Search PubMedSearch

Biomedical subjects

A Ueno

Publications and source records attributed to A Ueno.

At least 19 recordsLinked to original sources

Thrombin induces GRO alpha/MGSA production in human umbilical vein endothelial cells.

Thrombin, besides being a potent coagulation factor, exerts influence on endothelial and leukocyte functions and may thus be involved in the regulation of inflammatory reactions. The present study investigated whether thrombin stimulates the production of growth-related cytokine/melanoma growth-stimulatory activity (GRO alpha/MGSA) in endothelial cells. Human umbilical vein endothelial cells (HUVEC) stimulated with thrombin were found to product GRO alpha/MGSA in a dose- and time-dependent manner. This action of thrombin was completely suppressed by preincubation with either hirudin or antithrombin-III (AT-III)-heparin. Interestingly, the thrombin receptor-activating peptide SFLLRN mimicked the action of thrombin. In addition, staurosporine, a protein kinase C (PKC) inhibitor, attenuated the production of GRO alpha/MGSA by thrombin, SFLLRN and phorbol 12-myristate 13-acetate (PMA), but left the action of interleukin-1 beta (IL-1 beta) unchanged. These results suggest that catalytic activation of thrombin receptor by thrombin results in GRO alpha/MGSA production, at least in part, via a pathway involving PKC in HUVEC.

Alkaloids

A hypotensive response induced by des-Arg9-bradykinin in young brown/Norway rats pretreated with endotoxin.

A hypotensive effect of intravenously injected des-Arg9-bradykinin was found in Brown/Norway strain young male rats which were pretreated with a small amount of endotoxin 24 h before the experiment, whereas the hypotensive effect of bradykinin was unaffected by the endotoxin. The potency of des-Arg9-bradykinin for the hypotensive effect was comparable to that of bradykinin. On the other hand, in endotoxin-pretreated aged rats, this effect of des-Arg9-bradykinin was not observed. Only during the intravenous infusion of des-Arg9[Leu8]bradykinin, a bradykinin B1 receptor antagonist, was the hypotensive effect of des-Arg9-bradykinin inhibited, whereas that of bradykinin was potentiated. After the end of infusion of des-Arg9[Leu8]bradykinin, the response to des-Arg9-bradykinin rapidly recovered. The results suggest the possibility that des-Arg9-bradykinin might play a role in inflammatory diseases.

Amino Acid Sequence

Transforming growth factor-beta 1 has both promoting and inhibiting effects on induction of DNA synthesis in human fibroblasts.

Growth-arrested human normal fibroblasts, TIG-1, initiated DNA synthesis following addition of epidermal growth factor (EGF). Transforming growth factor-beta 1 (TGF-beta 1) by itself had no effect on induction of DNA synthesis. When EGF and TGF-beta 1 were added simultaneously to growth-arrested TIG-1 cells, induction of DNA synthesis was enhanced compared with that by EGF alone. Contrarily, when TGF-beta 1 was added earlier than 2 h or later than 2 h of EGF addition, induction of DNA synthesis was prevented. Induction of DNA synthesis by EGF was insensitive to pertussis toxin (PT, an inhibitor of Gi protein) and to staurosporine (a protein kinase inhibitor). The promoting effect of TGF-beta 1 on DNA synthesis was PT-insensitive and staurosporine-insensitive. Contrarily, inhibitory activity of TGF-beta 1 on DNA synthesis was PT-sensitive and staurosporine-insensitive. These studies suggest that the effect of TGF-beta 1 is to promote or to inhibit induction of DNA synthesis by EGF expressed through different signal transduction processes in the same cell.

Alkaloids

Heavy ion mutagenesis: linear energy transfer effects and genetic linkage.

We have characterized a series of 69 independent mutants at the endogenous hprt locus of human TK6 lymphoblasts and over 200 independent S1-deficient mutants of the human x hamster hybrid cell line AL arising spontaneously or following low-fluence exposures to densely ionizing Fe ions (600 MeV/amu, linear energy transfer = 190 keV/microns). We find that large deletions are common. The entire hprt gene (> 44 kb) was missing in 19/39 Fe-induced mutants, while only 2/30 spontaneous mutants lost the entire hprt coding sequence. When the gene of interest (S1 locus = M1C1 gene) is located on a nonessential human chromosome 11, multilocus deletions of several million base pairs are observed frequently. The S1 mutation frequency is more than 50-fold greater than the frequency of hprt mutants in the same cells. Taken together, these results suggest that low-fluence exposures to Fe ions are often cytotoxic due to their ability to create multilocus deletions that may often include the loss of essential genes. In addition, the tumorigenic potential of these HZE heavy ions may be due to the high potential for loss of tumor suppressor genes. The relative insensitivity of the hprt locus to mutation is likely due to tight linkage to a gene that is required for viability.

Animals

Mazusaponins I-IV, triterpene saponins from Mazus miquelii.

