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61.
1. The aim of the present study was to characterize the subtypes of bradykinin (BK) receptors that evoke the relaxation and contraction induced by BK and to identify the main contracting and relaxing factors in isolated porcine basilar artery by measuring changes in isometric tension and a thromboxane (TX) metabolite. 2. Endothelial denudation completely abolished both responses. [Thi5,8, D-Phe7]-BK (a B2-receptor antagonist) inhibited the BK-induced relaxation and contraction, whereas des-Arg9, [Leu8]-BK (a B1-receptor antagonist) had no effect. 3. L-nitro-arginine (L-NA, a nitric oxide synthase inhibitor) completely inhibited BK-induced relaxation. Indomethacin (a cyclo-oxygenase inhibitor) completely and ONO-3708 (a TXA2/prostaglandin H2 receptor antagonist) partially inhibited BK-induced contraction, whereas OKY-046 (a TXA2 synthase inhibitor) and nordihydroguaiaretic acid (a lipoxygenase inhibitor) did not. 4. In the presence of L-NA, the contractile response to BK was inhibited by indomethacin or ONO-3708 and was competitively antagonized by [Thi5,8, D-Phe7]-BK (pA2=7.50). In the presence of indomethacin, the relaxant response to BK was inhibited by L-NA and was competitively antagonized by [Thi5,8, D-Phe7]-BK (pA2=7.59). 5. TXA2 release was not induced by BK-stimulation. 6. These results suggest that the endothelium-dependent relaxation and contraction to BK in the porcine basilar artery is mediated via activation of endothelial B2-receptors. The main relaxing factor may be NO and the main contracting factor may be prostaglandin H2. 相似文献
62.
Kato Y Kita Y Nishio M Hirasawa Y Ito K Yamanaka T Motoyama Y Seki J 《European journal of pharmacology》1999,380(2-3):197-202
We have examined the potency of several adenosine receptor antagonists at adenosine A1 and A2A receptors using quantitative autoradiography and have compared the results with those of previous studies using the same radioligands in membrane preparations. The agonists [3H]cyclohexyladenosine and [3H]2-[p-(2-carbonylethyl)-phenylethylamino]-5′-N-ethylcarboxamido adenosine ([3H]CGS 21680) were used as radioligands for the two receptors. The results show that 1,3-dipropyl-8-cyclopentyl xanthine (DPCPX) is almost 1000-fold and 8-chloro-4-cyclohexyl-amino-1-(trifluoromethyl)[1,2,4]triazolo[4,3-a] quinoxaline (CP-68,247) about 300-fold more potent at adenosine A1 receptors in cortex and striatum than at striatal adenosine A2A receptors. Conversely, 5-amino-7-(2-phenylethyl)-2-(2-furyl)-pyrazolo-[4,3-e]-1,2,4-triazolo [1,5-c]pyrimidine (SCH 58261) is approximately 1000-fold and 4-(2-[7-amino-2-(2-furyl) [1,2,4]-triazolo[2,3-a][1,3,5]triazin-5-yl amino]ethyl)phenol (ZM 241,385) about 400-fold more potent at adenosine A2A than at A1 receptors. Caffeine and its metabolites did not show any selectivity. Other studied antagonists were non-selective or showed a modest (20- to 40-fold) adenosine A2A receptor selectivity. Thus, only a few of the antagonists show such high selectivity that it is not offset by differences in drug distribution and levels of receptor subtype expression. 相似文献
63.
Kohno J Asai Y Nishio M Sakurai M Kawano K Hiramatsu H Kameda N Kishi N Okuda T Komatsubara S 《The Journal of antibiotics》1999,52(12):1114-1123
Four new antibiotics, TMC-171A (2), B (3), C (4) and TMC-154 (5) have been isolated from the fermentation of fungal strains Gliocladium sp. TC 1304 and TC 1282, respectively. Spectroscopic and degradation studies have shown that TMC-171s and TMC-154 were new members of the TMC-151 class of antibiotics, unique polyketides modified with a D-mannose and a D-mannitol or a D-arabitol. These compounds showed moderate cytotoxicity to various tumor cell lines. 相似文献
64.
