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1.
Masahiro Yamauchi Hiroko Kusano Etsuko Saito Takeshi Iwata Masashi Nakakura Yasuki Kato Takaaki Uochi Shiro Akinaga Noboru Aoki 《Journal of controlled release》2006,114(2):268-275
Previously, we demonstrated that wrapping dextran fluorescein anionic/cationic lipid complexes with neutral lipids produced a stable formulation that markedly increased the duration of the compound in plasma after intravenous administration to rats. The improved drug-delivery properties of the wrapped liposomes (WL) relative to other formulations suggested that this technology could offer important advantages for the administration of other polyanionic drugs, including antisense oligodeoxynucleotides (ODN). In the present study, we investigated the value of WL for formulating fluorescence-labeled phosphorothioated ODN (F-ODN). WL encapsulating F-ODN/cationic lipid complexes were prepared efficiently using similar methodology to that used in our earlier study. Studies confirmed that these WL were stable in vitro. Following intravenous administration to mice, free F-ODN and naked F-ODN/cationic lipid complexes were rapidly eliminated whereas administration of the WL resulted in high blood concentrations of drug that were maintained for several hours. Additional studies were conducted in mice that were inoculated with tumor cells (Caki-1 xenograft model, human kidney); in these experiments, intravenous administration of WL delivered 13 times more F-ODN to the tumor site than achieved after injection of free F-ODN. 相似文献
2.
Kengo Maeda Shinji Kume Yoshihiko Nishio Shiro Maeda Yasuhiro Nishida Mikio Suzuki Takahiro Nakaguchi Toru Kawabata Osamu Hashimoto Takashi Hisanaga Atsunori Kashiwagi Hitoshi Yasuda 《Clinical neurology》2006,46(4):266-269
We report a 53-year-old woman with severe Graves' ophthalmopathy accompanied by uncontrolled myasthenia gravis. She presented remarkable exophthalmos, chemosis, and restriction of eye movement. Despite plasma exchange, steroid pulse therapy, local injection of steroid, and irradiation, ocular symptoms did not ameliorate. Since optic neuropathy was seen, orbital decompression surgery was performed in the left eye. Bilateral chemosis was improved after the surgery. Five years after surgery, there was no ocular palsy in the operated left eye, but in the contralateral eye. For the good prognosis of the eye movement, orbital decompression might be recommended in the severe Graves' ophthalmopathy accompanied by the optic neuropathy and/or ophthalmoplegia with proptosis. 相似文献
3.
Shiro Akinaga Tadashi Ashizawa Katsushige Gomi Hiroe Ohno Makoto Morimoto Chikara Murakata Masami Okabe 《Cancer chemotherapy and pharmacology》1992,29(4):266-272
Summary Novel derivatives of K-252a, (8R*,9S*,11S*)-(–)-9-hydroxy-9-methoxycarbonyl-8-methyl-2,3,9,10-tetrahydro-8, 11-epoxy-1H,8H,11H-2,7b,11a-triazadibenzo [a,g]-cycloocta[cde]trinden-1-one, an inhibitor of protein kinases and calmodulin-dependent phosphodiesterase, were synthesized and evaluated for their antitumor activity in vitro and in vivo. Of ten derivatives tested, four were active against the P388 murine leukemia i. p.-i. p. system, although K-252a was inactive. Among these derivatives, KT6124 was selected for further biological evaluation studies because its efficacy was the highest. KT6124 was also active against sarcoma 180 and B16 melanoma. It exerted a relatively broad spectrum of antiproliferative activity against 20 human tumor cell lines in vitro. To determine the mechanism(s) of action underlying the antitumor activity of KT6124, we tested the drug for inhibition of protein kinases, including Ca2+-and phospholipid-dependent protein kinase (PKC), in intact A431 human epidermoid carcinoma cells in comparison with the PKC-inhibitory activity of K-252a. KT6124 did not antagonize the action of phorbol 12-myristate 13-acetate (PMA) in A431 cells, whereas K-252a did, suggesting that KT6124 may not act on protein kinases in the cells. The interaction of KT6124 with DNA in living cells was examined by the alkaline elution method. KT6124 apparantly exhibited DNA scission both dose-and time-dependently in the target cells. The DNA breakage was dependent on proteinase K treatment, suggesting its possible interaction with DNA-related enzyme(s). These results indicate that KT6124 exerts antitumor activity by acting on DNA or on DNA-related enzyme(s) in tumor cells rather than via the inhibition of protein kinases. 相似文献
4.
