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排序方式: 共有980条查询结果,搜索用时 15 毫秒
941.
Requisite roles of Runx2 and Cbfb in skeletal development 总被引:8,自引:0,他引:8
Komori T 《Journal of bone and mineral metabolism》2003,21(4):193-197
942.
Ishikawa T Kasamatsu S Hagiwara Y Mitomo H Kato R Sumino Y 《Drug metabolism and pharmacokinetics》2003,18(3):194-202
Hitherto three variant forms of ABCG2 have been documented on the basis of their amino acid moieties (i.e., Arg, Gly, and Thr) at the position 482. In the present study, we have generated those variants of ABCG2 by site-directed mutagenesis and expressed them in Sf9 insect cells. The apparent molecular weight of the expressed ABCG2 variants was 130,000 under non-reductive conditions, whereas it was reduced to 65, 000 by treatment with mercaptoethanol. It is suggested that ABCG2 exists in the plasma membrane of Sf9 cells as a homodimer bound through cysteinyl disulfide bond(s). Both ATPase activity and drug transport of ABCG2 variants were examined by using plasma membrane fractions prepared from ABCG2-overexpressing Sf9 cells. The ATPase activity of the plasma membrane expressing ABCG2 (Gly-482) was significantly enhanced by prazosin. In contrast, ABCG2 (Arg-482) transports [(3)H]methotrexate in an ATP-dependent manner; however, no transport activity was observed with the other variants (Gly-482 and Thr-482). It is strongly suggested that the amino acid moiety at the position of 482 is critical for the substrate specificity of ABCG2. 相似文献
943.
Goi T Murakami M Hirono Y Maeda H Ishida M Kimura T Iida A Katayama K Hirose K Yamaguchi A 《Gan to kagaku ryoho. Cancer & chemotherapy》2003,30(12):1989-1991
We report a patient with multiple hepatic metastases from colorectal cancer effectively treated by hepatic arterial infusion therapy (5-FU/LV therapy). The patient was a 55-year-old man with sigmoid colon cancer and multiple hepatic metastases, 5 cm in diameter, in both lobes of the liver. First, we locally controlled the sigmoid colon cancer by sigmoid colectomy (with D3 lymph node dissection). After resection of the primary cancer lesions and dissection of the lymph nodes, we treated the patient by systemically administering 4 courses of Leucovorin/5-FU (once weekly for 6 weeks per course) from a port-catheter system during hospital stay and in the outpatient clinic after hospital discharge. Assessment of therapeutic effects by CT showed CR in the patient. CEA levels, which were abnormal before and after surgery, decreased to normal at the end of chemotherapy. After 1 year, neither CT evidence of tumor enlargement in the liver nor re-increase in CEA levels has been noted. Although the patient experienced side effects such as pigmentation, grade 1 loss of appetite, and leukopenia, he was able to maintain his QOL in the absence of severe side effects. 相似文献
944.
Gotoh Y Saitoh D Ookawara T Oh-ishi S Kizaki T Ohno H Takasu A Sakamoto T Okada Y 《Burns : journal of the International Society for Burn Injuries》2003,29(2):115-122
The aim of this study was to examine the changes in the tissue Cu/Zn- and the Mn-SOD contents and gene expression following mild and severe burns in a rodent burn model. Thirty-eight male Wistar rats, weighing 208-278g, were divided into a sham burn group and two burn groups, with one receiving burns to 35% of the body surface and the other to 60%. Twenty animals of the burn groups were monitored daily for 7 days after injuries to examine survival. Six animals in the sham, 35 or 60% burn group were sacrificed at 3h postburn, and the blood, lungs and kidneys were collected for a biological analysis. The Cu/Zn- and Mn-SOD contents of the tissue and plasma specimens were measured using ELISA. The mRNA expressions of Cu/Zn- and Mn-SOD were determined by a Northern blot analysis. The survival rate of the 60% burn group for 7 days was 30%, whereas the survival rate of the 35% burn group was 100%. The mRNA expressions of Mn-SODs in the lung and the kidney were significantly higher in the 60% burn group than in 35% burn or sham burn group, as was the mRNA expression of lung Cu/Zn-SOD. Nevertheless, the tissue SOD contents in the 60% burn group (mortality 70%) did not exceed those in the 35% group. Based on these findings, tissue SOD synthesis is thus suggested to be inhibited in lethal burns in spite of a strong mRNA expression of SOD. 相似文献
945.