Toshihiko Kotake Tsuneharu Miki Hideyuki Akaza Yoshinobu Kubota Yasunori Nishio Yosuke Matsumura Kazuo Ota Nobuya Ogawa 《Cancer chemotherapy and pharmacology》1991,27(4):253-257
Summary The effects of recombinant granulocyte colony-stimulating factor (rG-CSF) on the myelosuppression, especially neutropenia, induced by cancer chemotherapy in patients with urogenital cancer were investigated in a randomized, controlled clinical study. In this study, rG-CSF was given subcutaneously at a dose of 2 g/kg per day for 14 consecutive days. Changes in neutrophil counts were compared between the first (no rG-CSF) and second cycles (rG-CSF treatment period) of chemotherapy. rG-CSF administration was found to be effective in reducing the duration of neutropenia, in elevating the neutrophil nadir, and in reducing recovery time. Based on comparisons between the randomized rG-CSF treatment group (with rG-CSF) and the control group, treatment with rG-CSF resulted in the moderation or prevention of neutropenia and the acceleration of recovery. These results demonstrate that in chemotherapy of patients with urogenital cancer, in which neutropenia is a dose- or schedule-limiting factor, the concomitant use of rG-CSF may enable an increase in the dose (higher single dose or increased dose per unit of time) or shorten the chemotherapy period. 相似文献
65.
Use of cultured tubular cells isolated from human urine for investigation of renal transporter 总被引:2,自引:0,他引:2
AIM: To facilitate the understanding of the transporter function of human renal tubular cells, we have developed a simple method using primary cultured proximal tubule (PT) cells isolated from voided urine. METHODS: PT cells grown to confluence on glass coverslips could be identified by parallel arrays of spindle cells and hemicyst formation. Brush-border gamma-glutamyl transpeptidase (gammaGTP) activity was histochemically identified. Apical membrane Na+/H+ exchanger (NHE) activity was measured by monitoring changes in intracellular pH (pHi) after an acid load in a single cell level using the pH-sensitive dye 2'7'-bis-(2-carboxyethyl)-5.6'carboxyfluorescein (BCECF). RESULTS: Amiloride and 5-(N-ethyl-N-isopropyl) amiloride (EIPA) inhibited the NHE activity with half-maximal inhibition values (IC50) of 15.3 and 4.0 microM, respectively. NHE-3 mRNA was detected by the RT-PCR technique in clonally proliferated PT cells. CONCLUSION: These results suggest that cultured PT cells isolated from human urine express amiloride-resistant NHE-3 activity on the apical membranes, which can be compared to functional properties of PT in vivo. Our experimental strategy offers a useful experimental approach to investigating human renal tubular transport function in vitro. 相似文献
66.
Subependymoma of the lateral ventricles 总被引:7,自引:0,他引:7
Four subependymomas of the lateral ventricle were reviewed with regard to clinical presentation, neuroimaging features, treatment, histopathological features, and long-term follow-up. There were two male and two female patients ranging in age from 27 to 60 years (mean 48.3 years). While two patients presented with symptoms and signs of raised intracranial pressure, two others were found incidentally during neuroimaging investigations to have intraventricular tumors. Neuroimaging characteristics of these tumors included no paraventricular extension, iso- or hypodensity with minimal enhancement on computerized tomography (CT), or iso- or hypointensity on T1-weighted and hyperintensity on T2-weighted magnetic resonance images (MRI). The usual finding on MRI was of no or scarce contrast enhancement, but one case showed heterogeneous enhancement. Three patients underwent total resection of the tumor and one underwent partial resection. No patients received postoperative radiation therapy. All patients have been doing well 4.8 to 15.4 years (mean 8.8 years), after surgery. Although there are no absolutely specific features to distinguish these tumors from other intraventricular tumors preoperatively, subependymoma should be kept in mind for differential diagnosis, as this tumor may safely be removed without sacrificing contiguous normal tissue and with good long-term results. 相似文献
67.
Shigeto Taniyama Osamu Arakawa Masamitsu Terada Sachio Nishio Tomohiro Takatani Yahia Mahmud Tamao Noguchi 《Toxicon》2003,42(1):29-33
A clone of toxic dinoflagellate Ostreopsis sp. and six specimens of a parrotfish Scarus ovifrons were collected in October 1997 at Tokushima Prefecture, Japan. Ostreopsis sp. was cultured in ESM medium for 16 days, and after rearing the cell pellet (about 4.0x10(5) cells) was extracted with 50% methanol, partitioned between an aqueous layer and 1-butanol layer, and biochemically tested. Similarly, the crude toxin from S. ovifrons was extracted, and tested. The mice injected with each 1-butanol layer from Ostreopsis sp. and S. ovifrons showed the common symptoms of convulsion, drowsiness and collapse, and died within 48 h. The lethal potency of Ostreopsis sp. was calculated to be 1.0x10(-4) MU/cell. All specimens of S. ovifrons were found to be toxic, where the highest potency was determined as 2 MU/g in muscle of one specimen. After being injected with toxins, the serum creatine phosphokinase levels of mice were found to be elevated. Toxins from Ostreopsis sp. and S. ovifrons showed delayed haemolytic activity with mouse and human erythrocytes, which was inhibited by an anti-palytoxin (PTX) antibody antibody and ouabain. Toxins from Ostreopsis sp. and S. ovifrons thus resembled each other, and strongly suggested to be PTX or its akin substance. Additionally, a considerable number of adherent Ostreopsis sp. was found in the gut contents of S. ovifrons during the heavy occurrence of Ostreopsis sp. in October 1997 at Tokushima Prefecture. From the above results, it can be strongly postulated that the dinoflagellate Ostreopsis sp. is the origin of PTX which is sequestered by the parrotfish S. ovifrons through food chain. 相似文献
68.
