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1.
Eiji Kumazawa Akiko Tohgo Tsunehiko Soga Tsuneo Kusama Yasuaki Osada 《Cancer immunology, immunotherapy : CII》1992,35(5):307-314
Summary The antitumor effect of a synthetic lipid A analogue, DT-5461, was investigated using syngeneic tumor models in mice. Intravenous injection of DT-5461 into mice transplanted with solid tumors of MethA fibrosarcoma, MH134 hepatoma, MM46 mammary carcinoma, Lewis lung carcinoma (3LL), and colon adenocarcinomas 26 and 38 resulted in significant reductions in the weight of all tumors except Colon 26, with marked hemorrhagic necrosis of tumor tissues. Efficacy was almost equal to that of anEscherichia coli-type synthetic lipid A (compound 506), and also to those of some chemotherapeutics including Adriamycin, mitomycin C, fluorouracil and cisplatin. Furthermore, DT-5461 was more effective than other immunotherapeutics, including picibanil (OK-432) and lentinan. However, its antitumor effects were inferior to those of Adriamycin or OK-432 against the malignant ascites caused by intraperitoneal inoculation with MethA or with MH134 cells; life span was not prolonged by either intraperitoneal or intravenous administration. In addition, although DT-5461 showed direct inhibitory effects on the in vitro growth of MethA or MH134, these were much weaker than those of Adriamycin. These findings clearly indicated that DT-5461 with systemic administration is a highly effective antitumor agent on solid tumors, and suggest that the antitumor effect of DT-5461 with potent necrotizing activity might derive from indirect mechanisms related to the activation of host immune systems and not to the weak direct cytotoxicity. 相似文献
2.
Liposomes as model for taste cells: receptor sites for bitter substances including N-C=S substances and mechanism of membrane potential changes 总被引:1,自引:0,他引:1
Various bitter substances were found to depolarize liposomes. The results obtained are as follows: (1) Changes in the membrane potential of azolectin liposomes in response to various bitter substances were monitored by measuring changes in the fluorescence intensity of 3,3'-dipropylthiocarbocyanine iodide [diS-C3(5)]. All the bitter substances examined increased the fluorescence intensity of the liposome-dye suspension, which indicates that the substances depolarize the liposomes. There existed a good correlation between the minimum concentrations of the bitter substances to depolarize the liposomes and the taste thresholds in humans. (2) The effects of changed lipid composition of liposomes on the responses to various bitter substances vary greatly among bitter substances, suggesting that the receptor sites for bitter substances are multiple. The responses to N-C=S substances and sucrose octaacetate especially greatly depended on the lipid composition; these compounds depolarized only liposomes having certain lipid composition, while no or hyperpolarizing responses to these compounds were observed in other liposomes examined. This suggested that the difference in "taster" and "nontaster" for these substances can be explained in terms of difference in the lipid composition of taste receptor membranes. (3) It was confirmed that the membrane potential of the planar lipid bilayer is changed in response to bitter substances. The membrane potential changes in the planar lipid bilayer as well as in liposomes in response to the bitter substances occurred under the condition that there is no ion gradient across the membranes. These results suggested that the membrane potential changes in response to bitter substances stem from the phase boundary potential changes induced by adsorption of the substances on the hydrophobic region of the membranes. 相似文献
3.
Variations in mitochondrial tRNA gene organization of reptiles as phylogenetic markers 总被引:11,自引:2,他引:9
Amplification and sequencing of mitochondrial DNA regions corresponding to
three major clusters of transfer RNA genes from a variety of species
representing major groups of birds and reptiles revealed some new
variations in tRNA gene organization. First, a gene rearrangement from
tRNA(His)-tRNA(Ser)(AGY)-tRNA(Leu)(CUN) to tRNA(Ser)(AGY)-
tRNA(His)tRNA(Leu)(CUN) occurs in all three crocodilians examined
(alligator, caiman, and crocodile). In addition an exceptionally long
spacer region between the genes for NADH dehydrogenase subunit 4 and
tRNA(Ser)(AGY) is found in caiman. Second, in congruence with a recent
finding by Seutin et al., a characteristic stem-and-loop structure for the
putative light-strand replication origin located between tRNA(Asn) and
tRNA(Cys) genes is absent for all the birds and crocodilians. This
stem-and-loop structure is absent in an additional species, the Texas blind
snake, whereas the stem-and-loop structure is present in other snakes,
lizards, turtles, mammals, and a frog. The disappearance of the
stem-and-loop structure in the blind snake most likely occurred
independently of that on the lineage leading to birds and crocodilians.