Comparison of HERG channel blocking effects of various beta-blockers-- implication for clinical strategy
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Kawakami K Nagatomo T Abe H Kikuchi K Takemasa H Anson BD Delisle BP January CT Nakashima Y 《British journal of pharmacology》2006,147(6):642-652
beta-Blockers are widely used in the treatment of cardiovascular diseases. However, their effects on HERG channels at comparable conditions remain to be defined. We investigated the direct acute effects of beta-blockers on HERG current and the molecular basis of drug binding to HERG channels with mutations of putative common binding site (Y652A and F656C). beta-Blockers were selected based on the receptor subtype. Wild-type, Y652A and F656C mutants of HERG channel were stably expressed in HEK293 cells, and the current was recorded by using whole-cell patch-clamp technique (23 degrees C). Carvedilol (nonselective), propranolol (nonselective) and ICI 118551 (beta(2)-selective) inhibited HERG current in a concentration-dependent manner (IC(50) 0.51, 3.9 and 9.2 microM, respectively). The IC(50) value for carvedilol was a clinically relevant concentration. High metoprolol (beta(1)-selective) concentrations were required for blockade (IC(50) 145 microM), and atenolol (beta(1)-selective) did not inhibit the HERG current.Inhibition of HERG current by carvedilol, propranolol and ICI 118551 was partially but significantly attenuated in Y652A and F656C mutant channels. Affinities of metoprolol to Y652A and F656C mutant channels were not different compared with the wild-type. HERG current block by all beta-blockers was not frequency-dependent. Drug affinities to HERG channels were different in beta-blockers. Our results provide additional strategies for clinical usage of beta-blockers. Atenolol and metoprolol may be preferable for patients with type 1 and 2 long QT syndrome. Carvedilol has a class III antiarrhythmic effect, which may provide the rationale for a favourable clinical outcome compared with other beta-blockers as suggested in the recent COMET (Carvedilol Or Metoprolol European Trial) substudy. 相似文献
946.
The effects of U-37883A, a vascular ATP-sensitive K(+) channel (K(ATP) channel) blocker, on membrane currents were investigated in pig urethral myocytes by use of patch-clamp techniques (conventional whole-cell recordings, nystatin-perforated patches and cell-attached configuration). Tension measurement was also performed to study the effects of U-37883A on the levcromakalim-induced urethral relaxation and the urethral resting tone in the absence and presence of Bay K 8644. Although cumulative application of U-37883A produced a concentration-dependent inhibitory effect on the levcromakalim-induced urethral relaxation, U-37883A did not abolish the relaxation. In nystatin-perforated patch recording, K(ATP) currents activated by levcromakalim were inhibited by U-37883A in a concentration-dependent manner (K(i), 4.7 microM). Approximately 10% of the K(ATP) currents still remained even in the presence of 300 microM U-37883A. In cell-attached mode, extracellular application of U-37883A (100 microM) irreversibly inhibited the activity of the levcromakalim-induced K(ATP) channels. In whole-cell configuration, U-37883A suppressed the peak amplitude of voltage-dependent Ba(2+) currents in a concentration- and voltage-dependent manner, and at 30 microM, shifted the steady-state inactivation curve of the Ba(2+) currents to the left at -90 mV. These results demonstrate that U-37883A reduces not only the activities of K(ATP) channels but also voltage-dependent Ca(2+) channels. Therefore, it is not appropriate to define U-37883A as solely a vascular K(ATP) channel blocker. 相似文献
947.