Monolayer cultures of normal human bone cells contain multiple subpopulations of alkaline phosphatase positive cells 总被引:5,自引:0,他引:5
Toshikatsu Matsuyama K. -H. William Lau Jon E. Wergedal 《Calcified tissue international》1990,47(5):276-283
Summary Cytochemical staining of normal human bone cells in monolayer cultures for alkaline phosphatase (ALP) indicated that the cultures
contained mixed-cell populations. Time course evaluations of the cytochemical staining revealed, in addition to the ALP-negative
cell population, at least two subpopulations of ALP-positive human bone cells with different levels of ALP. A cytochemical
method has been developed which separates the ALP-positive cells into high and intermediate ALP subpopulations. In this method,
human bone cells were stained for ALP using an azo-dye method and incubating at 4°C for 10 and 30 minutes, respectively. We
defined the cell population that stained positively for ALP at 10 minutes as strong ALP-positive cells, and both strong and
intermediate cells were stained at 30 minutes. The intermediate cells were determined from the difference between the values
at the two time points. The intra- and interassay variations of the assay, with the same investigator in blinded investigations,
were both less than 10% and the interobserver variation was approximately 25%. Analysis of the distribution of ALP levels
in cells with a laser densitometer confirmed the presence of at least three cell subpopulations. 1,25(OH)2D3 treatment increased the proportions of both ALP-positive cell populations, whereas TGF-beta treatment increased only the
intermediate ALP-positive cell population. On the contrary, fluoride increased the proportion of the strong ALP cells, and
IGF-1 had no effect on the proportions of either ALP-positive subpopulation. When the ALP-specific activity was compared with
the percentage of each ALP-positive subpopulations for the cells treated with effectors, the ALP-specific activity correlated
with the total ALP-positive and with the strong ALP-positive populations but not with the intermediate ALP-positive subpopulation.
In summary, this study represents the first evidence that normal human bone cells in monolayer cultures contained at least
two subpopulations of ALP-positive cells, and that bone cell effectors could have differential effects on each cell population. 相似文献
5.
Masao Amari Katsuji Taguchi Minoru Iwahara K Shibuya Shiro Naoe 《Medical Electron Microscopy》2002,35(4):225-233
To elucidate the effect of fibroblast growth factor on the phenotypical conversion of fibroblasts to mesothelial cells, both immunohistochemical and ultrastructural examinations were carried out on cultured spheroids that were composed of fibroblasts obtained from the parietal pleura of rats with and without addition of antifibroblast growth factor receptor antibody. In the present study, antifibroblast growth factor receptor antibody was employed to block the effect of the autocrine component of fibroblast growth factor in the culture medium. Phenotypical conversion from fibroblast to mesothelial cells was clearly blocked in the experimental group, to which culture medium had been added with antifibroblast growth factor receptor antibody, whereas the control group, cultured without addition of antifibroblast growth factor receptor antibody, showed phenotypical conversion of fibroblasts that was confirmed by the development of macula adherens, microvilli, and positive expression of cytokeratin. These results indicate the possibility that fibroblast growth factor plays a key role in the process of phenotypic conversion of fibroblasts to regenerated mesothelial cells. 相似文献
6.
7.
This paper describes a new class of reaction, group-transfer alternating copolymerization (GTAC), between 2-phenyl-1,3,2-dioxaphosphorinane ( 1 ) and trimethylsilyl 2-(acryloyloxy)ethanesulfonate ( 2 ). The copolymerization took place without any added catalyst and proceeded via quantitative trimethylsilyl group-transfer process to give a 1:1 alternating copolymer 3a having a ketene silyl acetal group in the main chain. Results of spectroscopy as well as alkaline hydrolysis and bromination of the copolymer confirmed the structure. 相似文献
8.
