An Ultrastructural Study of the Intrauterine Development of Rabbit Metanephric Glomeruli.

The electron microscopic observations correlated with the light microscopic findings were carried out on the intrauterine development of rabbit metanephric glomeruli. The capillaries of the glomerulus develop from a stromal capillary of the metanephric blastema when this capillary localizes within the cleftal space between the middle and lower limbs of the S-shaped metanephric vesicle. The development of the glomerular capillaries is brought about by elongation and repeated branching of the original intracleftal capillary, resulting in the invagination of the hemispheric lower limb. On the other hand, the mesangial cells originate from mesenchymal cells with which the intracleftal capillarly is invariably associated in its ingrowth into the lower cleft. These observations raise an objection to the still widely accepted concept on glomerular differentiation that the glomerular capillaries develop independently from the general circulation of the metanephric kidney, with which they only later unite.departmental bulletin pape

Histo- and Immunopathological Studies on the Allergic Pneumonitis Induced in Sensitized Rabbits by Intravenous Provocative Injection of Ferritin Purified from Horse Spleen.

Histo- and immunopathological studies on the allergic pneumonitis induced in sensitized rabbits by intravenous provocative injection of ferritin purified from horse spleen were presented. The experimental results here obtained have been described and pathogenesis of the pneumonitis has been considered. The fundamental pathologic processes underlying the pneumonitis presented here are said to be characterized by a transformation of alveolar capillaries and intercapillary connective tissue into reticular or enmeshed structure simulating reticular tissue of antibody-forming organs which is induced by localization and fixation of immune complexes in the alveolar walls through the phagocytic activity of cellular components in this structure

Eosinophil Cationic Protein Shows Survival Effect on H9c2 Cardiac Myoblast Cells with Enhanced Phosphorylation of ERK and Akt/GSK-3β under Oxidative Stress

Eosinophil cationic protein (ECP) is well known as a cationic protein contained in the basic granules of activated eosinophils. Recent studies have reported that ECP exhibits novel activities on various types of cells, including rat neonatal cardiomyocytes. Here we evaluated the effects of ECP on rat cardiac myoblast H9c2 cells. Our results showed that ECP enhanced the survival of the cells, in part by promoting the ERK and Akt/GSK-3β signaling pathways. ECP attenuated the cytotoxic effects of H2O2 on H9c2 cells as well as the production of reactive oxygen species, the number of apoptotic cells and caspase 3/7 activity in the cells. In conclusion, ECP activated the ERK and Akt/GSK-3β pathways, resulting in anti-oxidative effects on H9c2 cells that attenuated apoptosis

Ultrasound flow phantom for transcranial Doppler: An assessment of angular mismatch effect on blood velocity measurement in comparison to optical particle image velocimetry

Detecting abnormal blood flow is possible through transcranial Doppler (TCD) ultrasound by measuring blood velocity in cerebral arteries. Velocity measurements are at the highest precision when the direction of blood flow coincides with the ultrasound beam. However, because TCD is typically performed blindly (i.e., without a B-mode), a 0° interrogation angle is usually assumed. This leads to a common issue of angular mismatch. This study quantitatively shows the angular mismatch effects on the measured velocities using a TCD ultrasound flow phantom compared with the velocities measured by optical particle image velocimetry (PIV) as control. Resulting errors with and without ultrasound machine angular correction were also considered. An ultrasound phantom developed by combining polyvinyl alcohol hydrogel (PVA-H), quartz glass as a scatterer, and a gypsum plate as a skull bone was utilized to approximate the middle cerebral artery TCD measurement from the temporal window. The PVA-H and quartz glass compositions were controlled to achieve transparency and enable PIV velocity measurement. Then, TCD velocity measurement was conducted on several interrogation and mismatch angles. Comparison results revealed that without an ultrasound machine angle correction, all measurements yielded underestimation with 73.9% at the highest in the 80° interrogation window at the 130 mL/min flow. On the other hand, with the correction, the errors in almost all angles were comparatively lower; however, at 80° at the 124 mL/min flow, a maximum overestimation rate of 113.7% was found, showing a larger error magnitude. Therefore, we find that angular mismatch, especially in larger angles, leads to inaccurate velocity measurements in TCD. Our results suggest that despite angle correction, velocity errors may still occur when the interrogation angle changes

Association of Habitual Physical Activity Measured by an Accelerometer with High-Density Lipoprotein Cholesterol Levels in Maintenance Hemodialysis Patients

After confirming the relationship between high-density lipoprotein cholesterol (HDL-C) levels and mortality in hemodialysis patients for study 1, we investigated the effect of physical activity on their HDL-C levels for study 2. In study 1, 266 hemodialysis patients were monitored prospectively for five years, and Cox proportional hazard regression confirmed the contribution of HDL-C to mortality. In study 2, 116 patients were recruited after excluding those with severe comorbidities or requiring assistance from another person to walk. Baseline characteristics, such as demographic factors, physical constitution, primary kidney disease, comorbid conditions, smoking habits, drug use, and laboratory parameters, were collected from patient hospital records. An accelerometer measured physical activity as the number of steps per day over five consecutive days, and multiple regression evaluated the association between physical activity and HDL-C levels. Seventy-seven patients died during the follow-up period. In study 1, we confirmed that HDL-C level was a significant predictor of mortality (P=0.03). After adjusting for patient characteristics in study 2, physical activity was independently associated with HDL-C levels (adjusted R2=0.255; P=0.005). In conclusion, physical inactivity was strongly associated with decreased HDL-C levels in hemodialysis patients

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