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21.
Takeshi Matsumoto Takahisa Asano Mami Takemoto Hiroyuki Tachibana Yasuo Ogasawara Fumihiko Kajiya 《Applied radiation and isotopes》2007,65(8):910-917
Using (3)H- and (125)I-labeled desmethylimipramine (DMI) for regional flow tracers, we established a two-time measurement method for the spatial pattern of myocardial perfusion in cross-circulated rat hearts. Myocardial extractions and retentions of these tracers were confirmed to be satisfactory; however, the latter were less than 90% after 3 min at a perfusion rate of 2.9 ml/min/g, limiting the present application to a short-time perfusion measurement. Distributions of myocardial depositions were separated by subtraction digital radiography with 400-microm pixel resolution. Its feasibility was examined by regression analysis between local deposition densities of (3)H- and (125)I-DMI injected simultaneously. The slope, y-intercept, and correlation coefficient (r) of the regression line were 0.98+/-0.04, 0.02+/-0.04, and 0.95+/-0.03, respectively, indicating the validity of the present image subtraction technique. The spatial pattern of myocardial perfusion in response to flow reduction was evaluated by the injections of (3)H- and (125)I-DMI, respectively, before and after a nearly 70% flow reduction. A significant correlation between normalized density distributions of these tracers was found in both subepicardium (r=0.77+/-0.12) and subendocardium (r=0.73+/-0.20), indicating the stable pattern of myocardial perfusion. However, the coefficient of variation of tracer densities showed a decrease of subendocardial flow heterogeneity from 35+/-15% to 31+/-16%. Thus, flow differences between originally high- and low-flow regions in subendocardium were reduced on a relative basis during low perfusion. 相似文献
22.
Yukiko Hasuike Takeshi Nakanishi Rintarou Moriguchi Yoshinaga Otaki Masayoshi Nanami Yasue Hama Miki Naka Koji Miyagawa Masaaki Izumi Yoshihiro Takamitsu 《Nephrology, dialysis, transplantation》2004,19(6):1474-1479
BACKGROUND: Cyanide is a toxic agent, and its detoxification product, thiocyanate, may be a major pathogenetic substance in uraemia. Recent studies examining the myeloperoxidase(MPO)/thiocyanate system have suggested a link between thiocyanate and atherosclerosis. However, inaccuracies in conventional assays for cyanide and thiocyanate have limited the understanding of their metabolism in haemodialysis (HD) patients. METHODS: We used high-performance liquid chromatography to measure cyanide in erythrocytes and thiocyanate in plasma in 43 HD patients and in a group of 46 healthy controls that included 15 current smokers. To clarify the metabolic conversion of cyanide to thiocyanate in uraemic patients, we also measured cysteine and sulfate. We then used stepwise regression analysis to analyse factors that determine erythrocyte cyanide and plasma thiocyanate. RESULTS: Mean cyanide and thiocyanate were significantly greater in HD patients than in non-smoking controls. However, cyanide was far below lethal concentrations in dialysis patients. Thiocyanate was six to seven times greater in HD patients than in non-smoking controls, and decreases in thiocyanate following dialysis were only 19.3+/-3.5%. Multiple regression analysis showed a positive correlation between cyanide and thiocyanate in controls, but a negative correlation in HD patients. In patients, an inverse relationship between thiocyanate and BUN was also observed. CONCLUSIONS: The elevation of thiocyanate in patients undergoing dialysis probably is secondary to both limited efficiency of HD and deranged metabolism of cyanide and thiocyanate. Because thiocyanate is a preferred substrate for MPO, it may play a role in uraemic complications including cardiovascular events. 相似文献
23.
Takeshi Sakata Yongmei Wang Bernard P Halloran Hashem Z Elalieh Jay Cao Daniel D Bikle 《Journal of bone and mineral research》2004,19(3):436-446
We showed that unloading markedly diminished the effects of IGF-I to activate its signaling pathways, and the disintegrin echistatin showed a similar block in osteoprogenitor cells. Furthermore, unloading decreased alphaVbeta3 integrin expression. These results show that skeletal unloading induces resistance to IGF-I by inhibiting activation of the IGF-I signaling pathways at least in part through downregulation of integrin signaling. INTRODUCTION: We have previously reported that skeletal unloading induces resistance to insulin-like growth factor-I (IGF-I) with respect to bone formation. However, the underlying mechanism remains unclear. The aim of this study was to clarify how skeletal unloading induces resistance to the effects of IGF-I administration in vivo and in vitro with respect to bone formation. MATERIALS AND METHODS: We first determined the response of bone to IGF-I administration in vivo during skeletal unloading. We then evaluated the response of osteoprogenitor cells isolated from unloaded bones to IGF-I treatment in vitro with respect to activation of the IGF-I signaling pathways. Finally we examined the potential role of integrins in mediating the responsiveness of osteoprogenitor cells to IGF-I. RESULTS: IGF-I administration in vivo significantly increased proliferation of osteoblasts. Unloading markedly decreased proliferation and blocked the ability of IGF-I to increase proliferation. On a cellular level, IGF-I treatment in vitro stimulated the activation of its receptor, Ras, ERK1/2 (p44/42 MAPK), and Akt in cultured osteoprogenitor cells from normally loaded bones, but these effects were markedly diminished in cells from unloaded bones. These results were not caused by altered phosphatase activity or changes in receptor binding to IGF-I. Inhibition of the Ras/MAPK pathway was more impacted by unloading than that of Akt. The disintegrin echistatin (an antagonist of the alphaVbeta3 integrin) blocked the ability of IGF-I to stimulate its receptor phosphorylation and osteoblast proliferation, similar to that seen in cells from unloaded bone. Furthermore, unloading significantly decreased the mRNA levels both of alphaV and beta3 integrin subunits in osteoprogenitor cells. CONCLUSION: These results indicate that skeletal unloading induces resistance to IGF-I by inhibiting the activation of IGF-I signaling pathways, at least in part, through downregulation of integrin signaling, resulting in decreased proliferation of osteoblasts and their precursors. 相似文献
24.
