実験的内臓型リーシュマニア症に関する研究

学位の種別:課程博士University of Tokyo(東京大学

Thermodynamics of the Schwinger model in a two-dimensional de Sitter space-time

The finite temperature Schwinger model in a background 1-1 de Sitter space is studied. We take account of the curvature effect on the two point Green\u27s function in a short distance. It is shown that the massless and massive boson excitations can not be decoupled and have the interactions through the de Sitter curvature

Morphology Control in Water of Polyion Complex Nanoarchitectures of Double-Hydrophilic Charged Block Copolymers through Composition Tuning and Thermal Treatment

Polyion complexes (PICs) are attractive as eco-friendly materials, because they offer simple and fast preparation methods to exert various functionalities in aqueous medium. However, control of nanoarchitectures in PIC materials has not been fully realized, except for the case of micelles and unilamellar vesicles formed from block ionomers. Here, the procedure to control PIC nanoarchitectures with various morphologies was established for the first time by careful tuning in the composition of PICs made from PEG-based block-ionomers with a varying amount of homoionomers as additive to modulate the PEG weight fraction (<i>f</i>_PEG) in the obtained PICs. Accordingly, the variation in <i>f</i>_PEG from 12.1% to 6.5% induced vigorous transition in the microphase separated structures of PICs basically from micelle to lamella via cylindrical network. Notably, uniformed lamella with alternative layers of PEG and PIC domains was found at elevated temperature (70 °C), which, by lowering temperature, reversibly transformed to cylindrical PIC network apparently with connected aqueous channel in mesoscopic scale

Hemophagocytosis in Experimental Visceral Leishmaniasis by <i>Leishmania donovani</i>

<div><p>Hemophagocytosis is a phenomenon in which macrophages phagocytose blood cells. There are reports on up-regulated hemophagocytosis in patients with infectious diseases including typhoid fever, tuberculosis, influenza and visceral leishmaniasis (VL). However, mechanisms of infection-associated hemophagocytosis remained elusive due to a lack of appropriate animal models. Here, we have established a mouse model of VL with hemophagocytosis. At 24 weeks after infection with 1 x 10⁷ <i>Leishmania donovani</i> promastigotes, BALB/cA mice exhibited splenomegaly with an average tissue weight per body weight of 2.96%. In the tissues, 28.6% of macrophages contained phagocytosed erythrocytes. All of the hemophagocytosing macrophages were parasitized by <i>L</i>. <i>donovani</i>, and higher levels of hemophagocytosis was observed in heavily infected cells. Furthermore, more than half of these hemophagocytes had two or more macrophage-derived nuclei, whereas only 15.0% of splenic macrophages were bi- or multi-nuclear. These results suggest that direct infection by <i>L</i>. <i>donovani</i> causes hyper-activation of host macrophages to engulf blood cells. To our knowledge, this is the first report on hemophagocytosis in experimental <i>Leishmania</i> infections and may be useful for further understanding of the pathogenesis.</p></div

The multinuclear character of hemophagocytes in the spleen of <i>L</i>. <i>donovani</i>-infected mice.

<p>(A) A representative light microscopic image of MGCs engulfing erythrocytes in a thin section of a spleen from <i>L</i>. <i>donovani</i>-infected mice (24 weeks p.i.). Scale bar, 20 μm. (B) Proportion of mononuclear and multinuclear cells in the total macrophage and hemophagocyte only populations.</p

Characterization of heavily infected and multinucleated macrophages by immunohistochemistry.

<p>Sections of the spleen of <i>L</i>. <i>donovani</i>-infected mice at 24 weeks post-infection were stained with anti-F4/80 (A), MOMA-2 (B) or anti-CD11b (C) antibody, followed by counterstain with hematoxylin. Cells in the red pulp with positive signal are shown. Parasites are visualized as blue dots. Scale bars, 20 μm.</p

Heavy infection of hemophagocytes by <i>Leishmania</i> parasites.

<p>The number of amastigotes per macrophage/hemophagocyte in the spleen of <i>L</i>. <i>donovani</i>-infected mice was analyzed by microscopy of HE-stained tissue sections. Host cells were categorized, based on the number of parasites per cell, into the groups none (0 amastigotes), low (1–10 amastigotes), moderate (11–20 amastigotes) and high (more than 20 amastigotes). The graph shows percentages of cells with no, low, moderate and high infection in either total macrophages or hemophagocytes only.</p

Hemophagocytosis in the spleen of <i>L</i>. <i>donovani</i>-infected mice.

<p>(A, B) Low magnification images of HE-stained sections of the red pulp of spleens from naïve (A) or <i>L</i>. <i>donovani</i>-infected mice (B). Hemophagocytes engulfing multiple erythrocytes (arrows) were found in the spleen of the infected mice, whereas such cells were not found in naïve mice. (C) A high magnification image of an HE-stained section of the spleen from infected mice. <i>L</i>. <i>donovani</i> amastigotes (arrowheads) were often found in hemophagocytes. Scale bars, 20 μm.</p