antinociceptive effect, the muricide effect, and impairment of avoidance learning induced by TD feeding, as compared to pair-fed controls. These results indicate the possibility that the TD-induced antinociceptive effect may result from irreversible changes in the spinal and/or brain neurons. To clarify the involvement of substance P (SP) and somatostatin (SST) systems in the spinal cord, we examined the effect of intrathecal (i.t.) injections of these agonists on TD feeding-inducd elevation of pain threshold. I.t. injection of SP and SST elicited a behavioral response consisting of reciprocal hindlimb scratching, biting and/or licking of hindpaws. There was no significant difference in the behavioral response to SP between TD mice and PF mice on the 5th day after feeding. However, on the 10th and 20th day after TD feeding the response to SP was significantly increased compared with PF mice. This phenomenon was also observed with SST on the 20th day after TD feeding. These results indicate the possibility that TD feeding may produce an increased behavioral response to SP and SST through an enhanced sensitivity of neurokinin-1 and SST receptors in the spinal cord. Taken together, the antinociceptive effect following TD feeding may result from a decrease in spinal SP and SST contents.

Analgesia↗
PubMed2001

Infected abdominal aortic aneurysm presenting with sudden appearance: diagnostic importance of serial computed tomography.

The case of an 86-year-old man with an infected abdominal aortic aneurysm (AAA) that developed suddenly over 3 weeks is presented here. Previous reports on the diagnosis of infected AAA have focused mainly on the findings of single computed tomography (CT). These include the presence of a saccular aneurysm with an irregular lumen, perianeurysmal fluid, gas and/or hematoma, osteomyelitis in adjacent vertebral bodies, disruption of intimal calcification, and obscuring of the aortic wall. Our case report presents a useful diagnostic technique for the diagnosis of infected AAA, emphasizing the importance of serial CT for suspected cases, even if the initial scan does not demonstrate the findings listed above.

Aged↗
PubMed2001

Influence of gender on intraluminal thrombus of abdominal aortic aneurysms.

BACKGROUND: The mechanisms of formation of intraluminal thrombus (ILT) of abdominal aortic aneurysms (AAA) remain unknown. The aim of this study was to investigate the pathogenesis of AAA by analysis of ILT. METHODS: We retrospectively analyzed the size of ILT in 98 consecutive patients with AAA undergoing abdominal computed tomography (CT) examination. The volume of ILT was estimated by the area ratio of ILT in CT images. Important baseline variables related to small ILT were determined using logistic-regression analysis. RESULTS: There were two apparent peaks in the distribution of ILT ratio. Thirteen of 98 patients had negligible ILT with ratio < or = 0.1. Female gender was the only patient characteristic independently significantly correlated with small ILT (odds ratio 5.214, P = 0.0096). CONCLUSION: Our findings provide important evidence that AAA is formed by at least two different pathogenic processes. It is likely that this difference in mechanisms may be caused partly by sex hormones.

Aged↗
PubMed2001

Effect of Antioxidants on Radical-initiated Peroxidation of Retinal Homogenate.

Purpose: To compare the effect of antioxidants on radical-initiated peroxidation of retinal homogenate.Methods: Lipid peroxides in bovine retinal homogenate were induced by 5 mM FeNO(3) (Fe), 25 mM 2, 2'-azobis(2, 4'-dimethylvaleronitrile) (lipid-soluble, AMVN) or 50 mM 2, 2'-azobis (2-amidinoprpane) dihydrochloride (water-soluble, AAPH) and the preventive effects of antioxidants were measured. Phosphatidylcholine hydroperoxide (PC-OOH) was analyzed with high performance liquid chromatography (HPLC) as the endpoint biomarker.Results and Conclusion: Troglitazone, an oral hypoglycemic agent, inhibited PC-OOH production by Fe and AMVN. Therefore, it may be effective for protecting against oxidative stress on the inner surface plasma membranes and subcellular organelle. Quercetin has radical scavenging effects on both sides of the membrane, because it prevents PC-OOH production by AMVN or AAPH. These results demonstrate the usefulness of an in vitro screening test that can accurately and rapidly determine the capacity of an antioxidant against lipid peroxidation or oxidative stress. (Jpn Ophthalmol Soc 104:466-70, 2000)

Journal Article↗
PubMed2001

Topical application of antiangiogenic agent AGM-1470 suppresses anastomotic intimal hyperplasia after ePTFE grafting in a rabbit model.