From whole plants of Mazus miquelii, four new saponins designated as mazusaponins I-IV and a known saponin, ilexoside VIII, were isolated and the structures of the new compounds elucidated as 3-O-alpha-L-arabinopyranosyl siaresinolic acid 28-O-beta-D-glucopyranosyl-(1-->6)-beta-D-glucopyranosyl ester, 3-O-alpha-L-arabinopyranosyl pomolic acid 28-O-beta-D-glucopyranosyl-(1-->6)-beta-D-glucopyranosyl ester, 3-O-alpha-L-rhamnopyranosyl-(1-->2)-alpha-L-arabinopyranosyl siaresinolic acid 28-O-beta-D-glucopyranosyl-(1-->6)-beta-D-glucopyranosyl ester and 3-O-alpha-L-rhamnopyranosyl-(1-->2)-alpha-L-arabinopyranosyl pomolic acid 28-O-beta-D-glucopyranosyl-(1-->6)-beta-D-glucopyranosyl ester, respectively, by spectroscopic data and chemical evidence.

Carbohydrate Sequence

Comparative study of endotoxin-induced hypotension in kininogen-deficient rats with that in normal rats.

1. The aim of this study was to clarify the role of endogenous bradykinin (BK) in the hypotensive response induced by lipopolysaccharide (LPS) by comparing the degree of hypotension caused by LPS in a strain of specific pathogen-free (SPF) Brown Norway (B/N), kininogen-deficient mutant Katholiek rats with that of B/N normal Kitasato rats. 2. The dose-dependent hypotensive responses caused by intravenous injection of BK (1-100 nmol kg-1) or platelet-activating factor (PAF, 0.003-1 microgram kg-1), were not different in the two strains of rats used. However, there was a strong difference in the hypotensive response induced by LPS in kininogen-deficient and normal rats; in normal rats the hypotensive response was composed of two phases (15 min and 70-80 min after LPS injection), but in kininogen-deficient rats LPS caused a delayed (second phase), but not an acute (first phase) hypotension. 3. We demonstrate that Hoe 140 (1 mg kg-1, i.v.) is a potent, selective, and long-lasting antagonist of the hypotensive effects of BK. Hoe 140 diminished the hypotension caused by LPS in normal rats to the level observed in kininogen-deficient rats, but had no effect on the hypotension caused by LPS in kininogen-deficient rats. 4. TCV309 (0.1 mg kg-1, i.v.) selectively inhibited the hypotension caused by repetitive injection of PAF for up to 180 min. Pretreatment with TCV309 caused a near complete inhibition of the LPS-induced hypotension in kininogen-deficient and normal B/N rats. 5. In the normal rats, dexamethasone (0.5 mg kg-1, i.p.) inhibited the second phase of the hypotension induced by LPS, but not the first phase of the hypotension. 6. A small amount of BK (0.1 nmol kg-1) potentiated the hypotensive action of PAF (0.01 microg kg-1),when they were injected simultaneously.7. In conclusion, we demonstrate that formation of endogenous BK contributes primarily to the acute,but not to the delayed hypotension afforded by endotoxin in the rat. In contrast, formation of endogenous PAF contributes to both the acute and the delayed hypotension afforded by endotoxin in vivo.

Amino Acid Sequence

Studies on differentiation inducers. V. Steroid glycosides from periplocae radicis cortex.

Six pregnane glycosides and three cardenolides were isolated as differentiation inducers using mouse myeloid leukemia (Ml) cells from Periplocae Radicis Cortex (bark of Periploca sepium BGE., Asclepiadaceae). The cardenolides showed much higher activities than the pregnane glycosides. Besides these nine compounds, commercially available cardenolides were tested for their differentiation inducing activities using Ml cells. Digitoxin and digoxin induced Ml cells into phagocytic cells, but others did not. In the presence of 1 nM of actinomycin-D, the activity of steroid glycosides was enhanced against Ml cells.

Animals

[Benefits and adverse effects of post-operative radiation therapy after radical cystectomy for patients with advanced bladder cancer].

BACKGROUND: The benefits and adverse effects of post-operative irradiation for advanced bladder cancer patients were investigated. METHODS: Ten patients with pT3b, pT4 or pN+ bladder cancer who underwent radical cystectomy at Yamanashi Medical University hospital during 7 years and 3 months from October 1983 to December 1991 received adjuvant chemotherapy and radiotherapy (Group 1). During the same period, six patients with recurrent tumor after radical cystectomy were treated by radiotherapy (Group II). Stages of the primary tumors were pT2 in 1, pT3a in 2, pT3b in 6 and pT4 in 7 cases. In addition, 10 of 16 patients (63%) had positive nodes. RESULTS: During the follow up period, seven patients died of cancer, and one died of other cause. As a result eight patients (5 in Group I, 3 in Group II) are alive. The cumulative 5-year survival rate is 50%. However, nine of the 16 patients (56%) suffered from the small bowel obstruction as an adverse effect of irradiation. Six patients required resection of the small bowel or bypass surgery. CONCLUSIONS: Radiation after radical cystectomy seemed to be effective for the local control of the tumor, but the adverse effect to the digestive system was very severe and common.