Finally, the blind snake has a novel type of tRNA gene arrangement in which
the tRNA(Gln) gene moved from one tRNA cluster to another. Sequence
substitution rates for the tRNA genes appeared to be somewhat higher in
crocodialians than in birds and mammals. As regards the controversial
phylogenetic relationship among the Aves, Crocodilia, and Mammalia, a
sister group relationship of birds and crocodilians relative to mammals, as
suggested from the common loss of the stem-and- loop structure, was
supported with statistical significance by molecular phylogenetic analyses
using the tRNA gene sequence data.
相似文献
4.
S Kanegasaki Y Kojima M Matsuura J Y Homma A Yamamoto Y Kumazawa K Tanamoto T Yasuda T Tsumita M Imoto 《European journal of biochemistry》1984,143(2):237-242
Lipid A analogues were chemically synthesized based on the model structure recently revised, and biological activities of the analogues were tested. The analogue, (beta-1,6)-linked glucosamine disaccharide carrying ester-bound 3-hydroxytetradecanoic acids at 3 and 3' position of reducing and nonreducing glucosamine in addition to amide-bound 3-hydroxytetradecanoic acids and glycosidic-linked and ester-linked phosphate groups, showed much stronger activities for mediator inducing and immunomodulating as well as endotoxic activities than those exhibited by the previously synthesized analogues based on the old model. Among the activities tested, induction of interferon and tumor necrosis factor as well as mitogenicity, adjuvanticity and pyrogenicity were, however, not expressed so strongly as natural lipid A used as controls. In contrast, the analogue exhibited comparable activities to those of control lipid A in the test of lethal toxicity to mice and gelating activity of Limulus amebocyte lysate. Other synthetic analogues carrying a phosphate group showed comparable, slightly stronger or weaker activities depending on the test, but nonphosphorylated analogue exhibited no apparent or only very weak activities. 相似文献
5.
K Yamazaki A Kumazawa K Ito K Kurihara M Nakayama T Wakabayashi 《Laboratory animal science》1992,42(4):378-381
Senescence-accelerated mice (SAM) are one of the animal models used for studying senescence, which consist of several substrains such as SAM-R/1, R/2, P/1, P/2. SAM-R/1/Eis maintained in Eisai Tsukuba Research Laboratories, Ibaraki, Japan, was originally introduced as a substrain of a normal control SAM-R/1 from Kyoto University, Japan. We have noted signs of convulsions in SAM-R/1/Eis mice during routine animal care, particularly while changing cages. We identified the clinical signs and determined the concentrations of glucose and immunoreactive insulin in plasma of SAM-R/1/Eis mice. There were no differences in the male:female ratios of mice showing prodrome only, grand mal, or no-signs. The ages at which prodrome and grand mal were first noted peaked between 20 and 25 weeks. Concentrations of glucose and immunoreactive insulin in plasma did not indicate the mice were in insulin hypoglycemia, which is one cause of convulsions. AKR strain mice, some of which originated with the SAM strain are known to become convulsive by repeated "throwing" stimulations. Conversely, in SAM-R/1/Eis, throwing stimuli are not needed to cause convulsive signs. Thus it is likely that in SAM-R/1/Eis mice the signs are triggered by repeating mild environmental changes, such as changing cages. The results of this study show that SAM-R/1/Eis is neither a normal control strain, nor an original SAM-R/1 strain. But it is possible that SAM-R/1/Eis is another useful animal model for studying spontaneous convulsion. 相似文献
6.
A novel method for the reconstitution of oxygen evolution in cholate-extracted spinach thylakoid membranes was established and a protein essential for the reconstitution was purified from cholate extracts. Purification of the protein was accomplished by chromatography on a DEAE-Sephacel column. This protein (Mr 17 000) was reinserted into vesicular membranes reconstituted from cholate-extracted thylakoids in the presence of 25% glycerol to reactivate oxygen evolution. 相似文献
7.
