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Y Nagamura

Publications and source records attributed to Y Nagamura.

At least 55 records · Page 3Linked to original sources
PubMed1993

Skin L-tryptophan-2,3-dioxygenase and rat hair growth.

We have identified a new enzyme, skin L-tryptophan-2,3-dioxygenase (skin TDO), that catalyzes the degradation of L-tryptophan into formylkynurenine in rats. The rate of this degradation peaks in all rats at 5 to 6 weeks after birth, and also, among rats depilated at 8 weeks old, at 10 to 11 weeks after birth. We have also observed that the properties of this enzyme are closer to those of hepatic L-tryptophan-2,3-dioxygenase (hepatic TDO) than to indoleamine 2,3-dioxygenase. Although an intraperitoneal injection of L-tryptophan increased the activity of skin TDO to approximately 2.2 times greater than control values, an intraperitoneal injection of hydrocortisone and alpha-methyl-DL-tryptophan, both compounds known to affect hepatic TDO activity, had no effect on skin TDO activity. The molecular weight of skin TDO was estimated to be 16.0 kDa, which is close to the molecular weight of hepatic TDO, yet a much larger molecule than indoleamine-2,3-dioxygenase. Increased hair growth rates paralleled increased levels of skin TDO activity in 5- to 6-week-old rats, and marked increases in the activity of skin TDO occurred 2 or 3 weeks after depilation. Enzyme activity was also greatest 2 days before the time of maximum hair root length. Therefore, skin TDO may play an important role in the initiation or suppression of rat hair growth.

Animals↗
PubMed1993

Comparison of cytoprotective effects of saponins isolated from leaves of Aralia elata Seem. (Araliaceae) with synthesized bisdesmosides of oleanoic acid and hederagenin on carbon tetrachloride-induced hepatic injury.

Glycosylations of 3-O-(2,3,4-tri-O-acetyl-alpha-L-rhamnopyranosyl(1-->2)- 3,4-di-O-acetyl-alpha-L-arabinopyranosyl)-23-O-acetylhederageni n (15) with mono- (16), di- (17) and trisaccharide bromide (18) gave the bisdesmoside peracetates 19, 20 and 22, respectively, which were treated with 5% KOH in MeOH to give the bisdesmosides 25-27. Hydrolysis of the glycosides 6 and 9 having beta-D-glucopyranose as a terminal sugar component with beta-glucosidase in acetate buffer (pH 4.7) gave compounds 28 and 29, respectively. Cytoprotective effects of the synthesized triterpenoidal saponins against CCl4-induced hepatic injury were compared with those of saponins isolated from the leaves of Aralia elata Seem. (Araliaceae) using isolated hepatocytes from rat liver. Although the monodesmosides 1-4 having neutral sugar components only at the O-3 position on the aglycones showed no cytoprotective effect, bisdesmosides having sugar components at both the O-3 and O-28 positions on the aglycones had potent effects, even when the species of the sugar components were different. The bisdesmosides 10, 11, and 27 having five monosaccharides in the molecules exhibited the most potent cytoprotective effects.

Animals↗
PubMed1993

Preparation of glycyrrhetic acid beta-glycosides having beta (1-->2)-linked disaccharides by the use of 2-O-trichloroacetyl-beta-D-pyranosyl chlorides and their cytoprotective effects on hepatic injury in vivo.

