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991.
Y Kasé M Kawaguchi K Takahama T Miyata I Hirotsu T Hitoshi Y Okano 《Arzneimittel-Forschung》1983,33(7):936-946
Antitussive effect, toxicity and other related pharmacological properties of dl-1,2,9,10-tetramethoxy-6a,alpha-aporphine phosphate (dl-glaucine phosphate, DL-832) were studied in comparison with those of codeine. Acute toxicity of DL-832 in mice was 2/5 to 7/10 of that of codeine for any routes of i.v., i.p., s.c. and p.o. The antitussive effect as tested by "coughing dog and cat" methods and Domenjoz's method in cats was 1/5 to 4/5 that of codeine, according to the routes administered. Safety margin in antitussive effect was similar to or less than that of codeine. Differing from codeine, levallorphan exerted no influence on the antitussive effect of DL-832. In vitro, DL-832 exerted moderate relaxant actions on normal tone and on contractions induced by histamine and acetylcholine of tracheal muscle. In vivo, it showed a moderate relaxant effect on histamine-induced bronchial constriction. The decrease in the volume of respiratory tract fluid caused by DL-832 was smaller than that by codeine. DL-832 slightly reduced the transportation rate of intratracheal foreign body, although to much lesser extent as compared to codeine. On respiration, blood pressure and heart rate, DL-832 showed depressant effects and moreover it caused changes in ECG. However, all of these effects were similar to and a little weaker than those observed with codeine. DL-832 prolonged hexobarbital sleeping time significantly. Neither analgesic nor anticonvulsant effect was observed. When given in larger doses, DL-832 inhibited intestinal transportation in vivo, although this effect was much weaker than that of codeine. DL-832 showed slight local anesthetic effect. 相似文献
992.
Toshio Nakaki Teruo Nakadate Satoshi Yamamoto Ryuichi Kato 《Naunyn-Schmiedeberg's archives of pharmacology》1982,318(3):181-184
Summary The effects of adrenoceptor agonists and antagonists on the cholera-toxin-induced intestinal fluid accumulation and the mucosal levels of cAMP were investigated in vivo. Cholera toxin produced a marked fluid accumulation. Adrenaline inhibited the effect of the toxin in a dose-dependent manner. An 1-adrenoceptor blocking agent yohimbine antagonized the effect of adrenaline. The 1-adrenoceptor blocking agents prazosin and phenoxybenzamine failed to antagonize the effect of adrenaline. A high dose of a -adrenoceptor blocking agent pindolol did not antagonize the effect of adrenaline. Yohimbine or pindolol alone did not produce any effects on the toxin-induced fluid accumulation. However, prazosin and phenoxybenzamine per se inhibited the toxin-induced fluid accumulation. An 2-selective agonist clonidine was slightly more potent than adrenaline, and was about 100-fold more potent than the 1-selective agonist methoxamine in inhibiting the cholera-toxin-induced intestinal secretion. Clonidine, adrenaline and methoxamine failed to reduce the mucosal levels of cAMP, while these -adrenoceptor agonists inhibited the toxin-induced fluid accumulation in the same preparations. These results suggest that the stimulation of 2-adrenoceptors inhibit the cholera-toxin-induced intestinal secretion without reducing the whole mucosal levels of cAMP. 相似文献
993.
Okano M Sakiyama Y Matsumoto S Mizuno F Osato T 《International journal of oncology》1993,2(6):1023-1026
Epstein-Barr virus (EBV)-immortalized lymphoblastoid cell lines derived from the peripheral blood of patients with ataxia telangiectasia (AT) and EBV genome-positive Burkitt's lymphoma (BL) were tested for expression of EBV-related lytic antigens by means of irradiation. We used 1 Gy in each experiment, according to the results of the P3HR-1 (derived from African BL) cell line. Significantly higher expression of early antigens (EA) and viral capsid antigen (VCA) was demonstrated in lymphoblastoid cell lines derived from both patients with AT and those with EBV genome-positive BL, as compared to those derived from healthy individuals. These results suggested that defective regulating mechanisms on B lymphocytes, responsible for EBV infection, may underlie for the pathogenesis of development of lymphoproliferative diseases both in patients with AT and EBV genome-positive BL. 相似文献
994.
