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排序方式: 共有2262条查询结果,搜索用时 46 毫秒
61.
Junichiro Miake Yasutaka Kurata Kazuhiko Iizuka Hitomi Furuichi Kasumi Manabe Norihito Sasaki Yasutaka Yamamoto Yoshiko Hoshikawa Shin-Ichi Taniguchi Akio Yoshida Osamu Igawa Naomasa Makita Goshi Shiota Eiji Nanba Shigetsugu Ohgi Toshio Narahashi Ichiro Hisatome 《Circulation journal》2004,68(7):703-711
BACKGROUND: Azimilide reportedly blocks Na(+) channels, although its mechanism remains unclear. METHODS AND RESULTS: The kinetic properties of the azimilide block of the wild-type human Na(+) channels (WT: hH1) and mutant DeltaKPQ Na(+) channels (DeltaKPQ) expressed in COS7 cells were investigated using the whole-cell patch clamp technique and a Markovian state model. Azimilide induced tonic block of WT currents by shifting the h infinity curve in the hyperpolarizing direction and caused phasic block of WT currents with intermediate recovery time constant. The peak and steady-state DeltaKPQ currents were blocked by azimilide, although with only a slight shift in the h infinity curve. The phasic block of peak and steady-state DeltaKPQ currents by azimilide was significantly larger than the blocking of the peak WT current. The affinity of azimilide predicted by a Markovian state model was higher for both the activated state (Kd(A) =1.4 micromol/L), and the inactivated state (Kd(I) =1.4 micromol/L), of WT Na(+) channels than that for the resting state (Kd(R) =102.6 micromol/L). CONCLUSIONS: These experimental and simulation studies suggest that azimilide blocks the human cardiac Na(+) channel in both the activated and inactivated states. 相似文献
62.
Seigo Takamatsu Hitomi Nakabayashi Yasuyuki Okamoto Hiroshi Nakano 《Journal of gastroenterology》1997,32(3):355-360
To evaluate the diagnostic utility of blood biochemical parameters in assessing degree of hepatic fibrosis, serum levels of aminoterminal type III procollagen peptide (P III P), type IV collagen (IV-collagen), 7S domain of type IV collagen (7S-collagen), and hyaluronan (HA) were measured in 54 patients with chronic viral liver disease. Liver collagen content was quantified by a computer-assisted image analysis method. Significant correlations were found between the amount of collagen in the liver and serum levels of P III P (r=0.482;P<0.02), IV-collagen (r=0.705;P<0.001), 7S-collagen (r=0.771;P<0.001), and HA (r=0.595;P<0.001). To optimize diagnostic efficacy, we applied multivariate regression analysis to to the combined results obtained for these blood biochemical parameters and some additional laboratory tests. The correlation coefficient obtained from the application of this model was 0.809. To measure the predictive value of the proposed model, we used it to estimate collagen content in an additional 16 patients with chronic liver disease and compared the estimated to the actual amount of collagen determined by direct measurement. The correlation coefficient was 0.937. These results suggest that application of the model would be useful for the assessment of collagen content of fibrotic liver. 相似文献
63.
Mizuno H Ohte N Wakami K Narita H Fukuta H Asada K Kimura G 《The American journal of cardiology》2008,101(10):1467-1471
The difference between peak mitral annular velocity during early diastole (Ea) and the propagation velocity of left ventricular (LV) early diastolic filling flow (Vp) obtained using Doppler imaging as LV relaxation parameters was not fully elucidated. Thus, this issue was investigated in 117 patients with suspected coronary artery disease. During cardiac catheterization, LV volumes, the LV relaxation time constant Tp, and inertia force of late systolic aortic flow were obtained. Ea significantly and closely correlated with Tp (r = -0.70, p <0.0001) and significantly but weakly correlated with LV ejection fraction (r = 0.37, p <0.0001) and inertia force (r = 0.34, p = 0.0002). Conversely, Vp significantly and closely correlated with both LV ejection fraction (r = 0.66, p <0.0001) and inertia force (r = 0.72, p <0.0001) and significantly but weakly correlated with Tp (r = - 0.35, p = 0.0001). In conclusion, Ea and Vp reflect different aspects of LV behavior from end-systole to early diastole. Ea can be used to index LV relaxation, whereas Vp might not be a proper parameter of LV intrinsic relaxation because it is significantly dependent on LV systolic function and LV chamber size at end-systole. Both parameters are not interchangeable as those of LV early diastolic function. Vp may be a noninvasive parameter of LV elastic recoil. 相似文献
64.
