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

Betamethasone 点眼投与後の前房水中および血中 Betamethasone 濃度と，前房水中 cAMP, cGMP 濃度の経時的変化

The levels of cyclic-AMP, cyclic-GMP and betamethasone (BM) in the aqueous humor and serum BM following topical treatment with BM were determined using radioimmunoassay (RIA) methods. One drop of a solution containing 0.1%, 0.5% or 1.0% BM was applied to the rabbit eye of 6 rabbits. The left eyes served as controls. BM was detected in the aqueous humor from right eyes 15 minutes after administration and peaked in 60-90 minutes. BM was also detected in the aqueous humor of the left eyes and in serum. Basal levels of cAMP and cGMP in the aqueous humor before BM treatment were 61.5 and 4.1 picomole/ml respectively, and changed little after BM treatment

March 2016 Arizona thoracic society ntoes

No abstract available. Article truncated at 150 words. The March 2016 Arizona Thoracic Society meeting was held on Wednesday, March 23, 2016 at the Scottsdale Shea Hospital beginning at 6:30 PM. This was a dinner meeting with case presentations. There were 17 in attendance representing the pulmonary, critical care, sleep, and radiology communities. Of note, Dr. Elijah Poulos drove from Flagstaff to attend the meeting. Dr. Rick Robbins gave a summary of ATS Hill Day and the possibility of collecting dues for the Arizona Thoracic Society along with American Thoracic Society dues. Dr. Robbins also presented the results of emailing the Table of Contents of the Southwest Journal of Pulmonary and Critical Care to the ATS members in Arizona, New Mexico, Colorado, and Nevada along with listing the contents in Inspirations the California Thoracic Society newsletter. The number of page views doubled over usual the following day. Dr. George Parides presented a short presentation on whether coccidioidomycosis nodules ..

Comparison of cadmium distribution in the root tissues of Solanum melongena and Solonum torvum, which have different abilities for cadmium transport from the root to shoot

Grafting the eggplant Solanum melongena onto Solanum torvum has been reported to be an effective method for reducing cadmium (Cd) concentration in the fruits of eggplant. Although Cd concentration in the roots of both species of eggplant was almost identical, it was observed to be higher in the shoot and xylem sap of S. melongena. We thus assumed that the translocation of Cd into the shoot of S. torvum was inhibited by a barrier function in its root tissues. Using synchrotron micro X-ray fluorescence (SR μ-XRF), we attempted to elucidate the role of root tissues in the inhibition of Cd transport to the shoot by comparing the microscale distribution pattern of Cd in the root tissues of S. melongena and S. torvum. Cd was localized in the central cylinder and epidermis in the transverse sections of S. melongena, regardless of the distance from the root apex. In the root section of S. torvum, the intensity of X-ray fluorescence from Cd, which was evenly distributed at 10 mm from the root apex, was very weak; in contrast, remarkable localization of Cd in the endodermis was observed in the root section at 40 mm. These contrasting distribution patterns of Cd explained the higher Cd concentration in the xylem sap of S. melongena than in the xylem sap of S. torvum. In conclusion, radial transport of Cd toward the central cylinder was restricted by an endodermal barrier—Casparian band or suberin lamella—present in the root of S. torvum. This barrier function of root tissue is one of the mechanisms responsible for low Cd loading to the xylem of S. torvum as compared to S. melongena

Combination of Aprepitant, Azasetron, and Dexamethasone as Antiemetic Prophylaxis in Women with Gynecologic Cancers Receiving Paclitaxel/Carboplatin Therapy

BACKGROUND: The aim of this study was to evaluate the antiemetic effect of aprepitant and to determine how to provide triple combination therapy (aprepitant/azasetron/dexamethasone) to women receiving paclitaxel/carboplatin moderately emetogenic chemotherapy (MEC). MATERIAL AND METHODS: The current study was a prospective study of 163 women with gynecologic cancers. We compared the digestive symptoms scores (nausea, vomiting, appetite loss, and dietary intake) of 37 women with ovarian cancers before and after aprepitant administration. We also compared these symptoms in women who underwent 193 cycles of triple combination therapy with symptoms of women who underwent 226 cycles of double combination therapy. For triple combination therapy, azasetron, dexamethasone (reduced dose: 40% of 20 mg), and aprepitant (125 mg) were administered on Day 1, followed by only aprepitant (80 mg) administration on Days 2 and Day 3. RESULTS: In 37 women with ovarian cancer, three symptoms, nausea, appetite loss, and dietary intake, were significantly improved by primarily adding aprepitant to double combination therapy in the delayed phase of MEC. Upon comparing their digestive symptoms in all cycles, however, these three symptoms were not significantly different in the delayed phase. Furthermore, all four symptoms in all cycles were worse following triple combination therapy than following double combination therapy in the acute phase (p<0.02). The control of digestive symptoms was generally insufficient without the administration of dexamethasone. CONCLUSIONS: Primary aprepitant as an addition to MEC demonstrated efficacy in improving digestive symptoms in the delayed phase. However, its effect may decrease with repeated use. To improve the antiemetic effect, the dose reduction of dexamethasone should be restricted on Day 1 and dexamethasone should be used throughout the delayed phase as well

Longitudinal long COVID symptoms in Japanese patients after COVID-19 vaccinations

We conducted a subgroup analysis of a study on the long-term effects of COVID-19 (long COVID) in Japan to assess the effect of vaccination on long COVID symptoms. We assessed the clinical course of 111 patients with long COVID at the time of vaccination. The follow-up period was one year from the onset of COVID-19 or until the administration of the third vaccine dose. Of the 111 patients, 15 (13.5%) reported improvement, four (3.6%) reported deterioration, and 92 (82.9%) reported no change in their long COVID symptoms after vaccination. The most common long COVID symptoms before vaccination were alopecia, dyspnea, muscle weakness, fatigue, and headache among participants whose symptoms improved. Reduced dyspnea and alopecia were the most frequently reported improvements in symptoms after vaccination. Some symptoms persisted, including sleep disturbance, myalgia, and hypersensitivity. Vaccination did not appear to have a clinically important effect on patients with long COVID symptoms