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51.
Antimetastatic Activity of Polymeric RGDT Peptides Conjugated with Poly(ethylene glycol) 总被引:1,自引:0,他引:1
Ikuo Saiki Junya Yoneda Yu Igarashi Miho Aoki Naoto Kusunose Kei-ichi Ono Ichiro Azuma 《Cancer science》1993,84(5):558-565
Polymeric peptides containing defined repetitive or cyclic structures of RGDT sequence, (RGDT)n (n = 1 to 11) and cyclo(RGDT)n (n=2 to 4), at a dose of 500 μg exhibited an inhibitory effect on experimental lung metastasis upon co-injection with tumor cells and the magnitude of the effect increased in parallel with the increase of degree of repetition of the RGDT sequence. The conjugation of (RGDT)n (n = 1, 5, 11) with poly(ethylene glycol), PEG as a polymeric carrier led to enhanced inhibition of lung metastasis in proportion to the degree of RGDT sequence repetition and in a dose-dependent manner. Multiple i.v. administrations of PEG-(RGDT)11, at 2-day and 3-day intervals before the excision of primary tumors, effectively inhibited spontaneous lung metastasis by s.c. inoculation of tumors, whereas (RGDT)11 exhibited inhibition of lung metastasis only when given at 2-day intervals. This indicates that the conjugation of PEG with (RGDT)n allowed the prolongation of administration interval, implying a sustained inhibitory effect on tumor metastasis. In support of this supposition, a decrease in the arrest of radiolabeled tumor cells in the lungs was observed when PEG-(RGDT)11 was co-injected i.v. with tumor cells, or injected i.v. one day before tumor inoculation. In contrast, (RGDT)11 significantly inhibited the tumor cell arrest in the lungs only upon co-injection with tumor cells. We also noted that (RGDT)n, cyclo(RGDT)n and PEG-(RGDT)11 inhibited tumor cell invasion into Matrigel in a concentration-dependent manner and in proportion to the degree of RGDT sequence repetition, indicating that the peptide-mediated antimetastatic effect is partly associated with the anti-invasive potential. Thus, the conjugation of anti-cell adhesive and antimetastatic RGDT peptide with PEG might provide a therapeutically promising basis for the prevention of cancer metastasis (“anti adhesion therapy”). 相似文献
52.
53.
Kohsuke Sasaki Daniel Pinkel Masato Tsukahara Ichiro Murano Joe W Gray 《Pathology international》1994,44(2):145-150
A human chromosomal translocation t(8;9) was detected using two-color fluorescence in situ hybridization with probes capable of staining the entire lengths of each of these chromosomes. The chromosome 8 probe was labeled with biotin and detected with Texas red, while the chromosome 9 probe was labeled with AAF and detected with FITC . In normal metaphase spreads, two metaphases from the proband, two red, one green and one part red and part green derivative chromosome were seen. The bicolor chromosome corresponded to translocation of a chromosome 8 segment to the distal part of the q region of one chromosome 9, as originally indicated by banding analysis. In interphase nuclei of the proband, four domains with bright fluorescence were recognized in many nuclei. Two were red, one was green, and the fourth had portions of both colors, indicating the presence of the translocation. 相似文献
54.
Satoshi Hasebe Chiaki Nakatsuka Ichiro Hamasaki Hiroshi Ohtsuki 《Ophthalmic & physiological optics》2005,25(4):310-314
PURPOSE: To clarify how the downward deviation of progressive addition lenses (PALs) reduces their near-addition effect in schoolchildren participating in a myopia control trial. METHODS: Among 95 schoolchildren wearing PALs for 6 months (age range: 6-12 years; refractive error range: -6.00 to -1.25 D), facial images were captured with a digital still camera placed 60 cm in front of the eyes while he or she was looking ahead with natural head posture. The vertical deviations of PALs from their ideal position (mm) were evaluated by analysing these images. RESULTS: The mean (+/-SD) downward deviations of PALs for the right and left eyes were 3.7 +/- 2.3 and 3.7 +/- 2.0 mm, respectively, and the largest downward deviation was 10.2 mm. For simulations using the average downward deviation, the near-addition effect of PALs was reduced to 30 and 63% of the expected value at the 10 degrees and 20 degrees downward eye positions, respectively. CONCLUSIONS: The downward deviation of PALs is a significant factor in reducing their therapeutic effect for near-addition. To ensure the proper alignment of PALs in children, the conventional spectacle-frame-fitting procedure is not sufficient, and repeated confirmation using a testing method similar to that used in this study is required. 相似文献
55.
