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71.
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Cheng CP Ukai T Onishi K Ohte N Suzuki M Zhang ZS Cheng HJ Tachibana H Igawa A Little WC 《American journal of physiology. Heart and circulatory physiology》2001,280(4):H1853-H1860
The diastolic dysfunction present at rest in congestive heart failure (CHF) is exacerbated during exercise (Ex). Increases in circulating ANG II and endothelin-1 (ET-1) during Ex may contribute to this response. We assessed the effect of Ex on circulating plasma levels of ANG II and ET-1 and left ventricular (LV) dynamics before and after pacing-induced CHF at rest and during Ex in nine conscious, instrumented dogs. Before CHF, there were modest increases in circulating levels of ANG II (but not ET-1) during Ex. LV diastolic performance was enhanced during Ex with decreases in the time constant of LV relaxation (tau), LV end-systolic volume (V(ES)), and LV minimum pressure with a downward shift of the LV early diastolic portion of the pressure-volume (P-V) loop. This produced an increase in peak LV filling rate without an increase in mean left atrial (LA) pressure. After CHF, the resting values of ANG II and ET-1 were elevated and increased to very high levels during Ex. After CHF, mean LA pressure, tau, and LV minimum pressure were elevated at rest and increased further during Ex. Treatment with L-754,142, a potent ET-1 antagonist, or losartan, an ANG II AT(1)-receptor blocker, decreased these abnormal Ex responses in CHF more effectively than an equally vasodilatory dose of sodium nitroprusside. Combined treatment with both ANG II- and ET-1-receptor blockers was more effective than either agent alone. We conclude that in CHF, circulating ANG II and ET-1 increase to very high levels during Ex and exacerbate the diastolic dysfunction present at rest. 相似文献
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Melanoma differentiation associated gene-7 (mda-7): a novel anti-tumor gene for cancer gene therapy 总被引:30,自引:0,他引:30
Mhashilkar AM Schrock RD Hindi M Liao J Sieger K Kourouma F Zou-Yang XH Onishi E Takh O Vedvick TS Fanger G Stewart L Watson GJ Snary D Fisher PB Saeki T Roth JA Ramesh R Chada S 《Molecular medicine (Cambridge, Mass.)》2001,7(4):271-282
BACKGROUND: The mda-7 gene (melanoma differentiation associated gene-7) is a novel tumor suppressor gene. The anti-proliferative activity of MDA-7 has been previously reported. In this report, we analyze the anti-tumor efficacy of Ad-mda7 in a broad spectrum of cancer lines. MATERIALS AND METHODS: Ad-mda7-transduced cancer or normal cell lines were assayed for cell proliferation (tritiated thymidine incorporation assay, Alamar blue assay, and trypan-blue exclusion assay), apoptosis (TUNEL, and Annexin V staining visualized by fluorescent microscopy or FACs analysis), and cell cycle regulation (Propidium Iodide staining and FACs analysis). RESULTS: Ad-mda7 treatment of tumor cells resulted in growth inhibition and apoptosis in a temporal and dose-dependent manner. The anti-tumor effects were independent of the genomic status of p53, RB, p16, ras, bax, and caspase 3 in these cells. In addition, normal cell lines did not show inhibition of proliferation or apoptotic response to Ad-mda7. Moreover, Ad-mda7-transduced cancer cells secreted a soluble form of MDA-7 protein. Thus, Ad-mda7 may represent a novel gene-therapeutic agent for the treatment of a variety of cancers. CONCLUSIONS: The potent and selective killing activity of Ad-mda7 in cancer cells but not in normal cells makes this vector a potential candidate for cancer gene therapy. 相似文献
75.