Okano M Mizuno F Aya T Osato T Sakiyama Y Matsumoto S 《International journal of oncology》1993,2(6):1027-1031
Ataxia telangiectasia (AT), an autosomal recessive disorder with a high incidence of lymphoreticular malignancies including Epstein-Barr virus (EBV)-induced lymphoproliferative disorders (LPD), was investigated to assess the susceptibility to EBV infection and oncogenesis. When the patients' lymphocytes were infected with B95-8 EBV, there was a tendency toward an enhanced growth in semisolid agar, as compared with the healthy donor counterparts. Among the preparations tested, from 14 patients, 2 cell lines showed extremely high colony forming efficiency. The lymphocytes from patients with AT did not contain a large number of EBV target cells, as determined by the maximum frequency of EBV-determined nuclear antigen (EBNA) induction prior to cellular DNA synthesis. Fourteen different lymphoblastoid cell lines derived from the 14 patients with AT were then examined for their EBV inducibility and superinfectibility. By treatment with 12-O-tetradecanoyl-phorbol-13-acetate TPA) and culturing at a lower temperature of 33-degrees-C, early antigen (EA) induction occurred approximately 6-fold and 5-fold higher, respectively, as compared with the lymphoblastoid cell lines derived from healthy controls. Viral capsid antigen (VCA) was also induced significantly by TPA or culturing at lower temperature in the lines from patients with AT, but only slightly in the control counterparts. When the lymphoblastoid cells from patients with AT were exposed to P3HR-1 EBV, EA and VCA syntheses were approximately 6- and 12-fold higher, respectively, than those in the cells derived from the healthy controls. This evidence suggested B lymphocytes of patients with AT were highly susceptible to EBV infection and possibly linked to the development of EBV-induced LPD. 相似文献
995.
Yuzuru Takemura Takao Ohnuma Ting-Chao Chou Tsuyoshi Okano James F. Holland 《Cancer chemotherapy and pharmacology》1985,14(3):206-210
Summary Ten human leukemia-lymphoma cell lines were tested for the growth-inhibitory effects of harringtonine (HT). HT was most active against HL-60 acute promyelocytic leukemia cells and least active against DND-41 acute lymphoblastic leukemia cells, with a 70-fold differential activity. Sensitivity of the cell lines is, in decreasing order: HL-60 > RPMI-8402 > DND-39A ML-2 MOLT-3 KG-1 > Daudi NALL-1 > BALM-2 > DND-41. The cell lines with rapid cell growth tended to be more sensitive to HT. To further elucidate the selectivity of the differential sensitivity, uptake and release of HT were compared in HL-60 and DND-41 cells. Uptake of [3H]HT into HL-60 and DND-41 cells showed no difference; however, the binding of [3H]HT to cellular components was > 16-fold higher in HL-60 cells than DND-41 cells. There were also minor, but significant differences in the inhibition of [3H]leucine incorporation into proteins of these two cell lines in the presence of 1 g/ml HT. To test whether the biological effects of HT are related to the concentration of, or exposure time to, HT, KG-1 cells were exposed to HT for different periods of time and the growth-inhibitory effects were compared. Increasing exposure time from 1 h to 3 h resulted in a 100-fold decrease in concentration x exposure time (c x t) at ID50; from 3 h to 6 h, in a 20-fold decrease at ID70; and from 6 h to 24 h, in a 16-fold decrease at ID90. HT was not inactivated by cells up to 24 h. These results indicate that (a) the sensitivity of different cell lines to HT may be related to the degree of HT binding; and (b) the effects of HT are more dependent on exposure time than concentration. Continuous infusion is thus rational for clinical trials of this drug, and the degree of HT binding to leukemic cells may be predictive of clinical response. 相似文献
996.
Ken Fukuda Naoki Kumagai Youichiro Fujitsu Teruo Nishida 《Allergology international》2006,55(2):121-129
Vernal keratoconjunctivitis (VKC), a severe form of ocular allergic disease, is characterized by the formation of giant papillae at the upper tarsal conjunctiva and corneal lesions that threaten vision. Recent evidence indicates that resident fibroblasts function as immune modulators in the pathogenesis of the chronic allergic inflammation associated with VKC. The T helper 2 (Th2) cell-derived cytokines interleukin (IL)-4 and IL-13 stimulate the migration and proliferation of conjunctival fibroblasts as well as protecting these cells from apoptotic cell death, effects that likely underlie the hyperplasia of fibroblasts that contributes to the formation of giant papillae. Conjunctival fibroblasts also synthesize extracellular matrix proteins and tissue inhibitors of metalloproteinases as well as down-regulate the expression of matrix metalloproteinases in response to these cytokines, effects that likely contribute to the excessive deposition of extracellular matrix that is characteristic of giant papillae. Stimulation of fibroblasts in the corneal stroma with the combination of a proinflammatory cytokine and either IL-4 or IL-13 results in up-regulation of the expression of the chemokine eotaxin and thymus- and activation-regulated chemokine as well as of vascular cell adhesion molecule-1, which together mediate the infiltration and activation of eosinophils and Th2 cells. Fibroblasts therefore appear to play a central role in the induction and amplification of ocular allergic inflammation and the consequent development of giant papillae and corneal disorders in individuals with VKC. Fibroblasts and fibroblast-derived factors thus represent new and potentially important therapeutic targets for treatment of the giant papillae and corneal disorders associated with VKC. 相似文献
997.
