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ABSTRACT: The pulsed electron electron double resonance (PELDOR) pulse sequence is applied to a three-spin system consisting of three
radicals (YD·, YZ· and QA−) generated in spinach PS II. The distance between YZ and QA has been determined to be 3.4 nm with the previously derived distances of the other radical pairs, 2.9 nm for YD·-YZ· and 3.9 nm for YD·-QA−. This distance has been derived from the YZ·-QA− radical pair trapped in YD-less mutants ofChlamydomonas reinhardtii. Furthermore the method was applied to the YD·-QA−-ChlZ+ system to find the unknown distance between QA and ChlZ. The derived distance was 3.4 nm. A triangular configuration was found in the membrane system that gives the relative positions
of the electron transfer components.
Applied Magnetic Resonance 04/2012; 23(3):557-569. · 0.75 Impact Factor
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K Narumi,
T Udagawa,
A Kondoh,
A Kobayashi, H Hara,
Y Ikarashi,
S Ohnami,
F Takeshita,
T Ochiya,
T Okada,
M Yamagishi,
T Yoshida,
K Aoki
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ABSTRACT: T cells recognize tumor-associated antigens under the condition of lymphopenia-induced homeostatic proliferation (HP); however, HP-driven antitumor responses gradually decay in association with tumor growth. Type I interferon (IFN) has important roles in regulating the innate and adaptive immune system. In this study we examined whether a tumor-specific immune response induced by IFN-α could enhance and sustain HP-induced antitumor immunity. An intratumoral IFN-α gene transfer resulted in marked tumor suppression when administered in the early period of syngeneic hematopoietic stem cell transplantation (synHSCT), and was evident even in distant tumors that were not transduced with the IFN-α vector. The intratumoral delivery of the IFN-α gene promoted the maturation of CD11c(+) cells in the tumors and effectively augmented the antigen-presentation capacity of the cells. An analysis of the cytokine profile showed that the CD11c(+) cells in the treated tumors secreted a large amount of immune-stimulatory cytokines including interleukin (IL)-6. The CD11c(+) cells rescued effector T-cell proliferation from regulatory T-cell-mediated suppression, and IL-6 may have a dominant role in this phenomenon. The intratumoral IFN-α gene transfer creates an environment strongly supporting the enhancement of antitumor immunity in reconstituted lymphopenic recipients through the induction of tumor-specific immunity and suppression of immunotolerance.
Gene therapy 05/2011; 19(1):34-48. · 4.75 Impact Factor
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ABSTRACT: A conditionally replicative adenovirus is a novel anticancer agent designed to replicate selectively in tumor cells. However, a leak of the virus into systemic circulation from the tumors often causes ectopic infection of various organs. Therefore, suppression of naive viral tropism and addition of tumor-targeting potential are necessary to secure patient safety and increase the therapeutic effect of an oncolytic adenovirus in the clinical setting. We have recently developed a direct selection method of targeted vector from a random peptide library displayed on an adenoviral fiber knob to overcome the limitation that many cell type-specific ligands for targeted adenovirus vectors are not known. Here we examined whether the addition of a tumor-targeting ligand to a replication-competent adenovirus ablated for naive tropism enhances its therapeutic index. First, a peptide-display adenovirus library was screened on a pancreatic cancer cell line (AsPC-1), and particular peptide sequences were selected. The replication-competent adenovirus displaying the selected ligand (AdDeltaCAR-SYE) showed higher oncolytic potency in several other pancreatic cancer cell lines as well as AsPC-1 compared with the untargeted adenovirus (AdDeltaCAR). An intratumoral injection of AdDeltaCAR-SYE significantly suppressed the growth of AsPC-1 subcutaneous tumors, and an analysis of adenovirus titer in the tumors revealed an effective replication of the virus in the tumors. Ectopic liver gene transduction following the intratumoral injection of AdDeltaCAR-SYE was not increased compared with the AdDeltaCAR. The results showed that a tumor-targeting strategy using an adenovirus library is promising for optimizing the safety and efficacy of oncolytic adenovirus therapy.
Gene therapy 03/2009; 16(5):669-80. · 4.75 Impact Factor
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ABSTRACT: To evaluate the thrombin-inhibitors (OM-inhibitors) synthetized by the authors, their actions in vitro and in vivo have been investigated. Results obtained are summarized as follows: 1.(i) The inhibitory action of the OM-inhibitor (OM-205) is highly selective to thrombin when compared with trypsin, plasmin or reptilase.2.(ii) The mode of inhibition of the OM-inhibitor (OM-46) to thrombin is competitive in the hydrolysis of Nα-benzoyl-DL-arginine p-nitroanilide.3.(iii) The decreasing effects of thrombin infusion in rabbits on plasma fibrinogen content and platelets in number are remarkably blocked by the presence of the OM-inhibitor (OM-189) in the blood, which suggests that the OM-inhibitors, very effective in vitro, possess the anti-thrombin activity also in vivo.
Thrombosis Research.
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ABSTRACT: Out-of-phase electron spin echo and free induction decay after selective excitation were studied for a spin-correlated radical pair P700+A1− in the PSI photosynthetic reaction center. Spin relaxation between the pair sublevels at the initial delays after laser flash was found to be much faster than at the longer delays. This initial fast relaxation in combination with chemical decay of the pair results in inversion of sublevel populations. Temperature dependence of this relaxation is much weaker than that for `normal' spin–lattice relaxation.
Chemical Physics Letters.
