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Biomedical subjects

Y Masuda

Publications and source records attributed to Y Masuda.

At least 379 records · Page 21Linked to original sources

Administration of phosphatidylcholine increases brain acetylcholine concentration and improves memory in mice with dementia.

Studies on the effect of phosphatidylcholine administration on memory are limited. We administered egg phosphatidylcholine to mice with dementia and to normal mice and compared the differences in memory and serum choline concentration, and choline and acetylcholine concentrations and choline acetyltransferase activities of three forebrain regions (cortex, hippocampus and the remaining forebrain). Mice with dementia were produced by mating sibling mice who had impaired memory for > 20 generations. These mice had poor memory and low brain acetylcholine concentration. We administered 100 mg of egg phosphatidylcholine (phosphatidylcholine group) or water (control group) by gavage to each mouse daily for about 45 d. Control mice with dementia had poorer memory in passive avoidance performance and lower brain choline (cortex and hippocampus) and acetylcholine (hippocampus and forebrain excluding cortex and hippocampus) concentrations and lower cortex choline acetyltransferase activity than the control normal mice (P < 0.05). The administration of phosphatidylcholine to mice with dementia improved memory and generally increased brain choline and acetylcholine concentrations to or above the levels of the control normal mice. In normal mice, phosphatidylcholine treatment did not affect memory or acetylcholine concentrations in spite of the great increase in choline concentrations in the three brain regions. Serum choline concentration in mice treated with phosphatidylcholine increased to a similar level in both strains of mice, indicating that the absorption of phosphatidylcholine was not impaired in mice with dementia. The results suggest that administration of egg phosphatidylcholine to mice with dementia increases brain acetylcholine concentration and improves memory.

Acetylcholine↗

Geranylgeraniol is a potent inducer of apoptosis in tumor cells.

We screened various isoprenoids to find inducers of apoptosis for human leukemia HL-60 cells, and found that GGO (geranylgeraniol) had the most potent apoptosis-inducing activity, as judged from DNA fragmentation in HL-60 cells. The apoptosis-inducing activity of GGO is concentration- and time-dependent. DNA synthesis by HL-60 cells was selectively inhibited on treatment with GGO. Besides HL-60 cells, apoptosis was induced by GGO in various tumor cell lines, including human myeloid multipotential leukemia K562, lymphoblastic leukemia Molt3, and colon adenocarcinoma COLO320 DM.

Adenocarcinoma↗

Clinical assessment of oxygen delivery and consumption during hypotensive anaesthesia--a clinical application of The Deep Picture.

Usual evaluation of the relationship between oxygen delivery (DO2) and oxygen uptake (VO2) is based on the arterial oxygen tension (pO2), oxygen saturation (sO2), haemoglobin concentration (ctHb), the same indicators in mixed venous blood and cardiac output, sometimes supplemented by the expiratory carbon dioxide concentration. And, so far, the relationship among DO2, VO2 and the new parameters for an evaluation of oxygen status (oxygen extraction tension: px, concentration of extractable oxygen: cx, oxygen compensation factor: Qx) (1) has not been discussed enough. Therefore, this study was designed to evaluate whether the new parameters give the clinically significant information to analyse the relationship between DO2 and VO2 during the acute haemodynamic change with intentionally induced hypotension in anaesthetized adult patients.

Adult↗

Detection of the Epstein-Barr virus in primary gastric lymphoma by in situ hybridization.

The Epstein-Barr virus (EBV) has been shown to be associated with numerous human malignancies including Burkitt's lymphoma and nasopharyngeal lymphoepithelioma. In addition, some typical gastric adenocarcinomas were also recently reported to demonstrate EBV relevance. The present study was designed to detect EBV in primary gastric lymphoma, using the in situ hybridization (ISH) method, in which oligonucleotide probes for the EBER1 RNA and the EBV DNA W region have been used. Of the 49 cases of primary gastric lymphoma studied, which all showed B cell immunophenotype, EBER1 sequences could only be found in four cases, including two low-grade cases and two high-grade cases of histological subtypes while the number of positive cells was less than 50% of the tumor cells. In one case of low-grade mucosa associated lymphoid tissue (MALT) lymphoma, the EBER1-positive neoplastic cells were found in the regional lymph node, but the primary site of the stomach showed no positive signals. The EBV presence was further confirmed by the EBV DNA ISH. Using the ISH method, rare or occasional positive lymphoid cells (probably non-tumorous bystander cells) could be detected in 10 other cases including all histological subtypes. The present study shows that only a small proportion of primary gastric lymphoma is associated with EBV, and such positive cases could be found in both high- and low-grade histological subtypes. It is also suggested that the EBV presence in the neoplastic cells of some cases of primary gastric lymphoma is most likely a secondary phenomenon.

