ヒト肺動脈血管内皮細胞障害における好中球エラスターゼの役割

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Establishment and evaluation of the suspension culture system for umbilical cord- derived mesenchymal stromal cells

Mesenchymal stromal cells (MSCs) derived from various tissues including bone marrow, adipose and umbilical cord tissues have been shown to modulate aberrantly activated immune system. With the features, MSC-based therapies targeting graft-versus-host disease (GvHD) by the administration of bone marrow-derived MSCs (BM-MSCs) have been available in some countries including Japan, and the expectations for the stable and cost effective supply system are getting higher and higher recently. However, the conventional culture systems which usually use plastic flask or multi-chamber equipment require space and manpower, thus the maximal expansion of MSCs at one production is likely to be limited. To compensate the limitation, repetitive productions have been unavoidable, and higher the production cost. Here, we introduced a new suspension-culture system, using micro-carriers and single-use-bioreactors, for the preparation of MSCs in anticipation of establishment of mass production system. Since the umbilical cord (UC) tissues can be collected through noninvasive procedure, and UC-derived MSCs (UC-MSCs) are shown to present higher proliferation rate and lower immunogenicity in comparison with BM-MSCs, we evaluated the potential and the versatility of UC-MSCs for the treatment of several diseases including GvHD. Results from several in vitro assays demonstrated that our new culture system maintains major key characteristics of MSCs, such as adhesiveness to cell culture surface, the expression of cell surface markers, differentiation capacities toward osteoblasts, chondroblasts, and adipocytes, and immunosuppressive effects on activated T cells. We are currently investigating cellular profiles and characteristics which are specific to the cells prepared in our suspension-culture system through meta-analysis. The established suspension-culture system is presumed to attain the mass production of UC-MSCs, contributing to lower the cost and also providing possible applications for MSCs from other origins

Precise Measurement of IMD Behavior in 5-GHz HTS Resonators and Evaluation of Nonlinear Microwave Characteristics

The intermodulation distortion (IMD) of a 5-GHz HTS resonator is precisely measured and a nonlinear analysis is conducted. When designing a radio communication system that uses an HTS microwave device, the device's IMD characteristic is one of the most important problems that must be quantitatively evaluated. The amplitudes of third-order IMD (IMD3) and higher-order IMD, which are generated in an HTS resonator given a two-tone fundamental signal, are measured in detail using a fundamental signal cancellation circuit. Moreover, the relative phase of IMD3 is obtained by using a novel measurement system constructed around a reference IMD3 generator. The measured IMD3 phase shows a drastic change in a relatively low IMD3 amplitude region. In addition, the measured resonator exhibits strong higher-order IMD. A nonlinear evaluation using complex power series representation confirms that the drastic phase change may be due to the higher-order distortions present in IMD3

Activation of caspase-3-like protease by digitonin-treated lysosomes

AbstractApoptosis, a naturally occurring programmed cell death or cell `suicide', has been paid much attention as one of the critical mechanisms for morphogenesis and tissue remodeling. Activation of cysteine aspartases (caspases) is one of the critical steps leading to apoptosis. Although a mitochondria-mediated pathway has been postulated to be one of the activation mechanism of caspase-3, another subcellular compartment might be involved in the activation of the enzyme. The present study shows that the supernatant fraction of digitonin-treated lysosomes strongly activates Ac-DEVD-CHO inhibitable caspase-3-like protease. Activation of caspase-3-like protease by digitonin-treated lysosomal fractions was specifically suppressed by leupeptin and E-64, inhibitors of cysteine protease. These results indicate that leakage of lysosomal cysteine protease(s) into the cytosolic compartment might be involved in the activation of caspase-3-like protease