Stepwise glycosidation was adopted for the construction of glycyrrhetic acid beta-glycosides (27-30) having beta (1-->2)-linked disaccharides such as 2-O-beta-D-glucuronopyranosyl-beta-D-glucopyranose, 2-O-beta-D-glucuronopyranosyl-beta-D-galactopyranose, 2-O-beta-D-glucopyranosyl-beta-D-glucuronopyranose and 2-O-beta-D-galactopyranosyl-beta-D-glucuronopyranose. In the first glycosidation, 2-O-trichloroacetyl-beta-D-payranosyl chlorides (9-11) were utilized as starting sugar derivatives to react with methyl glycyrrhetinate (5): Glycosidation of 5 with 9 and 10 gave beta- and alpha-monoglycosides (12) and (13), and (15) and (16), respectively. Treatment of the beta-glycosides 12 and 15 with ammonia-saturated ether gave products (14) and (17), respectively. The glycosidation of 5 with 11 followed by treatment with ammonia-saturated ether gave compounds (18) and (19), respectively. The second step glycosidations of 14 and 17 with methyl 2,3,4-tri-O-acetyl-alpha-D-glucuronatopyranosyl bromide (20) gave diglycoside derivatives (23) and (24), respectively, and that of 18 with 2,3,4,6-tetra-O-acetyl-alpha-D-glucopyranosyl bromide (21) and -alpha-D-galactopyranosyl bromide (22) gave diglycoside derivatives (25) and (26), respectively. The removal of the protecting groups of 23-26 gave diglycosides 27-30, respectively, having a beta-D-glucuronopyranose (beta-D-glcUA) as one of two sugar components in the molecules. The cytoprotective effects of the synthesized glycosides 27-30 on carbon tetrachloride (CCl4)-induced hepatotoxicity in vivo were compared with diglycosides 31-33 having only neutral sugar components and naturally occurring glycyrrhizin (34) having two acidic sugar components (beta-D-glcUA).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

[Change in levels of specific terminal sugar residues of glycoproteins in sera of patients with malignant tumor].

Serum sialic acid (N-acetylneuraminic acid, NANA) levels significantly increased in all of patients with stomach cancer, colo-rectal cancer, breast cancer and pancreas cancer. However, the positive rate for serum NANA levels was 35 approximately 60% in these diseases. In contrast, a significant increase in serum NANA-galactose (NANA-Gal) levels was found in only stomach cancer and colo-rectal cancer; especially, the positive rate for serum NANA-Gal levels was 77% in colo-rectal cancer. In colo-rectal cancer, increased serum NANA-Gal levels were decreased after operation. But, in patients with colo-rectal cancer, changes in serum NANA levels following operation were variable. These results indicate that the assay of serum NANA-Gal level provides more important clinical significances for the specificity of cancer and the change of its status than that of serum NANA level.

Biomarkers, Tumor↗
PubMed1992

Assessment of chemoembolization therapy for primary liver cancer using a stabilized adriamycin-lipiodol suspension.

We formulated a new lipiodol-Adriamycin suspension (ADM/lipiodol, 50 mg/10 ml) that remained stable for 48 h (half-life, 25 +/- 3 days). In five cases of hepatocellular carcinoma (HCC) resected after intra-arterial infusion of this agent, the ADM concentration in the tumor was quite high and the tumor necrosis rate was more than 80% on histological examination. Over a 5-year period, 180 patients with unresectable HCC underwent transcatheter arterial embolization therapy (TAE) in the presence or absence of this agent. The regimens consisted of suspension injection alone (A, n = 54), suspension injection + TAE using gelatin sponge (B, n = 29), TAE followed by suspension injection (C, n = 34), and TAE alone (D, n = 63). The estimated 1-year survival values determined for patients treated with these regimens were 70%, 73%, 43%, and 39% respectively, and the corresponding 3-year survival values were 27%, 31%, 15%, and 10%. The survival achieved using suspension injection was thus superior to that obtained using conventional TAE, and combined therapy with suspension injection followed by TAE seemed to enhance survival, although there were some biases in tumor size and in the stage of tumor progression. For patients with tumors measuring 5 cm or more in diameter, the survival obtained using regimen A was lower than that achieved using regimen D, but the combination of TAE and suspension injection improved the 1-year survival value obtained using regimen D from 34% to 52%. For patients with tumors measuring less than 5 cm in diameter, the survival achieved using regimen A was markedly better than that obtained using regimen D, although no difference was found between the survival value achieved using regimen A and that obtained using regimens B and C. On the basis of these results, our newly formulated ADM-lipiodol suspension was surmised to be effective by itself against relatively small HCC tumors, whereas it enhanced the efficacy of conventional TAE in large lesions.

Aged↗
PubMed1991

Characterization of the L-tryptophan transport system in the liver of growing rats.

