64 research outputs found
Effectiveness of Anti-PD-1 Antibody Monotherapy for the Primary Malignant Melanoma of the Esophagus: A Case Report
Primary malignant melanoma of the esophagus(PMME)is extraordinarily rare with a high degree of malignancy and poor prognosis, and a standard therapy remains to be established. The anti-PD-1 antibody nivolumab is a promising agent for various cancers. To our knowledge, this is the first case report of PMME where a complete response was achieved using nivolumab. We report an 80-year-old woman who was diagnosed with PMME with bone metastasis and lymph node metastases. Although dacarbazine combined chemotherapy was performed and continued for six cycles, the primary tumor progressed and liver metastases appeared. The patient then received nivolumab monotherapy. After three cycles, nivolumab monotherapy for PMME resulted in a complete response as shown by positron emission tomography, computed tomography, and esophagogastroduodenoscopy. In our case, nivolumab exerted a curative effect on PMME, thus suggesting that nivolumab can be effective in the treatment of this rare disease
Inhibition of autophagy exerts anti-colon cancer effects via apoptosis induced by p53 activation and ER stress
Spin dynamics and spin freezing behavior in the two-dimensional antiferromagnet NiGaS revealed by Ga-NMR, NQR and SR measurements
We have performed Ga nuclear magnetic resonance (NMR) and nuclear
quadrupole resonance (NQR) and muon spin rotation/resonance on the quasi
two-dimensional antiferromagnet (AFM) NiGaS, in order to investigate
its spin dynamics and magnetic state at low temperatures. Although there exists
only one crystallographic site for Ga in NiGaS, we found two distinct
Ga signals by NMR and NQR. The origin of the two Ga signals is not fully
understood, but possibly due to stacking faults along the c axis which induce
additional broad Ga NMR and NQR signals with different local symmetries. We
found the novel spin freezing occurring at , at which the specific
heat shows a maximum, from a clear divergent behavior of the nuclear
spin-lattice relaxation rate and nuclear spin-spin relaxation rate
measured by Ga-NQR as well as the muon spin relaxation rate
. The main sharp NQR peaks exhibit a stronger tendency of divergence,
compared with the weak broader spectral peaks, indicating that the spin
freezing is intrinsic in NiGaS. The behavior of these relaxation rates
strongly suggests that the Ni spin fluctuations slow down towards ,
and the temperature range of the divergence is anomalously wider than that in a
conventional magnetic ordering. A broad structureless spectrum and
multi-component were observed below 2 K, indicating that a static
magnetic state with incommensurate magnetic correlations or inhomogeneously
distributed moments is realized at low temperatures. However, the wide
temperature region between 2 K and , where the NQR signal was not
observed, suggests that the Ni spins do not freeze immediately below , but keep fluctuating down to 2 K with the MHz frequency range.Comment: 14 pages, 14 figures. To appear in Phys. Rev.
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
Inclusion body myositis in an older patient following a fall
Key Clinical Message After experiencing a fall, an 82‐year‐old woman developed progressive loss of lower limb strength and was diagnosed with inclusion body myositis. Although falls and muscle weakness are often regarded as consequences of aging, inclusion body myositis should be considered in a patient with a history of multiple falls
Novel Electrode Evaluation Method for Pulse Jet Solid Oxide Fuel Cells using Liquid Hydrocarbon Fuels
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