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Biomedical subjects

Y Oshima

Publications and source records attributed to Y Oshima.

At least 163 records · Page 9Linked to original sources

Specific CYP3A4 inhibitors in grapefruit juice: furocoumarin dimers as components of drug interaction.

Four components were isolated from grapefruit juice that inhibit human CYP3A-mediated drug oxidation. The structures of these compounds were identified as furocoumarin derivatives by absorption spectra, APCI-liquid chromatography/tandem mass spectrometry and nuclear magnetic resonance after their purification by reversed-phase high performance liquid chromatography. They include two new furocoumarins, 4-[[6-hydroxy-7-[[1-[(1-hydroxy-1-methyl)ethyl]-4-methyl-6- (7-oxo-7H-furo[3,2-g][1]benzopyran-4-yl)-4-hexenyl]oxy]-3,7-dimeth yl- 2-octenyl] oxy]-7H-furo[3,2-g][1]benzopyran-7-one (GF-I-1) and 4-[[6-hydroxy-7-[[4-methyl-I- (1-methylethenyl)-6-(7-oxo-7H-furo[3,2-g][1]benzopyran-4-yl)-4- hexenyl] oxy]-3,7-dimethyl-2-octenyl]oxy]-7H-furo[3,2-g][1]benzopyran-7-one (GF-I-4). These furocoumarins are strong candidates for causative agents of grapefruit juice-mediated drug interaction, because of an inhibition potential that is equal to or stronger than the prototypical CYP3A4 inhibitor, ketoconazole, on liver microsomal testosterone 6 beta-hydroxylation.

Beverages↗

[Pharmacological properties of pteleprenine, a quinoline alkaloid from Orixa japonica (Rutaceae), in guinea pig ileum and canine left atrium].

We investigated the pharmacological properties of pteleprenine, a quinoline alkaloid contained in the Rutaceous plant, Orixa japonica, on the contractile responses of the guinea pig ileum and on the inotropic responses of the canine left atrium. Contractile responses of the ileum to acetylcholine and histamine were not inhibited by less than 10(-6) M of pteleprenine. Meanwhile, the nicotine induced-contraction of the ileum was dose-dependently diminished by pteleprenine, but the contractile response to nicotine did not reach the maximum value in the presence of 10(-5) M of pteleprenine. The pA2 value of pteleprenine was 6.6 as determined from the Schild plot, which slope was nearly unity. Furthermore, the contraction of the ileum by 10(-5) M of 1,1-dimethyl-4-phenylpiperazinium (DMPP), a specific agonist of nicotinic acetylcholine receptors, was also dose-dependently suppressed by pteleprenine. On the other hand, 10(-5) M of pteleprenine did not have considerable inhibitory effects on acetylcholine- and nicotine-induced negative inotropic effects in the canine left atrium. From these results, it is suggested that pteleprenine has a specific inhibitory effect on nicotinic acetylcholine receptors in the guinea pig ileum.

Alkaloids↗

The phosphatase system in Saccharomyces cerevisiae.

The yeast Saccharomyces cerevisiae has at least six species of acid and alkaline phosphatases with different cellular localizations, as well as inorganic phosphate (Pi) transporters. Most of the genes encoding these enzymes are coordinately repressed and derepressed depending on the Pi concentration in the growth medium. The Pi signals are conveyed to these genes through a regulatory circuit consisting of a set of positive and negative regulatory proteins. This phosphatase system is interested as one of the best systems for studying gene regulation in S. cerevisiae due to the simplicity of phenotype determination in genetic analysis. With this methodological advantage, considerable amounts of genetic and molecular evidence in phosphatase regulation have been accumulated in the past twenty-five years. This article summarizes the current progress of research into this subject.

Amino Acid Sequence↗

[Treatment of age-related subfoveal choroidal neovascularization by low-dose external radiation: a preliminary study].