Akiba S Kumazawa S Yamaguchi H Hontani N Matsumoto T Ikeda T Oka M Sato T 《Biochimica et biophysica acta》2006,1763(8):797-804
Increases in matrix metalloproteinases (MMPs) at atherosclerotic lesions are involved in the migration of smooth muscle cells (SMCs) into the intima and to the rupture of plaques, being implicated in the progression of atherosclerosis. The present study examined the mechanisms underlying the production of MMP-1, interstitial collagenase-1, induced by oxidized low-density lipoprotein (oxLDL) and 4-hydroxynonenal (4-HNE), factors proposed to play a pivotal role in atherogenesis, in human coronary SMCs. oxLDL promoted the production of MMP-1 with the preceding phosphorylation of extracellular signal-regulated kinase (ERK) 1/2. Immunoprecipitation of platelet-derived growth factor receptor beta (PDGFR-beta) revealed that oxLDL induced tyrosine phosphorylation of the receptor. Inhibition of the activation of PDGFR-beta and ERK1/2 resulted in a suppression of the production of MMP-1. Consistently, 4-HNE also elicited the production of MMP-1 with the preceding phosphorylation of PDGFR-beta and ERK1/2. The 4-HNE-induced production of MMP-1 was prevented when the activation of PDGFR-beta and ERK1/2 was inhibited. The present results suggest that the activation of PDGFR-beta and ERK1/2 is involved in the production of MMP-1 in oxLDL- and 4-HNE-stimulated human coronary SMCs. 相似文献
8.
Takeshi Ishii Tomoe Yamada Taiki Mori Shigenori Kumazawa Koji Uchida Tsutomu Nakayama 《Free radical research》2013,47(11):1253-1260
Lipid peroxidation products contribute to protein aggregation that occurs during oxidative stress in a number of degenerative disorders. Acrolein (ACR), a highly toxic lipid peroxidation aldehyde, is a strong cross-linking agent of cellular components such as proteins. To understand the mechanisms of oxidative stress-induced protein aggregation, this study characterized the ACR modification of chain B from bovine insulin by mass spectrometry. To identify the cross-linking sites, the ACR-treated peptide was digested with a protease and the resulting peptides were analysed by liquid chromatography-tandem mass spectrometry. Inter- and intra-molecular cross-linking adducts were identified between amino groups and the side chain of histidine in the peptide. These results indicated that the ACR-induced cross-links were accompanied by two reactions, namely Michael addition and Schiff base formation. In conclusion, the use of mass spectrometric techniques provided chemical evidence for protein cross-linking with ACR. 相似文献
9.
Purification and characterization of two serine isoacceptor tRNAs from bovine mitochondria by using a hybridization assay method. 下载免费PDF全文
For large scale preparation of mitochondrial tRNAs, a new hybridization assay method using synthetic oligodeoxyribonucleotide probes (16-17mer) complementary to individual tRNA sequences was developed and applied for the purification of two serine isoacceptor tRNAs (tRNASerAGY and tRNASerUCN) from bovine mitochondria. It is about 100 times more sensitive than the conventional aminoacylation assay method. 2-4 A260 units each of both tRNASer isoacceptors were purified from 17.5 kg of bovine liver, and they were characterized by means of nuclease digestion, melting profiles and aminoacylation activity. It is suggested that tRNASerUCN possesses the D loop/T loop interaction like usual L-shaped tRNAs, and that tRNASerAGY lacking almost an entire D arm is aminoacylated with an efficiency not very much lower than that of tRNASerUCN. 相似文献
10.
N-haloacetylimino neonicotinoids: potency and molecular recognition at the insect nicotinic receptor
Tomizawa M Durkin KA Ohno I Nagura K Manabe M Kumazawa S Kagabu S 《Bioorganic & medicinal chemistry letters》2011,21(12):3583-3586
This structure-activity relationship study for neonicotinoids with an N-haloacetylimino pharmacophore identifies several candidate compounds showing outstanding insecticidal potency and consequently leads to establishing their molecular recognition at an insect nicotinic receptor structural model, wherein the neonicotinoid halogen atoms (fluorine, chlorine, bromine, and iodine) variously interact with the receptor loops C-D interfacial niche via H-bonding and/or hydrophobic interactions. 相似文献