Adult↗

Characterization of muscarinic receptors mediating relaxation and contraction in the rat iris dilator muscle.

1. The characteristics of muscarinic receptors mediating relaxation and/or contraction in the rat iris dilator muscle were examined. 2. Relaxation was induced in a dilator muscle by application of acetylcholine (ACh) at low doses (3 microM or less) and contraction was induced by high doses. Methacholine and carbachol also showed biphasic effects similar to those of ACh; in contrast, bethanechol, arecoline, pilocarpine and McN-A-343 induced mainly relaxation but no substantial contraction. 3. After parasympathetic denervation by ciliary ganglionectomy, the relaxant response to muscarinic agonists disappeared upon nerve stimulation. Application of McN-A-343 and pilocarpine induced only small contractions in denervated dilator muscles, indicating that these are partial agonists for contraction. 4. pA2 values of pirenzepine, methoctramine, AF-DX 116, himbacine, and 4-DAMP for antagonism to pilocarpine-induced relaxation in normal dilator muscles and those for antagonism to ACh-induced contraction in denervated dilator muscles were determined. The pA2 values for antagonism to relaxation of all these antagonists were most similar to those for M3-type muscarinic receptors. 5. Although pA2 values for contraction of these antagonists, except for methoctramine, were very close to those for relaxation, contraction was not significantly antagonized by methoctramine. Contraction might be mediated by M3-like receptors which have a very low affinity for methoctramine. 6. In conclusion, ACh-induced biphasic responses in rat iris dilator muscles were clearly distinguished from each other by specific muscarinic agonists and parasympathetic denervation, whereas muscarinic receptors could not be subclassified according to the pA2 values of 5 specific antagonists only.

(4-(m-Chlorophenylcarbamoyloxy)-2-butynyl)trimethy↗

Single- and multiple-dose pharmacokinetics of AM-1155, a new 6-fluoro-8-methoxy quinolone, in humans.

The pharmacokinetics of AM-1155, a new 6-fluoro-8-methoxy quinolone, was examined in healthy male volunteers after the oral administration of a single dose of 100, 200, 400, or 600 mg and multiple doses of 300 mg twice daily for 6.5 days (13 total doses). Throughout the whole study period, AM-1155 was well tolerated in every subject. In the single-dose study, the concentrations in serum reached a peak between 1 and 2 h, and the peak concentrations were 0.873, 1.71, 3.35, and 5.41 micrograms/ml at the doses of 100, 200, 400, and 600 mg, respectively. The elimination half-life was 7 to 8 h, independently of the doses. The unchanged drug was excreted mainly in the urine, with 82 to 88% of the doses appearing for 72 h. The fecal recovery of the unchanged drug amounted to 5.7% for 72 h after a single oral administration of a 400-mg dose. Urinary excretion of metabolites was minimal. The serum protein binding was 20%, independently of the concentrations in serum. The concentrations in saliva were approximately 80% of those in serum. The intake of food had no effect on the pharmacokinetic parameters and urinary excretion of AM-1155 except the slight decrease in area under the concentration-time curve. The concurrent administration of probenecid prolonged the elimination half-life, increased the area under the concentration-time curve, and decreased the apparent total body clearance, renal clearance, urinary recovery of unchanged drug, and the excretion ratio (intrinsic renal clearance of AM-1155/creatinine clearance). This indicated that the tubular secretion contributed to the renal excretion of AM-1155. In the multiple-dose study, the concentrations of AM-1155 in serum and urine reached a steady state within 2 to 3 days. The measured concentrations in serum fitted well the simulation curve, which reflected the persistence of linear pharmacokinetics of AM-1155. In conclusion, AM-1155 is expected to be clinically useful because of its potent antibacterial activity and favorable pharmacokinetics.

Adult↗

[Three simple maze tests employing mice housed in maze apparatuses].

