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91.
Potentiation of the ligand-binding activity of integrin alpha3beta1 via association with tetraspanin CD151 总被引:2,自引:0,他引:2 下载免费PDF全文
Nishiuchi R Sanzen N Nada S Sumida Y Wada Y Okada M Takagi J Hasegawa H Sekiguchi K 《Proceedings of the National Academy of Sciences of the United States of America》2005,102(6):1939-1944
CD151, one of the tetraspanins, forms a stable complex with integrin alpha3beta1, the major laminin receptor on the cell surface. We found that 8C3, an anti-CD151 mAb obtained by screening for reactivity with integrin alpha3beta1-CD151 complexes, was capable of dissociating CD151 from integrin alpha3beta1, thereby allowing us to deplete CD151 from purified integrin alpha3beta1-CD151 complexes. The CD151-free integrin alpha3beta1 thus obtained showed a significant reduction in its ability to bind to laminin-10/11, a high-affinity ligand for integrin alpha3beta1, with a concomitant reduction in its reactivity with mAb AG89, which recognizes activated beta1-containing integrins. These results raised the possibility that the association of integrin alpha3beta1 with CD151 potentiates the ligand-binding activity of the integrin through sustaining its activated conformation. In support of this possibility, the ligand-binding activity was restored when CD151-free integrin alpha3beta1 was reassociated with purified CD151. 8C3-induced dissociation of CD151 from integrin alpha3beta1 was also demonstrated on the surface of living cells by fluorescent resonance energy transfer imaging, accompanied by a concomitant reduction in the cell adhesion to laminin-10/11-coated substrates. CD151 knock-down by RNA interference also resulted in a reduction in the adhesive activity of the cells. Taken together, these results indicate that CD151 association modulates the ligand-binding activity of integrin alpha3beta1 through stabilizing its activated conformation not only with purified proteins but also in a physiological context. 相似文献
92.
Treatment of rheumatoid arthritis with humanized anti-interleukin-6 receptor antibody: a multicenter, double-blind, placebo-controlled trial 总被引:25,自引:0,他引:25
Nishimoto N Yoshizaki K Miyasaka N Yamamoto K Kawai S Takeuchi T Hashimoto J Azuma J Kishimoto T 《Arthritis and rheumatism》2004,50(6):1761-1769
OBJECTIVE: Interleukin-6 (IL-6) is a pleiotropic cytokine that regulates the immune response, inflammation, and hematopoiesis. Overproduction of IL-6 plays pathologic roles in rheumatoid arthritis (RA), and the blockade of IL-6 may be therapeutically effective for the disease. This study was undertaken to evaluate the safety and efficacy of a humanized anti-IL-6 receptor antibody, MRA, in patients with RA. METHODS: In a multicenter, double-blind, placebo-controlled trial, 164 patients with refractory RA were randomized to receive either MRA (4 mg/kg body weight or 8 mg/kg body weight) or placebo. MRA was administered intravenously every 4 weeks for a total of 3 months. The clinical responses were measured using the American College of Rheumatology (ACR) criteria. RESULTS: Treatment with MRA reduced disease activity in a dose-dependent manner. At 3 months, 78% of patients in the 8-mg group, 57% in the 4-mg group, and 11% in the placebo group achieved at least a 20% improvement in disease activity according to the ACR criteria (an ACR20 response) (P < 0.001 for 8-mg group versus placebo). Forty percent of patients in the 8-mg group and 1.9% in the placebo group achieved an ACR50 response (P < 0.001). The overall incidences of adverse events were 56%, 59%, and 51% in the placebo, 4-mg, and 8-mg groups, respectively, and the adverse events were not dose dependent. A blood cholesterol increase was observed in 44.0% of the patients. Liver function disorders and decreases in white blood cell counts were also observed, but these were mild and transient. There was no increase in antinuclear antibodies or anti-DNA antibodies. Anti-MRA antibodies were detected in 2 patients. CONCLUSION: Treatment with MRA was generally well tolerated and significantly reduced the disease activity of RA. 相似文献
93.