In order to characterize the system of L-tryptophan (TRP) transport into liver during the growing period of 10 to 42 days, the changes of tryptophan 2,3-dioxygenase (TDO) activity, levels of serum, liver, brain, and muscle TRP, and the rate and mode of TRP uptake into isolated hepatocytes were examined in male Wistar rats. Liver TDO activity increased rapidly at 16 days of age. A marked and rapid decrease in free serum TRP level occurred before weanling, while a small decrease in total serum TRP level was found after weanling. The change of liver TRP level was similar to that of free serum TRP level and correlated well. There was a significant inverse correlation between liver TDO activity and either free serum TRP level or liver TRP level. A rapid change in TRP level did not occur in brain and muscle during the growing period. The concentrations of brain and muscle TRP correlated better with those of total serum TRP than with those of free serum TRP. The rate of TRP uptake into hepatocytes isolated from rats aged 10 days was lower than that from rats aged 21 and 42 days. The former hepatocytes were lacking in a high-affinity saturable transport component for TRP uptake which was present in the latter ones. The present results indicate that a great change in the system of TRP transport into liver occurs in growing rats, and that in suckling rats a high level of free serum TRP contributes to the efficient transport of the amino acid into the liver.

Animals↗
PubMed1991

Preparation of glycyrrhetic acid glycosides having various beta(1----2)-linked disaccharides and their cytoprotective effects on carbon tetrachloride-induced hepatic injury.

Glycyrrhetic acid glycosides (1-7) having beta(1----2)-linked disaccharides such as 2-O-beta-D-glucopyranosyl-beta-D-galactopyranose, 2-O-beta-D-galactopyranosyl-beta-D-galactopyranose, 2-O-beta-D-glucuronopyranosyl-beta-D-galactopyranose, 2-O-beta-D-glucopyranosyl-beta-D-glucuronopyranose, 2-O-beta-D-galactopyranosyl-beta-D-glucuronopyranose, 2-O-beta-D-galactopyranosyl-beta-D-glucopyranose, 2-O-beta-D-glucuronopyranosyl-beta-D-glucopyranose, respectively, were synthesized by stepwise construction; from glycyrrhetic acid monoglycosides to the diglycosides. The cytoprotective activities of the glycosides 1-7 and 2-O-(beta-D-glucopyranosyl)-beta-D-glucopyranosyl-11-oxoolean-12-e n-30-oate (8) were compared with natural occurring glycyrrhizin (9). Among these glycosides 1-8, glycosides 3 and 7 having beta-D-glucuronopyranose (glcUA) as the only terminal sugar component were more effective materials against hepatic injury than glycyrrhizin 9.

Animals↗
PubMed1991

[The inhibitory effect of gamma-glutamylcysteinylethyl ester (gamma-GCE) instillation on experimental diabetic cataract formation in rats].

The effect of the instillation of gamma-glutamylcysteinylethyl ester (gamma-GCE), which has been reported to function as a precursor of glutathione, on cataract formation was examined in rats in which diabetes had been induced by Streptozotocin (STZ). Three days after i.p. treatment with 50 mg/kg body weight of STZ, male Wistar rats aged 6 weeks received instillations of gamma-GCE in solution or liposomes prepared with dipalmitoylphosphatidylcholine (DPPC) for a period of 9 weeks. Cataract formation and development were observed by use of a cataract camera every week. After 9 weeks' observation, the lenses were enucleated and the content of the lens GSH was measured. Instillation of gamma-GCE in solution or liposomes to STZ-diabetic rats not only inhibited cataract formation but also kept lens GSH level almost at the control level. In addition, the inhibitory effect of the instillation of gamma-GCE in liposome was stronger than that of gamma-GCE in solution. The present results indicate that the administration of gamma-GCE in solution or in liposomes inhibits diabetic cataract formation, possibly by preventing lens GSH depletion.

Animals↗
PubMed1990

Relationship between L-tryptophan uptake and L-tryptophan 2,3-dioxygenase activity in rat hepatocytes.

