Biomedical subjects

Y Asai

Publications and source records attributed to Y Asai.

At least 73 records · Page 4Linked to original sources

PubMed2000

Optimization of the formulation and characterization of the physicochemical properties of the novel platelet-activating factor receptor antagonist E5880.

The injectable formulation of E5880, a novel platelet-activating factor (PAF) receptor antagonist, was determined from the study of pH stability, the selection of excipient, and the relationship between moisture and stability. The physicochemical properties of E5880 in the optimized formulation (0.6 mg/ml of E5880, 0.1% [4.8 mM] citric acid, 10% lactose, pH 2.8) were characterized. The critical micelle concentration of E5880 in the buffer was 0.1 mg/ml, and the structure was of spherical micelles. The micellar size was 5.6 nm and did not change before and after lyophilization and storage. The number of the molecules per micelle was 40. The micropolarity around the hydrocarbon region of the micelle was similar to that of butanol.

Chemistry, Pharmaceutical↗

PubMed2000

The effect of lipid A analog E5531 on membrane properties of dipalmitoylphosphatidylcholine.

The effect of the lipid A analog E5531 on the phospholipid membrane was determined and compared with that of the lipid A from Escherichia coli (EC). E5531 decreased the phase transition temperature of dipalmitoylphosphatidylcholine (DPPC) membrane and increased the fluidity and permeability. On the other hand, EC increased the phase transition temperature and decreased the membrane fluidity and permeability. These results suggest that the reason for the difference of biological effects of E5531 and lipid A from EC would be caused by the differences from the effect on the cell membranes.

1,2-Dipalmitoylphosphatidylcholine↗

PubMed2000

Formation and stability of the dispersed particles composed of retinyl palmitate and phosphatidylcholine.

The purpose of this study was to develop an intravenous formulation composed of retinyl palmitate (RP) for the treatment of cancer. RP was dispersed with soybean phosphatidylcholine (PC) using sonication and the dispersal mechanism was evaluated by characterizing the dispersed particles using dynamic light-scattering, fluorescence spectroscopy, and surface monolayer techniques. The dispersions in the RP mole fraction range of 0.1-0.8 were stable at room temperature for 3 days. A limited amount of RP was incorporated into PC bilayer membranes (approximately 3 mol%). The excess RP separated from the PC bilayers was stabilized as emulsion particles by the PC surface monolayer. When the PC content was less than the solubility in RP, the PC monolayer did not completely cover the hydrophobic RP particle surfaces and separation into oil/water occurred. The miscibility between RP and PC and the lipid composition were critically important for the stability of the dispersed particles (coexistence of emulsion particles [surface monolayer of PC + core of RP] with vesicular particles [bilayer]) of the lipid mixtures.

Anticarcinogenic Agents↗

PubMed2000

Prevention of endotoxin-induced lethality in mice by calmodulin kinase activator.

Porphyromonas gingivalis strain 381 lipid A showed lower activity in inducing interleukin (IL)-1alpha and IL-1beta production and cytokine mRNA expression than synthetic Escherichia coli lipid A (compound 506) in alveolar macrophages of C57BL/6 mice. Both the lipid As induced tumor necrosis factor alpha in alveolar macrophages and IL-6 in peritoneal macrophages. A calmodulin (CaM) antagonist, W-7, inhibited IL-1beta production and its mRNA expression induced by P. gingivalis lipid A but not compound 506 in alveolar macrophages. A CaM kinase activator reduced the induction of IL-1beta in the serum of mice when administered with compound 506, and protected the mice against the lethal toxicity. The modulation of a variety of intracellular enzymes including the CaM kinase may result in clinical control of endotoxic sepsis.

Animals↗

PubMed2000

Immunobiological activities of a chemically synthesized lipid A of Porphyromonas gingivalis.