Reconstruction of hepatic stellate cell‐incorporated liver capillary structures in small hepatocyte tri‐culture using microporous membranes 下载免费PDF全文
Junichi Kasuya Ryo Sudo Genta Masuda Toshihiro Mitaka Mariko Ikeda Kazuo Tanishita 《Journal of tissue engineering and regenerative medicine》2015,9(3):247-256
In liver sinusoids, hepatic stellate cells (HSCs) locate the outer surface of microvessels to form a functional unit with endothelia and hepatocytes. To reconstruct functional liver tissue in vitro, formation of the HSC‐incorporated sinusoidal structure is essential. We previously demonstrated capillary formation of endothelial cells (ECs) in tri‐culture, where a polyethylene terephthalate (PET) microporous membrane was intercalated between the ECs and hepatic organoids composed of small hepatocytes (SHs), i.e. hepatic progenitor cells, and HSCs. However, the high thickness and low porosity of the membranes limited heterotypic cell–cell interactions, which are essential to form HSC–EC hybrid structures. Here, we focused on the effective use of the thin and highly porous poly( d , l ‐lactide‐co‐glycolide) (PLGA) microporous membranes in SH–HSC–EC tri‐culture to reconstruct the HSC‐incorporated liver capillary structures in vitro. First, the formation of EC capillary‐like structures was induced on Matrigel‐coated PLGA microporous membranes. Next, the membranes were stacked on hepatic organoids composed of small SHs and HSCs. When the pore size and porosity of the membranes were optimized, HSCs selectively migrated to the EC capillary‐like structures. This process was mediated in part by platelet‐derived growth factor (PDGF) signalling. In addition, the HSCs were located along the outer surface of the EC capillary‐like structures with their long cytoplasmic processes. In the HSC‐incorporated capillary tissues, SHs acquired high levels of differentiated functions, compared to those without ECs. This model will provide a basis for the construction of functional, thick, vascularized liver tissues in vitro. Copyright © 2012 John Wiley & Sons, Ltd. 相似文献
94.
Keisuke Itotani Masahito Murakami Motoko Itotani Atsushi Nagai Yuzo Imabori Kazuyuki Fujimoto Mamoru Tanaka Junichi Kato 《Journal of Physical Therapy Science》2015,27(2):321-323
[Purpose] This study investigated the association between the weight-bearing ratio (WBR)
and gait ability of a paretic lower limb while walking using a shoe-type load-measuring
apparatus. [Subjects] The Subjects comprised 17 stroke patients who were classified into
the following two groups: the independent walking group, and the non-independent walking
group. [Methods] The 10-m walking time (inside and outside parallel bars) and the Berg
Balance Scale (BBS) were measured. The WBR of the paretic lower limb was measured during
static standing and while walking inside and outside parallel bars, and the coefficient of
variation (CV) was calculated. WBR was evaluated using the Step Aid. [Results] The BBS and
WBR were significantly decreased in the non-independent walking group, while the 10-m
walking time and the CV were significantly increased in the non-independent walking group.
[Conclusion] The CV and WBR of a paretic lower limb while walking appear to be important
indices of achievement of independent gait in hemiplegic stroke patients, and they may be
used in gait rehabilitation for diseases requiring weight-bearing training to follow the
course of training using a shoe-type load-measuring apparatus.Key words: Stroke, Weight-bearing ratio, Shoe-type load-measuring apparatus 相似文献
95.
Development and internal validation of a nomogram for predicting stone‐free status after flexible ureteroscopy for renal stones 下载免费PDF全文
96.
