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Biomedical subjects

Y Miyake

Publications and source records attributed to Y Miyake.

At least 541 records · Page 30Linked to original sources

Corneal permeability of aldose reductase inhibitor, M79175. II. In vivo study on pharmacokinetic aspect.

Transcorneal permeability of M79175 was estimated in vivo and the effects of pH and thickening agent on it were examined. The aqueous humor concentration of M79175 versus time profile showed the peak concentration of 850 ng/ml at 20 min after instillation of pH 7.0 eye drop solution. The permeability constant of M79175 was estimated by applying a physiologically based pharmacokinetic model to this profile. As was expected from the results in vitro, high permeability constant was observed in vivo. Lowering the pH of the solution demonstrated the tendency to decrease the concentration at 20 min. Thickening agent, Hydroyethylcellulose, did not change the aqueous humor concentration versus time profile. Ocular tissue distribution was examined using 14C-M79175. As was expected from the results of corneal permeability, high levels of M79175 accumulated to the lens.

Aldehyde Reductase↗

Effects of ethylenediaminetetraacetic acid and gentamicin on the antibacterial activity of pyridone carboxylic acid derivatives against gram-negative bacilli.

Ofloxacin (9-fluoro-3-methyl-10-(4-methyl-1-piperazynyl)-7-oxo-2,3-dihydro-7 H-pyrido-(1,2,3-de)1,4-benzoxazine-6-carboxylic acid) and enoxacin (1-ethyl-6-fluoro-1,4-dehydro-4-oxo-7-(1-piperazinyl)-1, 8-naphthyridine-3-carboxylic acid) are newly developed pyridone carboxylic acid derivatives with broad and potent antibacterial activities against Gram-negative and Gram-positive bacteria. Antibacterial activities of six pyridone carboxylic acid derivatives, including these two new antibiotics, were examined against Gram-negative bacilli in the presence and absence of ethylenediaminetetraacetic acid (EDTA) or gentamicin. The minimal inhibitory concentrations (MICs) of nalidixic acid, cinoxacin and piromidic acid were reduced by the addition of EDTA or gentamicin. However, the MICs of pipemidic acid, ofloxacin and enoxacin were unaffected. These findings indicated the high permeability of pipemidic acid, ofloxacin and enoxacin through the outer membrane. The effects of EDTA and gentamicin against Serratia marcescens were different from those against other Gram-negative bacilli.

Anti-Bacterial Agents↗

Purification and characterization of human kidney renin.

By means of a new rapid and small scale purification method, human kidney renin has been purified from a single kidney in a homogeneous state, as judged on SDS-PAGE. The kidney which showed unusually high renin activity was from a patient with cardiomyopathy. 8,000-fold purification was attained by means of only pepstatin-aminohexyl-Sepharose chromatography and FPLC on a Mono Q column, and the yield was 34%. The specific activity was 5.63 mg angiotensin I per mg protein per h at 37 degrees C and pH 6.5 with porcine angiotensinogen as the substrate. The molecular weight was estimated to be 37,000 by SDS-PAGE and 38,000 by HPLC on a TSK G-3000 SW column. The preparation showed three bands on isoelectric focusing. The molecular weight and the profile on isoelectric focusing of the purified renin agreed with those found for the extracts of both the patient's kidney and a kidney with the usual low renin activity.

Adolescent↗

A resonance Raman study on the structures of complexes of flavoprotein D-amino acid oxidase.

Resonance Raman (RR) spectra were obtained for the purple complexes of D-amino acid oxidase (DAO) with D-lysine or N-methylalanine. RR spectra of a complex of oxidized DAO with the oxidation product of D-lysine or D-proline were also measured. The isotope shifts of the observed bands of the purple complex with D-lysine upon 13C- or 15N-substitution of lysine indicate that the ligand is delta 1-piperideine-2-carboxylate. That the band at 1671 cm-1 for the purple intermediate with N-methylalanine shifts to 1666 cm-1 in D2O solution indicates that the imino acid, N-methyl-alpha-iminopropionate, has a protonated imino group. Many bands due to a ligand in the RR spectra of the complex of oxidized DAO with an oxidation product can be observed below 1000 cm-1, but no band for the purple complex is seen in this frequency region. The band associated with the CO2-symmetric stretching mode of the product, such as delta 1-piperideine-2-carboxylate or delta 1-pyrrolidine-2-carboxylate, complexed with the oxidized DAO shifts in D2O solution. This suggests that the product imino acid interacts with the enzyme through some proton(s).

