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Biomedical subjects

N Asano

Publications and source records attributed to N Asano.

At least 91 records · Page 5Linked to original sources
PubMed1991

Role of free radical scavengers in pancreatic carcinomas of hamsters.

The involvement of free radicals in the carcinogenic mechanism has been suggested, however, little is known about the role of free radicals in the pancreatic cancer. In this study, the effects of active oxygen on the carcinogenesis of the tumor were examined by measuring the levels of scavengers in pancreatic cancer of Syrian golden hamsters. Pancreatic cancer was induced by di-iso-propanol nitrosamine (500 mg/kg body weight/week x 24 weeks). Activities of superoxide dismutase (SOD), catalase, glutathion peroxide (GSH-Px) and malon dialdehyde (MDA) in the tumor and border zone were compared with those in the non-tumor region and control normal tissue. Activities of SOD and catalase in the tumor and border zone were significantly lowered than those in non-tumor region and normal tissue. GSH-Px levels were significantly higher in the tumor than those in the non-tumor region and normal tissue. MDA levels also tended to be high in the tumor. These results suggest that the development of cancer in pancreatic tissue is related to a reduction of SOD and catalase. GSH-Px and MDA are suggested to be involved in the reactions of free radicals.

Animals↗
PubMed1991

[Effect of synthetic protease inhibitor on the oncogenesis of pancreatic cancer in hamsters: study on pancreatic endocrine cells and free radicals].

In order to study the effect of synthetic trypsin inhibitor on the oncogenesis of pancreatic cancer, the histology, the kinetics of the B, A and D cells in the islets of Langerhans and activities of free radical scavengers, superoxide dismutase (SOD), glutathion peroxide (GSH-Px) and malon dialdehyde (MDA) in the tumor bearing tissues were measured in hamsters with pancreatic cancer induced by di-iso-propanol nitrosamine (DIPN) with or without camostat (FOY-305). In DIPN group (DIPN alone), the tubular adenocarcinoma was found in 80%, however, in FOY group (DIPN+FOY-305), papillary adenocarcinoma was found in 91%. In both DIPN and FOY groups, the number of B cells was decreased at 8 weeks and the number of A and D cells was decreased at 16 weeks. Activities of SOD in the tumor and borderzone in DIPN group were significantly lower than those in non-tumor region and normal tissue. However, activities of SOD in the tumor and borderzone in FOY group were higher than those in DIPN group. GSH-Px and MDH levels were significantly higher in FOY group suggesting the involvement in the reaction of free radicals. These results suggest that trypsin inhibitors have a prophylactic effect on the development of pancreatic cancer.

Animals↗
PubMed1991

Changes of A, B and D cells in Langerhans islets in pancreatic cancers of hamsters.

In order to clarify the effect of pancreatic hormones on the oncogenesis of pancreatic cancer, the kinetics of the B, A and D cells in the islets of Langerhans were studied in hamsters with pancreatic cancer induced by di-iso-propanol nitrosamine (DIPN). Tumors appeared histologically 8 weeks and duct adenocarcinomas became evident 12 weeks after the administration of DIPN. Although the area of the islets did not change in 8 to 16 weeks, the numbers of B cells was decreased 8 weeks after the administration of DIPN and of A and D cells was decreased at 16 weeks. The area occupied by B cells in proportion to the number of islet cells showed a significant decrease 8 weeks after the administration of DIPN. Since insulin has been reported to have a trophic effect on the exocrine pancreas, our findings suggest that pancreatic B cells start to decrease at the same time that pancreatic cancer begins to form. Thus, insulin appears to play an important role locally in the oncogenesis of pancreatic cancer in acinar cells.

Animals↗
PubMed1991

All eight possible mono-beta-D-glucosides of validoxylamine A. I. Preparation and structure determination.

Validamycin A is the major and most active compound among the validamycin complex. Since the site of beta-glucosidic attachment to validoxylamine A (1) was expected to affect the activity against the pathogenic fungus, Rhizoctonia solani, all eight possible mono-beta-D-glucosides of 1 were prepared. 2-O-, 4-O-, 4'-O-, and 7'-O-beta-D-glucopyranosylvalidoxylamine A (2, 4, 6 and 9, respectively) were prepared by microbial beta-glycosylation of 1 with strains of Rhodotorula sp. 7-O- and 6'-O-beta-D-glucopyranosylvalidoxylamine A (5a and 8a, respectively) were prepared semisynthetically through microbial formation of 7-O-beta-D-glucopyranosylvalidamine (10), oxidation of the primary amine of 10 to a ketone, and coupling of the ketone derivative with valienamine, and through microbial formation of 6-O-beta-D-glucopyranosylvalienamine (11), and coupling of 11 with (2R)-(2,4/3,5)-2,3,4-trihydroxy-5-hydroxymethylcyclohexanone (12), respectively. 3-O- and 5'-O-beta-D-glucopyranosylvalidoxylamine A (3a and 7a, respectively) were chemically synthesized.