Dr. Ichiro Shimoyama Yoshio Nakajima Toshihiko Ito Tadahiko Shibata 《Brain topography》1997,9(4):271-274
Summary We recorded visual evoked potentials (VEPs) elicited with high or low imaginable Chinese characters (HIC or LIC), representing concrete objects or absolute concepts, respectively. A closed circle (CC) acts as control stimulus. These were displayed (at 1.6° visual angle) for 35 ms on a TV monitor. Twenty-one channel VEPs (band-pas filter: 0.05–60 Hz), using balanced non-cephalic electrodes, were recorded from –100 to 924 ms for 11 right-handed male volunteers. The VEPs were analyzed by multivariate analysis of variance (MANOVA) and comparison of topographies at four remarkable peaks (P110, N160, P230 and N320). MANOVA showed significant differences (p< 0.001) for both conditions of channel and stimuli (HIC, LIC or CC). P100 for the CC-VEPs, N160 for the HIC-and LIC-VEPs, P230 for the CC-VEPs, and N320 for the HIC-VEPs were remarkable in the posterior scalp regions. Topographies at P100 and N160 showed no difference between the HIC-and LIC-stimuli. However, those at N320 showed difference between the HIC-and LIC-stimuli over the occipital and posterior temporal areas. Those results suggest that the responses at P100 and N160 might segregate Chinese characters from non Chinese characters. N320 suggested certain processes in imagery on recognizing Chinese characters over the occipital and posterior temporal areas.We are grateful to Dr. Yoshiji Kojima of Hamamatsu University for helpful comments. 相似文献
56.
Utilizing a lateral fluid percussion injury as a model of cerebral concussion, rats were studied histochemically measuring the degree of cytochrome oxidase activity present within different structures at different times following injury. After concussion, the cerebral cortex ipsilateral to the site of injury exhibited a diffuse decrease in its level of chromotome oxidase (CO) activity beginning at as soon as one day and lasting for up to 10 days after the insult. The ipsilateral dorsal hippocampus also exhibited an injury-induced decrease in CO activity, however, it was not as severe as in the cortex. These results indicate that oxidative metabolism is depressed primarily within the cerebral cortex and hippocampus for several days following a cerebral concussion. We propose that this period of metabolic depression may delineate a period of time during which the injured brain is unable to function normally and thus would be vulnerable to a second insult. 相似文献
57.
K Tadera M Arima S Yoshino F Yagi A Kobayashi 《Journal of nutritional science and vitaminology》1986,32(3):267-277
In experiments designed to examine interactions between pyridoxine (PN) and food components, PN was found to be converted into an unidentified compound in the presence of the homogenates of various plant foods under mild conditions. The formation of the compound tended to be higher when food samples had a higher ascorbic acid (AsA) content. The reaction was neither thermal decomposition nor photodecomposition. This compound was also formed by incubating PN with AsA in the dark. Conversion of PN into the compound proceeded with oxidation of AsA, and was negligible under anaerobic conditions. The pH optimum for the reaction was between 4 and 7, and the temperature optimum was between 30 and 50 degrees C. The compound was purified by ion-exchange chromatography, isolated as colorless needles, and identified as 6-hydroxypyridoxine from UV, PMR, IR and MS spectral data. 6-Hydroxypyridoxine had neither vitamin B6 nor antivitamin B6 activity for Saccharomyces carlsbergensis 4228 (ATCC 9080). From these results, we inferred that hydroxylation of PN in the presence of food components, especially AsA, caused loss of vitamin B6 in plant foods during food processing, storage and cooking. 相似文献
58.
