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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.
Concurrent presence of metabolic syndrome in obstructive sleep apnea syndrome exacerbates the cardiovascular risk: a sleep clinic cohort study. 总被引:2,自引:0,他引:2
Kazuki Shiina Hirofumi Tomiyama Yoshifumi Takata Yasuhiro Usui Kihiro Asano Yoji Hirayama Takeshi Nakamura Akira Yamashina 《Hypertension research》2006,29(6):433-441
This cross-sectional study was conducted to examine whether the obstructive sleep apnea syndrome (OSAS) is associated with elevation of the pulse wave velocity (PWV) and increase in the plasma levels of C-reactive protein (CRP), both of which are known markers of cardiovascular risk, and also to determine if the concurrent presence of the metabolic syndrome might exacerbate this elevation in the levels of these cardiovascular risk markers in subjects with OSAS. With these objectives, the PWV and serum CRP were measured in 184 subjects attending a sleep clinic. It was found that the PWV and CRP were higher in the subjects with OSAS (n=94) than in those without OSAS (n=90). Furthermore, among the subjects with OSAS, the PWV and CRP were higher in those with the concurrent presence of the metabolic syndrome (n= 41; PWV=1,562+/-19 cm/s; CRP=1.8+/-0.2 mg/l) than in those without metabolic syndrome (n=53; PWV=1,432+/-21 cm/s; CRP=1.2+/-0.1 mg/l) (p<0.05). A general linear model analysis demonstrated that OSAS and metabolic syndrome were independently associated with elevated PWV and increase of the plasma levels of CRP. OSAS appears to be associated with increased cardiovascular risk, as reflected by both elevated PWV and increase of the plasma CRP. The concurrent presence of metabolic syndrome may exacerbate this increase in cardiovascular risk in subjects with OSAS. Therefore, the concurrent presence of metabolic syndrome may constitute an additive cardiovascular risk factor in subjects with OSAS. 相似文献
4.
5.
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
6.
Tanaka Takeo Kobayashi Masao Saito Osamu Kamada Nanao Kuramoto Atsushi Usui Tomofusa 《Clinica chimica acta; international journal of clinical chemistry》1981,117(2):121-131
The biochemical activities of 8 lysosomal acid hydrolases in leukemic cells from 48 patients were examined. Characteristic alterations were found in α-mannosidase, β-galactosidase and N-acetyl-β-glucosaminidase activities of leukemic cells. The level of α-mannosidase activity was much higher in myelo(mono)genous leukemias (AML, AMoL, AMMoL, CML and CMMoL) than in lymphogenous ones (ALL, T-cell leukemia, hairy cell leukemia and CLL) without exception. The β-galactosidase activity also differed as a result of α-mannosidase, except in T-cell leukemia. In T-cell leukemia it was within the range of normal lymphocytes, but in the other lymphogenous leukemias it was significantly below normal. N-acetyl-β-glucosaminidase activity in myelo(mono)genous leukemic cells was above the range of normal granulocytes. The changes in these enzyme levels were consistent. The lymphocytic or myelocytic nature of three cases of acute undifferentiated leukemia could be determined by enzyme studies. In two cases it was lymphocytic and in one it was myelocytic. The enzymatic abnormalities were also found in morphologically mature neutrophils from patients with not only chronic types (CML, CMMoL) but also acute types (AMoL, AMMoL) of leukemias, and were similar to those of their respective leukemic cells. Analysis of lysosomal enzymes (at least three of those mentioned above), can elucidate one of the biochemical properties of leukemic cells and may be valuable in the differentiation of leukemias. 相似文献
7.
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
8.
9.
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
10.
M Usui T Kimura J Yamazaki 《The Journal of bone and joint surgery. American volume》1990,72(9):1370-1373
We successfully replanted five amputated legs in five patients and followed the patients for two years or more (average, six years and three months). Although some patients found it impossible to squat and to run because of joint contractures, muscle weakness, or deformities of the foot, all patients could perform other activities without difficulty. None had important pain or any intolerance to cold, and all were satisfied with the results of the replantation. 相似文献