Antifungal Agents↗
PubMed1991

All eight possible mono-beta-D-glucosides of validoxylamine A. II. Biological activities.

The biological activities of all eight possible mono-beta-D-glucosides of validoxylamine A against Rhizoctonia solani were studied. The attachment of the D-glucosyl residue to validoxylamine A generally diminished the inhibitory activity against trehalase. The introduction of the D-glucosyl residue at the C-3 position did not cause serious loss in activity, while substitution at the C-6' position caused complete loss in trehalase inhibitory activity. Of the eight beta-D-glucosides, 4-O-beta-D-glucopyranosylvalidoxylamine A (4-O-beta-Glc-VA), 3-O-beta-Glc-VA and 5'-O-beta-Glc-VA exhibited very strong activity against R. solani in the "dendroid-test method". The antagonistic activity of sugars (1 mM) against validoxylamine A and 4-O-beta-Glc-VA was examined using the "dendroid-test method". The inhibitory effect of validoxylamine A on hyphal extension was not antagonized by any sugars tested, whereas that of 4-O-beta-Glc-VA was antagonized by beta-1,3- and beta-1,4-glucooligosaccharides. Of 2-O-, 3-O-, 4-O- and 7-O-beta-Glc-VAs, 7-O-beta-Glc-VA exhibiting the lowest activity was not antagonized by any beta-glucooligosaccharides tested. The inhibitory effect of 3-O- and 4-O-beta-Glc-VAs was antagonized by most beta-glucooligosaccharides. The uptake of 4-O-beta-Glc-VA into the mycelia was inhibited by laminaribiose and cellobiose but not by maltose.

Antifungal Agents↗
PubMed1990

Spantide II, a novel tachykinin antagonist having high potency and low histamine-releasing effect.

Two undecapeptide substance P (SP) analogues, Spantide I and Spantide II, were tested for their capacity to block the contractile effect of SP on the guinea pig isolated taenia coli and the contractile effect of electrical stimulation of the rabbit isolated (and atropinized) iris sphincter, and for their capacity to mobilize histamine from rat isolated peritoneal mast cells. Spantide I and Spantide II have one feature in common, namely D-tryptophan in positions 7 and 9. Spantide I: D-Arg, Pro2, Lys3, Pro4, Gln5, Gln6, D-Trp7, Phe8, D-Trp9, Leu10, Leu11-NH2. Spantide II: D-NicLys1, Pro2, 3-Pal3, Pro4, D-Cl2Phe5, Asn6, D-Trp7, Phe8, D-Trp9, Leu10, Nle11-NH2. Both Spantide I and II were found to be competitive antagonists to SP on the taenia coli and to be capable of blocking the electrically induced non-cholinergic contraction of the iris sphincter. Spantide II had higher pA2 value (taenia coli) than Spantide I, 7.7 versus 7.0, and higher pIC50 value (blockade of tachykinin-mediated neurotransmission in iris sphincter), 6.0 versus 5.1. Both Spantide I and II mobilized histamine from rat peritoneal mast cells but Spantide II was less effective. Spantide I and II were tested for antagonistic specificity. Both blocked contractions of the taenia induced by SP and neurokinin A. In the concentration used, Spantide II in addition blocked the response to neurokinin B. The contractions induced by carbachol, 5-hydroxytryptamine, histamine and prostaglandins (F2 alpha and E1) were not affected; the contractile response to bombesin was inhibited by Spantide I but not by Spantide II.

Amino Acid Sequence↗
PubMed1990

Spantide II, an effective tachykinin antagonist having high potency and negligible neurotoxicity.