Effects of ulinastatin on endotoxin shock in dogs] 总被引:1,自引:0,他引:1
S Okano M Tagawa N Urakawa R Ogawa 《Masui. The Japanese journal of anesthesiology》1992,41(3):413-420
The therapeutic effect of ulinastatin, an inhibitor of the protease activity, on endotoxin shock was evaluated using 17 Beagle dogs. Single intravenous injection of ulinastatin at a dose of 5,000 or 25,000 U.kg-1 failed to suppress the endotoxin-induced circulatory disturbance but significantly inhibited increases in pulmonary arterial pressure and pulmonary vascular resistance that occur early following administration of endotoxin. Elevation of PGI2, TXA2 and LTB4 by endotoxin shock was significantly inhibited by administration of 25,000 U.kg-1 of ulinastatin. Elevation of the granulocytic elastase activity was inhibited dose-dependently by administration of ulinastatin. The above results indicate that ulinastatin may be a promising drug for the treatment of endotoxin shock. 相似文献
998.
H Ohtsuki S Hasebe Y Tadokoro N Kishimoto S Watanabe M Okano 《Ophthalmologica. Journal international d'ophtalmologie. International journal of ophthalmology. Zeitschrift für Augenheilkunde》1992,204(2):82-87
Vertical deviation of the affected eye caused by horizontal change of gaze was measured with a synoptometer in 5 cases of Duane's retraction syndrome type III. Step-by-step measurement clearly showed two types of incomitance patterns, i.e. upshoot and up- and downshoot in adduction. The former suggests a paradoxical synergistic innervation between the medial rectus and superior rectus muscles, and the latter suggests an abnormal vertical movement of the lateral rectus muscle over the globe on elevation or depression of the eye. Recession of the lateral rectus muscle, however, reduced the vertical deviation regardless of the incomitance pattern. 相似文献
999.
H Mizutani T Okano Y Minegishi K Matsuda J Sudoh K Kitamura R Noro C Soeno A Yoshimura M Seike A Gemma 《Oncology letters》2010,1(6):1011-1016
Epithelial to mesenchymal transition (EMT) is induced by transforming growth factor-β1 (TGF-β1) and is a crucial event for cancer cells to acquire invasive and metastatic phenotypes. However, the signals that induce EMT in cancer cells have yet to be adequately defined. In this study, a proteomic investigation was performed to understand the signaling pathway of the EMT of lung cancer using two-dimensional difference gel electrophoresis (2D-DIGE) and mass spectrometry. The protein expression profiles of A549 were compared to those of A549 cells treated with TGF-β1. Of more than 2,000 protein spots shown by 2D-DIGE, 53 were found to be up- or down-regulated upon induction with TGF-β1. In the 53 protein spots, the protein level of heat shock protein (HSP) 27 was found to increase significantly. HSP27 protein was higher in two different lung cancer cell lines, demonstrating the EMT phenomenon with TGF-β1. Notably, the silencing of HSP27 enhanced spindle integration, resulting in an additive effect with TGF-β1-induced EMT. Furthermore, the TGF-β1-induced HSP27 increase was not affected by the suppression of Smad2 and Smad3 in A549 cells. These results suggest that HSP27 was involved in TGF-β1-induced EMT in a Smad-independent manner in lung cancer cells and may provide an effective clinical strategy in lung cancer patients whose tumors are dependent on TGF-β1-induced EMT. 相似文献
1000.
Matsuo T Sugita T Kubo T Yasunaga Y Ochi M Murakami T 《Journal of biomedical materials research. Part A》2003,66(4):747-754
Small-sized magnetic liposomes with incorporated recombinant human bone morphogenetic protein-2 (rhBMP-2) were prepared, and the efficiency for bone formation after topical injection was evaluated in a rat bone-defect model. A critical-sized segmental bone defect was created in the mid-part of the femoral shaft, and a permanent magnet was attached. Topical injection onto the defects was performed with different liposomal preparations (nonmagnetic and magnetic liposomes) using different treatment modalities (different doses and different treatment timing of rhBMP-2). Weekly evaluations were made radiographically and microcomputed tomographically, histologically, and/or by mechanical testing at 9 weeks after surgery. A single topical application of magnetic liposomes with an appropriate amount of rhBMP-2 (approximately 3 microg) incorporated under magnetic induction immediately after surgery was effective for new bone formation. The combined treatment of topical magnetic rhBMP-2 liposomes and magnetic implantation at the injury site was effective for the treatment of bone defects. This injectable carrier for BMP is expected to have many advantages over solid carriers because it can be prepared easily and can be less invasively applied to the injured site at any time after surgery. 相似文献