Jose S. Pulido Ikuko Sugaya Jordan Comstock Kiminobu Sugaya 《Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie》2007,245(6):889-893
Purpose Reelin is important in the guidance of neuronal stem cells in the central nervous system during normal development. We wished
to determine whether reelin is expressed in the retina and cornea after injury.
Methods Mice underwent laceration of their retina as well as corneal epithelial debridement. The mice were sacrificed at 3 days, and
eyes were fixed and stained for reelin expression and reelin messenger ribonucleic acid (mRNA).
Results In normal eyes, reelin was expressed only at very low levels in the ganglion cell layer of the retina and the endothelial
cell layer of the cornea. In injured eyes, there was marked expression in reelin immunoreactivity in the retina and cornea.
Reelin gene expression was seen in the retina and cornea.
Conclusions Reelin is expressed during normal retinogenesis. This study shows that reelin is also upregulated following injury to the
retina and cornea. The expression of reelin following injury suggests that reelin may play an important role in regulating
stem cell trafficking in neuronal and nonneuronal tissues following injury similar to its role in normal organogenesis.
For consideration of publication in Graefe’s Archive for Clinical and Experimental Ophthalmology. 相似文献
25.
Hang Zhao Takeshi Sugawara Shihiro Miura Tetsuya Iijima Satoshi Kashimoto 《Journal canadien d'anesthésie》2007,54(3):201-207
PURPOSE: The purpose of this study was to determine if intrathecal landiolol, a beta1-blocker, can modulate formalin-induced nociception and spinal c-Fos expression in mice, in the absence of anesthesia. METHODS: Thirty-two mice were randomly assigned to one of four groups: the control group (n = 8) received intrathecal normal saline 10 microL, while the other three groups (n = 8 for each) received intrathecal landiolol at escalating doses of 250 microg.kg(-1), 500 microg.kg(-1) and 750 microg.kg(-1) respectively, immediately after induction of anesthesia with isoflurane. After awakening, inflammatory pain was induced by 10 microL of 5% formalin solution injected into the dorsal surface of the right hind paw. The nociceptive behaviours including licking, biting and lifting of the injected paw were cumulatively recorded as seconds of behaviours/min during phase I (0-10 min) and phase II (10-45 min). The c-Fos protein expressions in the spinal dorsal horn were detected with immunohistochemical techniques in the control and landiolol 750 microg.kg(-1) groups. RESULTS: Compared to the control group, intrathecal injection of landiolol 750 microg.kg(-1) significantly decreased pain-related behaviours in phase I, while intrathecal landiolol 250 microg.kg(-1), 500 microg.kg(-1) and 750 microg.kg(-1) significantly decreased pain-related behaviours in phase II during the formalin test. The numbers of c-Fos immunoreactive nuclei in the L5 spinal dorsal horn were significantly lower in the landiolol 750 microg.kg(-1) group compared to the control group (landiolol 750 microg.kg(-1) 2.4 +/- 1.1 vs control 9.2 +/- 3.9; P < 0.01). CONCLUSION: The present study indicates that intrathecally administered landiolol produces significant antinociceptive effects in the formalin test. Although further studies exploring the detailed mechanism are needed, these data suggest a potential role of beta1-adrenoreceptors in spinal nociceptive processing. 相似文献
26.
27.