Lung deflation impairs alveolar epithelial fluid transport in ischemic rabbit and rat lungs 总被引:3,自引:0,他引:3
Sakuma T Tsukano C Ishigaki M Nambu Y Osanai K Toga H Takahashi K Ohya N Kurihara T Nishio M Matthay MA 《Transplantation》2000,69(9):1785-1793
BACKGROUND: Because the fluid transport capacity of the alveolar epithelium after lung ischemia with and without lung deflation has not been well studied, we carried out experimental studies to determine the effect of lung deflation on alveolar fluid clearance. METHODS: After 1 or 2 hr of ischemia, we measured alveolar fluid clearance using 125I-albumin and Evans blue-labeled albumin concentrations in in vivo rabbit lungs in the presence of pulmonary blood flow and in ex vivo rat lungs in the absence of any pulmonary perfusion, respectively. RESULTS: The principal results were: (1) lung deflation decreased alveolar fluid clearance while inflation of the lungs during ischemia preserved alveolar fluid clearance in both in vivo and ex vivo studies; (2) alveolar fluid clearance was normal in the rat lungs inflated with nitrogen (thus, alveolar gas composition did not affect alveolar fluid clearance); (3) amiloride-dependent alveolar fluid clearance was preserved when the lungs were inflated during ischemia; (4) terbutaline-simulated alveolar fluid clearance was preserved in the hypoxic rat lungs inflated with nitrogen; (5) lecithinized superoxide dismutase, a scavenger of superoxide anion, and N(omega)-nitro-L-arginine methyl ester, an inhibitor of nitric oxide, preserved normal alveolar fluid clearance in the deflated rat lungs. CONCLUSION: Lung deflation decreases alveolar fluid clearance by superoxide anion- and nitric oxide-dependent mechanisms. 相似文献
69.
Kasai T; Ohe Y; Nishio K; Kunitoh H; Tamura T; Sekine I; Kubota K; Yamamoto N; Nakamura Y; Shinkai T; Kodama T; Saijo N 《Japanese journal of clinical oncology》1998,28(3):214-221
BACKGROUND: It is important to minimize the incidence of ineligible cases
to improve the quality of clinical trials. To determine factors which may
influence the incidence of ineligible cases, the incidence of and reasons
for ineligibility in clinical trials were retrospectively analyzed.
METHODS: We retrospectively examined the incidence of and reasons for
ineligibility for inclusion in eight clinical trials conducted by the Lung
Cancer Chemotherapy Study Group of the Japan Clinical Oncology Group and
four trials financed by trust funds from a pharmaceutical company. RESULTS:
In these 12 clinical studies, the incidence of ineligibility was 4.2%
(32/762) (range 0-10.6%). Specific factors that might influence the
incidence of ineligible cases were then analyzed. There was a significant
difference in the incidence of ineligibility between the methods of
registration (P < 0.05). The incidences using a central registration and
without using a central registration system were 2.8% (9/322) and 5.2%
(23/440) respectively. We also analyzed ineligible cases in clinical
studies published in the Journal of Clinical Oncology. In clinical studies
published in the Journal of Clinical Oncology recently and 10 years ago,
the incidences of ineligible cases were 5.0% (942/18 878) and 4.1%
(206/4995) respectively. In clinical studies on lung cancer published in
the Journal of Clinical Oncology from 1984 to 1995, the incidence of
ineligible cases was 4.7% (900/19,116). There was no significant difference
in the incidence of ineligible cases between our 12 studies and the Journal
of Clinical Oncology clinical studies by the chi 2 test (P > 0.05).
CONCLUSIONS: We conclude that the incidence of ineligible cases in our
studies is similar to that in clinical trials published in the Journal of
Clinical Oncology. Central registration systems are useful for checking for
ineligibility, and to increase the quality of clinical trials.
相似文献
70.