A synthetic lipid A of Porphyromonas gingivalis strain 381 (compound PG-381), which is similar to its natural lipid A, demonstrated no or very low endotoxic activities as compared to Escherichia coli-type synthetic lipid A (compound 506). On the other hand, compound PG-381 had stronger hemagglutinating activities on rabbit erythrocytes than compound 506. Compound PG-381 also induced mitogenic responses in spleen cells from lipopolysaccharide (LPS)-hyporesponsive C3H/HeJ mice, as well as LPS-responsive C3H/HeN mice. The addition of polymyxin B resulted in the inhibition of mitogenic activities, however, compound 506 did not show these capacities. Additionally, compound PG-381 showed a lower level of activity in inducing cytokine production in peritoneal macrophages and gingival fibroblasts from C3H/HeN mice, but not C3H/HeJ mice, in comparison to compound 506. Thus, this study demonstrates that the chemical synthesis of lipid A, mimicking the natural lipid A portion of LPS from P. gingivalis, confirms its low endotoxic potency and immunobiological activity.

Animals↗

PubMed2000

A slow-motility phenotype caused by substitutions at residue Asp31 in the PomA channel component of a sodium-driven flagellar motor.

PomA is thought to be a component of the ion channel in the sodium-driven polar-flagellar motor of Vibrio alginolyticus. We have found that some cysteine substitutions in the periplasmic region of PomA result in a slow-motility phenotype, in which swarming and swimming speeds are reduced even in the presence of high concentrations of NaCl. Most of the mutants showed a sodium ion dependence similar to that of the wild type but with significantly reduced motility at all sodium ion concentrations. By contrast, motility of the D31C mutant showed a sharp dependence on NaCl concentration, with a threshold at 38 mM. The motor of the D31C mutant rotates stably, as monitored by laser dark-field microscopy, suggesting that the mutant PomA protein is assembled normally into the motor complex. Mutational studies of Asp31 suggest that, although this residue is not essential for motor rotation, a negative charge at this position contributes to optimal speed and/or efficiency of the motor.

Amino Acid Sequence↗

PubMed2000

Cysteine-scanning mutagenesis of the periplasmic loop regions of PomA, a putative channel component of the sodium-driven flagellar motor in Vibrio alginolyticus.

The sodium-driven motor consists of the products of at least four genes, pomA, pomB, motX, and motY, in Vibrio alginolyticus. PomA and PomB, which are homologous to the MotA and MotB components of proton-driven motors, have four transmembrane segments and one transmembrane segment, respectively, and are thought to form an ion channel. In PomA, two periplasmic loops were predicted at positions 21 to 36 between membrane segments 1 and 2 (loop(1-2)) and at positions 167 to 180 between membrane segments 3 and 4 (loop(3-4)). To characterize the two periplasmic loop regions, which may have a role as an ion entrance for the channel, we carried out cysteine-scanning mutagenesis. The T186 residue in the fourth transmembrane segment and the D71, D148, and D202 residues in the predicted cytoplasmic portion of PomA were also replaced with Cys. Only two mutations, M179C and T186C, conferred a nonmotile phenotype. Many mutations in the periplasmic loops and all of the cytoplasmic mutations did not abolish motility, though the five successive substitutions from M169C to K173C of loop(3-4) impaired motility. In some mutants that retained substantial motility, motility was inhibited by the thiol-modifying reagents dithionitrobenzoic acid and N-ethylmaleimide. The profiles of inhibition by the reagents were consistent with the membrane topology predicted from the hydrophobicity profiles. Furthermore, from the profiles of labeling by biotin maleimide, we predicted more directly the membrane topology of loop(3-4). None of the loop(1-2) residues were labeled, suggesting that the environments around the two loops are very different. A few of the mutations were characterized further. The structure and function of the loop regions are discussed.

Amino Acid Sequence↗

PubMed2000

Dehydroepiandrosterone retards atherosclerosis formation through its conversion to estrogen: the possible role of nitric oxide.

