A case of the paired inferior venae cavae

解剖実習遺体に重複下大静脈の1例を見い出した。この例は左右の上主静脈の残存に起因するものと考えられ,McClureとButler(1925),及びChuangら(1974)の分類法のBC型に分類される。重複下大静脈はさほど稀な変異ではなく,臨床家は注意をはらう必要がある。下大静脈の重複は,右精巣または卵巣静脈の流入部位が下大静脈から右腎静脈に移行するなどの,静脈系の他の変化を誘因するかもしれない。また,この変異は精巣または卵巣静脈の重複を引き起こすことを示唆する。We encountered a case of duplication of the inferior vena cava in a cadaver. This was thought to be caused by persistence of the right and the left supracardinal veins, and this case was classified as type BC in the classification systems developed by McClure and Butler (1925) and Chuang et al. (1974). Double inferior vena cava is not a rare anomaly, and clinicians should be aware of this anomaly. Duplication of the inferior vena cava may cause other changes in the venous system, such as dislocation of the drainage position of the right gonadal vein from the inferior vena cava to the right renal vein. We also suggest that this anomaly causes duplication of the gonadal vein

Two cases of bifid ribs observed in the fourth and the fifth rib

岩手医科大学歯学部の解剖学実習において2例の二分肋骨に遭遇した。1例は第4肋骨に,他の1例は第5肋骨に存在していた。1例では肋骨の分岐と再癒合が骨部でおこっていたが,他の1例では,分岐と再癒合が軟骨部でおこっていた。分枝の間は正常と思われる肋間筋で充たされていた。どちらの例においても,内胸動脈からの小枝が二分肋骨の上方の分枝と肋間筋に分布していたが,肋間神経は上方の分枝には分布せず,下方の分枝の下縁にのみ沿って走行していた。Two cases of bifid rib were found in two cadavers during routine dissections at Iwate Medical University School of Dentistry. They were found in the fourth rib in one cadaver, and in the fifth rib in the other cadaver. In one case both the branching and the reunion of the rib occurred in the osseous part, and in the other case they occurred in the cartilage part. The space between the two branches was filled with presumably normal intercostal muscles. The blood supply had been maintained by small branches from the internal thoracic artery to the upper branch and the intercostal muscles. However, the intercostal nerves did not branch toward the upper branch but only ran along the lower margin of the lower branch of the bifid rib in both cases

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

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

Functional Expression of GABAB Receptors in Airway Epithelium

γ-Aminobutyric acid (GABA) is the major inhibitory neurotransmitter in the mammalian central nervous system and exerts its actions via both ionotropic (GABAA) and metabotropic (GABAB) receptors. The GABAB receptor is a dimer composed of R1 and R2 components and classically couples to the heterotrimeric Gi protein. In addition to their location on neurons, GABA and functional GABAB receptors have been detected in peripheral tissue such as airway smooth muscle. We questioned whether airway epithelium expresses receptors that could respond to GABA. We detected the mRNA encoding multiple-splice variants of the GABABR1 and GABABR2 in total RNA isolated from native human and guinea pig airway epithelium and human airway epithelial cell lines (BEAS-2B and H441). Immunoblots identified the GABABR1 and GABABR2 proteins in both guinea pig airway epithelium and BEAS-2B cells. The expression of GABABR1 protein was immunohistochemically localized to basal mucin-secreting and ciliated columnar epithelial cells in guinea pig trachea. Baclofen inhibited adenylyl cyclase activity, induced ERK phosphorylation and cross-regulated phospholipase C, leading to increased inositol phosphates in BEAS-2B cells in a pertussis toxin–sensitive manner, implicating Gi protein coupling. Thus, these receptors couple to Gi and cross-regulate the phospholipase C/inositol phosphate pathway. The second messengers of these pathways, cyclic AMP and calcium, play pivotal roles in airway epithelial cell primary functions of mucus clearance. Furthermore, the enzyme that synthesizes GABA, glutamic acid decarboxylase (GAD65/67), was also localized to airway epithelium. GABA may modulate an uncharacterized signaling cascade via GABAB receptors coupled to Gi protein in airway epithelium