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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
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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
4.
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
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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
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M Oishi H Yokoyama N Abe K Iwasaki F Okuguchi K Kawai H Sugimoto H Takamura H Takeda K Doi K Hirao S Ikeda 《Diabetic medicine》2007,24(10):1149-1155
AIMS: To study the time and cost involved in the care of newly registered outpatients with Type 2 diabetes mellitus (DM), compared with patients with hypertension and/or hyperlipidaemia (HTL). METHODS: A total of 313 patients with DM and 58 patients with HTL without diabetes were registered on their first visits to 11 diabetes clinics across Japan. The time and cost involved in their care was recorded over the following 5 months. RESULTS: In the first 3 months, there was an extensive time commitment to both groups. The time spent by physicians was 1.5 times longer for DM than for HTL. The total care time spent by all the care providers for DM was twice that for HTL. The cost of DM care was twice that for HTL, with the cost of medicines excluded. However, half of the cost for DM was for laboratory tests. When these were excluded, and the remaining cost divided by the time spent, the amount for DM was half of that for HTL. Over the 5 months, mean glycated haemoglobin (HbA(1c)) in DM patients improved from 8.0% to 6.5%, and 72% of DM patients achieved the glycaemic target of HbA(1c) < or = 6.5%. CONCLUSIONS: DM care in a diabetes clinic requires a great deal more time and resources than HTL to achieve the best outcome. An educational system for self care, presently lacking in the primary care setting in Japan, would improve glycaemic control for DM patients in the community. 相似文献
9.
Kenichi Yokoyama Toshiaki Nitatori Nahoko Kanke Shinju Suzuki 《Magnetic resonance in medical sciences》2006,5(1):33-40
With the development of fast scan techniques and technical advances in software, cardiac MRI can now be used for morphological and functional evaluation of the heart with good reliability and high spatial and temporal resolution. Cardiac MRI is employed at many institutions, mainly for assessing ischemic heart disease. Cardiac MRI can be used to identify coronary artery stenosis, evaluate myocardial viability, assess left ventricular wall motion and function, measure coronary blood flow and flow reserve, and obtain other useful information for the diagnosis of ischemic heart disease in a single examination, serving as a true comprehensive cardiac study. With regard to the evaluation of coronary artery stenosis, new techniques, such as whole-heart coronary MRA, permit visualization of the coronary arteries to their peripheral branches without contrast agent. Good results have been reported for whole-heart MRA as compared with X-ray coronary angiography (CAG). Attempts to evaluate plaque characteristics by visualizing the walls of the coronary arteries have also been reported recently. Technical improvements have been made in myocardial perfusion MRI to detect myocardial ischemia and in delayed contrast-enhanced MRI to assess myocardial viability, and some researchers have recently reported that the diagnostic capabilities of these techniques match or surpass those of cardiac nuclear medicine studies. We outline the features of the latest MR imaging techniques for the diagnosis of ischemic heart disease, discuss their practical applications, and compare them with other imaging modalities. 相似文献
10.
M Tokitsu M Nakamura H Yokoyama H Watanabe M Hara K Takeuchi 《No shinkei geka. Neurological surgery》1990,18(2):189-192
Two cases of skullbase-penetrating injuries caused by umbrella tips are reported. Case 1: 24-year-old male. Admitted with disturbance of consciousness, left hemiparesis, nasal bleeding, and laceration of left lower eyelid because of having been stabbed by an umbrella tip. Pupils and fundi revealed no definite findings. Plain skull X-ray showed turbid ethmoid sinus and fracture of planum sphenoidale. Cranial CT showed right putaminal hematoma with intraventricular hemorrhage and pneumocephalus. Increased ICP necessitated surgery two days after the injury. Dural laceration of planum sphnoidale, laceration of left optic nerve, right rectal gyrus contusion and rebleeding from the right lenticulostriate branch were observed. Dural plasty and removal of hematoma with external decompression were carried out. He had a good postoperative course, but left visual loss and left hemiparesis remained. Case 2: 29-year-old male. Admitted with excoriation of his right nostril because of having been stabbed by an umbrella tip, severe headache, and nasal discharge. Oculomotor palsy was observed as well as CSF rhinorrhea and meningeal irritability. Plain skull X-ray showed niveau in sphenoidal sinus, pneumocephalus, and fracture of sella turcica. His complaint disappeared after conservative therapy. We reviewed the literature and found only 4 similar cases. The skullbase, because of its anatomical character, is likely to be penetrated in orbital and periorbital injury caused by umbrella tips. Cases which include disturbance of consciousness have a poor prognosis. We hope the fact that umbrella tips can easily become life-threatening objects will come to the attention of the general public so that similar cases may be avoided. 相似文献