Dehydroepiandrosterone (DHEA) is speculated to have an antiatherosclerotic effect, although the mechanism of action remains unclear. The objective of the current study was to determine whether the antiatherosclerotic effect of DHEA is related to its conversion to estrogen and to define the role of nitric oxide (NO) in the antiatherosclerotic effect of DHEA. Forty-eight oophorectomized rabbits were divided into 5 groups and fed the following diets for 10 weeks: group 1, a regular rabbit diet plus 1% cholesterol (a high-cholesterol diet [HCD]); group 2, an HCD plus 0.3% DHEA; group 3, an HCD plus 0.3% DHEA and fadrozole (2.0 mg x kg(-1) x d(-1)), a specific aromatase inhibitor; group 4, an HCD plus 17beta-estradiol (20 microg x kg(-1) x d(-1)); and group 5, a regular diet. Atherosclerotic lesions, lipid deposition in aortic vessels, and basal and stimulated NO release were measured in the aforementioned groups of rabbits. NO release was measured by using an NO-selective electrode as well as by measuring vascular responses and the plasma NO metabolites nitrite and nitrate. The plasma total cholesterol level was increased, but there were no significant differences in lipid profile in the 4 groups of rabbits that were fed the HCD. The area occupied by atherosclerosis in the thoracic aorta was diminished by approximately 60% in the DHEA-treated rabbits (group 2) compared with the HCD group of rabbits (group 1); there was a corresponding 80% decrease in the estradiol group (group 4) but only a 30% decrease in the DHEA plus fadrozole group (group 3). In the aortas of rabbits from groups 1 and 3, the acetylcholine-induced and tone-related basal NO-mediated relaxations were diminished compared with those of the controls (group 5). However, these relaxations were restored in the aortas of group 2 and 4 rabbits, and an increase in NO release was observed in groups 2 and 4 compared with groups 1 and 3, as measured by an NO-selective electrode. Injection of neither solvent (20% ethanol/distilled water) nor fadrozole significantly affected the atherosclerotic area or the NO-related responses described above. We conclude that approximately 50% of the total antiatherosclerotic effect of DHEA was achieved through the conversion of DHEA to estrogen. NO may also play a role in the antiatherosclerotic effect of DHEA and 17beta-estradiol.

Acetylcholine↗

PubMed2000

Physiological concentration of 17beta-estradiol retards the progression of severe atherosclerosis induced by a high-cholesterol diet plus balloon catheter injury: role of NO.

The molecular mechanisms of the antiatherosclerotic effects of estrogen are not yet known. We evaluated the effects of 17beta-estradiol (E(2)) on high cholesterol diet- (HCD; standard diet and 1% cholesterol) and balloon injury-induced atherosclerosis in female New Zealand White rabbits. The abdominal aortas of 40 oophorectomized (Groups 1 through 5) and 8 nonoophorectomized (Group 6) rabbits were injured by balloon catheter, and the animals were then divided into the following groups and treated for 10 weeks: Group 1, standard diet; Group 2, standard diet plus a moderate dose of E(2) (100 microg x kg(-1) x d(-1)); Group 3, HCD; Group 4, HCD plus a moderate dose of E(2); Group 5, HCD plus a low dose of E(2) (20 microg x kg(-1) x d(-1)); and Group 6, HCD in nonoophorectomized rabbits. After the treatment phase, plasma E(2) was increased up to 282.2+/-45.5 pg/mL in Group 2, 263.0+/-41.5 pg/mL in Group 4, 87. 9+/-18.8 pg/mL in Group 5, and 45.6+/-7.3 pg/mL in Group 6. HCD-mediated increases in plasma lipid levels were not changed by E(2) treatment, whereas E(2) decreased the aortic intimal thickening in Group 2 animals compared with those in Group 1 and reduced atherosclerosis in the thoracic and abdominal aortas of Group 4, 5, and 6 rabbits compared with those in Group 3. E(2) restored the impaired abdominal aortic endothelium-dependent relaxation of balloon-injured and HCD-supplemented rabbits, and E(2) increased basal nitric oxide (NO) release. The basal NO-releasing effect showed a significant, inverse relation with the severity of atherosclerosis. Plasma E(2) concentration also showed a significant, inverse relation with atherosclerotic area. In conclusion, physiological concentrations of E(2) can retard the progression of severe atherosclerosis and stabilize atheromas induced by HCD and balloon injury. The retardation may be partially mediated by endothelial NO function in vessels treated with E(2).