Alanine↗

The heterogeneity of brewer's yeast old yellow enzyme.

Heterogeneity of brewer's yeast old yellow enzyme (OYE) was found by anion-exchange high-performance liquid chromatography (HPLC) as well as by 13C-NMR spectroscopy of [4a-13C]FMN reconstituted into apo OYE. Though the OYE sample prepared according to the conventional procedure gave a single protein band on sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), the OYE sample was found to consist of five species on anion-exchange HPLC. The 13C-NMR spectrum of the [4a-13C]FMN-reconstituted OYE gave multiple peaks corresponding to 4a-13C. This multiplicity indicates that this OYE preparation possesses heterogeneity in the environment surrounding FMN, i.e., the active site of OYE. The different species of OYE were separately obtained by preparative HPLC on an anion-exchange column. These species as well as the unresolved sample showed identical mobility on SDS-PAGE and similar but slightly different NADPH oxidase activities. This heterogeneity was shown not to have resulted from proteolytic modification during the conventional purification procedure, which includes autolysis of the yeast cells, since the enzyme extracted by mechanical destruction of the yeast cells in the presence of various protease inhibitors exhibited identical heterogeneity. The pure OYE forms obtained by preparative anion-exchange HPLC are homogeneous in the flavin environment as revealed by a single 13C-NMR signal for the [4a-13C]FMN-reconstituted species.

Chromatography, Affinity↗

31P- and 13C-NMR studies on the flavin-protein and flavin-ligand interactions in brewer's yeast old yellow enzyme.

The 31P- and 13C-NMR spectra of old yellow enzyme (OYE) were measured. The 31P-NMR signal of FMN bound to apo OYE-I, one of the pure forms of OYE, was observed at a substantially lower field compared to that of free FMN. While the 31P-signal of free FMN is pH-titratable with a pK value of about 6.5, which corresponds to the monoanion-dianion transition of the phosphate group, the 31P-signal of FMN bound to OYE-I shows no pH-dependence at pH 5-9, indicating that the phosphate group of FMN bound to OYE-I is fixed in the dianionic form in the pH region of 5-9. Apo OYE(0), i.e., the OYE preparation obtained by the conventional method, was reconstituted with [2-13C]FMN or [4,10a-13C2]FMN, while apo OYE-I was reconstituted with [4a-13C]FMN. The 13C-NMR spectra of these reconstituted OYE species were measured in the absence and presence of phenolic compounds which form complexes with OYE. Each 13C-signal of the 13C-labeled FMN became broader in the bound state compared to the free state, indicating restriction of flavin mobility in the bound form. Complex formation of the reconstituted OYE species with p-bromophenol did not shift the 10a-13C signal but shifted the 2- and 4-13C signals slightly upfield, whereas the 4a-13C signal was shifted significantly upfield in the complexed form. This complex-induced upfield shift of the 4a-13C signal was measured with various p-substituted phenols.(ABSTRACT TRUNCATED AT 250 WORDS)

D-Amino-Acid Oxidase↗

N-terminal amino acid sequence of human urinary prokallikrein.

The N-terminal amino acid sequences of human urinary prokallikrein and kallikrein have been determined. Their amino acid sequences are as follows. (Formula; see text) The results showed that prokallikrein comprises an additional seven amino acids at the amino terminus of the kallikrein, of which the sequence is (H2N)Ala-Pro-Pro-Ile-Gln-Ser-Arg(COOH). Comparison of the structure of this peptide with those of other proteins revealed extensive sequence identity with the propeptide portions of rat and mouse tissue kallikreins, that were predicted from the preproenzyme-encoded nucleotide sequences. The amino acid sequence of the peptide was also highly homologous to that of the propeptide portion of EGF-binding protein, that was predicted from the nucleotide sequence, and that of the alpha-subunit of NGF. The N-terminal amino acid sequence of kallikrein was completely identical to the reported one (Lottspeich, F., et al. (1979) Hoppe-Seyler's Z. Physiol. Chem. 360, 1947-1950) and shows considerable amino acid sequence homology with the porcine and rat pancreatic kallikreins. As far as the present results are concerned, it is strongly indicated that the inactive kallikrein in human urine is a tissue type prokallikrein which is activated on the release of the N-terminal peptide consisting of seven amino acids.