BACKGROUND: Anastomotic intimal hyperplasia (AIH) remains an unsolved problem. Angiogenesis around the anastomosis is one of the important mechanisms accelerating AIH. In this study, we investigated the effects of an antiangiogenic agent AGM-1470 (O-[chloroacetyl-carbamoyl] fumagillol: AGM) on the thickness of AIH after expanded polytetrafluoroethylene grafting. METHODS: Study 1: Smooth muscle cells (SMCs) were cultured to form 3-mm-side square colonies by using 4 kinds of culture medium, containing AGM at concentrations of 0, 0.1, 1.0, and 10 ng/mL. The SMC colony spreading distance in each group was measured as an index of mitogenic activity. The isolated proliferative activity of SMCs was also assessed. Study 2: Male New Zealand white rabbits underwent inlay expanded polytetrafluoroethylene grafting of the carotid arteries. They were divided in 4 groups (control, vehicle, AGM [0.5], and AGM [5]) in which no topical application, Vaseline ointment, Vaseline ointment containing 0.5 mg AGM, or Vaseline ointment containing 5 mg AGM was applied to the anastomoses, respectively. Rabbits were fed a high-cholesterol diet for 2 weeks before and 8 weeks after the operation. AIH thickness was measured and capillary formation and SMC accumulation around the anastomoses were examined with immunohistochemical staining. RESULTS: Study 1: AGM suppressed SMC migratory activity in a cytostatic, but not cytotoxic, manner. Study 2: AGM ointment inhibited AIH in proportion to its concentration and also suppressed new capillary formation around the anastomoses and SMC accumulation in AIH. CONCLUSIONS: Topical application of the antiangiogenic agent AGM may become an important strategy for preventing AIH.

Angiogenesis Inhibitors↗
PubMed2001

Ex vivo fluorescence microscopy provides simple and accurate assessment of neutrophil-endothelial adhesion in the rat lung.

Neutrophil adhesion to the pulmonary endothelium is prerequisite to neutrophil transmigration and activation, both of which may lead to lung injury. A simple method to evaluate neutrophil adherence in the lung would be useful for developing new strategies for neutrophil-mediated lung injury. The purpose was to establish a simple method to evaluate neutrophil adhesion in the lung using ex vivo fluorescence microscopy. Rats were anesthetized, and the right jugular veins were catheterized. Neutrophils were isolated from another set of rats and labeled with 5,(6)-carboxyfluorescein diacetate. Animals were killed 120 s after a 1 x 10(6) labeled neutrophil injection. The pulmonary labeled neutrophil number was counted under a fluorescence microscope. In the first experiment, rats were given 0, 20, 200, or 2000 microg/kg lipopolysaccharide (LPS) i.p. At 4 h after challenge, the pulmonary labeled neutrophil number was determined. Kinetic studies were also performed at 0, 1, 4, and 8 h after 200 microg/kg LPS. Finally, anti-ICAM-1 Ab was injected i.v. before LPS 200 microg/kg, and the labeled neutrophil number in the lung was determined at 4 h. The number of pulmonary labeled neutrophils was higher after LPS 200 or 2000 microg/kg than after the other doses. The pulmonary labeled neutrophil number was increased at 4 h compared with the other time points. ICAM-1 blocking normalized the pulmonary labeled neutrophil number in the LPS group. In conclusion, our method seems to reflect ICAM-1-mediated neutrophil adherence to the endothelium in the present setting. This simple technique may be useful for evaluating neutrophil adhesion.

Animals↗
PubMed2001

Central serotonergic mechanisms on head twitch response induced by benzodiazepine receptor agonists.

Intraperitoneal injection of benzodiazepine receptor agonists (estazolam, zopiclone, triazolam: 0.03-0.24 mmol/kg) induces the head twitch response (HTR). The present study was undertaken to examine the possible participation of the serotonergic system in the mechanism of head twitches induced by benzodiazepine receptor agonists (BZ-RAs). The HTR induced by BZ-RAs was suppressed by pretreatment with ketanserine (1 mg/kg, i.p.), a selective 5-HT(2) receptor antagonist. Pretreatment with fluoxetine (10 mg/kg, i.p.), a 5-HT reuptake inhibitor, and 8-hydroxy-2-(di-n-propylamino)tetralin, a 5-HT(1A) receptor agonist, also suppressed the HTR induced by BZ-RAs. These results suggest that the HTR induced by BZ-RAs may be the result of an activation of postsynaptic 5-HT(2) receptors, probably due to direct action.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed2001

[Retinal hazard from blue light emitting diode].

PURPOSE: To compare the effect of exposure time from a blue(460 nm) light emitting diode(LED) on the morphology of the outer retina and determine conditions where damage occurs. MATERIALS AND METHODS: Young adult rhesus monkeys were anesthetized, and received blue LED exposure from a modified slit-lamp. A 3 mm beam of 0.85 mW was imaged onto the retina through a lens positioned before the cornea and exposure damage was determined at time intervals for 12 to 90 min. Fundus photography, fluorescein angiography(FAG), retinal tomography(HRT), and s-cone electororetinogram(S-ERG) were recorded at baseline, 2, and 30 days. RESULTS: Two days after 40 min exposure, there was a grey, discolored region, which was over-fluorescent in FAG, and an incresse in HRT and S-ERG corresponding to the site which was exposed to LED light. In histological examination at 30 days, the LED had caused produced a marked disruption of the disks of photoreceptor cells, damaged retinal pigment epithelium(RPE) apical villi, and a loss of RPE melanin after 90 min exposure. CONCLUSION: A threshold level was found around 40 min. This morphological damage may impair function and continuous exposure to blue light is potentially dangerous to vision.

