155 research outputs found

    Kinetic analysis of thyroxine outside thyroid with 131-I-tyroxine by aid of computer--with special reference to liver diseases

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    By assuming a three-compartment model, kinetic analysis of peripheral hyroxine distributions in various organs was represented by the alues calculated on the basis of the disappearance curve of 131I-T4 radioactivity in the serum, time&#12288;dependent curve of radioactivity over the liver&#12288;and urinary excretion of 131I-T4 in attempts to clarify the kinetic distribution&#12288;of the thyroxine and the time&#12288;dependent pool size of thyroxine in each&#12288;compartment such as serum pool, liver pool, and the other pool,&#12288;As a result it has been demonstrated that pool size3 of tyroxine, in the serum, liver and the other pool are enlarged in&#12288;hyperthyroidism, while&#12288;they are decreased in&#12288;hypothyroidism in respective pools.&#12288;We have recognized the reduction in the values of the liver pool size&#12288;of 131I-thyroxine and 131I-thyroxine excretion into the bile, while the increase&#12288;of 131I-thyroxine excretion into the urine in the cases of chronic hepatitis&#12288;and cirrhosis of the liver, but the thyroxine concentration in the serum to remain within the normal level in liver diseases. As a result of the reduction&#12288;in the liver pool size of 131I-thyroxine and in its uptake into the liver,&#12288;the other pool size enlarges to compensate the reduction and the function of the other pool is elevated.</p

    Borehole Observatory System Installed in Tohoku Earthquake Zone with the Deep-sea Drilling Vessel Chikyu

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    日本船舶海洋工学会平成24年春季講演会(講演番号: OS3-2, 2012年5月17日~18日, 神戸市産業振興センター)にて講演 / 論文番号: 2012S-OS3-

    「ちきゅう」の新しい水中テレビシステム

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    「ちきゅう」では、水深3000m以深での掘削や観測装置設置オペレーションで使用する、水中テレビシステムを装備している。本稿では、新たに搭載された水中テレビシステムを、旧来のものと比較しつつ紹介する。海洋理工学会平成28年度春季大会(2016年5月26日~27日, 東京海洋大学品川キャンパス

    The whole blood transcriptional regulation landscape in 465 COVID-19 infected samples from Japan COVID-19 Task Force

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    「コロナ制圧タスクフォース」COVID-19患者由来の血液細胞における遺伝子発現の網羅的解析 --重症度に応じた遺伝子発現の変化には、ヒトゲノム配列の個人差が影響する--. 京都大学プレスリリース. 2022-08-23.Coronavirus disease 2019 (COVID-19) is a recently-emerged infectious disease that has caused millions of deaths, where comprehensive understanding of disease mechanisms is still unestablished. In particular, studies of gene expression dynamics and regulation landscape in COVID-19 infected individuals are limited. Here, we report on a thorough analysis of whole blood RNA-seq data from 465 genotyped samples from the Japan COVID-19 Task Force, including 359 severe and 106 non-severe COVID-19 cases. We discover 1169 putative causal expression quantitative trait loci (eQTLs) including 34 possible colocalizations with biobank fine-mapping results of hematopoietic traits in a Japanese population, 1549 putative causal splice QTLs (sQTLs; e.g. two independent sQTLs at TOR1AIP1), as well as biologically interpretable trans-eQTL examples (e.g., REST and STING1), all fine-mapped at single variant resolution. We perform differential gene expression analysis to elucidate 198 genes with increased expression in severe COVID-19 cases and enriched for innate immune-related functions. Finally, we evaluate the limited but non-zero effect of COVID-19 phenotype on eQTL discovery, and highlight the presence of COVID-19 severity-interaction eQTLs (ieQTLs; e.g., CLEC4C and MYBL2). Our study provides a comprehensive catalog of whole blood regulatory variants in Japanese, as well as a reference for transcriptional landscapes in response to COVID-19 infection

