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排序方式: 共有626条查询结果,搜索用时 31 毫秒
1.
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
2.
3.
László Prónai Hiroe Nakazawa Kohji Ichimori Yoshinori Saigusa Tomoichi Ohkubo Kazuko Hiramatsu Shigeru Arimori János Fehér 《Inflammation》1992,16(5):437-450
This study was performed to examine the pattern of Superoxide (O
2
–
·) generation from leukocytes using the O
2
–
· specific chemiluminescence (CL) method.Cypridina luciferin analog, 2-methyl-6-(p-methoxyphenyl)-3,7-dihydroimidazo[1,2-alpha]pyrazin-3-one (MCLA) was used as a CL probe. The appropriate conditions of the MCLA method was first determined for the evaluation of the time course of O
2
–
· generation by leukocytes. The time course of O
2
–
· generation obtained by the MCLA-CL system was compared with that by the luminol-dependent CL, electron spin resonance (ESR)/spin trapping, and cytochromec systems. Following stimulation by three different stimulants (PMA, OZ, FMLP), leukocytes continuously generated O
2
–
· for up to 5 h in the MCLA-CL system, irrespective of the kind of stimulation. The curves obtained by generation ceased more rapidly in the luminol-CL, ESR/spin trapping, and cytochromec systems. A 50% activity of the initial value was observed at 70 min in the MCLA-CL system, but 30, 10 and 35 min in the other systems, respectively. The CL or O
2
–
· generation value decreased to less than 1% (possible termination) at 300, 90, 120 and 180 min, respectively. With the exception of ESR studies with OZ, the cell viability was not significantly affected in any of the trials. These results indicate that leukocytes can generate O
2
–
· much longer than previously estimated and that the MCLA-CL-system is the most suitable system for the measurement of the O
2
–
· generation by leukocytes. 相似文献
4.
5.
Yoshinori Seko Shigeru Ishiyama Toshiro Nishikawa Takeshi Kasajima Michiaki Hiroe Shin Suzuki Sugao Ishiwata Sachio Kawai Yuetsu Tanaka Miyuki Azuma Tetsuji Kobata Hideo Yagita Ko Okumura Ryozo Nagai 《Cardiovascular pathology》2002,11(3):166-170
BACKGROUND: T-cell-mediated myocardial damage is known to be involved in acute myocarditis and dilated cardiomyopathy. Recently, we found that tumor necrosis factor (TNF) ligand superfamily costimulatory molecules, especially 4-1BBL, played an important role in the myocardial damage of murine acute viral myocarditis. METHODS AND RESULTS: To investigate the roles for CD27L, CD30L, OX40L and 4-1BBL, which belong to TNF ligand superfamily, in the development of acute myocarditis and dilated cardiomyopathy, we analyzed the expression of these antigens in the myocardial tissues of patients with acute myocarditis and dilated cardiomyopathy. We also examined expression of the receptors for these molecules, CD27, CD30, OX40 and 4-1BB, which belong to TNF receptor superfamily, on the infiltrating cells. Strong expression of CD27L, CD30L and 4-1BBL and weak to moderate expression of OX40L was found in the cardiac myocytes of patients with acute myocarditis. Moderate expression of CD27L, CD30L and 4-1BBL and weak expression of OX40L was found on the cardiac myocytes of patients with dilated cardiomyopathy. Most of the infiltrating cells expressed CD27, CD30 and 4-1BB and a part of the infiltrating cells expressed OX40. CONCLUSIONS: Our findings suggest that expression of TNF ligand superfamily costimulatory molecules on cardiac myocytes may play a role in the cell-mediated myocardial damage in patients with acute myocarditis and dilated cardiomyopathy as in murine viral myocarditis. 相似文献
6.
John L. Johnson Hiroe Shiratsuchi Zahra Toossi Jerrold J. Ellner 《Journal of clinical immunology》1997,17(5):387-395
The pathophysiologic basis for the exuberant intracellular growth of Mycobacterium avium complex (MAC) in AIDS patients is unclear but may relate to altered expression of modulatory cytokines. Interleukin (IL)-1, IL-6, and TNF- expression by monocytes from AIDS patients and healthy subjects (HS) stimulated with isogeneic MAC strains (SmT, smooth-transparent, virulent; SmD, smooth-domed, avirulent) was examined. Spontaneous cytokine production was not observed in patients with AIDS. MAC strains induced less IL-1 and IL-1 release in AIDS patients than HS (P < 0.05). The ratio of cell-associated to supernatant IL-1 also was increased in AIDS patients (P = 0.03). IL-1 mRNA expression paralleled protein release in either group of subjects. In both HS and AIDS patients, stimulation with SmD induced more IL-1 and TNF- release by monocytes compared to SmT. In AIDS patients, SmD also induced greater IL-6 release than SmT (P < 0.01). Alterations in monocyte expression and compartmentalization of the regulatory cytokines IL-1 and IL-6 may enhance bacterial replication and contribute to the patho-genesis of MAC infection in AIDS. 相似文献
7.