Mika Takahashi Go Sato Naoki Toda Takahiro Azuma Katsuhiko Nakamura Hidetaka Iwasaki Hitomi Miyoshi Kazunori Matsuda Yoshiaki Kitamura Koji Abe Shoichiro Takao Masafumi Harada Noriaki Takeda 《Auris, nasus, larynx》2021,48(3):347-352
ObjectiveThe correlation between enhancement of the vestibulocochlear nerves on gadolinium-enhanced magnetic resonance imaging (MRI) and vestibulocochlear functional deficits was examined in patients with Ramsay Hunt syndrome (RHS).MethodsNineteen patients with RHS who showed herpes zoster oticus, peripheral facial palsy, and vertigo were enrolled. Canal paresis (CP) in the caloric test, abnormal response to ocular and cervical vestibular myogenic potentials (oVEMP and cVEMP), and refractory sensorineural hearing loss were evaluated. MRI images perpendicular to the internal auditory canal were reconstructed to identify the superior (SVN) and inferior vestibular nerves (IVN) and the cochlear nerve (CV). The signal intensity increase (SIinc) of the four-nerve enhancement was calculated as an index.ResultsAmong RHS patients, 79%, 53%, 17% and 26% showed CP in the caloric test, abnormal responses to oVEMP and cVEMP, and refractory sensorineural hearing loss, respectively. SIinc rates of the SVN were significantly increased in RHS patients with CP in the caloric test, and with abnormal responses to oVEMP and cVEMP. SIinc rates of the SVN tended to increase in RHS patients with refractory sensorineural hearing loss (p = 0.052). SIinc rates of the IVN were significantly increased in RHS patients with abnormal responses to oVEMP and cVEMP, and refractory sensorineural hearing loss, but not in those with CP in the caloric test. SIinc rates of the CN were significantly increased in RHS patients with CP in the caloric test, abnormal response to oVEMP and refractory sensorineural hearing loss, but not in those with abnormal response to cVEMP.ConclusionIn patients with RHS, the origin of vertigo may be superior vestibular neuritis, which is affected by reactive varicella-zoster virus from the geniculate ganglion of the facial nerve through the faciovestibular anastomosis. The results also suggested that in some RHS patients, inferior vestibular neuritis contributes to the development of vertigo and that the origin of refractory sensorineural hearing loss is cochlear neuritis. 相似文献
65.
Junya Kuroda Yuji Shimura Kensuke Ohta Hirokazu Tanaka Hirohiko Shibayama Satoru Kosugi Shinichi Fuchida Masayuki Kobayashi Hitomi Kaneko Nobuhiko Uoshima Kazuyoshi Ishii Shosaku Nomura Masafumi Taniwaki Akifumi Takaori-Kondo Chihiro Shimazaki Mitsuru Tsudo Masayuki Hino Itaru Matsumura Yuzuru Kanakura 《International journal of hematology》2014,99(4):441-449
We retrospectively investigated clinical outcomes and prognostic factors of 131 patients with transplant-ineligible newly diagnosed multiple myeloma (NDMM) who received melphalan and prednisolone (MP) as first-line therapy from 2006 to 2013. Eighty-one patients received salvage therapies incorporating bortezomib, lenalidomide, and/or thalidomide. The overall response rate to MP was 54.2 %, including 9.2 % of better than very good partial response. With a median follow-up period of 30.2 months, median overall survival (OS) and median time to next treatment (TNT) were 54.4 and 19.0 months, respectively. Univariate analysis revealed that performance status and serum calcium level significantly associated with both OS and TNT, and multivariate analysis revealed that the higher serum calcium level had a significantly unfavorable impact on OS and TNT. Importantly, staging informed by the international staging system (ISS) was not predictive for OS or TNT in the analyzed cohort. Our study revealed that, in the context of first-line MP therapy for NDMM, the salvage therapy incorporating novel agents produced a survival period of >30 months after the initiation of second-line therapy, suggesting that the predictive value of ISS for OS and TNT may be limited in the era of novel agents. 相似文献
66.