    DOCK2 is involved in the host genetics and biology of severe COVID-19

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    「コロナ制圧タスクフォース」COVID-19疾患感受性遺伝子DOCK2の重症化機序を解明 --アジア最大のバイオレポジトリーでCOVID-19の治療標的を発見--. 京都大学プレスリリース. 2022-08-10.Identifying the host genetic factors underlying severe COVID-19 is an emerging challenge. Here we conducted a genome-wide association study (GWAS) involving 2, 393 cases of COVID-19 in a cohort of Japanese individuals collected during the initial waves of the pandemic, with 3, 289 unaffected controls. We identified a variant on chromosome 5 at 5q35 (rs60200309-A), close to the dedicator of cytokinesis 2 gene (DOCK2), which was associated with severe COVID-19 in patients less than 65 years of age. This risk allele was prevalent in East Asian individuals but rare in Europeans, highlighting the value of genome-wide association studies in non-European populations. RNA-sequencing analysis of 473 bulk peripheral blood samples identified decreased expression of DOCK2 associated with the risk allele in these younger patients. DOCK2 expression was suppressed in patients with severe cases of COVID-19. Single-cell RNA-sequencing analysis (n = 61 individuals) identified cell-type-specific downregulation of DOCK2 and a COVID-19-specific decreasing effect of the risk allele on DOCK2 expression in non-classical monocytes. Immunohistochemistry of lung specimens from patients with severe COVID-19 pneumonia showed suppressed DOCK2 expression. Moreover, inhibition of DOCK2 function with CPYPP increased the severity of pneumonia in a Syrian hamster model of SARS-CoV-2 infection, characterized by weight loss, lung oedema, enhanced viral loads, impaired macrophage recruitment and dysregulated type I interferon responses. We conclude that DOCK2 has an important role in the host immune response to SARS-CoV-2 infection and the development of severe COVID-19, and could be further explored as a potential biomarker and/or therapeutic target

    Chikyu: The First Three Years of Operation

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    Effects of autoimmune abnormalities on skeletal muscle regeneration after needle puncture in mice

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    Regeneration of injured skeletal muscles is supported by the activation of satellite cells, and excessive traumatic injuries may trigger abnormal processes, such as fibrosis. Because the participation of immune cells is crucial during skeletal muscle repair, systemic autoimmune diseases impair their regeneration. This study focused on a traumatic injury by injection and investigated the effect of autoimmune diseases on skeletal muscle regeneration. Male mice of MRL/MpJ-Fas(lpr/lpr) and MRL/MpJ (6-7 months old) were used for autoimmune disease and healthy groups. The abdominal walls punctured by a needle were histologically analyzed at 1, 3, and 8 days postinjection. In both groups, injured skeletal muscle tissues showed necrosis and inflammatory cell infiltrations on day 1, increased cell density at 3 days, and regenerative myotubes with central nuclei without fibrosis at 8 days. Gr-1(+) neutrophils at injured skeletal muscle were abundant at 1 day, and then substantially decreased starting from 3 days in both groups. The number of CD3(+) T cells was remarkably higher in MRL/MpJ-Fas(lpr/lpr) than that in MRL/MpJ at 1 day, and a similar tendency was observed in B220(+) B cells. The numbers of IBA1(+) macrophages and bromodeoxyuridine-incorporating cells tended to be higher at 3 days, and those of the latter, mainly proliferating paired-box-7(+) satellite cells, showed significance at other time points and negatively correlated with the autoimmune disease indices, such as spleen weights or serum autoantibody level. Thus, this result suggested that injured skeletal muscle by minor trauma is normally regenerated regardless of the effects of autoimmune diseases, although lymphocyte infiltrations during these processes were more severe in MRL/MpJ-Fas(lpr/lpr)

    「ちきゅう」紹介

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    Expression of Indian hedgehog signaling in murine oviductal infundibulum and its relationship with epithelial homeostasis

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    Homeostasis of the oviductal infundibulum epithelium is continuously regulated by signaling pathways under physiological and pathological conditions. Herein, we investigated the expression of hedgehog (Hh) signaling-related components in the murine oviductal infundibulum, which is known to maintain homeostasis in the adult epithelium. Additionally, using autoimmune disease-prone MRL/MpJ-Fas(lpr/lpr) (MRL/lpr) mice showing abnormal morphofunction of the ciliated epithelium of the infundibulum related to the oviductal inflammation, we examined the relationship between Hh signaling and pathology of the infundibulum. The expression and localization of Pax8, a marker for progenitor cells in the oviductal epithelium, and Foxj1, a marker for ciliogenesis, were examined in the infundibulum. The results showed that Pax8 was downregulated and Foxj1 was upregulated with aging, suggesting that homeostasis of the infundibulum epithelium of MRL/lpr mice was disturbed at 6 months of age. In all mice, the motile cilia of ciliated epithelial cells in the infundibulum harbored Hh signaling pathway-related molecules: patched (Ptch), smoothened (Smo), and epithelial cells harbor Gli. In contrast, Ptch, Smo, and Gli2 were significantly downregulated in the infundibulum of MRL/lpr mice at 6 months of age. The expression levels of Pax8 and Foxj1 were significantly positively correlated with those of Ptch1, Smo, and Gli2. Hh signaling is thought to be involved in homeostasis of the ciliated epithelium in the infundibulum. In MRL/lpr mice, which show exacerbated severe systemic autoimmune abnormalities, molecular alterations in Hh signaling-related components are considered to interact with local inflammation in the infundibulum, leading to disturbances in epithelial homeostasis and reproductive function
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