Kazunari Matsumoto Keiichiro Fujishima Akie Moriuchi Hiroe Saishoji Yukitaka Ueki 《Metabolism: clinical and experimental》2010,59(3):320-25573
Soluble adhesion molecule E-selectin (sE-selectin) is a marker of endothelial activation. To investigate whether high serum concentrations of sE-selectin could predict cardiovascular events, we followed 392 Japanese patients with type 2 diabetes mellitus who had no history of cardiovascular disease for a mean period of 6 years. The cardiovascular end points were defined as fatal and nonfatal myocardial infarction, angina pectoris, stroke, and sudden death. During the follow-up period, 51 patients reached end point. Patients who reached end point were significantly older and had longer duration of diabetes, higher systolic blood pressure, higher hemoglobin A1c, higher plasma glucose, higher sE-selectin, and lower high-density lipoprotein cholesterol compared with those free of such events. The mean serum concentration of sE-selectin was higher in patients who reached end point (81.1 ± 32.2 ng/mL) than event-free patients (66.7 ± 33.7 ng/mL, mean ± SD; P < .01). Multiple logistic regression analysis identified age, systolic blood pressure, total cholesterol, sE-selectin, and low high-density lipoprotein cholesterol as independent factors related to cardiovascular events. The odds ratio for cardiovascular events for 1-SD increase in sE-selectin concentration was 1.45 (95% confidence interval, 1.22-1.71). Kaplan-Meier analysis demonstrated a significantly higher cardiovascular event rate in the highest tertile of sE-selectin compared with the lowest or middle tertile of sE-selectin (P < .01). The results suggest that high serum concentrations of sE-selectin can predict cardiovascular events in Japanese patients with type 2 diabetes mellitus. 相似文献
8.
Hideto?KamedaEmail author Koichi?Amano Naoya?Sekiguchi Hirofumi?Takei Hiroe?Ogawa Hayato?Nagasawa Tsutomu?Takeuchi 《Modern rheumatology / the Japan Rheumatism Association》2004,14(6):442-446
Methotrexate (MTX) is the most commonly used disease-modifying antirheumatic drug (DMARD) throughout the world. In Japan,
MTX is recommended by the Japanese Ministry of Health, Labour, and Welfare to be given as the second or third DMARD and at
a dosage of no more than 8 mg/week. We analyzed the efficacy of MTX in Japanese patients with RA in order to determine whether
it is comparable to that in Western countries, where 15–20 mg/week of MTX is used, as well as to elucidate the factors associated
with the favorable response to MTX. Around 8 mg/week of MTX was effective in half of the RA patients in the current study,
and male sex was the only factor associated with a good response to MTX from a multivariate regression model analysis. Some
of the patients who had a poor response to MTX showed an improvement with the addition of bucillamine or prednisolone. For
the remaining patients, an increase in the MTX dosage to more than 8 mg/week or the use of biologics such as the anti-tumor
necrosis factor (TNF)-α monoclonal antibody may be required. 相似文献
9.
Acceleration of blood flow ejected from the ventricle into the aorta and the hydraulic power state of blood flow in the aorta may be affected by asynchronous or locally depressed contraction of the left ventricle as well as by arterial impedance. In order to evaluate the effect of an infarcted heart on the hydraulic power state of blood flow, the aortic input impedance spectrum and the hydraulic power spectrum were calculated from simultaneous recordings of pulsatile aortic pressure and flow velocity at the aortic root in 6 normal controls (group 1), 6 patients with old myocardial infarction (OMI) without aneurysm (group 2), and 6 patients of OMI with aneurysm (group 3). The ratios (Rh) of power in high harmonics to that of fundamental harmonics, that is, Rh = (E2 + E3 + ...E10)/E1, where E represents hydraulic power and the numbers represent harmonic numbers, were 0.64 +/- 0.17, 0.23 +/- 0.09, and 0.22 +/- 0.10 in groups 1, 2, and respectively (p less than 0.001 between groups 1 and 2; p less than 0.001, between groups 1 and 3). As the acceleration of ejecting flow of blood by the left ventricle is inversely related with arterial impedance, Rh will be also inversely related with arterial impedance. Then, the product of Rh and the characteristic impedance (Zc) would be an indicator of the left ventricular contractility. In fact, the products were 64 +/- 15, 32 +/- 14, and 31 +/- 13 dyne.sec.cm-5 in groups 1, 2, and 3 respectively (p less than 0.005, between groups 1 and 2; p less than 0.005, between groups 1 and 3). These results suggest that asynchronous or locally depressed contractions of the left ventricular wall are closely related to depressed Rh and further to depressed values of the products of Rh and Zc. It is concluded that analysis of the power spectrum of blood flow in the root of the aorta provides information of the left ventricular contractility in connection with arterial impedance. 相似文献
10.
Spagnolo P Renzoni EA Wells AU Sato H Grutters JC Sestini P Abdallah A Gramiccioni E Ruven HJ du Bois RM Welsh KI 《American journal of respiratory and critical care medicine》2003,168(10):1162-1166
Sarcoidosis is thought to result from the interaction between an unknown environmental antigenic trigger and the host's genetic susceptibility. We hypothesized that sarcoidosis, or one of the disease subsets, could be associated with single nucleotide polymorphisms of C-C chemokine receptor 2 (CCR2) gene. Eight single-nucleotide polymorphisms in CCR2 were studied in a total of 304 Dutch individuals (90 non-L?fgren sarcoidosis, 47 L?fgren's syndrome, 167 control subjects). From the investigated CCR2 polymorphisms, nine haplotypes were deduced (haplotypes 1-9). In patients with L?fgren's syndrome, a strongly significant increase in the frequency of CCR2-haplotype 2, which includes four unique alleles (A at nucleotide position -6752, A at 3,000, T at 3,547, and T at 4,385), was observed compared with control subjects (74% vs. 38% respectively, p < 0.0001), whereas no difference was found between non-L?fgren sarcoidosis and control subjects (both 38%). The association between CCR2-haplotype 2 carriage frequency and L?fgren's syndrome (odds ratio, 4.4; p < 0.0001) remained significant after adjustment for human leukocyte antigen haplotype DRB1*0301-DQB1*0201 (odds ratio, 11.5; p < 0.0001) and female sex (odds ratio, 3.2; p = 0.003), two known risk factors for L?fgren's syndrome. In conclusion, this report describes a strong association between CCR2-haplotype 2 and L?fgren's syndrome. Further studies are needed to understand the molecular mechanisms underlying this association. 相似文献