We applied low dose external beam radiation (6 MV) to 17 eyes of 17 patients (Mean age 70.9 years, range 58 approximately 85) who had subfoveal choroidal neovascularization associated with age-related macular degeneration. None of the cases were suitable for photocoagulation according to the Macular Photocoagulation Study protocol, and no feeding vessels underlying choroidal neovascular membrane could be detected. Corrected visual acuity ranged from 0.02 to 0.6 before treatment. The patients were divided into two groups. One group of 11 eyes was treated with 10 Gy and the other group of 6 eyes with 21 Gy. Mean follow up period was 347 +/- 89 (mean +/- standard deviation) days in the 10 Gy group and 312 +/- 100 days in the 21 Gy group. We evaluated the outcome as "effective' if no progression in neovascular membrane was found by ophthalmoscopic and angiographic examination. Only 3 eyes (21%) of patients in the 10 Gy group and 2 eyes (33%) in 21 Gy group showed any effect. Although the rate of progression in choroidal neovascular membrane was significantly smaller in the 10 and 21 Gy group than in the controls, the corrected visual acuity in the treated group was not improved over that of the controls. No serious complications were seen. Only one case showed a stabilized neovascular membrane in the control group of 7 patients. Although the present results seem to be worse than those in previous reports, the efficacy of this treatment still needs to be evaluated because no beneficial strategies in the treatment of subfoveal neovascularization have been established.

Aged↗

[DDD pacemaker implantation--cardiac pacemaker tips in the left atrium and ventricle by the left thoracotomy].

Recently DDD pacemaker implantation for the children has undergone trials world wide; though regarding the approach, ways and positions of the epicardial lead, a few problems are still remained to be discussed. Now we report 9 cases (5 males, 4 females) of DDD pacemaker implantations by the left anterolateral thoracotomy approach. The 9 patients weighing 6.5 to 33 kg, were aged 11 months to 12 years (mean 6 years) of whom male 5, female 4 with degree of Block; 2 and 7. To all patients the stab-in type epicardial tips were implanted in the left atrium, the screw-in type ventricular epicardial tips were in the left ventricle by the 4th intercostal thoracotomy, and the pacemaker generators were beneath the fascia of the abdominal rectus muscle. We have no sensing and pacing failure, all pacemakers are working in the DDD mode well.

Child↗

Unifocalization and systemic-to-pulmonary shunt using internal mammary artery for tetralogy of Fallot and pulmonary atresia with diminutive pulmonary artery and arborization anomaly.

We report successful palliation of tetralogy of Fallot and pulmonary atresia with diminutive pulmonary arteries and arborization anomaly. Unifocalization and systemic-to-pulmonary artery shunt using an internal mammary artery were successfully performed. The internal mammary artery shunt provided a sufficient blood supply for a diminutive and fragile pulmonary artery, and brought a progressive improvement of exercise intolerance and polycythemia probably due to the growth potential.

Cardiovascular Surgical Procedures↗

[Effects of aprotinin on blood loss reduction in children undergoing repair of tetralogy of Fallot].

The effect of aprotinin on the blood loss reduction was studied in children undergoing repair of tetralogy of Fallot. We administered aprotinin to consecutive 21 patients during the repair of tetralogy of Fallot and examined the blood loss and operative time in comparison with that in a control group of 20 patients. 30,000 KIU/kg of aprotinin was infused as the initial cardiopulmonary bypass (CPB) dose and 10,000 KIU/kg/hr was continuously administered as the maintenance dose during CPB. There was no resternotomy case due to bleeding and no operative death in both groups. Blood loss after CPB during operation and total blood loss during operation were significantly lower in aprotinin group than in control group. There were no differences between two groups in the volume of chest tube drainage in the postoperative 24 hours and the duration of chest tube drainage. Time from cessation of CPB to skin closure and total operative time were significantly shorter in aprotinin group than in control group. In conclusion, aprotinin was effective on the reduction of blood loss and the shortening of operative time in children undergoing repair of tetralogy of Fallot.

Aprotinin↗

Electroporation and bleomycin in glaucoma-filtering surgery.