Yonson Ku Masahiro Tominaga Takeshi Iwasaki Tetsushi Kitagawa Ichiro Maeda Masafumi Shiotani Shinya Kusunoki Yoko Maekawa Masahiro Samizo Takumi Fukumoto Yoshikazu Kuroda Shozo Hirota Yoichi Saitoh 《Surgery today》1996,26(5):305-313
The results of treating 12 consecutive patients with unresectable colorectal hepatic metastases with a hepatic arterial infusion of high-dose Adriamycin, 100–120 mg/m2, using hepatic venous isolation (HVI) and charcoal hemoperfusion (CHP) are reported herein. Adriamycin was administered over 5–15 min under extracorporeal drug elimination by HVI-CHP. HVI was percutaneously accomplished by either the double-balloon technique using a Fogarty occlusion catheter (8/22F) or a balloon-tipped catheter (16F). During the infusion, isolated hepatic venous blood was filtered by CHP and pumped into the left axillary vein. There were no lethal complications, and good hemodynamic tolerance to HVI-CHP was confirmed. Tumor liquefaction accompanied by a sharp decrease in serum carcinoembryonic antigen levels by more than 50% of pretreatment levels was observed in 6 of the 12 patients 1 month after treatment. Apart from chemical hepatitis, which developed in 11 (92%) of the patients, the Adriamycin toxicities were well controlled following the development of nausea and vomiting in 2 patients (17%), leukopenia <2,000/mm3 in 3 (25%), and gastric ulcer in 1 (8%). These results indicate that this method is a safe and useful procedure for otherwise hazardous high-dose intraarterial chemotherapy in patients with unresectable hepatic tumors. 相似文献
59.
Ichiro Ikegaki Yoshio Suzuki Shin-ichi Satoh Toshio Asano Masato Shibuya Kenichiro Sugita 《Naunyn-Schmiedeberg's archives of pharmacology》1989,340(4):431-436
Summary The effects of calcitonin gene-related peptide (CGRP) on canine cerebral arteries and on vertebral blood flow were investigated in-vivo and in-vitro and the findings compared with the effects of vasoactive intestinal peptide (VIP) and substance P. Administration of CGRP into the vertebral artery caused a dose-dependent and long-lasting increase in blood flow. The in-vivo vasodilatory effects of substance P and VIP were short-lasting. CGRP (0.1 to 100 nmol/l) elicited a concentration-dependent relaxation of the isolated middle cerebral and basilar arteries when the tissues were precontracted by exposure to prostaglandin F2 (PGF2). This effect was not antagonized by propranolol, atropine, tetrodotoxin, (N-Ac-Tyr1, D-Phe2)-growth hormone-releasing factor(1–29)-NH2 or (D-Pro2, D-Trp7,9) substance P. CGRP also reduced concentration-dependently the contraction of cerebral arteries induced by KCl or 9,11-epithio-11,12-metano-thromboxane A2 (STXA2). Mechanical removal of the endothelium did not abolish the vasodilatory response to CGRP. In PGF2-contracted canine cerebral arteries, VIP (0.1 to 100 nmol/l) was less potent a vasodilator than CGRP. At low concentrations (0.01 to 1 nmol/l) substance P elicited a rapid and short-lasting relaxation, and in the absence of endothelium this relaxation disappeared. These findings are clear evidence that CGRP modulates vascular tone. 相似文献
60.
Transient induction of single GST-P positive hepatocytes by DEN 总被引:12,自引:3,他引:9
Satoh Kimihiko; Hatayama Ichiro; Tateoka Noboru; Tamai Katsuto; Shimizu Toshio; Tatematsu Masae; Ito Nobuyuki; Sato Kiyomi 《Carcinogenesis》1989,10(11):2107-2111
The single cells positive for placental glutathione S-transferase(GST-P), detectable in livers of rats soon after treatment withhepatocarcinogens, are possible initiated cells,the hypothesis tested in the present series of experiments.No low dose threshold was observed in male Sprague-Dawley ratsat different single doses of diethylnitrosamine (DEM) althougha plateau was reached between 160 and 200 mg/kg body weight.At the latter single dose 12 400 positive cells/cm3 were observedimmunohistochemically in rat livers after one week, the numbersthen decreasing to week 8 and thereafter rising again. In thenumbers then decreasing to week 8 and thereafter rising again.In the early stages single cells predominated but with timea gradual increase in mini-foci and larger lesions became evident.Application of selection pressure (feeding of diet containing0.02% 2-AAF plus partial hepatectomy) to rats 224 weeksafter single DEN-treatment resulted in the formation of largefoci positive for GST-P, especially in the early stages, thegrowth response being less pronounced with time. The numberof foci, on the other hand. was correlated with the number offoci, on the other hand, was correlated with the number ofsingle cells/mini-foci detected inhepatectomy tissue of thesame individuals. These results suggest that the early GST-Ppositive populations could be the precursor for preneoplasticfoci and nodules. 相似文献