Spantide (D-Arg1-Pro2-Lys3-Pro4-Gln5-Gln6-D-Trp7-Phe8-D-Trp9-++ +Leu10-Leu11-NH2) was introduced as a tachykinin antagonist in 1984 and has served as a starting point in the design of new antagonists that have proven to be more effective and have exhibited no neurological side effects. The most remarkable and unpredictable structural change that significantly increased potency was deletion of a methylene group by changing Gln6 to Asn6. On the basis that D-Arg1 and Lys3 of spantide contribute to neurological side effects, many new designs led to D-Lys(Nic)1-Pro2-Pal(3)3-Pro4-D-Phe(Cl2)5-Asn6-D-Trp7-Phe8-D-Trp9- Leu10-Nle11- NH2 [spantide II, where D-Lys(Nic) is N epsilon-nicotinoyllysine, Pal(3) is 3-(3-pyridyl)alanine, D-Phe(Cl2) is 3,4-dichloro-D-phenylalanine, and Nle is norleucine], which is a potent antagonist without neurotoxicity. Spantide II, an undecapeptide, has a total of seven substitutions in the sequence of substance P, consisting of two natural L amino acids, and one unnatural L amino acid, and four unnatural D amino acids. The pi- and sigma-bond amino acid substituents of substance P and spantide II are compared toward a future understanding of the essential substituents for mechanism and inhibition binding. Spantide II has five pi-bond and six sigma-bond amino acid moieties, and substance P has two pi-bond and nine sigma-bond moieties.

Amino Acid Sequence↗
PubMed1990

Inhibitory effect of validamine, valienamine and valiolamine on activities of carbohydrases in rat small intestinal brush border membranes.

Three pseudo-aminosugars, validamine, valienamine and valiolamine, produced by Streptomyces hygroscopicus subsp. limoneus showed potent inhibitory action on rat small intestinal carbohydrase activities such as sucrase, maltase, glucoamylase, isomaltase and trehalase activities, but negligible action on lactase activity and pancreatic alpha-amylase activity. Where inhibition was seen, kinetic analysis showed fully competitive inhibition of the carbohydrase activities by all three inhibitors. Valiolamine has more potent carbohydrase inhibitory activity than validamine or valienamine, and the apparent Ki values of valiolamine for sucrase, maltase, glucoamylase, isomaltase and trehalase activities were 3.2 x 10(-7), 2.9 x 10(-6), 1.2 x 10(-6), 9.1 x 10(-7) and 4.9 x 10(-5) M, respectively, which are 10(-5) to 10(-3) times smaller than the apparent Km values.

Animals↗
PubMed1990

Intracranial and intraspinal dissemination from pineal yolk sac tumor treated by PVB therapy--case report.

A 15-year-old male was admitted because of diplopia and persistent headache. Postcontrast computed tomography (CT) revealed a homogeneously enhanced large mass, 3 x 4 cm in size, in the pineal region and moderate obstructive hydrocephalus. A right ventriculoperitoneal shunt was installed. At that time, the serum alpha-fetoprotein (AFP) level increased to 23,036 ng/ml, but the level of serum beta-subunit of human chorionic gonadotropin was less than 0.2 ng/ml. These data indicated the tumor to be a pure yolk sac tumor. Following cisplatin-vinblastine-bleomycin (PVB) therapy and whole-brain irradiation (50 Gy), the tumor disappeared on CT, although the AFP level did not return to normal. Eight months after the completion of initial therapy, he had lumbago. Spinal magnetic resonance imaging revealed a metastatic mass at the L5-S2 levels, which was subtotally removed and histologically diagnosed as yolk sac tumor. Postoperative local irradiation (30 Gy) was performed. Seven months after the operation, spinal dissemination at the Th7 level occurred and, 1 month later, intracranial dissemination in the left cerebellopontine angle was detected. He died 25 months after the first admission. PVB therapy did not prevent spinal dissemination in this case.

Adolescent↗
PubMed1990

Spinal cord glioblastoma multiforme with intracranial dissemination--case report.

A case of spinal cord glioblastoma multiforme with intracranial dissemination is reported. A 23-year-old female was admitted to a local hospital complaining of lumbago. Myelography revealed an intramedullary thoracic tumor. The tumor was partially removed through a laminectomy at Th11-L1. The histological diagnosis was glioblastoma multiforme, and focal irradiation (total 50 Gy) was given. Eight months after the operation, symptoms of increased intracranial pressure appeared. Computed tomographic (CT) scans showed marked hydrocephalus, and multiple tumors at anterior horns of bilateral lateral ventricles. A ventriculoperitoneal shunt and an Ommaya reservoir into the left lateral ventricle were emplaced. Three months later, she was transferred to our hospital. CT scans showed enhanced lesions in the fourth ventricle, anterior horn of the left lateral ventricle, septum pellucidum, and pituitary gland. Suboccipital craniectomy was performed, and the mass around the fourth ventricle was partially removed. Histological examination of the tumor specimens showed glioblastoma multiforme. Postoperatively, she received whole brain irradiation (total 50 Gy), and intrathecal injection of beta-interferon via the Ommaya reservoir. However, she died of respiratory insufficiency. It is considered that the spinal cord glioblastoma multiforme disseminated into the intracranial space.