Animals↗

PubMed2000

The effect of divalent cations on the membrane properties and pharmacokinetics in rat of the lipid A analogue E5531.

To obtain information on the effects of Ca2+ on the membrane properties of the lipid A analogue E5531, we have determined the aggregate size, zeta potential, membrane fluidity, micropolarity and permeability of the E5531 membrane as a function of Ca2+ levels. Within the molar ratios of [Ca2+]/[E5531] = 1 and 3, Ca2+ increased the zeta potential of the E5531 membrane but had no effect on aggregate size (approximately 20 nm). Within the above ratios, Ca2+ decreased the membrane fluidity, as measured by micropolarity of E5531 and increased the phase transition temperature. The pharmacokinetics in rats for these samples with different membrane fluidity, prepared by changing the pre-dose formulation concentration of Ca2+, was determined and a correlation between membrane fluidity and pharmacokinetics was clearly observed. It thus appears that Ca2+ effects the membrane fluidity of E5531 as well as its pharmacokinetics in rats.

Animals↗

PubMed2000

Formation of spherical micelles by the novel platelet activating factor receptor antagonist, E5880.

E5880, a novel platelet activating factor receptor antagonist, was dispersed in water for the preparation of injectable formulation and the physicochemical properties of the micelles were characterized. The critical concentration for formation of micelles was 0.12 mM. Using the area per molecule results, the critical packing parameter was calculated and showed that the structure was composed of spherical micelles and the number of the molecules per micelle was 88. The diameter of a micelle was 8.1 nm. The fluidity and micropolarity around the hydrocarbon region of the micelles were evaluated and compared to the surfactants, stearyltrimethylammmonium chloride and cetyltrimethylammonium chloride.

Lipids↗

PubMed2000

Eating habits and intensity of medication in elderly hypertensive outpatients.

Several dietary factors have been shown to lower blood pressure in elderly patients in clinical trials, but it is not known how eating habits affect blood pressure control in outpatients treated with antihypertensive drugs. We obtained data on dietary information regarding food groups rich in potassium, magnesium, and calcium by submitting a questionnaire to 190 elderly outpatients. Blood pressure levels and the intensity and cost of antihypertensive treatment were obtained from clinical records. The mean age and blood pressure were 72.3 +/- 9.3 years and 138.7 +/- 15.2/74.6 +/- 8.8 mmHg, respectively. Patients were divided into three groups on the basis of the intensity of medication: the LS group (n=52), treated with a low dose of a single drug; the HS group (n=95), treated with a high dose of a single drug; and the M group (n=43), treated with multiple drugs. Average age, body mass index, blood pressure levels, and extent of target organ damage were similar among the three groups. Intake frequency (rarely, once or twice per week, 3 to 6 times per week, or every day) of the food groups was compared among the three groups. The LS group ate fruit (p < 0.05) and seaweed (p < 0.01) with significant frequency compared with the other groups, whereas milk and dairy products were taken with similar frequency by all groups. The monthly cost of antihypertensive medications averaged 17,218 +/- 620 yen in the LS group, 17,746 +/- 375 yen in the HS group, and 20,066 +/- 1,364 yen in the M group. These data suggest that habitual intake of foods rich in potassium and magnesium are associated with reduced intensity and cost of medication and with preservation of blood pressure control in elderly hypertensive outpatients.

Aged↗

PubMed2000

[A case of teratoma in both the mediastinum and the intrapulmonary system].