This report deals with three different maze methods using spontaneous learning behavior. Forty-eight mice housed in an apparatus with a multiple maze mastered the maze task on the 5th day after the start of housing. Then they were divided into four groups, and two of the groups were treated with AF64A (3.5 nmol, i.c.v.) or trimethyltin (TMT, 3 mg/kg, p.o.), and the other two groups were treated with the vehicle as the respective control. Seven days after the treatment, their memory retrieval was tested. Subsequently, the same mice were housed in the apparatus with a T-maze. After the finish of the experiment using the T-maze, they were housed in the apparatus with an eight arm radial maze. The control groups mastered the T-maze task with a 3-sec delay on the 4th day after the start of housing and the radial maze task on the 10th day after the start of housing. Both the treatments lowered the performance in all maze tasks. These results show that the mice housed in the apparatus with maze learned to negotiate the maze spontaneously, and the apparatuses are useful for estimating memory in mice with little effort.

Animals↗

The effects of potassium channel openers and blockers on the specific binding sites for [3H]glibenclamide in rat tissues.

The effects of K+ channel openers (PCOs), NIP-121, levcromakalim and nicorandil, and the blockers of the specific binding sites for [3H]glibenclamide, ATP-sensitive K+ channel blocker, were investigated in rat brain and cardiac ventricle membrane preparations. When the microsomes were incubated with [3H]glibenclamide, the specific glibenclamide binding was fully inhibited by unlabeled glibenclamide (1 microM) and apamin (100 microM). However, the specific glibenclamide binding was not influenced by excess NIP-121, levcromakalim and nicorandil, although glibenclamide antagonized the increase in the 86Rb+ efflux by PCOs. On the other hand, the binding of [3H]glibenclamide after a long pre-incubation (60 min) at 37 degrees C with NIP-121 and levcromakalim at pharmacological effective concentrations (10 nM to 1 microM) was significantly influenced. Both PCOs partially reduced both Kd and Bmax values of the specific [3H]glibenclamide binding in a concentration-dependent manner that was not regulated by GTP gamma S. The dose-effect relationships for the Bmax's of NIP-121 and levcromakalim seemed similar to those for vasorelaxation. These findings indicate that the pharmacological effect of PCO may be caused by the binding to its own specific sites but not to the specific sulfonylurea sites. The binding of PCOs may inhibit, in a negative allosteric manner the binding of sulfonylureas.

Animals↗

Comparative study of vasodilator effects of the potassium channel openers NIP-121 and levcromakalim in dogs and rats.

The effects of potassium channel openers NIP-121 ((+)-7,8-dihydro-6,6-dimethyl-7-hydroxy-8-(2-oxo-piperidine-1-yl)-6H- pyrano[2,3-ss]benz-2,1,3-oxadiazole) and levcromakalim were examined in vitro and in vivo. In isolated canine vascular beds, NIP-121 (3 x 10(-9) to 10(-7) M) and levcromakalim (3 x 10(-8) to 10(-6) M) produced a concentration-dependent reduction in the vasoconstrictor responses to U46619. The effects were antagonized by glibenclamide, an ATP-sensitive potassium channel blocker. The maximal relaxation was more than 70% of the maximal vasodilation induced by papaverine (10(-4) M), except in the basilar artery. These compounds had very potent effects on the coronary and cranial mesenteric arteries and saphenous vein. In the coronary perfused rat heart, both compounds (10(-7) M) also increased coronary perfusion flow. The effects were also inhibited by glibenclamide (10(-6) M). In anesthetized dogs, NIP-121 (1 to 10 micrograms/kg (3.2 to 32 nmol/kg), i.v.) and levcromakalim (3 to 30 micrograms/kg (10.5 to 105 nmol/kg), i.v.) dose-dependently increased coronary and renal blood flow. NIP-121 and levcromakalim at higher doses produced the greatest increase in coronary blood flow among the blood vessels examined, in spite of the hypotensive effect. In conclusion, NIP-121 and levcromakalim were similarly selective vasodilators on the canine isolated coronary and cranial mesenteric arteries and saphenous vein, and they selectively increased coronary blood flow in vivo. With respect to increasing the coronary blood flow, NIP-121 had a fourfold greater potency than levcromakalim. This effect might be related to the glibenclamide-sensitive potassium channels.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗

Vasopressin V1-receptor stimulation produces a positive inotropic response without affecting pHi in guinea pig papillary muscles.

Effects of arginine-vasopressin (AVP) on the contractile force, action potential (AP) and intracellular pH (pHi) were studied in isolated guinea pig papillary muscles using conventional and ion-selective microelectrode techniques. AVP increased the developed tension and the resting tension, and these responses were attenuated by the V1-receptor antagonist OPC-21268 (1-(1-[4-(3-acetylaminopropoxy)benzoyl]-4-piperidyl)-3,4-dihydro-2 (1H)- quinolinone). However, AVP failed to affect AP configuration or pHi. These results suggest that AVP produces a positive inotropy by mechanism(s) other than intracellular alkalinization.

