97 research outputs found
Stability Testing of Drug Products Approved by the Japanese Government in 2014
2014年に日本で承認された新医療用製剤に対し、安定性試験の現状を調査した。我々は、2014年に安定性試験の記述がある134の新医療用製剤を特定した。長期保存試験としては、82製剤が25±2℃/60±5%相対湿度の条件下で、48製剤が5±3℃の条件下で、4製剤が10℃未満の条件下で試験が実施されていた。また、光安定性試験では、78製剤が光学的に安定であったが、48製剤は光学的に不安定であった.光学的に不安定な製剤は、遮光保存をするといった適切な保存方法がとられている.これらの結果から、2014年に日本で承認された新医療用製剤は、ICH ガイドラインに従って、適正に承認されていることがわかった。We investigated the current status of stability testing of new drug products in Japan. One hundred thirty-four new drug products that had undergone stability testing in 2014 were identified. Among these, 82 were tested at 25℃ ± 2℃ / 60% ± 5% relative humidity, 48 were tested at 5℃ ± 3℃, and 4 were tested at less than 10℃ on long-term testing. Based on photostability testing, 78 new drug products were found to be optically stable and 48 were optically unstable. New drug products that appeared unstable in photostability testing were stored in the dark. Based on these results, the new drug products approved in Japan according to the ICH guidelines in 2014 were found to have been adequately tested
Comparative Study of Chemical Oxygen Demand and Total Organic Carbon in Omura Bay
化学的酸素要求量(COD)と全有機炭素量(TOC)を測定することにより、大村湾における有機汚濁レベルを評価した。本研究では、2008年5月から2010年5月にかけ、水深別(0、2、6、10m)に5地点(湾口部、湾央部、湾奥部3地点)より採水し、両者を測定した。その結果、COD は 0.68~3.94mg/L(平均 1.95mg/L)、TOC は 0.811~2.170mg/L(平均 1.345mg/L)となり、COD では試料の約半数が環境基準の 2mg/L 以上を示したのに対し、TOC ではほぼ全試料で 2mg/L 以下となり、COD と比べて低値を示した。両者とも表層で高く、深度とともに低い傾向を示した。Pearson の積率相関分析を行った結果、両者の間には正の相関がみられた(相関係数:0.604)。また、海水交換が十分でないと示唆される湾奥部ほど、両者の相関性が高くなる傾向がみられた。以上の結果より、閉鎖性海域ほど両者の相関性が高く、TOC の測定は水質汚濁を把握するには有効であることが示唆された。The organic pollutant levels in Omura Bay were evaluated by measuring chemical oxygen demand(COD)and total organic carbon(TOC). We investigated these factors in Omura Bay from May 2008 to May 2010, in order to clarify the relationship between them. Samples were collected from four depths(0, 2, 6, and 10 m)at five sites. The COD values ranged from 0.68 to 3.94 mg/L with a mean value of 1.95 mg/L, while the TOC values ranged from 0.811 to 2.170 mg/L with a mean value of 1.345 mg/L. Although half of the samples showed high COD values(>2.0 mg/L), most of the samples showed low TOC values(<2.0 mg/L). The samples from the upper layer showed higher COD and TOC values than the samples from the middle or bottom layers. A significant positive correlation between the COD and TOC values was obtained(0.604); furthermore, a strong correlation between these parameters was observed for the samples obtained from the inner bay. These results suggest that measuring TOC may be useful for estimating the degree of pollution in enclosed coastal sea areas
Intraoperative and fluorescein angiographic findings of a secondary macular hole associated with age-related macular degeneration treated by pars plana vitrectomy
Meltrin β/ADAM19 Interacting with EphA4 in Developing Neural Cells Participates in Formation of the Neuromuscular Junction
BACKGROUND: Development of the neuromuscular junction (NMJ) is initiated by the formation of postsynaptic specializations in the central zones of muscles, followed by the arrival of motor nerve terminals opposite the postsynaptic regions. The post- and presynaptic components are then stabilized and modified to form mature synapses. Roles of ADAM (A Disintegrin And Metalloprotease) family proteins in the formation of the NMJ have not been reported previously. PRINCIPAL FINDINGS: We report here that Meltrin beta, ADAM19, participates in the formation of the NMJ. The zone of acetylcholine receptor alpha mRNA distribution was broader and excess sprouting of motor nerve terminals was more prominent in meltrin beta-deficient than in wild-type embryonic diaphragms. A microarray analysis revealed that the preferential distribution of ephrin-A5 mRNA in the synaptic region of muscles was aberrant in the meltrin beta-deficient muscles. Excess sprouting of motor nerve terminals was also found in ephrin-A5 knockout mice, which lead us to investigate a possible link between Meltrin beta and ephrin-A5-Eph signaling in the development of the NMJ. Meltrin beta and EphA4 interacted with each other in developing motor neurons, and both of these proteins localized in the NMJ. Coexpression of Meltrin beta and EphA4 strongly blocked vesicular internalization of ephrin-A5-EphA4 complexes without requiring the protease activity of Meltrin beta, suggesting a regulatory role of Meltrin beta in ephrin-A5-Eph signaling. CONCLUSION: Meltrin beta plays a regulatory role in formation of the NMJ. The endocytosis of ephrin-Eph complexes is required for efficient contact-dependent repulsion between ephrin and Eph. We propose that Meltrin beta stabilizes the interaction between ephrin-A5 and EphA4 by regulating endocytosis of the ephrinA5-EphA complex negatively, which would contribute to the fine-tuning of the NMJ during development
The whole blood transcriptional regulation landscape in 465 COVID-19 infected samples from Japan COVID-19 Task Force
「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
「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
Generation of a monoclonal antibody reactive to prefusion myocytes.
We established a novel monoclonal antibody, Yaksa that is specific to a subpopulation of myogenic cells. The Yaksa antigen is not expressed on the surface of growing myoblasts but only on a subpopulation of myogenin-positive myocytes. When Yaksa antigen-positive mononucleated cells were freshly prepared from a murine myogenic cell by a cell sorter, they fused with each other and formed multinucleated myotubes shortly after replating while Yaksa antigen-negative cells scarcely generated myotubes. These results suggest that Yaksa could segregate fusion-competent, mononucleated cells from fusion-incompetent cells during muscle differentiation. The Yaksa antigen was also expressed in developing muscle and regenerating muscle in vivo and it was localized at sites of cell-cell contact between mono-nucleated muscle cells and between mono-nucleated muscle cells and myotubes. Thus, Yaksa that marks prefusion myocytes before myotube formation can be a useful tool to elucidate the cellular and molecular mechanisms of myogenic cell fusion
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