98 research outputs found

    「あを本」の青の色々

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    中野三敏教授退官記念

    Development of Kupffer cell targeting type-I interferon for the treatment of hepatitis via inducing anti-inflammatory and immunomodulatory actions

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    Because of its multifaceted anti-inflammatory and immunomodulatory effects, delivering type-I interferon to Kupffer cells has the potential to function as a novel type of therapy for the treatment of various types of hepatitis. We report herein on the preparation of a Kupffer cell targeting type-I interferon, an albumin-IFNα2b fusion protein that contains highly mannosylated N-linked oligosaccharide chains, Man-HSA(D494N)-IFNα2b, attached by combining albumin fusion technology and site-directed mutagenesis. The presence of this unique oligosaccharide permits the protein to be efficiently, rapidly and preferentially distributed to Kupffer cells. Likewise IFNα2b, Man-HSA(D494N)-IFNα2b caused a significant induction in the mRNA levels of IL-10, IL-1Ra, PD-L1 in RAW264.7 cells and mouse isolated Kupffer cells, and these inductions were largely inhibited by blocking the interferon receptor. These data indicate that Man-HSA(D494N)-IFNα2b retained the biological activities of type-I interferon. Man-HSA(D494N)-IFNα2b significantly inhibited liver injury in Concanavalin A (Con-A)-induced hepatitis model mice, and consequently improved their survival rate. Moreover, the post-administration of Man-HSA(D494N)-IFNα2b at 2 h after the Con-A challenge also exerted hepato-protective effects. In conclusion, this proof-of-concept study demonstrates the therapeutic effectiveness and utility of Kupffer cell targeting type-I interferon against hepatitis via its anti-inflammatory and immunomodulatory actions

    EOSINOPHILS OF OVINE PERIPHERAL BLOOD IN ELECTRON MICROSCOPY

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    The fine structures of the eosinophils of the peripheral blood obtained from 5 clinically normal sheep were examined under an electron microscope. The results thus obtained were summarized as follows : 1) The cells with nuclei of two to four lobes were most commonly observed on the cut planes. 2) The nuclear lobes of the cells showed a clear maculous appearance with two distinct densities, one light and the other dark, according to the amount of the chromatin condensation. 3) On the basis of the internal structures of the specific granules, they were classified into six types and the basic type of the granules seemed to be those containing middle plates. 4) A small number of mitochondria measuring 0.3 by 0.7μ on the average, Golgi complex, a number of smooth- and a few rough-surfaced endoplasmic reticulum, and some other micro-organelles were observed in the cytoplasm

    NEUTROPHILS OF OVINE PERIPHERAL BLOOD IN ELECTRON MICROSCOPY

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    Fine structures of the neutrophils obtained by hemolytic method from the peripheral blood of 5 clinically normal sheep were examined by an electron microscope. The results thus obtained were summarized as follows. 1) The nuclei of the cells showed one to several nuclear lobes, and the nuclei with 2 to 4 nuclear lobes were observed most commonly. 2) The nuclear lobes of the cells showed a clear maculous appearance with two distinct densities, one light and the other dark, according to the amount of the chromatin condensation. 3) The specific granules were classified into two types on the basis of their electron density, the one with high density and the other with less density. 4) Most of the specific granules had the homogeneous interior without any internal structures. However, some of them had internal structures such as a middle plate-like substance, round defects with or without vacancy, sacs with small vesicles and clear spaces between the membrane and matrix of the granules. 5) A small number of mitochondria measuring 0.3 by 0.7μ on the average, Golgi complex, a number of smooth-surfaced and a few rough-surfaced endoplasmic reticulum, and a few large round or oval bodies supposed to be lysosome were observed in the cytoplasm
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