The relationship between L-tryptophan uptake and tryptophan 2,3-dioxygenase activity in hepatocytes was examined and compared with the change of hepatic L-leucine, L-phenylalanine, and L-tyrosine uptakes using isolated hepatocytes of rats in which the oxygenase was induced with L-tryptophan or hydrocortisone. In L-tryptophan- or hydrocortisone-treated rat hepatocytes, the rate of L-tryptophan uptake into hepatocytes via the saturable high-affinity transport component significantly increased but the hepatic uptake rate of L-leucine did not change at all. In hydrocortisone-treated rat hepatocytes, a little stimulated hepatic uptake of L-phenylalanine or L-tyrosine was observed. In the stimulated hepatic uptake of L-tryptophan via the high-affinity transport component, the Km value did not change but the Vmax value increased. Liver plasma membranes prepared from rats treated with L-tryptophan or hydrocortisone showed the same binding rate of L-tryptophan to the membranes as those from control rats. In addition, hepatic L-tryptophan uptake via the high-affinity transport component correlated well with hepatic tryptophan 2,3-dioxygenase activity (r = 0.787). The present results indicate that the uptake of L-tryptophan into hepatocytes via a transport system which works under physiological conditions is closely related to hepatic tryptophan 2,3-dioxygenase activity.

Animals↗
PubMed1990

[Change in levels of specific terminal sugar residues of glycoproteins in sera of patients with complication of diabetes and liver injury].

The concentrations of specific terminal sugar residues of glycoproteins were determined in sera of patients with diabetes, liver injury or complication of both diseases. A significant increase in serum galactose (Gal) concentration was found in all patients. Serum N-acetylneuraminic acid-galactose (NANA-Gal) concentration was significantly decreased in patients with complication of diabetes and liver injury, whereas a high concentration of serum N-acetylneuraminic acid (NANA) was observed only in diabetic patients. Thus the determination of serum Gal and NANA-Gal should be added to one of clinical tests to provide new information on the pathological conditions of diabetes and liver injury.

Diabetes Mellitus↗
PubMed1989

Tryptophan 2,3-dioxygenase activity in rat skin.

We have found an enzyme system that catalyzes the conversion of L-tryptophan to L-kynurenine, presumably via L-formylkynurenine, in soluble and insoluble fractions of rat skin. The enzymatic activity was stimulated by hematin, ascorbate, and catalase, but not by methylene blue. Highest activity was located in the skin of the dorsal posterior region and lowest activity in the abdominal region. The activity in plucked (depilated) skin was only about 25% of that obtained from unplucked (depilated) tissue of the same region. D-Tryptophan, 5-hydroxytryptophan, and tryptamine were not degraded by the skin enzyme and the Km for L-tryptophan determined with the crude enzyme was 1 microM. The decycling activity of rat skin and liver for L-tryptophan began to be stimulated after birth and reached the highest level at 6 weeks. But, 1 week later, most of the skin activity suddenly disappeared and the low level continued at least until 12 weeks. In contrast, the hepatic enzyme did not change so drastically. These findings suggest that an enzyme that catalyzes L-tryptophan to L-kynurenine via L-formylkynurenine is present in rat skin.

Age Factors↗
PubMed1989

[Effect of vitamin E-containing liposome on experimental sugar cataract].

The effect of vitamin E-containing liposome on experimental sugar cataract formation in vitro was investigated. The lenses of male Wistar rats aged 6 weeks were prepared by incubating with 55. 6 mM glucose with vitamin E-containing liposome (dipalmitoyl phosphatidylcholine: DPPC). We examined the formation of lens opacity and assayed vitamin E and its related compounds. Incubation with vitamin E-containing liposome prevented sugar cataract formation. In Addition, vitamin E concentration in lens was significantly elevated by incubation with vitamin E-containing liposome. In lenses of the high level glucose group incubated without vitamin E-containing liposome, lipid peroxide (LPO) content was increased, but in lenses of the high-level glucose group incubated with vitamin E-containing liposome the increase was significantly inhibited at each incubation time. Vitamin E had no effect either on the decrease of reduced glutathione (GSH) or the increase of sorbitol content in lens incubated with high level glucose medium. In conclusion vitamin E-containing liposome was transported from medium to lens well and was significantly effective in preventing experimental sugar cataract formation in vitro. The protective effects of vitamin E are probably caused not only by its antioxidative action.

Animals↗