Effects of normobaric hyperoxia in a rat model of focal cerebral ischemia-reperfusion. 总被引:2,自引:0,他引:2
Aneesh B Singhal Xiaoying Wang Toshihisa Sumii Tatsuro Mori Eng H Lo 《Journal of cerebral blood flow and metabolism》2002,22(7):861-868
Recent studies suggest that normobaric hyperoxia can be beneficial, if administered during transient stroke. However, increased oxygenation theoretically may increase oxygen free-radical injury, particularly during reperfusion. In the present study, the authors assessed the benefit and risks of hyperoxia during focal cerebral ischemia and reperfusion. Rats were subjected to hyperoxia (Fio2 100%) or normoxia (Fio2 30%) during 2-hour filament occlusion and 1-hour reperfusion of the middle cerebral artery. At 24 hours, the hyperoxia group showed 70% (total) and 92% (cortical) reduction in infarct volumes as compared to the normoxia group. Levels of oxidative stress were evaluated using three indirect methods. First, since oxygen free radicals increase blood-brain barrier (BBB) damage, Evan's blue dye extravasation was quantified to assess BBB damage. Second, the expression of heme oxygenase-1 (HO-1), a heat shock protein inducible by oxidative stress, was assessed using Western blot techniques. Third, an immunoblot technique ("OxyBlot") was used to assess levels of protein carbonyl formation as a marker of oxidative stress-induced protein denaturation. At 24 hours, Evan's blue dye extravasation per average lesion volume was similar between groups. There were no significant differences in HO-1 induction and protein carbonyl formation between groups, in the ipsilateral or contralateral hemispheres, at 6 hours and at 24 hours. These results indicate that hyperoxia treatment during focal cerebral ischemia-reperfusion is neuroprotective, and does not increase oxidative stress. 相似文献
948.
Genital tuberculosis occurring in the spermatic cord is a rare disease. A 70-year-old man presented with a mass on the left side of the scrotum which had been painless and had gradually enlarged over the previous 4 months. Surgical excision was performed. The tumorous mass was located in the spermatic cord but did not connect with the testis or epididymis. The removed specimen was 15 x 20 x 15 mm in size and weighed 6 g. Histopathological diagnosis was tuberculosis. At present, 27 months after surgery, recurrence has not been found. 相似文献
949.
Osteoarthritis (OA) is one of the most common diseases among the elderly. For many years, OA was considered a normal result of the aging process with few treatment options. Remarkable progress in understanding OA cartilage has been achieved in recent years. The application of technical advances to clinical studies of chondrocytes and cartilage tissue metabolism will provide important new insights concerning the pathophysiology of OA and identify new therapeutic strategies to regulate and inhibit the degenerative process of OA. However, many problems remain unresolved. In this review we try to focus on recent advances in the field of cartilage metabolism and molecular markers to facilitate the determination of a patients prognosis and the need for cartilage protective treatment. 相似文献
950.
Runx2 and Runx3 are essential for chondrocyte maturation, and Runx2 regulates limb growth through induction of Indian hedgehog 总被引:9,自引:0,他引:9
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Yoshida CA Yamamoto H Fujita T Furuichi T Ito K Inoue K Yamana K Zanma A Takada K Ito Y Komori T 《Genes & development》2004,18(8):952-963
The differentiation of mesenchymal cells into chondrocytes and chondrocyte proliferation and maturation are fundamental steps in skeletal development. Runx2 is essential for osteoblast differentiation and is involved in chondrocyte maturation. Although chondrocyte maturation is delayed in Runx2-deficient (Runx2(-/-)) mice, terminal differentiation of chondrocytes does occur, indicating that additional factors are involved in chondrocyte maturation. We investigated the involvement of Runx3 in chondrocyte differentiation by generating Runx2-and-Runx3-deficient (Runx2(-/-)3(-/-)) mice. We found that chondrocyte differentiation was inhibited depending on the dosages of Runx2 and Runx3, and Runx2(-/-)3(-/-) mice showed a complete absence of chondrocyte maturation. Further, the length of the limbs was reduced depending on the dosages of Runx2 and Runx3, due to reduced and disorganized chondrocyte proliferation and reduced cell size in the diaphyses. Runx2(-/-)3(-/-) mice did not express Ihh, which regulates chondrocyte proliferation and maturation. Adenoviral introduction of Runx2 in Runx2(-/-) chondrocyte cultures strongly induced Ihh expression. Moreover, Runx2 directly bound to the promoter region of the Ihh gene and strongly induced expression of the reporter gene driven by the Ihh promoter. These findings demonstrate that Runx2 and Runx3 are essential for chondrocyte maturation and that Runx2 regulates limb growth by organizing chondrocyte maturation and proliferation through the induction of Ihh expression. 相似文献