Yui Kunio Imataka George Sasaki Hitomi Shiroki Ryoichi 《Metabolic brain disease》2020,35(7):1101-1108
Metabolic Brain Disease - The role of malondialdehyde-modified low-density lipoprotein (MDA-LDL), an oxidized LDL, in the pathophysiology of autism spectrum disorder (ASD) is unclear. We studied... 相似文献
67.
Ai Miyashiro MD Naoko Matsui MD Yoshimitsu Shimatani MD Hiroyuki Nodera MD Yuishin Izumi MD Satoshi Kuwabara MD Tomihiro Imai MD Masayuki Baba MD Tetsuo Komori MD Masahiro Sonoo MD Takahiro Mezaki MD Jun Kawamata MD Takefumi Hitomi MD Nobuo Kohara MD Kimiyoshi Arimura MD Shuji Hashimoto PhD Kokichi Arisawa MD PhD Susumu Kusunoki MD Ryuji Kaji MD 《Muscle & nerve》2014,49(3):357-361
68.
Ryo Wada MD PhD Masaya Shinohara MD PhD Tadashi Fujino MD PhD Shingo Matsumoto MD PhD Shintaro Yao MD PhD Kensuke Yano MD Shintaro Dobashi MD PhD Katsuya Akitsu MD PhD Hideki Koike MD PhD Hiroshi Ohara MD PhD Toshio Kinoshita MD PhD Hitomi Yuzawa MD PhD Rine Nakanishi MD PhD Takanori Ikeda MD PhD 《Pacing and clinical electrophysiology : PACE》2023,46(1):73-83
69.
Takeru Ehara Osamu Irie Takatoshi Kosaka Takanori Kanazawa Werner Breitenstein Philipp Grosche Nils Ostermann Masaki Suzuki Shimpei Kawakami Kazuhide Konishi Yuko Hitomi Atsushi Toyao Hiroki Gunji Frederic Cumin Nikolaus Schiering Trixie Wagner Dean F. Rigel Randy L. Webb Jürgen Maibaum Fumiaki Yokokawa 《ACS medicinal chemistry letters》2014,5(7):787-792
70.
Hitoshi Uchiyama Masayuki Tsujimoto Tadakazu Shinmoto Hitomi Ogino Tomoko Oda Takuya Yoshida Taku Furukubo Satoshi Izumi Tomoyuki Yamakawa Hidehisa Tachiki Tetsuya Minegaki Kohshi Nishiguchi 《Toxins》2014,6(9):2612-2625
The risk of myopathy and rhabdomyolysis is considerably increased in statin users with end-stage renal failure (ESRF). Uremic toxins, which accumulate in patients with ESRF, exert cytotoxic effects that are mediated by various mechanisms. Therefore, accumulation of uremic toxins might increase statin-induced cytotoxicity. The purpose of this study was to determine the effect of four uremic toxins—hippuric acid, 3-carboxy-4-methyl-5-propyl-2-furanpropionate, indole-3-acetic acid, and 3-indoxyl sulfate—on statin-induced myopathy. Differentiated rhabdomyosarcoma cells were pre-treated with the uremic toxins for seven days, and then the cells were treated with pravastatin or simvastatin. Cell viability and apoptosis were assessed by viability assays and flow cytometry. Pre-treatment with uremic toxins increased statin- but not cisplatin-induced cytotoxicity (p < 0.05 vs. untreated). In addition, the pre-treatment increased statin-induced apoptosis, which is one of the cytotoxic factors (p < 0.05 vs. untreated). However, mevalonate, farnesol, and geranylgeraniol reversed the effects of uremic toxins and lowered statin-induced cytotoxicity (p < 0.05 vs. untreated). These results demonstrate that uremic toxins enhance statin-induced apoptosis and cytotoxicity. The mechanism underlying this effect might be associated with small G-protein geranylgeranylation. In conclusion, the increased severity of statin-induced rhabdomyolysis in patients with ESRF is likely due to the accumulation of uremic toxins. 相似文献