Assessment of Olfactory Nerve by SPECT-MRI Image with Nasal Thallium-201 Administration in Patients with Olfactory Impairments in Comparison to Healthy Volunteers

Purpose: The aim of this study was to assess whether migration of thallium-201 (201Tl) to the olfactory bulb were reduced in patients with olfactory impairments in comparison to healthy volunteers after nasal administration of 201Tl. Procedures: 10 healthy volunteers and 21 patients enrolled in the study (19 males and 12 females; 26-71 years old). The causes of olfactory dysfunction in the patients were head trauma (n = 7), upper respiratory tract infection (n = 7), and chronic rhinosinusitis (n = 7). 201TlCl was administered unilaterally to the olfactory cleft, and SPECT-CT was conducted 24 h later. Separate MRI images were merged with the SPECT images. 201Tl olfactory migration was also correlated with the volume of the olfactory bulb determined from MRI images, as well as with odor recognition thresholds measured by using T&T olfactometry. Results: Nasal201Tl migration to the olfactory bulb was significantly lower in the olfactory-impaired patients than in healthy volunteers. The migration of 201Tl to the olfactory bulb was significantly correlated with odor recognition thresholds obtained with T&T olfactometry and correlated with the volume of the olfactory bulb determined from MRI images when all subjects were included. Conclusions: Assessment of the 201Tl migration to the olfactory bulb was the new method for the evaluation of the olfactory nerve connectivity in patients with impaired olfaction. © 2013 Shiga et al

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

Assessment of olfactory nerve by SPECT-MRI image with nasal thallium-201 administration in patients with olfactory impairments in comparison to healthy volunteers.

PURPOSE: The aim of this study was to assess whether migration of thallium-201 ((201)Tl) to the olfactory bulb were reduced in patients with olfactory impairments in comparison to healthy volunteers after nasal administration of (201)Tl. PROCEDURES: 10 healthy volunteers and 21 patients enrolled in the study (19 males and 12 females; 26-71 years old). The causes of olfactory dysfunction in the patients were head trauma (n = 7), upper respiratory tract infection (n = 7), and chronic rhinosinusitis (n = 7). (201)TlCl was administered unilaterally to the olfactory cleft, and SPECT-CT was conducted 24 h later. Separate MRI images were merged with the SPECT images. (201)Tl olfactory migration was also correlated with the volume of the olfactory bulb determined from MRI images, as well as with odor recognition thresholds measured by using T&T olfactometry. RESULTS: Nasal (201)Tl migration to the olfactory bulb was significantly lower in the olfactory-impaired patients than in healthy volunteers. The migration of (201)Tl to the olfactory bulb was significantly correlated with odor recognition thresholds obtained with T&T olfactometry and correlated with the volume of the olfactory bulb determined from MRI images when all subjects were included. CONCLUSIONS: Assessment of the (201)Tl migration to the olfactory bulb was the new method for the evaluation of the olfactory nerve connectivity in patients with impaired olfaction

Correlation between olfactory ²⁰¹Tl migration and olfactory function as assessed by T&T olfactometry.

<p>Nasal ²⁰¹Tl migration to the olfactory bulb as a function of odor recognition threshold in patients and healthy volunteers (n = 31). Spearman <i>r</i> = –0.62, <i>P</i> = 0.0002. Closed circles, patients; Open squares, healthy volunteers.</p

SPECT-MRI fusion image (coronal view) of nasal ²⁰¹Tl migration to the olfactory bulb.

<p>White arrows indicate the olfactory bulb and olfactory nerve. (A) A 60-year-old healthy male volunteer. (B) A 44-year-old female with hyposmia after head trauma. (C) A 42-year-old female with hyposmia after upper respiratory tract infection. (D) A 67-year-old female with hyposmia due to chronic rhinosinusitis. The index of ²⁰¹Tl migration from the olfactory epithelium to the olfactory bulb in the selected subjects was shown in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0057671#pone-0057671-t002" target="_blank">Table 2</a>.</p

MRI image (T2 weighted, coronal view).

<p>White arrows indicate the olfactory bulb and olfactory nerve. (A) A 60-year-old healthy male volunteer. (B) A 44-year-old female with hyposmia after head trauma. (C) A 42-year-old female with hyposmia after upper respiratory tract infection. (D) A 67-year-old female with hyposmia due to chronic rhinosinusitis.</p

²⁰¹Tl migration in patients with impaired olfaction in comparison to healthy volunteers.

<p>Nasal ²⁰¹Tl migration to the olfactory bulb in healthy volunteers (n = 10) and patients with impaired olfaction due to head trauma (n = 7), upper respiratory tract infection (respiratory infection; n = 7), or chronic rhinosinusitis (n = 7). <i>P</i> values were obtained with Bonferroni’s multiple comparison test and the Kruskal-Wallis test. Bars: Mean ± S.D.</p