Aged

[Cystic disease of the kidney].

The kidney is one of the most common sites of cyst. Since cystic disease of the kidney includes various disorders, it is difficult to classify the diseases systematically. It appears that the classification of the American Academy of Pediatrics is suitable for clinical side for the present. In this paper the cystic disease of the kidney is explained on actual cases. Recently, development of imaging diagnosis is contributing widely to the diagnosis of the diseases. Treatment of the diseases, however, is not established satisfactorily. It is hoped that the mechanism of occurrence of the diseases is known further and that regulation of the classification and establishment of the treatment will become available.

Aged

Development of a novel method for determination of acetyl-CoA:1-alkyl-sn-glycero-3-phosphocholine acetyltransferase activity and its application to screening for acetyltransferase inhibitors. Inhibition by magnolol and honokiol from Magnoliae cortex.

A method was developed for determining the activity of acetyl-CoA:1-alkyl-sn-glycero-3-phosphocholine acetyltransferase (EC 2.3.1.67), a key enzyme in the biosynthesis of platelet-activating factor (PAF, 1-alkyl-2-acetyl-sn-glycero-3-phosphocholine). The assay involves measurement of the radioactivity in the trichloroacetic acid (TCA)-precipitated complex of radioactive product and albumin after incubation of 1-alkyl-sn-glycero-3-phosphocholine and [3H]acetyl-CoA with rat spleen microsomes or membrane fractions of human polymorphonuclear leukocytes (PMNs). The radioactive product associated with the precipitate was identified as PAF using an ultrahigh-sensitivity TV camera system after extraction and separation by TLC. This TCA method was then used to screen the components of crude preparations that inhibited acetyltransferase activity. Major components from the cortex of Magnoliae (magnolol and honokiol), which have anti-inflammatory and anti-bacterial actions, inhibited the acetyltransferase activity in rat spleen microsomes (IC50, 150 and 150 microM, respectively) and membrane fractions of human PMNs (IC50, 70 and 60 microM, respectively). The inhibitory action of magnolol and honokiol was reversible, and similar to or higher than that of nordihydroguaiaretic acid. PAF production in human PMNs stimulated by the ionophore A23187 was also suppressed dose dependently by magnolol and honokiol. These activities may be relevant to the claimed therapeutic effects of the extract from Magnoliae cortex.

Acetyltransferases

Oleanane-triterpene saponins from Clinopodium chinense var. parviflorum.

From the whole plants of Clinopodium chinense var. parviflorum three new saponins, named clinoposaponins IX-XI, were isolated together with three known saponins and their structures elucidated from spectroscopic data and chemical evidence. Clinoposaponins IX, X and XI were identified as 13 beta,28-epoxy-16 beta,23-dihydroxyolean-11-en-3 beta-yl-beta-D- glucopyranoside,13 beta,28-epoxy-16 beta,23-dihydroxyolean-11-en-3 beta-yl-beta- D-glucopyranosyl-(1-->6)-beta-D-glucopyranoside and 13 beta,28-epoxy-16 beta-hydroxyolean-11-en-3 beta-yl-beta-D-glucopyranosyl- (1-->2)-[beta-D-glucopyranosyl-(1-->3)]-beta-D-fucopyranoside.

Carbohydrate Sequence

Phenylethanoid glycoside from Veronica undulata.

From a water extract of whole plants of Veronica undulata, a new phenylethanoid triglycoside and five known glycosides were isolated. The structure of the new compound was elucidated from chemical and spectroscopic evidence.

Carbohydrate Sequence

Cell differentiation-inducing diterpenes from Andrographis paniculata Nees.

The methanol extract of the aerial part of Andrographis paniculata Nees showed potent cell differentiation-inducing activity on mouse myeloid leukemia (M1) cells. From the ethyl acetate-soluble fraction of the methanol extract, six new diterpenoids of ent-labdane type, 14-epi-andrographolide (3), isoandrographolide (4), 14-deoxy-12-methoxyandrographolide (7), 12-epi-14-deoxy-12-methoxyandrographolide (8), 14-deoxy-12-hydroxyandrographolide (9) and 14-deoxy-11-hydroxyandrographolide (10) as well as two new diterpene glucosides, 14-deoxy-11,12-didehydroandrographi-side (12) and 6'-acetylneoandrographolide (14), and four new diterpene dimers, bis-andrograpolides A (15), B (16), C (17) and D (18), were isolated along with six known compounds. The structures of the diterpenoids were determined by means of spectral methods. Some of these compounds showed potent cell differentiation-inducing activity towards M1 cells.

Animals