振動流中に置かれた様々な断面形状の物体周りの流れ特性に関する研究

取得学位：博士(工学)，学位授与番号：博甲第413号，学位授与年月日：平成13年3月22日,学位授与年：200

A Field Study of Telemetry-Recording of The Body Temperature in Wild Mongolian Pikas

The pika inhabiting in cold zone or in high mountains is thought to be adapted to cold as well as high-altitude environment. We have reported pika\u27s high body temperature (39.6℃), high metabolism and poor heat loss ability such as poor panting, small ear pinnae and lack of thermal salivation. In this study, we measured the body temperature of wild pikas (Ochotona daurica) with a telemetry device in their natural burrows in Mongolia. Two pikas captured at Undur Dov were implanted with transmitters in the abdominal cavity under anesthesia, and were returned to the own habitat. The mean body temperatures of the pikas were 39.65℃ and 39.96℃ though the data were limited to a short period of less than one day. The present results in wild pikas support pika\u27s high body temperature in our previous studies

TAK1 inhibition in myeloma

Along with the tumor progression, the bone marrow microenvironment is skewed in multiple myeloma (MM), which underlies the unique pathophysiology of MM and confers aggressiveness and drug resistance in MM cells. TGF-β-activated kinase-1 (TAK1) mediates a wide range of intracellular signaling pathways. We demonstrate here that TAK1 is constitutively overexpressed and phosphorylated in MM cells, and that TAK1 inhibition suppresses the activation of NF-κB, p38MAPK, ERK and STAT3 in order to decrease the expression of critical mediators for MM growth and survival, including PIM2, MYC, Mcl-1, IRF4, and Sp1, along with a substantial reduction in the angiogenic factor VEGF in MM cells. Intriguingly, TAK1 phosphorylation was also induced along with upregulation of vascular cell adhesion molecule-1 (VCAM-1) in bone marrow stromal cells (BMSC) in cocultures with MM cells, which facilitated MM cell-BMSC adhesion while inducing IL-6 production and receptor activator of nuclear factor κ-Β ligand (RANKL) expression by BMSC. TAK1 inhibition effectively impaired MM cell adhesion to BMSC to disrupt the support of MM cell growth and survival by BMSC. Furthermore, TAK1 inhibition suppressed osteoclastogenesis enhanced by RANKL in cocultures of bone marrow cells with MM cells, and restored osteoblastic differentiation suppressed by MM cells or inhibitory factors for osteoblastogenesis overproduced in MM. Finally, treatment with the TAK1 inhibitor LLZ1640-2 markedly suppressed MM tumor growth and prevented bone destruction and loss in mouse MM models. Therefore, TAK1 inhibition may be a promising therapeutic option targeting not only MM cells but also the skewed bone marrow microenvironment in MM

Menadione 処理した Candida albicans ROS 生産機構の解析

Menadione shows anti Condida activity by promoting ROS production. However, the ROS production mechanism has not been clarifield. Thus, in this study, we studied thr relation between anti Candida activity of menadione and ROS production. Menadione inhibited the growth of C. albicans BWP17 strain, the growth of C. albicans JM02 strain was not inhibited. ROS production in C. albicans BWP17 strain was enhanced by addition of menadione. The ROS production in C. albicans JM02 strain was also enhanced by menadione, however, the amount of ROS was lower than that in menadione untreated C. albicans BWP17 strain. NDH51 is 51-kDa subunit of NADH dehydrogenase complex I, and C. albicans JM02 strain is deficient in NDH51 strain. Rotenone, an NADH dehydrogenase complex I inhibitor, decreased the menadione sensitivity of the C. albicans BWP17 strain, indicating that NDH51 related to the menadione sensitivity of C. albicans. The expression of NDH51 mRNA was increased by menadione in C. albicans BWP17 strain. These results indicated that menadion inhibited the growthe of C. albicans by stimulating the ROS production system though activation of NDH51 in C. albicans

N-アセチルノイラミン酸によるCandida albicans形態変化の制御について

Candida albicans is a dimorphic fungus and generally grows in hyphal form in RPMI1640 medium. However, addition of N-acetylneuraminic acid inhibited the hyphal growth. The expression of CGR1 mRNA in C. albicans was inhibited by addition of N-acetylneuraminic acid. Diltiazem, a calcium channel blocker, inhibited the yeast to hyphal transformation in C. albicans as well as addition of N-acetylneuraminic acid. These results indicated that inhibition of hyphal growth of C. albicans by N-acetylneuraminic acid was mediated by interruption of CGR1 mRNA expression

菌密度変化に伴うCandida albicansの増殖時形態変化メカニズムの解析

Candida albicans generally grows in hyphal form in RPMI-1640 medium. However, transformation of hyphal form to yeast form is observed by increasing of the cell density in RPMI-1640 medium. Intracellular Ca^ was increased in yeast growth condition (high cell density condition) compared with that of hyphal growth condition. The expression of CGR1 mRNA was inhibited in the yeast growth condition. These results indicated that the transformation of C. albicans was mediated by Ca^-dependent stimulation system, and the system was regulated by CGR1 expression

pH変化によるCandida albicans形態変化シグナルの解析

Candida albicans generally grows in hyphal form in RPMI-1640 medium. However, transformation of hyphal form to yeast form is inhibited by declining pH in RPMI-1640 medium and low pH enhance the yeast like forming. The expressions of RAS1, EFG1, ALS1 and CYR1 mRNA in low pH conditions are significantly decreased compared with that of neutral pH conditions. These results suggested that the transformation of C. albicans may be regulated by pH-dependent stimulation system, and the system was regulated by RAS1 expression

Trends in hepatocellular carcinoma incident cases in Japan between 1996 and 2019

We examined the epidemiological trends, including the distribution of sex, age, and disease etiology, in HCC incident cases, over 24 years. Data of 20,547 HCC patients (1996–2019) were analyzed in this prospective study. We divided the study period into four 6-yearly quarters. HCC etiology was categorized as hepatitis B virus (HBV) infection, HBV + hepatitis C virus (HCV) infection, HCV infection, and both negative (non-BC). The incident cases of HCC per quarter of the study period were 4311 (21.0%), 5505 (26.8%), 5776 (28.1%), and 4955 (24.1%), sequentially. Overall, 14,020 (68.2%) patients were male. The number of HCC cases in patients < 60 years, 60–69 years, 70–79 years, and ≥ 80 years were 3711 (18.1%), 6652 (32.4%), 7448 (36.2%), and 2736 (13.3%), respectively. The average age of newly-diagnosed patients increased in each quarter. HCC was associated with HBV, HBV + HCV, and HCV infections and non-BC in 2997 (14.6%), 187 (0.9%), and 12,019 (58.5%), and 5344 (26.0%) cases, respectively. The number of HCV-associated cases decreased in each quarter, while that of non-BC-associated cases increased. HCC incident cases tend to increase in the elderly and in non-BC patients; in contrast, HCC incident cases due to HCV tend to decrease