A rare case of mature teratoma in both the mediastinum and the intrapulmonary system is presented. A 30-year-old male was admitted to our hospital due to tumor masses in the mediastinum and the left lung. We performed mediastinal tumor resection and left upper partial lobectomy. Neither tumor communicated with each other. Pathological findings revealed teratoma in the mediastinal lymph node and the intrapulmonary system including no malignant cells in either tumor. In this case, because metastasis and perforation were negative, we proposed that both tumors occurred at the same time in the early embryo.

Adult↗

PubMed2000

Selective inhibitor of p38 mitogen-activated protein kinase inhibits lipopolysaccharide-induced interleukin-8 expression in human pulmonary vascular endothelial cells.

Adult respiratory distress syndrome (ARDS) characterized by permeability edema is observed in severe insults such as bacteremia sepsis. Interleukin (IL)-8, which chemoattracts and activates neutrophils, has been suggested to play an important role in the production of ARDS. Therefore, the inhibition of IL-8 production is an important strategy for the treatment of ARDS. Recent studies have revealed the role of p38 mitogen-activated protein (MAP) kinase in cytokine expression and the inhibition by a selective inhibitor of p38 MAP kinase activity of cytokine expression in a variety of cell types. However, little is known about the role of p38 MAP kinase in lipopolysaccharide (LPS)-induced IL-8 expression in pulmonary vascular endothelial cells and the effect of a selective p38 MAP kinase inhibitor on it. In the present study, we therefore attempted to clarify these issues. The results showed that LPS induced p38 MAP kinase phosphorylation and activity, and SB 203580 as a selective inhibitor of p38 MAP kinase activity inhibited p38 MAP kinase activity and IL-8 expression in LPS-stimulated pulmonary vascular endothelial cells. These results indicate that p38 MAP kinase regulates LPS-induced IL-8 expression in pulmonary vascular endothelial cells. Although it is currently not known whether SB 203580 is capable of producing beneficial effects on ARDS, a strategy of inhibiting p38 MAP kinase activity by a selective p38 MAP kinase inhibitor may apply to the therapy for ARDS.

Blotting, Northern↗

PubMed2000

[Blood pressure measurement by primary care physicians: comparison with the standard method].

OBJECT: To examine the usual methods of blood pressure (BP) measurement by primary care physicians and to compare them with the standard methods. METHOD DESIGN: Cross-sectional survey by self-administered questionnaire. SUBJECTS: Primary care physicians who graduated from Jichi Medical School and were working at clinics. Each standard method for 20 items was defined as the one that was most frequently recommended by 6 guidelines (USA 3, UK 1, Canada 1, Japan 1) and a recent comprehensive review about BP measurement. RESULTS: Of 333 physicians, 190 (58%) responded (median age 33, range 26 to 45 years). Standard methods and percentages of physicians who follow them are: [BP measurement, 17 items] supported arm 96%; measurement to 2 mmHg 91%; sitting position 86%; mercury sphygmomanometer 83%; waiting > or = 1 minute between readings 58%; palpation to assess systolic BP before auscultation 57%; check accuracy of home BP monitor 56%; Korotkoff Phase V for diastolic BP 51%; bilateral measurements on initial visit 44%; small cuff available 41%; > or = 2 readings in patients with atrial fibrillation 38%; > or = 2 readings on one visit 20%; cuff deflation rate of 2 mmHg/pulse 14%; large cuff available 13%; check accuracy of monitor used for home visit 8%; waiting time > or = 5 minute 3%; readings from the arm with the higher BP 1%. [Knowledge about BP monitor, 2 items] appropriate size bladder: length 11%; width 11%. [Check of sphygmomanometer for leakage, inflate to 200 mmHg then close valve for 1 minute] leakage < 2 mmHg 6%; median 10 (range 0-200) mmHg. Average percentage of all 20 items was 39%. Number of methods physicians follow as standard: median 8 (range 4 to 15) and this number did not correlate with any background characteristics of the physicians. Furthermore, we also obtained information on methods not compared with the standard. Fifty-four percentage of physicians used more standard methods in deciding the start or change of treatment than in measuring BP of patients with good control. About 80% of physicians use home BP readings in diagnosis or treatment of hypertension, but about half of physicians with ambulatory BP monitors use their measured readings. CONCLUSION: Primary care physicians used various techniques for routine BP measurement and no physician completely followed the standard. Such measurements may affect the diagnosis and treatment of hypertension, but measuring all BPs solely by the standard is not practical. We need to have a practical and efficient method of BP measurement for routine practice in the primary care setting.