EPR studies on a Hipip type iron-sulfur center in the succinate dehydrogenase segment of the respiratory chain 总被引:1,自引:0,他引:1
T Onishi D B Winter J Lim T E King 《Biochemical and biophysical research communications》1974,61(3):1017-1025
In addition to the two species of ferredoxin-type iron-sulfur centers (Centers S-1 and S-2), a Hipip-type iron-sulfur center (Center S-3) has been detected in the reconstitutively active soluble succinate dehydrogenases. Em7,4 determined in a particulate, antimycin A sensitive succinate-cytochrome reductase is +60 ± 15 mV. This center is extremely labile towards oxygen in a manner similar to the reconstitutive activity of the dehydrogenase. Even freshly prepared reconstitutively active enzyme shows a considerably diminished content of Center S-3 relative to flavin and displays a partly modified spectra. All reconstitutively inactive dehydrogenases give rise to a highly modified or no Center S-3 spectra at all. These observations indicate that Center S-3 is a constituent of succinate dehydrogenase and plays a role in the physiological function of the enzyme, transferring electrons most probably to ubiquinone. 相似文献
76.
Identification and Characterization of a Constitutively Active STAT5 Mutant That Promotes Cell Proliferation 总被引:24,自引:2,他引:24 下载免费PDF全文
77.
Chijiwa T Hamai S Tsubouchi S Ogawa T Deshimaru M Oda-Ueda N Hattori S Kihara H Tsunasawa S Ohno M 《Journal of molecular evolution》2003,57(5):546-554
Trimeresurus flavoviridis (Crotalinae) snakes inhabit the southwestern islands of Japan: Amami-Oshima, Tokunoshima, and Okinawa. Affinity and conventional chromatographies of Amami-Oshima T. flavoviridis venom led to isolation of a novel phospholipase A2 (PLA2). This protein was highly homologous (91%) in sequence to trimucrotoxin, a neurotoxic PLA2, which had been isolated from T. mucrosquamatus (Taiwan) venom, and exhibited weak neurotoxicity. This protein was named PLA-N. Its LD50 for mice was 1.34 µg/g, which is comparable to that of trimucrotoxin. The cDNA encoding PLA-N was isolated from both the Amami-Oshima and the Tokunoshima T. flavoviridis venom-gland cDNA libraries. Screening of the Okinawa T. flavoviridis venom-gland cDNA library with PLA-N cDNA led to isolation of the cDNA encoding one amino acid-substituted PLA-N homologue, named PLA-N(O), suggesting that interisland mutation occurred and that Okinawa island was separated from a former island prior to dissociation of Amami-Oshima and Tokunoshima islands. Construction of a phylogenetic tree of Crotalinae venom group II PLA2s based on the amino acid sequences revealed that neurotoxic PLA2s including PLA-N and PLA-N(O) form an independent cluster which is distant from other PLA2 groups such as PLA2 type, basic [Asp49]PLA2 type, and [Lys49]PLA2 type. Comparison of the nucleotide sequence of PLA-N cDNA with those of the cDNAs encoding other T. flavoviridis venom PLA2s showed that they have evolved in an accelerated manner. However, when comparison was made within the cDNAs encoding Crotalinae venom neurotoxic PLA2s, their evolutionary rates appear to be reduced to a level between accelerated evolution and neutral evolution. It is likely that ancestral genes of neurotoxic PLA2s evolved in an accelerated manner until they had acquired neurotoxic function and since then they have evolved with less frequent mutation, possibly for functional conservation.
The nucleotide sequences reported in this paper are available from the GenBank/EMBL/DDBJ databases under accession numbers AB102728 and AB102729. 相似文献
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R Morita S Morimoto E Koh K Fukuo S Kim K Itoh K Taniguchi T Onishi T Ogihara 《Biochemistry international》1989,18(3):647-653
Low density lipoprotein (LDL), a major cholesterol-carrying lipoprotein in the plasma, binds to its receptor through apoprotein B (Apo-B). The addition of LDL and Apo-B induced rapid (5 s), but transient increase in the inositol 1,4,5-trisphosphate (Ins-1,4,5-P3) level with K0.5 values of 1.1 and 0.07 microgram/ml, accompanied by increases of cytosolic free Ca2+ concentration [( Ca2+]i), in vascular smooth muscle cells (VSMC). The increases by LDL and Apo-B were both reduced by pretreatment of the VSMC with pertussis toxin. The early change in Ins-1,4,5-P3 involving a GTP-binding protein may function as an initial signal for the action of LDL in VSMC. 相似文献
80.