Reconstruction of bilateral branch pulmonary artery stenosis caused by Takayasu's aortitis. 总被引:1,自引:0,他引:1
Hiroo Shikata Shigeru Sakamoto Yoshimichi Ueda Shuji Tsuchishima Toshiaki Matsubara Hisateru Nishizawa Shinji Shono Masahiro Kanno Takashi Shimizu Junichi Matsubara 《Circulation journal》2004,68(8):791-794
A 63 year-old female presented with dyspnea on exertion. Her chest X-ray showed cardiomegaly, and right ventricular overload and tricuspid regurgitation were detected. Her pulmonary ventilation and blood flow scintigraphy findings were suspicious of pulmonary vascular disease; the diagnosis was pulmonary hypertension and bilateral branch pulmonary artery stenosis. After the inflammation settled, the stenotic bilateral branch pulmonary artery was reconstructed with a prosthetic vessel and the pulmonary pressure normalized immediately. A resected specimen revealed that the stenotic changes were from Takayasu's disease. The patient's postoperative course was uneventful, and pulmonary ventilation and blood scintigraphy returned to an almost normal range. At follow-up 5 years and 6 months after the operation, there was no evidence of pulmonary artery disease (eg, stenosis and/or ischemia) or of any change in the central vessels of the retina, the so-called Takayasu's retinopathy. 相似文献
97.
Liu H Hanawa H Yoshida T Elnaggar R Hayashi M Watanabe R Toba K Yoshida K Chang H Okura Y Kato K Kodama M Maruyama H Miyazaki J Nakazawa M Aizawa Y 《Circulation》2005,111(13):1593-1600
98.
99.
Yoshiji H Kuriyama S Noguchi R Yoshii J Ikenaka Y Yanase K Namisaki T Kitade M Yamazaki M Masaki T Fukui H 《Journal of hepatology》2005,42(5):687-693
BACKGROUND/AIMS: Chemoprevention should be a promising approach to improve the prognosis of the patients with hepatocellular carcinoma (HCC). Angiogenesis is now recognized as a crucial step not only in tumor growth, but also in early carcinogenesis. The aim of this study was to elucidate the combination effect of the clinically used vitamin K(2) (VK) and the angiotensin-converting enzyme inhibitor, perindopril (PE), on hepatocarcinogenesis, especially in conjunction with angiogenesis. METHODS: In a diethylnitrosamine-induced rat hepatocarcinogenesis model, the effects of VK and PE on the development of liver enzyme-altered preneoplastic lesions and angiogenesis were examined. RESULTS: Treatment with both VK and PE markedly inhibited the development of preneoplastic lesions in association with suppression of neovascularization in the liver. The combination treatment with VK and PE exerted a more potent inhibitory effect as compared with the single agent treatments. The in vitro study demonstrated that VK and PE inhibited the endothelial cell (EC) tubular formation. VK also suppressed the EC proliferation in a dose-dependent manner. CONCLUSIONS: The combination of VK and PE exerted a chemopreventive effect against rat liver carcinogenesis via suppression of angiogenesis. Since both agents are widely used in the clinical practice, this combination therapy may represent a potential new strategy for chemoprevention against HCC in the future. 相似文献
100.
Washio M Saitoh S Arai Y Takagi S Oonishi H Isobe T Takeuchi H Oohata J Mori M Shimamoto K 《Nihon Ronen Igakkai zasshi. Japanese journal of geriatrics》2005,42(2):221-228
OBJECTIVE: The present study was conducted in order to investigate risk factors for heavy burden of family caregivers. STUDY DESIGN: Cross-sectional study. PARTICIPANTS: 51 pairs of the frail elderly and their family caregivers in one town in Hokkaido. RESULTS: Compared to those with a lighter burden, family caregivers with heavier burden looked after the frail elderly with more behavior disturbances due to dementia. They cared for the elderly longer and had less time to go out without accompanying their charges than less burdened caregivers. On the other hand, the elderly had similar activities of daily living and degree of need of care between the two groups. In addition, physical caring time did not differ between the two groups. These findings suggest that the psychological burden may be more important than the physical burden. In addition, caregivers used only 30-40% of services they had the right to use with long-term care insurance. These findings suggest that more convenient services for users should be provided. 相似文献