PURPOSE: To develop a new treatment in glaucoma-filtering surgery using combined treatment with electroporation and the antiproliferative drug bleomycin. METHODS: Pigmented rabbits were treated with both bleomycin (10 micrograms/ml) and localized electric pulses (EP) using a special probe (5 V/cm, 100 msec, 8 pulses) (n = 10; group A). After EP treatment, bleomycin was washed out with 50 ml balanced salt solution, and then a posterior lip sclerectomy was performed on the same area. We also studied rabbits undergoing a posterior lip sclerectomy with bleomycin treatment alone (n = 10; group B), a posterior lip sclerectomy with EP treatment alone (n = 5; group C) and a posterior lip sclerectomy alone using the same operation (n = 5; group D, negative control). The intraocular pressure (IOP) was measured before and 1, 3, 5, 7, 10, 15, and 20 days after surgery. The formation of blebs, the conjunctiva, and the cornea were periodically examined by slit-lamp biomicrography. RESULTS: In every group, the IOP decreased until day 7, and no significant difference was observed among the four groups. In groups B, C, and D (control), the IOP increased gradually from day 10 and thereafter returned to the preoperative level after 15 days. However, in group A, the IOP remained lower than the preoperative level for 20 days; it was also significantly lower than each of the other three groups (P < 0.01). The survival rate of a filtering bleb was significantly higher in group A than in groups B, C, or D, but the survival rate in group B was not higher than groups C or D. No adverse effects were clinically observed in the ocular tissue, such as the cornea and conjunctiva. CONCLUSIONS: The combined treatment with EP and bleomycin was found to decrease IOP more prominently than EP or bleomycin treatment alone in filtering surgery. This treatment thus makes filtering surgery effective by decreasing the dose of the antiproliferative drug and by possibly localizing the drug delivery.

Animals↗

Regulation of phosphatase synthesis in Saccharomyces cerevisiae--a review.

Transcription of the genes encoding acid and alkaline phosphatases and the inorganic phosphate (Pi) transporter of Saccharomyces cerevisiae are coordinately repressed and derepressed depending on the Pi concentration in the culture medium. This phosphatase system is particularly suited for the study of regulatory mechanisms, because the acid phosphatase activity of each colony on a plate is easily detected by specific staining methods and there is a 500-fold difference between the repressed and derepressed levels of acid phosphatase activity. With these advantages, considerable amounts of genetic and molecular evidence have been accumulated in the past two decades. This article summarizes our current knowledge on this subject.

Acid Phosphatase↗

A putative membrane protein, Pho88p, involved in inorganic phosphate transport in Saccharomyces cerevisiae.

Transcription of a regulatory gene, PHO81, in the phosphatase regulon of Saccharomyces cerevisiae is repressed by inorganic phosphate (Pi) in the medium via that same regulatory system. The activity of Pho81p, the product of PHO81, is also inhibited by a high concentration of Pi in the medium. Increased dosage of PHO86, a gene encoding a putative membrane protein associated with a Pi transporter complex, activates the Pi-inhibited Pho81p produced under the control of the GAL1 promoter. A new gene, PHO88/ YBR106w, has now been identified as a multicopy suppressor of the rAPase- phenotype of the cells caused by the Pi inhibition of Pho81p. The pho86 disruptant expressed rAPase activity in high-Pi medium, while the pho88 disruptant did not. The delta pho86 delta pho88 double disruption resulted in enhanced synthesis of rAPase under the high-Pi condition and conferred arsenate resistance on the cells than those in single disruptants of these genes. Its hydropathy profile and the results of an analysis of its cellular localization suggested that Pho88p is a membrane protein similar to Pho86p. Both disruption and high dosage of PHO88 or PHO86 resulted in reduced Pi uptake. These findings suggest that Pho88p is also involved in Pi transport and modulates Pho81p function together with Pho86p.

Acid Phosphatase↗

A putative new membrane protein, Pho86p, in the inorganic phosphate uptake system of Saccharomyces cerevisiae.

The PHO84 gene in Saccharomyces cerevisiae encodes the P(i) transporter Pho84p. The other three genes, GTR1, PHO86 and PHO87, are also suggested to be involved in the P(i) uptake system. We cloned and sequenced PHO86 and found that it encodes a 34-kDa protein consisting of 311 amino acid residues with two strongly hydrophobic segments in its N-terminal half. Western blotting analysis of cell extracts revealed that Pho86p, tagged with c-Myc, was fractionated into a water-insoluble fraction. Disruption of PHO86 did not affect cell viability even in combination with the pho84 and/or pho87 disruptions. The triple disruptants showed high levels of constitutive rAPase synthesis and arsenate resistance similar to the pho84 mutant, but showed slower cell growth than the pho84 mutant. PHO86 has two putative binding sites for the transcriptional activator, Pho4p, at nucleotide positions -191 and -497 relative to the ATG start codon, and showed substantial levels of transcription under high-P(i) conditions and more enhanced levels in low-P(i) medium.

Adaptor Proteins, Vesicular Transport↗

Saccharomycodes ludwigii has seven chromosomes.