Amino Acid Sequence↗

Cell-surface hydrophobicity of Candida species as determined by the contact-angle and hydrocarbon-adherence methods.

Cell-surface hydrophobicities of six Candida species were studied by two methods: measurement of the contact angle, and partitioning with aqueous-hydrocarbon (n-octane, n-hexadecane and p-xylene) mixtures. C. tropicalis, C. glabrata and C. krusei adhered better to the hydrocarbons than did C. albicans, C. stellatoidea and C. parapsilosis. Contact angles for the less adherent species were smaller than those for the more adherent species. Thus the two methods gave results that were similar overall and indicated that C. tropicalis, C. glabrata and C. krusei have greater cell-surface hydrophobicities than C. albicans, C. stellatoidea and C. parapsilosis.

Adhesiveness↗

Gyrate atrophy of the choroid and retina: 15 Japanese patients.

We examined 15 Japanese patients who had gyrate atrophy of the choroid and retina with hyperornithinaemia. Their visual acuities fell to 0.2 or worse in the second or third decade of life. Myopia developed late in the first decade, and the refractions decreased to -10 or -15 dioptres at age 20. Tunnel vision developed at approximately age 20. Our results suggested that the visual functions of Japanese patients were worse in the third decade or later than similarly affected Finnish patients.

Adolescent↗

In vitro and in vivo evaluation of a sustained release preparation containing phenylpropanolamine hydrochloride.

The relationship between dissolution behaviour and plasma concentration after administration of a sustained-release preparation containing phenylpropanolamine hydrochloride was studied in 11 male volunteers. The testing for dissolution was carried out using the JP X rotating basket procedure, and human plasma samples were assayed for phenylpropanolamine hydrochloride by a specific high-performance liquid chromatography. Three hours after dosing, the mean peak plasma concentration was 104.1 ng/ml and the plasma concentration declined with a half-life of 4.85 h. The time course of plasma and dissolution data were analyzed by a non-linear least squares curve fitting method to compare in vivo and in vitro release behaviour. Plasma concentration changes of phenylpropanolamine hydrochloride were correlated with in vitro release behaviour of the sustained-release preparation.

Adult↗

Peptide hormone production in small cell lung carcinomas with particular reference to gastrin-releasing peptide.

Tissues of 50 small cell lung carcinomas were examined for production of 17 peptide hormones. Only when the concentration of a peptide detected in the tumor was 10 pmol or more per g wet weight, was the peptide considered to be produced by the tumor. The frequency of production of at least one of these peptide hormones was 84%, and that of two or more hormones was 50%. These results indicate that peptide hormone production is a very common phenomenon in small cell lung carcinoma. Of the peptide hormones examined, gastrin-releasing peptide is produced with the highest frequency, suggesting that this peptide could play an important role in small cell lung carcinoma.

Adult↗

Oscillatory potentials and pattern electroretinogram: are they related?

The possible relationship between the pattern electroretinogram (ERG) and oscillatory potentials was investigated in two patients with night blindness. One patient had congenital stationary night blindness of Schubert-Bornschein type, and the other had Oguchi's disease. Both had normal visual acuity, normal mass photopic (cone) ERG and normal local macular ERG. In each patient, scotopic (rod) ERG after 20-minute dark adaptation was nonrecordable and the single bright flash ERG was of the negative type. The difference between the ERG pattern of the two patients was found in the oscillatory potentials. The patient with congenital stationary night blindness showed no oscillatory potentials, whereas the patient with Oguchi's disease had good oscillatory potentials. The pattern ERG in both patients was normal. Based on the data of these two patients, it was thought that the pattern ERG is not closely related to the oscillatory potentials and may have different mechanisms of generation.

Electroretinography↗

Surface hydrophobicity and adherence of Candida to acrylic surfaces.

The relationship between cell surface hydrophobicities and adherence capacities to acrylic surfaces was investigated with seven laboratory strains and eighteen clinical isolates of Candida species. C. albicans was less adherent to acrylic surfaces than were other species and hardly adhered to hexadecane, whereas other strains, which had a high affinity to hexadecane, were more adherent to acrylic surfaces. A correlation was observed between the adherence capacities of Candida species to acrylic surfaces and their cell hydrophobicities. When acrylic plates were coated with human whole saliva, the contact angle of the plate became smaller than that of the nontreated plate and adherence of hydrophobic strains decreased, whereas the adherence of C. albicans was not affected.

Acrylic Resins↗