Adult↗
PubMed1990

Trehalase inhibitors, validoxylamine A and related compounds as insecticides.

Validoxylamine A showed a potent inhibitory activity against insect trehalase in a competitive manner with a Ki value of 4.3 x 10(-10) M. The other validoxylamines and validamycins also exhibited the activity in vitro. Injection of these compounds to young last instar larvae of the tobacco cutworm, Spodoptera litura, elicited the morphological abnormality followed by death after the cessation of feeding. Validoxylamine A showed 100% mortality at a dose of 10 micrograms/ last instar larva.

Animals↗
PubMed1990

[Organ specific ESR features in mouse main organs and ESR application to the model of pancreatic disorders].

Nine main organs in the mouse were studied by ESR spectroscopy at 77K. Manganese ions were readily detected in the pancreas, small intestine, stomach and kidney. In particular, the pancreas gave strong ESR signals for the transition metal, suggesting that Mn(II) plays an important role in pancreatic function. All organs reveal different ESR spectra indicating organ specificity. C-centered radical, R-OO radical and C0Q10 or ascorbate radical are stable in the tissue. In the brain, heart and pancreas, N-centered radical heme-NO adduct was detected at 6 and 24 h after excision since common process is involved in tissue degeneration and ESR is sensitive to proteolysis and necrosis of tissues. In endotoxemia and/or CDE-diet-induced pancreatic lesions, R-OO radical and Mn(II) ion were detected in the signal at 77K. By the spin-trapping method (DMPO) at 25 degrees C, DMPO-OH adduct and 3-Line and 6-Line were detected in CDE diet-induced acute pancreatitis. These results suggest that damaged pancreatic tissues are in a highly oxidative environment that probably contains oxygen radicals, and that free radicals are considered to play an important role in the development of pancreatic lesions.

Animals↗
PubMed1989

Radical pancreatectomy for ductal cell carcinoma of the head of the pancreas.

Seventy-four patients were treated with a radical or a nonradical pancreatectomy for ductal cell carcinoma of the head of the pancreas. Their survival rates and the selection of the operative procedure were evaluated. In 32 patients, a radical pancreatectomy was attempted where there was sufficient clearance of regional or juxta-regional lymph nodes beyond the group of suspected metastatic nodes, as well as a resection of a greater margin of soft tissue around the pancreas. These patients' cumulative 5-year survival rate was 33.4%. In 14 Stage I or Stage II patients, the cumulative 5-year survival rate was 46.4%. In 18 Stage III or Stage IV patients, the cumulative 5-year survival rate was 20.7%. For 42 patients treated with a nonradical pancreatectomy with the dissection of lymph nodes adjacent to the pancreas or of regional lymph nodes but with insufficient clearance of the soft tissue around the pancreas, the cumulative 2-year and 3-year survival rates were 5.4% and 0%, respectively. In seven patients with Stage II carcinoma, the survival rate was 16.7% after 2 years and 0% after three years. In 35 Stage III or Stage IV patients, the survival rate was 3.2% after 2 years and 0% after 3 years. Thus, the survival rates were significantly higher in patients treated with radical operation than in patients who had nonradical operation. These results indicate that a radical pancreatectomy with sufficient lymph node clearance with the surrounding connective tissue around the pancreas is indispensable to cure patients with ductal cell carcinoma of the pancreas.

Adult↗
PubMed1989

Direct ESR measurement of free radicals in mouse pancreatic lesions.

In this experiment, free radicals in the pancreas of endotoxemia and ethionine induced acute pancreatitis in mice were attempted to be detected directly by ESR spectroscopy, using 77 K freeze-trapping and 25 degrees C DMPO spin trapping techniques. In the 77 K freeze-trapping method, Mn (II) ion and R-00. radical were detected in endotoxemia and ethionine induced pancreatic lesions. The heme-NO radical was observed at 6 and 24 h after isolation of the normal pancreas, and signal intensity was increased with time. This finding supports that ESR spectroscopy is a useful method for detecting the tissue degeneration process from ischemia to necrosis. Using the DMPO spin trapping technique (25 degrees C), 6-line was detected at 6 h after intraperitoneal administration of E. coli in the model of endotoxemia, and 3- and 6-lines and a signal suggestive of DMPO-OH adduct were noted at 12 and 24 h in ethionine pancreatitis. These findings suggest that impaired pancreatic tissues exist in a considerably oxidative environment and oxygen derived free radicals may be considered to play an important role in the development of pancreatic lesions.