Jong Il Kim Takeshi Tsujino Yoshio Fujioka Komei Saito Mitsuhiro Yokoyama 《Hypertension research》2003,26(4):307-313
We examined cellular membrane fatty acid composition and insulin sensitivity in patients with mild essential hypertension and hyperlipidemia, and investigated whether bezafibrate, a lipid-lowering drug, could improve elevated blood pressure and insulin sensitivity in these subjects by ameliorating cellular membrane fatty acid composition. Twenty-seven subjects were recruited. Twelve men with mild essential hypertension [systolic blood pressure (SBP) between 140 mmHg and 160 mmHg] and hypertriglyceridemia (plasma triglyceride concentration over 150 mg/dl) were designated the HL group. Fifteen men with mild essential hypertension and normotriglyceridemia (plasma triglyceride concentration below 150 mg/dl) were designated the NL group. Subjects in the HL group were given bezafibrate 400 mg/dl and those in the NL group were given placebo for 3 months. Bezafibrate significantly reduced SBP (140 +/- 2.6 to 131.8 +/- 2.6 mmHg, mean +/- SEM), diastolic blood pressure (DBP) (87.8 +/- 2.0 to 82.8 +/- 2.6 mmHg), fasting plasma triglyceride concentration (225.5 +/- 23.5 to 102.9 +/- 10.9 mg/dl), fasting plasma insulin concentration (9.6 +/- 0.8 to 7.1 +/- 0.8 microU/ml), and homeostasis model assessment scores (HOMA-R, 2.4 +/- 0.2 to 1.7 +/- 0.2), and significantly improved the insulin sensitivity index (56.0 +/- 3.0 to 70.7 +/- 4.8 mg x l2/mmol x mU x min) in the HL group. Regarding erythrocyte membrane fatty acid composition, bezafibrate reduced the percentages of saturated fatty acids (SFA) and increased the percentage of polyunsaturated fatty acids (PUFA). Plasma triglyceride concentrations were positively correlated with HOMA-R (r = 0.50, p < 0.01) and SFA (r = 0.39, p < 0.05), and negatively correlated with PUFA (r = -0.45, p < 0.05) before administration of placebo or bezafibrate. In conclusion, an improvement of hyperlipidemia by bezafibrate may be attributed to reduction of blood pressure and amelioration of insulin sensitivity. Abnormalities in membrane lipid composition may play an important role in these metabolic disorders. 相似文献
28.
29.
Shigeji Matsumoto Mizuho Ikeda Toshimi Nishikawa Shinki Yoshida Takeshi Tanimoto Masahiro Ito Chikako Saiki Mamoru Takeda 《The Journal of pharmacology and experimental therapeutics》2002,300(2):597-604
The excitatory responses of deflationary slowly adapting pulmonary stretch receptor (SAR) activity to lung deflation ranging from approximately -15 to -25 cm of H(2)O for approximately 5 s were examined before and after administration of flecainide, a Na(+) channel blocker, and K(+) channel blockers, such as 4-aminopyridine (4-AP) and tetraethylammonium (TEA). The experiments were performed in anesthetized, artificially ventilated rats after unilateral vagotomy. The deflationary SARs increased their activity during lung deflation and its effect became more pronounced by increasing the degree of negative pressure. During lung deflation the average values for the deflationary SAR adaptation index (AI) were below 40%. Intravenous administration of veratridine (50 microg/kg), an Na(+) channel opener, stimulated deflationary SAR activity: one maintained excitatory activity mainly during deflation and the other receptors showed a tonic discharge during both deflation and inflation. Despite the difference in deflationary SAR firing patterns after veratridine administration, flecainide treatment (6.0 mg/kg) blocked veratridine-induced deflationary SAR stimulation and also caused strong inhibition of the excitatory responses of deflationary SARs to lung deflation. Under these conditions, the average values for deflationary SAR AI were over 90%. The responses of deflationary SARs and deflationary SAR AI to lung deflation were not significantly altered by pretreatment with either 4-AP (0.7 and 2.0 mg/kg) or TEA (2.0 and 6.0 mg/kg). These results suggest that the excitatory effect of lung deflation on deflationary SAR activity is mediated by the activation of flecainide-sensitive Na(+) channels on the nerve terminals of deflationary SARs. 相似文献
30.
Association of Vascular Endothelial Growth Factor Expression with Tumor Angiogenesis and with Early Relapse in Primary Breast Cancer 总被引:10,自引:0,他引:10
Masakazu Toi Seigo Hoshina Toshiaki Takayanagi Takeshi Tominaga 《Cancer science》1994,85(10):1045-1049
Angiogenesis is an independent prognostic indicator in breast cancer. In this report, the relationship between expression of vascular endothclial growth factor (VEGF; a selective mitogen for endothelial cells) and the microvessel density was examined in 103 primary breast cancers. The expression of VEGF was evaluated by immunocytochemical staining using anti-VEGF antibody. The microvessel density, which was determined by immunostaining for factor VIII antigen, in VEGF-rich tumors was clearly higher than that in VEGF-poor tumors ( P <0.01). There was a good correlation between VEGF expression and the increment of microvessel density. Furthermore, postoperative survey demonstrated that the relapse-free survival rate of VEGF-rich tumors was significantly worse than that of VEGF-poor tumors. It was suggested that the expression of VEGF is closely associated with the promotion of angiogenesis and with early relapse in primary breast cancer. 相似文献