PubMed Health⌕ Search

Biomedical subjects

T Akao

Publications and source records attributed to T Akao.

At least 19 recordsLinked to original sources
PubMed1992

Purification and characterization of a peptide essential for formation of streptolysin S by Streptococcus pyogenes.

Peptides in a pronase digest of bovine serum albumin were required for streptolysin S formation by Streptococcus pyogenes besides maltose and a carrier (the oligonucleotide fraction obtained by treatment of Saccharomyces cerevisiae RNA with RNase A). A peptide essential for streptolysin S formation was purified to homogeneity from a pronase digest of bovine serum albumin by Sephadex G-25 column chromatography, and anion-exchange, reverse-phase, and gel filtration high-performance liquid chromatography. The purified peptide was divided into more than two peptides by HCOOOH oxidation and was composed of four residues of cysteine, three of leucine, and one each of aspartic acid and glutamic acid. Leucine and cysteine were detected as amino-terminal residues, and leucine and glutamic acid were detected as carboxyl-terminal residues, suggesting that two or three peptides are linked by a disulfide bond(s). A disulfide bond structure in the peptide seemed to be required for streptolysin S formation.

Amino Acid Sequence↗
PubMed1992

Inhibitory effects of glycyrrhetic acid and its related compounds on 3 alpha-hydroxysteroid dehydrogenase of rat liver cytosol.

Glycyrrhetic acid (GA), aglycone of glycyrrhizin (GL), inhibited potently (I50 = 7 x 10(-6) M) and non-competitively the activity of NAD(P)+-linked 3 alpha-hydroxysteroid dehydrogenase of rat liver cytosol. The inhibition was slightly weaker than that of indomethacin, a potent anti-inflammatory agent, but stronger than that of dexamethasone, another anti-inflammatory agent. GL, GA monoglucuronide, and 3-epi-glycyrrhetic acid also inhibited this enzyme activity, but did so less effectively (I50 = 5-8 x 10(-5) M). Carbenoxolone (GA 3-hemisuccinate) and 3-keto-glycyrrhetic acid showed potent inhibitory effects similar to GA, and 18 alpha-GA showed the most powerful inhibition of the activity.

3-Hydroxysteroid Dehydrogenases↗
PubMed1992

Inhibitory effects of glycyrrhetic acid derivatives on 11 beta- and 3 alpha-hydroxysteroid dehydrogenases of rat liver.

Glycyrrhetic acid (GA), an aglycone of glycyrrhizin (GL), is a potent inhibitor of 11 beta- and 3 alpha-hydroxysteroid dehydrogenases. 11 beta-Hydroxysteroid dehydrogenase activity of rat liver microsomes was potently inhibited by GA, 3-deoxyglycyrrhetic acid (3-deoxyGA), 3-ketoglycyrrhetic acid (3-ketoGA), 3-epiglycyrrhetic acid (3-epiGA) and 11-deoxoglycyrrhetic acid (11-deoxoGA), with I50 values of 2-4 x 10(-7) M. However, 18 alpha-stereoisomers (I50 = 3-7 x 10(-6) M) of GA, 3-deoxyGA and 11-deoxoGA were one tenth less inhibitory on the enzyme activity than the corresponding 18 beta-isomers. On the other hand, 18 alpha-stereoisomers of GA, 3-deoxyGA and 11-deoxoGA inhibited 3 alpha-hydroxysteroid dehydrogenase activity of rat liver cytosol more potently than the corresponding 18 beta-isomers. I50 values of 18 alpha- and 18 beta-isomers were 2 and 7 x 10(-6) M, respectively, in the case of GA, 8 and 20 x 10(-6) M in 3-deoxyGA, 3 and 20 x 10(-6) M in 11-deoxoGA. These results indicate that the 18 beta-conformation of oleanane is important for the inhibition of 11 beta-hydroxysteroid dehydrogenase but on the contrary the 18 alpha-conformation is important for the inhibition of 3 alpha-hydroxysteroid dehydrogenase.