Animals↗
PubMed1989

Micronucleus test with colchicine given by intraperitoneal injection and oral gavage.

The effects of micronucleus induction in mouse bone marrow cells by intraperitoneal injection (i.p.) and oral administration (p.o.) were studied with the spindle poison colchicine in 2 strains of mice (MS/Ae and CD-1). The final micronucleus test was performed with a 24-h sampling time at doses of 0.25-2.0 mg/kg by the i.p. route and 2-16 mg/kg by the p.o. route based on a simple acute toxicity test and a pilot micronucleus experiment. Colchicine induced micronuclei in both strains and at all doses tested. Micronuclei were induced more effectively by the i.p. route.

Administration, Oral↗
PubMed1989

Changes of xanthine oxidase, lipid peroxide and superoxide dismutase in mouse acute pancreatitis.

The role of free radicals in the development of pancreatitis was evaluated by measuring the level of activities of xanthine oxidase (XOD), lipid peroxide (LPO) and superoxide dismutase (SOD). Acute pancreatitis was induced in female mice fed a choline-deficient meal containing 0.5% DL-ethionine (CDE meal). Acute pancreatitis was confirmed by the changes in serum amylase level and other typical features observed microscopically 24 h after the meal was taken. Activity of XOD was elevated significantly (p less than 0.05) from the baseline of 1.13 +/- 0.19 U/g tissue to 2.34 +/- 0.46, 2.59 +/- 0.33 and 3.46 +/- 0.70 U/g tissue, 8, 12 and 24 h, respectively, after the CDE meal. The LPO level was also increased from an undetectable amount to 1.10 +/- 0.47 nmol/ml (p less than 0.05), 1.03 +/- 0.18 (p less than 0.01) at 6 and 8 h, respectively, and then returned to an undetectable amount at 12 h. The peak level of LPO was shown at 24 h, 1.76 +/- 0.40 nmol/ml (p less than 0.01) and gradually decreased until 48 h, 1.17 +/- 0.37 nmol/ml (p less than 0.01) after the CDE meal. Changes of LPO took a biphasic pattern. SOD was decreased significantly from 47.1 +/- 3.4 mU/g tissue to 30.7 +/- 2.5, 24.8 +/- 1.7 and 20.6 +/- 1.1 mU/g tissue at 8 (p less than 0.01), 12 (p less than 0.01), and 24 (p less than 0.01) h, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗
PubMed1989

Effect of endotoxin on digestive enzyme and superoxide dismutase in mouse pancreas.

In order to clarify the effect of endotoxin on pancreatic lesions, changes in the level of activity of pancreatic proteolytic enzymes and superoxide dismutase (SOD) were measured following the intraperitoneal administration of Escherichia coli endotoxin in mice. Microscopic examination revealed that congestion of zymogen granules in acinar cells appeared in the early stages. The accumulation increased gradually and was widespread at 24 h after E. coli endotoxin administration. The serum amylase level increased significantly from its basal level of 1,630 +/- 128 SU to 2,395 +/- 42 SU at 4 h (p less than 0.05), 3,172 +/- 513 SU at 8 h (p less than 0.05), and 2,572 +/- 229 SU at 12 h (p less than 0.05) after E. coli endotoxin administration. The serum lipase level also increased significantly from its basal level of 37.6 +/- 1.6 IU/l to 65.8 +/- 8.9 IU/l at 12 h (p less than 0.05). The level of trypsinogen in the pancreas increased markedly from its basal level of 161.8 +/- 15.7 U/g tissue to 270.0 +/- 9.6 U/g tissue at 2 h (p less than 0.001) after E. coli endotoxin administration and showed continued increases at 8 h (313.3 +/- 10 U/g tissue, p less than 0.001) and 24 h (352.9 +/- 19.3 U/g tissue, p less than 0.001); however, the level of net stimulated secretion of trypsinogen in the medium decreased significantly at 4 h (p less than 0.05) and 8 h (p less than 0.01) after E. coli endotoxin administration.(ABSTRACT TRUNCATED AT 250 WORDS)

Amylases↗