Tetrad distributions for 108 different gene pairs in 1346 asci of 113 diploids heterozygous for various combinations of 24 genes in Saccharomycodes ludwigii were investigated. Tetratype tetrads occurred only rarely and the 24 genes tested were classified into seven linkage groups. Electrophoretic karyotypes of three independent strains of S'codes ludwigii showed seven bands of chromosome-sized DNA having molecular sizes of 0 center dot 8 to 2 center dot 3 Mb with strain-specific polymorphic chromosomal DNAs as determined based on their migration distances.

Chromosomes, Fungal↗

Autotrophic carbon dioxide fixation in Acidianus brierleyi.

The autotrophic CO2 fixation pathway in Acidianus brierleyi, a facultatively anaerobic thermoacidophilic archaebacterium, was investigated by measuring enzymatic activities from autotrophic, mixotrophic, and heterotrophic cultures. Contrary to the published report that the reductive tricarboxylic acid cycle operates in A. brierleyi, the enzymatic activity of ATP:citrate lyase, the key enzyme of the cycle, was not detected. Instead, activities of acetyl-CoA carboxylase and propionyl-CoA carboxylase, key enzymes of the 3-hydroxypropionate cycle, were detected only when A. brierleyi was growing autotrophically. We conclude that a modified 3-hydroxypropionate pathway operates in A. brierleyi.

Acetyl-CoA Carboxylase↗

Staged repair of tetralogy of Fallot and pulmonary atresia without central pulmonary arteries.

A 15-year-old boy with tetralogy of Fallot and pulmonary atresia without central pulmonary arteries who was successfully treated using a staged approach is presented. The first stage consisted of the creation of central pulmonary arteries. In the second stage, the continuity between the right ventricle and the pulmonary arteries was established with closure of the ventricular septal defect. Some patients previously considered to be unsuitable candidates for correction may be successfully repaired using this approach.

Adolescent↗

Indocyanine green angiographic findings in Vogt-Koyanagi-Harada disease.

PURPOSE: To report the indocyanine green angiographic findings associated with Vogt-Koyanagi-Harada disease and compare them with fluorescein angiographic findings and monochromatic scanning laser images. METHODS: In a prospective study, indocyanine green angiography, by scanning laser ophthalmoscopy or infrared fundus photography, was performed in ten consecutive patients (20 eyes) with Vogt-Koyanagi-Harada disease during the acute stage before and recovery stage after corticosteroid treatment. Findings were compared with fluorescein angiographic features and monochromatic scanning laser imaging. RESULTS: During the acute stage of the disease, indocyanine green angiography disclosed a dark background in the early phase and multiple, non-uniform hypofluorescent lesions in the midphases. Lesions were more numerous and extensive than areas either of serous retinal detachment on monochromatic scanning laser imaging or of punctate hyperfluorescence on fluorescein angiography. During the recovery stage, the abnormal dark background on indocyanine green angiography at initial examination resolved, with choroidal vessels visible in all cases, but nonuniform hypofluorescent lesions persisted in most eyes. Fluorescein angiography disclosed hypofluorescent patchy areas, and confocal infrared laser imaging showed some bright reflective lesions in three patients with especially severe clinical symptoms. On final examination after an average of 17.7 months, both angiographies still disclosed abnormal findings in these three patients. CONCLUSIONS: Indocyanine green angiographic findings suggest that choroidal inflammation may cause a transient choroidal circulatory disturbance during the acute stage of Vogt-Koyanagi-Harada disease. In more severe cases, this dysfunction may secondarily damage the retinal pigment epithelium.

Acute Disease↗

Isolation and structure of prorocentrolide B, a fast-acting toxin from Prorocentrum maculosum.

A new toxin, prorocentrolide B (1), has been isolated following bioassay-guided fractionation of a BuOH extract of the tropical dinoflagellate, Prorocentrum maculosum Faust. This compound produces a rapid toxic response in the mouse bioassay, a type of activity not accounted for by other diarrhetic shellfish poisoning toxins produced by P. maculosum. The structure 1 was established by NMR and MS and is similar to prorocentrolide (2), a toxin from a strain of Prorocentrum lima. NMR data and the modeling program ConGen have been used to establish the relative stereochemistry of some individual ether ring systems and the hexahydroisoquinoline ring.

Animals↗