11-beta-Hydroxysteroid Dehydrogenases↗
PubMed1992

[Pseudosarcomatous fibromyxoid tumor of the urinary bladder: a case report].

A 41-year-old man was referred to our clinic for gross hematuria. Cystoscopy revealed a 6 x 5 x 5 cm wide-based tumor located at the dome of the bladder. Pathological diagnosis of the biopsy was pseudosarcomatous fibromyxoid tumor. Microscopically this tumor was composed of spindle cells and myxoid stroma, and immunohistochemical and ultrastructural studies showed benign characteristics of this tumor. Therefore partial cystectomy was performed. It is important to recognize the histological characteristics of this essentially benign condition so that total cystectomy can be avoided.

Adult↗
PubMed1991

Metabolism of glycyrrhetic acid by rat liver microsomes--III. Male-specific glycyrrhetinate dehydrogenase.

Glycyrrhetinate (GA) dehydrogenase localized in microsomes of rat liver catalyses the oxidation and reverse reduction of 18 beta-glycyrrhetic acid (GA), an aglycone of glycyrrhizin and a main component of liquorice, to 3-keto-18 beta-glycyrrhetic acid (3-ketoGA). The enzyme activity was detected in microsomes of adult males, but not in those of adult females. It was not observed in infant males but appeared 6 weeks after birth, increased gradually and reached the maximum level at 12 weeks after birth, whereas it was not detected in the hepatic microsomes of females of any age. The administration of estradiol valerate to intact adult males decreased GA dehydrogenase activity remarkably. Castration of male rats also caused a marked reduction of the activity, but the administration of testosterone proprionate to these rats restored it to close to the normal level. On the other hand, ovariectomy of female rats did not bring the activity into existence, but the injection of testosterone proprionate to the ovariectomized rats brought it into a slight existence, in spite of no appearance of the activity by the treatment of testosterone proprionate to intact adult females. The sex-related difference in the activity in adults was eliminated by hypophysectomy of male and female rats, their microsomal activities after the operation being the same, 20-40% of the activity in intact males. Moreover, the administration of estradiol valerate to the hypophysectomized rats did not affect the activity. These results indicate that GA dehydrogenase is male-specific and regulated by sex-hormones through the pituitary.

3-Hydroxysteroid Dehydrogenases↗
PubMed1991

Formation of nitrogen-containing metabolites from geniposide and gardenoside by human intestinal bacteria.

During the course of our studies on the metabolism of iridoid glycosides by human intestinal bacteria, we found that geniposide (1) and gardenoside (4) were transformed to new nitrogen-containing compounds, genipinine (3) and gardenine (6), respectively, along with the known aglycones. Although the amounts of new metabolites were somewhat lower than those of the aglycones, they were quantitatively analyzed by means of liquid chromatography/mass spectrometry (LC/MS). Of 25 strains of human intestinal bacteria, Peptostreptococcus anaerobius, Klebsiella pneumoniae, Fusobacterium nucleatum, and Bacteroides fragilis ssp. thetaotus produced appreciable amounts of 3, while a bacterial mixture of human feces produced 10 times or more higher amounts of 3, as compared to the individual strains.

Bacteria↗
PubMed1991

Enzymatic sulfation of polyphenols related to tannins by arylsulfotransferase.

This report discusses a novel type of arylsulfotransferase (AST) which was derived from human intestinal bacterium sulfated polyphenolic compounds when p-nitrophenyl sulfate (PNS) was taken as a donor substrate. (+)-Catechin, (+/-)-catechin, (-)-epicatechin and (-)-epicatechin gallate were better substrates than tyramine. (-)-Epigallocatechin and (-)-epigallocatechin gallate were slightly worse substrates than tyramine. Although gallic acid was a bad substrate, alkyl gallate esters were better substrates than tyramine. The degree of acceptor specificity increased in proportion to the length of the alkyl group up to the carbon number of five. Pedunculagin, geraniin and corilagin were less effective than tyramine. Rosmarinic acid and penta-O-galloyl-beta-D-glucose were similarly well sulfated. Two products, 4'-monosulfate and 4',5-disulfate of (+)-catechin, were detected at a two-fold molar excess of PNS over (+)-catechin. When (+)-catechin-4'-monosulfate as an acceptor was enzymatically sulfated with PNS as a donor, only the 4',5-disulfate was produced. Thus, arylsulfotransferase was useful for the convenient preparation of sulfate esters of polyphenols at their specific hydroxyl groups.

