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121.
122.
123.
Prognostic factors of recurrent disease in upper urinary tract urothelial cancer after radical nephroureterectomy: Subanalysis of the multi‐institutional national database of the Japanese Urological Association
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124.
Suguru?Yamashita Kiyoshi?Hasegawa Michiro?Takahashi Junichi?Arita Yoshihiro?Sakamoto Taku?Aoki Yasuhiko?Sugawara Norihiro?KokudoEmail author 《Surgery today》2015,45(4):511-516
Liver resection is recognized as the preferred treatment for patients with colorectal liver metastases (CLM) because it offers long-term survival; it is the only hope for a cure. However, in the majority of cases, liver surgery is contraindicated due to the small volume of the future remnant liver. To extend the surgical indications for CLM, a planned two-stage hepatectomy procedure with portal vein embolization (PVE) was developed specifically for patients with multiple and bilobar CLM. The rationale for performing the procedure was a concern about the possible overgrowth of intrafuture remnant liver lesions following PVE, and it was therefore recommended for all multiple bilobar CLM cases, even when one-stage hepatectomy was technically feasible. We recently performed Hobson’s choice two-stage hepatectomy in two cases for reasons different from those of the original planned two-stage hepatectomy. In the present report, we describe our Hobson’s choice two-stage hepatectomy strategy, which provided favorable short-term outcomes. 相似文献
125.
126.
Takahisa Matsuda Peiyong Zhai Yasuhiro Maejima Chull Hong Shumin Gao Bin Tian Kazumichi Goto Hiromitsu Takagi Mimi Tamamori-Adachi Shigetaka Kitajima Junichi Sadoshima 《Proceedings of the National Academy of Sciences of the United States of America》2008,105(52):20900-20905
Glycogen synthase kinase-3 (GSK-3) is a master regulator of growth and death in cardiac myocytes. GSK-3 is inactivated by hypertrophic stimuli through phosphorylation-dependent and -independent mechanisms. Inactivation of GSK-3 removes the negative constraint of GSK-3 on hypertrophy, thereby stimulating cardiac hypertrophy. N-terminal phosphorylation of the GSK-3 isoforms GSK-3α and GSK-3β by upstream kinases (e.g., Akt) is a major mechanism of GSK-3 inhibition. Nonetheless, its role in mediating cardiac hypertrophy and failure remains to be established. Here we evaluated the role of Serine(S)21 and S9 phosphorylation of GSK-3α and GSK-3β in the regulation of cardiac hypertrophy and function during pressure overload (PO), using GSK-3α S21A knock-in (αKI) and GSK-3β S9A knock-in (βKI) mice. Although inhibition of S9 phosphorylation during PO in the βKI mice attenuated hypertrophy and heart failure (HF), inhibition of S21 phosphorylation in the αKI mice unexpectedly promoted hypertrophy and HF. Inhibition of S21 phosphorylation in GSK-3α, but not of S9 phosphorylation in GSK-3β, caused phosphorylation and down-regulation of G1-cyclins, due to preferential localization of GSK-3α in the nucleus, and suppressed E2F and markers of cell proliferation, including phosphorylated histone H3, under PO, thereby contributing to decreases in the total number of myocytes in the heart. Restoration of the E2F activity by injection of adenovirus harboring cyclin D1 with a nuclear localization signal attenuated HF under PO in the αKI mice. Collectively, our results reveal that whereas S9 phosphorylation of GSK-3β mediates pathological hypertrophy, S21 phosphorylation of GSK-3α plays a compensatory role during PO, in part by alleviating the negative constraint on the cell cycle machinery in cardiac myocytes. 相似文献
127.
Potentiation of the ligand-binding activity of integrin alpha3beta1 via association with tetraspanin CD151 总被引:2,自引:0,他引:2
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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
128.
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
129.
Reconstruction of hepatic stellate cell‐incorporated liver capillary structures in small hepatocyte tri‐culture using microporous membranes
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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
130.
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