Adult↗

PubMed2000

[A case of anaphylaxic shock due to latex glove used on internal examination and on the probe of intrauterine echogram].

A 15 year old female with uterus bicornis bicollis was admitted for operation. She had a history of atopic dermatitis and allergy to buckwheat, raw egg and latex. Two months previously she had developed whole body flushing during dental treatment, and latex glove used by the dentist had been suspected as the cause. Prior to the operation she underwent internal examination and intrauterine echogram in which a latex glove was carelessly used by another gynecologist who had not confirmed her past history. After 30 minutes, dyspnea and urticaria without itching, appeared suddenly. Blood pressure decreased to 80/50 mmHg and heart rate increased to 120 beats.min-1. She was then transferred to our ICU. Methylprednisolone was administered intravenously for dyspnea and circulatory collapse. After 3 hours, the patient made an uneventful recovery. The increased plasma latex protein-specific IgE levels confirmed anaphylaxis to latex. The increasing incidence of potentially life-threatening allergic reactions to latex has caused mounting concern over recent years. We may suspect latex allergy when an anaphylaxic reaction or shock of unknown origin occurs. In hospitals, latex free products must be prepared for use with latex allergic patients and for protection of medical staff with this allergy.

Adolescent↗

PubMed2000

[Three cases of primary acute pulmonary cavitation in sarcoidosis].

Sarcoidosis has a variety of pulmonary manifestations including the nodular, or infiltrative form. However, primary cavitary formation is rare. In this report, we describe three cases of sarcoidosis with primary acute pulmonary cavitations. All three patients were young adults (2 men and 1 woman) and chest radiography and chest CT showed bilateral Hilary lymphadenopathy, multiple cavitations with thin, smooth walls, and diffuse granular shadows. Primary acute pulmonary cavitation of sarcoidosis was diagnosed, since a transbronchial biopsy specimen revealed sarcoid granuloma, and there was no evidence of infection, emphysematous change, or fibrotic or cystic bronchiectatic changes on chest radiography in any case. Corticosteroid therapy was given in all cases for severe extrathoracic disease (2 of severe uveitis and 1 of CNS involvement). After the treatment, the multiple cavities and diffuse granular shadows in the lung fields disappeared. We accordingly suggest that corticosteroid therapy is effective for primary acute cavitation in sarcoidosis.

Adult↗

PubMed1999

A HMG-CoA reductase inhibitor improved regression of atherosclerosis in the rabbit aorta without affecting serum lipid levels: possible relevance of up-regulation of endothelial NO synthase mRNA.

We determined the role of Fluvastatin: HMG-CoA reductase inhibitor on the regression of atherosclerosis following removal of dietary cholesterol. Male rabbits fed a 0.5% cholesterol diet for 12 weeks were divided into three groups: A1, hypercholesterolemic; A2, fed a regular diet for an 12 additional weeks; and A3, fed a regular diet with fluvastatin (2 mg/kg/day). Fluvastatin treatment (A3) did not affect serum lipid levels compared with A2. However, it decreased the atherosclerotic area in the aortic arch and decreased total and esterified cholesterol concentrations in the descending aorta. Tone-related basal NO release in the thoracic aorta was larger in A3 than in A2. eNOS mRNA in vessel was determined by competitive RT-PCR assay. It increased in A1, compared with normal aorta and decreased in A2; however, it did not decrease in A3. This is the first report of a decrease in eNOS mRNA in atherosclerosis after removal of dietary cholesterol and a reversal of it by a HMG-CoA reductase inhibitor, which may contribute to the regression of atherosclerosis.

Acyl Coenzyme A↗