Arylsulfotransferase↗
PubMed1991

Metabolism of aloesin and related compounds by human intestinal bacteria: a bacterial cleavage of the C-glucosyl bond and the subsequent reduction of the acetonyl side chain.

By anaerobic incubation with a bacterial mixture from human feces, aloesin (aloeresin B; 1) was converted to 2-acetonyl-7-hydroxy-5-methylchromone (aloesone; 3) and dl-7-hydroxy-2-(2'-hydroxypropyl)-5-methylchromone (aloesol; 4a + 4b) through a cleavage of the C-glucosyl bond, followed by reduction of the acetonyl side chain. An analogous compound, aloeresin A (2), was converted to p-coumaric acid and aloesin (1), the latter being subsequently transformed to aloesone (3) and dl-aloesol (4a + 4b). On the other hand, 7-O-methylated derivatives (7, 5a and 5b) of aloesin and of 8-C-glucosylaloesol were not cleaved to the corresponding aglycones, suggesting the importance of a free hydroxy group adjacent to the C-glucosyl group in the molecule for the bacterial cleavage of aloesin derivatives. This is the first report on the cleavage of the C-glycosyl bond of chromone C-glucosides by intestinal bacteria.

Acetone↗
PubMed1991

Barbaloin stimulates growth of Eubacterium sp. strain BAR, a barbaloin-metabolizing bacterium from human feces.

Eubacterium sp. strain BAR, isolated from human feces, transformed barbaloin to aloe-emodin anthrone in a basal medium lacking carbohydrate. Barbaloin remarkably stimulated the growth of strain BAR in the basal medium, the stimulative extent of the growth depending on the amount of barbaloin added. The addition of D-glucose, D-galactose, maltose, cellobiose, sucrose or D-amygdalin to the basal medium containing barbaloin caused a decrease of the growth stimulated by barbaloin to the growth level with each sugar, resulting in a complete inhibition of the barbaloin transformation. On the other hand, the addition of D-fructose, which itself stimulated the growth of strain BAR, further increased the growth in the presence of barbaloin and little inhibited barbaloin transformation. Nojirimycin bisulfite, a specific inhibitor of glucosidases, potently inhibited the growth with barbaloin, but did not affect the growth with glucose or cellobiose. Also, nojirimycin bisulfite completely inhibited the transformation of barbaloin to aloe-emodin anthrone. These results indicate that a unique enzyme capable of cleaving the C-glycosyl bond is induced in strain BAR by barbaloin and, consequently, strain BAR grows by utilizing as a nutrient the carbohydrate liberated from barbaloin. It is further suggested that the barbaloin-cleaving enzyme is inhibited by nojirimycin bisulfite and that the induction of the enzyme is repressed with D-glucose and D-galactose.

Anthracenes↗
PubMed1991

[Combination chemotherapy of methotrexate, etoposide, adriamycin and cisplatin (M-EAP) for advanced urothelial cancer].

Combination chemotherapy with methotrexate, etoposide, adriamycin and cisplatin (M-EAP regimen) was administered to 4 patients with advanced epithelial cancer of the urinary tract (Methotrexate 30 mg/M2 day 1, 15 and 22; Etoposide 100 mg/M2 day 1, 2, 15 and 22; Adriamycin 30 mg/M2 day 2; Cisplatin 70 mg/M2 day 2, every 4 weeks). In an attempt to improve the anti-cancer effect of the M-VAC regimen, etoposide was substituted for vinblastine. This series comprised 3 males and 1 female ranging in age from 54 to 68 years (mean age: 63), with a performance status of 1 to 2. The site of the primary lesion was bladder in 3, and left ureter in 1. The clinical response was assessed in 3 of the 4 patients: one achieved complete response and two had partial response. Two of the four died of disease 5 months after chemotherapy. Two of them have been alive for 10 and 8 months with no evidence of disease after chemotherapy. Toxicity included moderate or severe myelosuppression in two patients, and mild to moderate anorexia, vomiting, alopecia, and hiccups in all patients. These preliminary results suggest that the M-EAP regimen is effective against advanced epithelial carcinoma of the urinary tract. However, myelosuppression was a dose-limiting factor.

