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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.
Previous studies have demonstrated that granulocyte-macrophage colony-stimulating factor (GM-CSF) both increases and decreases levels of 3'-azido-3'-deoxythymidine (AZT) nucleotides in certain human myeloid cells. The present studies have examined the effects of GM-CSF on AZT metabolism in U-937 cells. The results demonstrate that GM-CSF stimulated AZT nucleotide formation in these cells. This stimulation was detectable during concurrent exposure to GM-CSF and AZT or as a result of pretreatment with GM-CSF. The GM-CSF-induced enhancement in AZT nucleotide formation was associated with a 4-fold increase in AZT uptake. The finding that uptake of AZT into U-937 cells was only partially sensitive to 6-[(4-nitrobenzyl)thio]-9-beta-D-ribofuranosylpurine (NBMPR) suggested a process primarily involving nonfacilitated diffusion. The results also demonstrate that treatment of U-937 cells with GM-CSF was associated with nearly a 2-fold increase in thymidine kinase activity. Moreover, the findings indicate that retention of AZT-MP and AZP-TP was prolonged significantly (P less than 0.05 and P less than 0.01 respectively) in association with GM-CSF treatment. Taken together, these results suggest that GM-CSF enhances the formation of AZT nucleotides by increasing AZT uptake and phosphorylation, as well as increasing retention of phosphorylated derivatives. 相似文献
5.
Yoshiro Matsui Mizuho Ohta Kohsuke Ohno Masao Nagumo 《Journal of oral and maxillofacial surgery》2006,64(10):1540-1545
PURPOSE: This study evaluated the bone volume, height, and width that can be obtained in alveolar ridge augmentation using titanium mesh and autogenous bone particles in patients with cleft lip/palate. PATIENTS AND METHODS: Subjects were 15 patients with cleft lip/palate requiring tertiary bone graft for implant therapy. Computed tomography (CT) scans were taken before removing the mesh, from 1 to 21 months after bone grafting. Forty-three reconstructed images corresponding to the positions for implant placement were selected for this study. The percent defect filled with bone (%BONE), defined as the percentage of newly formed bone in the space created by the mesh, was measured for image analyses. In linear analyses, 4 parameters were used: increased bone height (IBH), percent increased bone height (%IBH), increased bone width (IBW), and percent increased bone width (%IBW). Factors influencing the quantitative data and the clinical courses of placed implants were also explored. RESULTS: The average %BONE was 91.1%. IBH averaged 4.4 mm, whereas %IBH averaged 88.5%. IBW averaged 4.6 mm, whereas %IBW averaged 86.4%. Little correlation was present between the quantitative data and patient age, or time interval. A significant correlation was identified between the data for span of the grafted area and %BONE (correlation coefficient value = -0.36). However, the diminishing rate was very low. No implants were lost postoperatively. CONCLUSIONS: Alveolar ridge augmentation with titanium mesh and autogenous bone particles from the anterior iliac crest has very high predictability as a preimplant procedure in patients with cleft lip/palate. 相似文献
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Ryo Wakita Yuka Ohno Saori Yamazaki Hikaru Kohase Masahiro Umino 《Oral surgery, oral medicine, oral pathology, oral radiology, and endodontics》2006,102(6):e28-e32
Two cases of vasovagal syncope (VVS) during venous access are reported. Both patients had a history of fainting episodes and experienced bradycardia with asystole, hypotension, and fainting. Pain and phobic stress during venous access triggered an increase in parasympathetic tone, resulting in bradycardia with asystole and hypotension in both cases. Hypotension and bradycardia likely caused cerebral hypoperfusion, leading to fainting. The intense parasympathetic tone triggered by somatic or emotional stress was likely responsible for directly depressing the sinus node, leading to asystole and bradycardia. Bradycardia with asystole progressing to syncope is a potentially fatal dysrhythmia in patients with cardiovascular disease or older patients with decreased cardiac function. Appropriate treatment for VVS includes the administration of intravenous fluids, vagolytics, ephedrine, and the rapid use of the Trendelenburg position. Intravenous fluids and atropine were used to treat the present patients. 相似文献
8.
Binding profile of SM-9018, a novel antipsychotic candidate 总被引:3,自引:0,他引:3
T Kato A Hirose Y Ohno H Shimizu H Tanaka M Nakamura 《Japanese journal of pharmacology》1990,54(4):478-481
The present study employed various receptor-binding assays to clarify the biochemical characteristics of SM-9018. SM-9018 possessed very high affinity for 5-HT2, D2 and 5-HT1A receptors (Ki = 0.61, 1.4 and 2.9 nM, respectively), and it had moderate affinity for alpha 1 and D1 receptors (Ki = 17 and 41 nM, respectively). However, SM-9018 had only negligible affinity for alpha 2, opiate, glutamate, phencyclidine, benzodiazepine and GABAA receptors. These results suggest that SM-9018 may be a novel antipsychotic agent with binding affinity for 5-HT2 and 5-HT1A receptors. 相似文献
9.
A case of MELAS (mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes) which presented as migraine
complicated by stroke is reported. Strokes associated with migraine have often been reported, but the mechanism remains unclear
and may include a variety of pathologies. MELAS also presents with migrainous headache, vomiting, and stroke-like symptoms.
Magnetic resonance imaging demonstrates characteristic findings. MELAS should be considered in the differential diagnosis
of infarct-like lesions with migrainous headaches in young adults, especially if the symptoms fluctuate and are accompanied
by a homonymous hemianopia.
Received: 23 September 1996 Accepted: 19 February 1997 相似文献
10.
Phase I study of E1040, a new parenteral cephem antibiotic 总被引:1,自引:0,他引:1
M Nakashima T Uematsu M Kanamara K Ueno T Setoyama Y Tomono T Ohno K Okano N Morishita 《Journal of clinical pharmacology》1989,29(2):144-150
The safety and pharmacokinetics of E1040, a new injectable cephem antibiotic, were evaluated in healthy volunteers. In single-dose studies, 125, 250, 500, 1000 and 2000 mg of E1040 were administered by I.V. infusion over 1 hour. Results of 5 minutes I.V. infusions of 500, 1000 and 2000 mg of the drug were also studied. Plasma concentration-time profiles were well suited to a two-compartment open model. The half-life of elimination from plasma was 1.85 +/- 0.16 hours, and the Cmax and AUC paralleled the doses given. The mean urinary recovery within the first 24 hours was 85.7 +/- 6.43% of the dose. In a multiple-dose study, 2000 mg of E1040 (I.V. over 1 hour) was administered every 12 hours (total 9 times) and no abnormal accumulation of the drug in plasma was observed. There were no significant differences in plasma levels or in urinary recoveries between single- and multiple-dose regimens. There were no subjective or objective abnormal findings definitely attributable to the drug except that one subject given 250 mg over 1 hour reported diarrhea, and another complained of nausea during the infusion of 2000 mg over 5 minutes. From these results E1040 was concluded to be safe and well tolerated. 相似文献