Animals↗
PubMed2000

Successful surgical treatment for spontaneous retroperitoneal hematoma in polycythemia vera: report of a case.

Bleeding is a common complication of such myeloproliferative disorders as polycythemia vera, and it usually occurs in either the skin or mucosa. We experienced a case of a massive retroperitoneal hematoma with no history of trauma in association with polycythemia vera. A 68-year-old man was referred to our hospital as a case of acute abdomen, and was diagnosed as having a retroperitoneal hematoma and polycythemia vera based on radiological and hematological examinations. Because the mass effect of the hematoma caused a progressive deterioration of his respiratory condition, surgical drainage was necessitated and successfully undertaken. Although conservative treatment is reportedly sufficient and uncontrollable intraoperative bleeding may occur, especially in cases of myeloproliferative disorders, our experience suggests that an operation may nevertheless be occasionally advisable for this rare condition.

Aged↗
PubMed2000

Gastric carcinoma presenting with extensive extraluminal growth: report of a case.

We report a 48-year-old-man with gastric carcinoma presenting with an unusual extraluminal growth. The patient underwent a barium meal examination and gastrofiberscopy because of progressive anemia over 6 months. These examinations revealed a Borrmann type 3 advanced gastric carcinoma of the greater curvature of the antrum. Biopsies showed moderately differentiated tubular adenocarcinoma. The intraoperative findings showed gastric carcinoma associated with extensive extraluminal invasion into the adjacent organs, i.e., the transverse colon and mesocolon. A palliative distal gastrectomy with a partial resection of the transverse colon was performed because of peritoneal dissemination found in the mesocolon and rectovesical pouch. A histological examination of the specimen confirmed adenocarcinoma which had massively infiltrated the transverse colon and mesocolon. His postoperative course was uneventful. However, he died of peritonitis carcinomatosa 9 months later.

Adenocarcinoma↗
PubMed2000

Tuberculous peritonitis defying diagnosis: report of a case.

A case of tuberculous peritonitis, which has been scarcely encountered in clinical practice in recent years, is reported. A 32-year-old man was admitted to our hospital complaining of abdominal fullness, anorexia, and a 15 kg weight loss. His abdomen was distended. There was neither any previous history nor recent contact with tuberculosis. The laboratory data indicated increased C-reactive protein and erythrocyte sedimentation rate, but the white blood cell count was normal. A chest X-ray examination revealed no abnormalities. Abdominal X-ray showed scattered, small-intestinal gas shadows. Abdominal computed tomography scanning revealed a diffuse thickening of the dilated bowel wall, mainly adjacent to the mesentery. After a detailed examination a diagnosis of peritonitis carcinomatosa of unknown origin was suspected, and an exploratory laparotomy was done. Severe adhesions between the parietal peritoneum and the bowel were found. An excisional biopsy specimen was taken from the peritoneum, and a diagnosis of tuberculosis was thus made. Triple therapy with isoniazid, rifampicin, and kanamycin was started, and both the intestinal obstruction and anorexia were thus resolved.

Adult↗
PubMed2000

Near-infrared spectroscopy grades the severity of intermittent claudication in diabetics more accurately than ankle pressure measurement.

BACKGROUND: The aim of this study was to evaluate near-infrared spectroscopy (NIRS), combined with a treadmill-walking test, as a method of assessment of intermittent claudication (IC) in diabetic patients. METHODS: Some 208 symptomatic legs in 153 consecutive patients who complained of calf IC due to atherosclerotic disease were studied with NIRS and resting ankle : brachial pressure index (ABPI). RESULTS: There was good reproducibility of NIRS measurements. Three distinct types of IC were detected by NIRS. ABPI was significantly different between these three types in non-diabetic patients, but could not grade the severity of IC in diabetic patients. Recovery time (RT) of muscle oxygenation differentiated more accurately between severe and moderate claudication than ABPI in diabetics, although RT and ABPI had similar accuracy in non-diabetics. There was a significant correlation between RT and ABPI in non-diabetic patients and patients who had been diabetic for less than 10 years, while there was no correlation in patients who had had diabetes for over 10 years. CONCLUSION: Measurement of muscle oxygenation during exercise by NIRS graded the severity of IC in diabetic patients more accurately than resting ABPI. An abstract based on this paper was presented to the symposium of the 18th World Congress of the International Union of Angiology in Tokyo, Japan, September 1998

Adult↗