Aged↗
PubMed1990

Characterization of NADP+: 3 beta-hydroxysteroid dehydrogenase from microsomes of rat liver.

A NADP(+)-dependent 3 beta-hydroxysteroid dehydrogenase activity was localized in the microsomal fraction of rat liver. This enzyme was solubilized and separated completely from 3 alpha-hydroxysteroid dehydrogenase by Matrex red A column chromatography. Partially purified 3 beta-hydroxysteroid dehydrogenase catalyzed the oxidation and reduction between the 3 beta-hydroxyl and 3-ketonic group of steroids or bile acids having no double bond in the A/B ring, but was inactive toward 3 alpha-hydroxyl group. The enzyme required NADP+ for oxidation and NADPH for reduction. The activity was inhibited by p-chloromercuribenzoic acid or p-chloromercuribenzenesulfonic acid at the concentration of 10(-4) M. The molecular weight of the enzyme was estimated to be about 43,000 by Sephadex G-200 column chromatography. From these results, it is concluded that the enzyme is a new type of microsomal NADP+:3 beta-hydroxysteroid dehydrogenase.

3-Hydroxysteroid Dehydrogenases↗
PubMed1990

Metabolism of glycyrrhetic acid by rat liver microsomes-II. 22 alpha- and 24-hydroxylation.

18 beta-Glycyrrhetic acid (GA, an aglycone of glycyrrhizin) is converted to 3-oxo-18 beta-glycyrrhetic acid (3-oxoGA) in the presence of NADP+ by rat liver homogenates, but GA was converted in the presence of NADPH to two other metabolites showing lower Rf values on thin-layer chromatography (TLC) than those of GA and 3-oxoGA by postmitochondrial supernatant of rat liver. The GA-metabolizing activity in the presence of NADPH was localized in microsomes, similar to localization of GA-oxidizing activity to 3-oxoGA. The GA-metabolizing activity required NADPH as a cofactor and O2 for full activity and was inhibited with CO, suggesting the hydroxylation reaction of GA by cytochrome P450. Two metabolites (I and II, lower and higher Rf values on TLC, respectively) were purified on preparative TLC. Mass spectral (MS) analyses of II and methyl ester of acetylated I indicated the formation of monohydroxylated metabolites. On the basis of 3H- and 13C-NMR assignments I and II were identified to be 22 alpha- and 24-hydroxy-18 beta-glycyrrhetic acids, respectively. 3-OxoGA and 3-epi-18 beta-glycyrrhetic acid (3-epiGA) seem to be also hydroxylated at C-22 and C-24. A metabolite of 3-oxoGA showing a lower Rf value was also identified as 22 alpha-hydroxy-3-oxo-18 beta-glycyrrhetic acid by MS and 3H- and 13C-NMR spectral analyses. In 22 alpha-hydroxylation the best substrate was 3-oxoGA, followed by GA and 3-epiGA. On the other hand, for 24-hydroxylation the best substrate was GA, then 3-oxoGA, and 3-epiGA in order. However, 18 alpha-glycyrrhetic acid (18 alpha-GA) was a poor substrate for both 22 alpha- and 24-hydroxylation.

Animals↗
PubMed1990

Metabolism of glycyrrhetic acid by rat liver microsomes: glycyrrhetinate dehydrogenase.