Animals↗

Evidence that the expression of the gene for NADPH-cytochrome P-450 reductase is n-alkane-inducible in Candida maltosa.

A gene coding for NADPH-cytochrome P-450 reductase of an n-alkane-assimilating yeast, Candida maltosa, was isolated and sequenced. Northern analysis and assay of the expression of the reporter gene under the control of the promoter of this gene showed that the transcriptional level was induced 4 to 8-fold in cells grown on n-alkane relative to cells grown on glucose.

Alkanes↗

Physiological significance of plasma sulfoconjugated dopamine: experimental and clinical studies.

Sulfoconjugated catecholamines have been regarded simply as metabolites of free catecholamines. However, a conjugated form of the catecholamine, dopamine has recently attracted much attention because it is present at high levels in the plasma of humans and experimental animals. We carried out experimental and clinical studies to determine the physiological significance of this large amount of dopamine conjugate in the plasma. Clinical studies showed that the plasma level of dopamine sulfate decreased significantly during the acute phase of heart failure, whereas that of free dopamine increased. Moreover, the plasma level of conjugated dopamine in patients with essential hypertension was higher than that in control subjects, and being highest in patients with renal hypertension. In experimental studies, we examined the activity for deconjugating DA sulfate in homogenates of organs from dogs. The kidney and liver exhibited the highest activities, and in the heart, the activity was higher in the atrium than the ventricle. We also examined the effect of dopamine sulfate on isolated perfused rat heart. Dopamine sulfate was found to be converted to free dopamine, which was responsible for the positive inotropic action, in atrial tissue. Moreover, deconjugation of DA sulfate to the free form was accelerated by a high work lord on the heart. From these results, we conclude that the formation of dopamine sulfate plays a role in regulating the level of plasma free dopamine and that plasma dopamine sulfate may be a storage or reserve form of dopamine. Free (or active) dopamine may be formed through a deconjugation reaction when necessary.

Adult↗

Blood microvascular organization of the nasal-associated lymphoid tissue of the guinea pig: a scanning electron microscopic study of corrosion casts.

It has previously been confirmed that the guinea pig has aggregations of 10-20 lymphoid follicles at the junction of the nasal cavity and the nasopharyngeal duct. The vascular architecture of this nasal-associated lymphoid tissue (NALT) was studied by the corrosion cast/scanning electron microscope method. The NALT was supplied by branches of the inferior nasal artery. These afferent arterial branches gave off arterioles to the follicles and the interfollicular regions, where the arterioles ramified into capillaries. Some of these arterioles reached the subepithelial region to form a single-layer dense capillary network. The subepithelial capillaries gathered into short collecting venules, which in turn drained into high endothelial venules (HEV) in the interfollicular region. The HEV, which also receives tributaries from the follicular and interfollicular capillary plexuses, descended in the interfollicular regions and finally flowed into the efferent veins at the bottom of the NALT. Indentations impressed by high endothelial cells (HEC) were prominent on the surface of the HEV casts, and their frequency was larger in the upper course or segments than in the lower. This suggests that the incidence of HEC in the upper segments is higher than in the lower segments, and these findings are consistent with the hypothesis that some substances which are taken up into the subepithelial capillaries and transported to the venules induce differentiation and maintain of HEVs.

Animals↗

Major basic protein, eosinophil cationic protein, and arylsulfatase in nasal secretions of patients with Japanese cedar pollinosis.

In 15 patients with Japanese cedar pollinosis and 10 healthy control subjects, levels of major basic protein (MBP), eosinophil cationic protein (ECP), and arylsulfatase B (As) in the nasal secretions were examined before and after challenge with Japanese cedar pollen extract. The MBP and ECP levels in the patients were significantly higher 30 min after challenge than those before challenge (P < 0.005). MBP and ECP levels after challenge were significantly higher in the nasal secretions of patients than in the controls (MBP: P < 0.01, ECP: P < 0.05). The level of As after challenge was significantly higher in the nasal secretions of patients than in the controls. These results suggest that eosinophils activate or modify the immediate, nasal allergic reaction and have a role in regulating immunological responses.

Adolescent↗

Toxicological study on rats fed haloperidol: 80 week chronic toxicity test.

