A Study of Correlation between Gd-EOB-DTPA-enhanced MRI Using the 3T MRI System and Tc-99m-GSA Hepatic Scintigraphy / Hepatic Function Tests in Prehepatectomy Cases

This study compared results from Gd-EOB-DTPA on two different phases of 3T MRI with those from Tc-99m-GSA hepatic scintigraphy and hepatic function tests. Twenty-four patients with liver tumor were included in this study. All patients underwent Gd-EOB-DTPA-enhanced-MRI and Tc-99m-GSA hepatic scintigraphy. Clearance index (HH15) and receptor index (LHL15) were calculated for the Tc-99m-GSA, while signal intensities (SI) of liver at pre-injection and at 4/20min post-injection, and of spleen at 4 min/20min were measured (SIpre, SI4min, SI20min, SIsp4min, SIsp20min, respectively) for the Gd-EOB-DTPA-MRI. Liver activity at 15min by Tc-99m-GSA scintigraphy or biochemical liver function values were compared with liver spleen contrast at 4min (LSC4min = SI4min/SIsp4min) or 20min post-injection (LSC20min = SI4min/SIsp20min), and the increase in ratio at 4min (IR4min=SI4min/SIsp4min) or 20min (IR20min= SI20min/SIpre). Total bilirubin levels (T-bil), serum albumin levels (Alb), prothrombin activity, and the indocyanine green clearance test (ICG) results were also analyzed. There were statistically significant correlations in all comparisons between Gd-EOB-DTPA and Tc-99m-GSA. The highest coefficient of correlation was obtained in IR4min (LHL15: r = 0.795, P<0.001; HH15: r = -0.782, P<0.001), with IR20min (LHL15: r = 0.690, P<0.01; HH15: r = -0.528, P<0.05), LSC4min (LHL15: r = 0.458, P<0.05; HH15: r = -0.626, P<0.05), and LSC20min (LHL15: r = 0.443, P<0.05, HH15: r = -0.609, P<0.05) also significantly correlated. Correlations in hepatic function data were observed between IR4min and T-bil/Alb, and IR20min and Alb. In 3T-MRI using Gd-EOB-DTPA, the SI of liver at pre- to post-injection (especially at 4 min) significantly correlated with the corresponding Tc-99m-DTPA scintigraphy results, and with some biochemical liver function data

Clinical Significance of Reverse Redistribution Phenomenon for 201Tl Scintigraphy in Nonischemic Disease

The reverse redistribution phenomenon (RR) on 201Tl SPECT has been focused mainly on ischemic improvement regions after reperfusion therapy or vasospastic angina pectoris. However, RR analysis has not been used in the context of non-ischemic disease. The aim of this study was to evaluate the clinical role of RR on 201Tl SPECT in patients without a history of myocardial ischemia. We retrospectively enrolled 86 patients showing RR by myocardial perfusion SPECT and studied 75 other patients as a control group. For quantitative analysis, each 201Tl SPECT polar map was divided into 13 segments. Differences between the RR and control group were assessed with respect to patient characteristics and cardiac event-free survival using the Kaplan-Meier method. RR was detected frequently in the inferoposterior wall, septal portion of the anterior wall, and septum. The two groups showed signi_cant differences in rates of heart failure (P ＜ 0.01), hypertrophic cardiomyopathy (P ＜ 0.05), and wall motion abnormality (P ＜ 0.05), but not in the rate of event occurrence. The study demonstrated that RR on 201Tl SPECT could indicate the existence of myocardial damage ; however, it would not be a factor that determines the prognosis

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

Use of the index of pulmonary vascular disease for predicting long-term outcome of pulmonary arterial hypertension associated with congenital heart disease

AimsLimited data exist on risk factors for the long-term outcome of pulmonary arterial hypertension (PAH) associated with congenital heart disease (CHD-PAH). We focused on the index of pulmonary vascular disease (IPVD), an assessment system for pulmonary artery pathology specimens. The IPVD classifies pulmonary vascular lesions into four categories based on severity: (1) no intimal thickening, (2) cellular thickening of the intima, (3) fibrous thickening of the intima, and (4) destruction of the tunica media, with the overall grade expressed as an additive mean of these scores. This study aimed to investigate the relationship between IPVD and the long-term outcome of CHD-PAH.MethodsThis retrospective study examined lung pathology images of 764 patients with CHD-PAH aged &lt;20 years whose lung specimens were submitted to the Japanese Research Institute of Pulmonary Vasculature for pulmonary pathological review between 2001 and 2020. Clinical information was collected retrospectively by each attending physician. The primary endpoint was cardiovascular death.ResultsThe 5-year, 10-year, 15-year, and 20-year cardiovascular death-free survival rates for all patients were 92.0%, 90.4%, 87.3%, and 86.1%, respectively. The group with an IPVD of ≥2.0 had significantly poorer survival than the group with an IPVD &lt;2.0 (P = .037). The Cox proportional hazards model adjusted for the presence of congenital anomaly syndromes associated with pulmonary hypertension, and age at lung biopsy showed similar results (hazard ratio 4.46; 95% confidence interval: 1.45–13.73; P = .009).ConclusionsThe IPVD scoring system is useful for predicting the long-term outcome of CHD-PAH. For patients with an IPVD of ≥2.0, treatment strategies, including choosing palliative procedures such as pulmonary artery banding to restrict pulmonary blood flow and postponement of intracardiac repair, should be more carefully considered

Gene expression and genetic mapping analyses of a perennial ryegrass glycine-rich RNA-binding protein gene suggest a role in cold adaptation

A perennial ryegrass cDNA clone encoding a putative glycine-rich RNA binding protein (LpGRP1) was isolated from a cDNA library constructed from crown tissues of cold-treated plants. The deduced polypeptide sequence consists of 107 amino acids with a single N-terminal RNA recognition motif (RRM) and a single C-terminal glycine-rich domain. The sequence showed extensive homology to glycine-rich RNA binding proteins previously identified in other plant species. LpGRP1-specific genomic DNA sequence was isolated by an inverse PCR amplification. A single intron which shows conserved locations in plant genes was detected between the sequence motifs encoding RNP-1 and RNP-2 consensus protein domains. A significant increase in the mRNA level of LpGRP1 was detected in root, crown and leaf tissues during the treatment of plants at 4°C, through which freezing tolerance is attained. The increase in the mRNA level was prominent at least 2 h after the commencement of the cold treatment, and persisted for at least 1 week. Changes in mRNA level induced by cold treatment were more obvious than those due to treatments with abscisic acid (ABA) and drought. The LpGRP1 protein was found to localise in the nucleus in onion epidermal cells, suggesting that it may be involved in pre-mRNA processing. The LpGRP1 gene locus was mapped to linkage group 2. Possible roles for the LpGRP1 protein in adaptation to cold environments are discussed