Glycyrrhetic acid, derived from a main component of liquorice, was converted to 3-ketoglycyrrhetic acid reversibly by rat liver homogenates in the presence of NADPH or NADP+. Glycyrrhetic acid-oxidizing and 3-ketoglycyrrhetic acid-reducing activities were localized in microsomes among the subcellular fractions of rat liver. Glycyrrhetic acid-oxidizing activity and 3-ketoglycyrrhetic acid-reducing activities showed pH optima at 6.3 and 8.5, respectively, and required NADP+ or NAD+ and NADPH or NADH, respectively, indicating that these activities were due to glycyrrhetinate dehydrogenase. The dehydrogenase was not solubilized from the membranes by the treatment with 1 M NaCl or sonication, indicating that the enzyme is a membrane component. The dehydrogenase was solubilized with detergents such as Emalgen 913, Triton X-100 and sodium cholate, and then separated from 3 beta-hydroxysteroid dehydrogenase (5 beta-androstan-3 beta-ol-17-one-oxidizing activity) by butyl-Toyopearl 650 M column chromatography. Partially purified enzyme catalyzed the reversible reaction between glycyrrhetic acid and 3-ketoglycyrrhetic acid, but was inactive toward 3-epiglycyrrhetic acid and other steroids having the 3 beta-hydroxyl group. The enzyme required NADP+ and NADPH for the highest activities of oxidation and reduction, respectively, and NAD+ and NADH for considerable activities, similar to the results with microsomes. From these results the enzyme is defined as glycyrrhetinate dehydrogenase, being quite different from 3 beta-hydroxysteroid dehydrogenase of Ruminococcus sp. from human intestine, which is active for both glycyrrhetic acid and steroids having the 3 beta-hydroxyl group.

3-Hydroxysteroid Dehydrogenases↗
PubMed1990

Synthetic cationic amphiphiles for liposome-mediated DNA transfection.

The compounds with efficient DNA transfection ability into eukaryotic cells were searched from various synthetic amphiphiles which have cationic heads and long saturated hydrocarbon tails. The efficiency of amphiphiles in gene transfer was examined by the transient expression of cytochrome b5 from its cDNA in COS cells. Among various synthetic amphiphiles, including N-[1-(2,3-dioleyloxy)propyl]-N,N,N-trimethylammonium chloride which is commercially available lipid, O,O'-didodecyl-N-[p-(2-trimethylammonioethyloxy)benzoyl]-(L) -glutamate bromide was highest in efficiency. The optimum condition for the amount of the amphiphile and DNA, and the incubation time were established to be 7.5-15 micrograms/22 mm dish and 1-10 micrograms/22 mm dish, and 48-72 h, respectively.

Animals↗
PubMed1979

In vitro sensitivity test of stomach cancer tissues by the use of metal grid method.

Ninety-nine specimens obtained from 53 patients with stomach cancer were cultured for about 3 days by means of the stainless steel grid method. In vitro effects of antitumor drugs on the cancer cells were evaluated autoradiographically or biochemically using a liquid scintillation counter to measure the uptake of 3H-thymidine. The radioactivity of the labeled tumor cells of both control fragments and fragments affected by drugs varied greatly among individual tumors. Therefore, the in vitro efficacy of antitumor drugs was represented as a comparison with that of control fragments. Positive correlation between in vitro tests and the clinical effects of antitumor drugs was observed in the specimens of 18 cases.

Antineoplastic Agents↗
PubMed1977

Protracted oral chemotherapy with fluorinated pyrimidines as an adjuvant to surgical treatment for stomach cancer.

Studies of oral chemotherapy of 5-fluroruracil (5-FU) combined with FT-207, a furanyl analog of 5-FU, as an adjuvant to surgical treatment of stomach cancer have been performed since 1970 in the first department of surgery of Chiba University, Japan. These studies were performed on 107 patients with curative stomach cancer and 22 patients with non-curative stomach cancer. These patients received consecutively 3.5mg/kg/day of 5-FU and 8mg/kg/day of FT-207 for 24 to 36 months and were compared with control patients who had undergone only surgical treatment. A significant higher survival was observed in the curatively resected patients receiving oral 5-FU and FT-207, as compared to the control group. Studies on non-curative stomach cancer patients treated with the same dose schedule gave encouraging results. Because of the limited number of patients treated in this study, the drawing of reliable conclusions must wait the results of further studies.

Administration, Oral↗