Haloperidol (HPL) was administered by presenting HPL-admixed food to 20 male and 19 female Sprague-Dawley rats from the age of 5 weeks at a target dose of 1.0 mg/kg/day for 80 weeks. The range of the actual daily dose was 0.48-1.11 mg/kg in males and 0.34-0.73 mg/kg in females. The control rats(13 males and 13 females) were given normal food. In the present study, the general condition and locomotor activity of these rats were examined. 1. The number of HPL-treated animals that died during the administration periods (11 males and 9 females) and the symptoms observed immediately before their death were comparable to those in the control group. Vacuous chewing movement developed in HPL-treated animals (12 males and 11 females) after the 28th week of administration. These movements showed a tendency of decrease after the 68th week. Blepharitis was observed in all females and 3 males of the HPL-treated group, but in none of the controls of either sex. Subcutaneous masses in the chest and abdomen were observed in 3 HPL-treated females and 6 control females, but there was no significant difference in their incidence between the two groups. 2. The body weight gain in the HPL-treated group was suppressed in males, but was promoted and then suppressed in females. The food consumption in the HPL-treated group was similar, but the water consumption was reduced in both sexes as compared with the control groups. 3. Locomotor activity was reduced in the HPL-treated group for both males and females, and no tolerance developed. These results suggest that HPL does not have a possibility to cause death even by chronic administration at the doses examined in the present study. However, the occurrence of body weight losses and blepharitis indicated the need for particular attention to these symptoms during chronic administration.

Animals↗

Morphogenesis and cell wall changes in maize shoots under simulated microgravity conditions.

Various plant organs show a spontaneous curvature on a three-dimensional clinostat. Changes in the cell wall metabolism underlying the curvature were examined in maize shoots. In coleoptile nodes, no differences were detected in either the level or the composition of cell wall polysaccharides between the convex and the concave halves. However, the convex side showed a higher activity of (1 --> 3),(l --> 4)-beta-glucan breakdown, which appears to be associated with the curvature. In the elongating region of coleoptiles, the accumulation of wall polysaccharides occurred in the convex side. There was no significant difference in the glucanase activity between both sides. Thus, the spontaneous curvature in different regions of maize shoots may be brought about through different mechanisms under simulated microgravity conditions.

Cell Wall↗

Observation of head-shaking nystagmus with an infrared Frenzel's glass.

It has been reported that a head-shaking test is very useful in clinical practice. To observe head-shaking nystagmus (HSN) a Frenzel's glass and electronystagmography (ENG) have been used. Although observation with Frenzel's glass is a simple method, it tends to suppress after shaking nystagmus, as gazing is not completely eliminated with Frenzel's glass. An electronystagmogram in darkness can eliminate gazing completely, but it requires much trouble in routine use. We therefore tried to use Frenzel's glass with an infrared CCD camera. We observed highly provoked HSN like ENG in darkness and were able to use it without difficulty. We recognized the second phase in several cases with only an infrared Frenzel's glass and the rotatory component of the nystagmus. This method is more convenient and valuable for clinical use than ENG and Frenzel's glass.

Dizziness↗

Simplified PET quantitation of myocardial glucose utilization.

UNLABELLED: The purpose of this study was to validate experimentally a simple method to quantify tissue glucose utilization with the brain reference index (BRI) using 14C-deoxyglucose and assess its clinical feasibility for myocardial PET. METHODS: To validate the BRI method, glucose utilization in myocardial and skeletal muscle was studied in rats with 14C-deoxyglucose after increasing doses of oral glucose loading. To assess clinical feasibility of the method, the BRI was applied to nine patients undergoing myocardial PET and compared to rMGU measured by the deoxyglucose model of Sokoloff et al. and by Patlak graphical analysis. The normal range of myocardial FDG uptake expressed as the BRI was estimated with four normal volunteers. RESULTS: In skeletal muscle, a dose-dependent increase of glucose utilization was observed during oral glucose loading with doses up to 4 mg/g. In the myocardium, glucose utilization increased with a glucose loading dose of up to 1 mg/g without increasing further at greater glucose doses. Ratios of maximal glucose utilization in glucose-loaded rats to 19-hr fasted rats (controls), expressed as the BRI for left and right ventricular myocardium and skeletal muscle were 4.16, 3.74 and 7.39, respectively. Glucose utilization of right ventricular myocardium was approximately 70% of left ventricular myocardium for all glucose-loaded conditions. For patients, the BRI correlated with rMGU; four of these patients had a constant plasma glucose concentration. CONCLUSION: Myocardial BRI is a sensitive indicator of rMGU that does not require dynamic data acquisition or constant plasma glucose concentrations.

Animals↗