Kohji Matsushita Kazuo Kitagawa Tomohiro Matsuyama Toshiho Ohtsuki Akihiko Taguchi Kenji Mandai Takuma Mabuchi Yoshiki Yagita Takehiko Yanagihara Masayasu Matsumoto 《Brain research》1996,743(1-2)
The divalent cation zinc has been reported to possess several physiological properties such as blocking apoptotic cell death through an inhibitory effect on Ca2+-Mg2+ endonuclease activity, or modulating the neurotoxicity via glutamate receptor subtypes. In the present study, we investigated the effect of peripherally injected zinc on delayed neuronal death seen in the hippocampus after transient global ischemia, in order to elucidate a possible beneficial role on zinc in ischemic neuronal cell death. Forty-five adult Mongolian gerbils of both sexes underwent transient bilateral clipping of the common carotid arteries for 3 min. In the pretreated animals, ZnCl2 (20 mg/kg) was injected subcutaneously once, 1 h before ischemia (superacute group; n=6) or twice at 24 and 48 h before ischemia (subacute group; n=14). Histological survey was carried out 3 days later by in situ DNA fragmentation method and 4 days later by hematoxylin-eosin staining by semiquantatively counting dead neurons in the CA1 sector. Subacute zinc pre-administration significantly reduced the nuclear damage and subsequent neuronal death; however, superacutely pre-administered zinc did not protect hippocampal neurons against ischemia but it did not aggravate the effect of ischemia, either. The present study suggested that transfer of exogenous zinc into the intracellular space is required for neuroprotection, presumably via the anti-endonuclease activity. 相似文献
9.
Shiro Oka Shinji Tanaka Iwao Kaneko Hiroyuki Kanao Kazuaki Chayama 《Digestive endoscopy》2007,19(Z1):S30-S33
Endoscopic submucosal dissection (ESD) for colorectal tumors is steadily being developed. Safety and standardization of ESD for colorectal tumors have not been yet established because of the technical difficulties and the unsuitable anatomical characteristics of the colon and rectum. The authors mainly use a Flex knife for mucosal incision and a Hook knife for submucosal dissection to perform ESD safely. Skillful colonoscopic control, selection of scope, distal attachment tip hood, adequate high‐frequency generator and correct approach strategy should all be considered for safe performance of ESD. However, the incidence of indicative lesions is rare because the majority of colorectal tumors are adenomatous large laterally spreading tumors, which can be cured by intentional endoscopic piecemeal resection. At present, ESD for colorectal tumors should be performed only at central facilities that have expert colonoscopists. With the development of new devices and associated techniques, technical standardization of ESD for colorectal tumors is expected in the near future. 相似文献
10.
Minoru Sasano Mihoko Tanaka Katsuhiko Nakata Shiro Mita 《Immunopharmacology and immunotoxicology》1991,13(1):121-133
(4R)-Hexahydro-7, 7-dimethyl-6-oxo-1, 2, 5-dithiazocine-4-carboxylic acid (SA3443) is a newly synthesized cyclic disulfide compound which offers potential hepatoprotective properties.
The effect of SA3443 on the induction of natural killer (NK) and cytotoxic T lymphocyte (CTL) activities was investigated. NK activity in BALB/c mice splenic cells was investigated using YAC-1 cells as target cells. SA3443, at a dose range of 30-300 mg/kg/day, augmented NK activity significantly when administered orally once daily for 4 days before the assay. Alloantigen-specific CTL activity in splenic cells from BALB/c mice was detected 9 days after sensitization with C57BL/6 mice splenic cells. SA3443, at a dose of 100 mg/kg/day, augmented CTL activity significantly when administered orally, once daily for 4 days beginning after the sensitization and for 2 days before the assay, while a high dose of SA3443, at 300mg/kg, suppressed CTL activity.
From these results, it is thought that SA3443 may assist in the elimination of hepatitis viruses from the liver in patients with chronic active hepatitis, by the activation of NK and/or CTL activities. 相似文献
The effect of SA3443 on the induction of natural killer (NK) and cytotoxic T lymphocyte (CTL) activities was investigated. NK activity in BALB/c mice splenic cells was investigated using YAC-1 cells as target cells. SA3443, at a dose range of 30-300 mg/kg/day, augmented NK activity significantly when administered orally once daily for 4 days before the assay. Alloantigen-specific CTL activity in splenic cells from BALB/c mice was detected 9 days after sensitization with C57BL/6 mice splenic cells. SA3443, at a dose of 100 mg/kg/day, augmented CTL activity significantly when administered orally, once daily for 4 days beginning after the sensitization and for 2 days before the assay, while a high dose of SA3443, at 300mg/kg, suppressed CTL activity.
From these results, it is thought that SA3443 may assist in the elimination of hepatitis viruses from the liver in patients with chronic active hepatitis, by the activation of NK and/or CTL activities. 相似文献