The effect of adipose-derived stem cell sheets and CTGF on early flexor tendon healing in a canine model

Oral History interview of Curt Sawyer. Interview conducted by Robin Dunn

Meteor Radar Study of Ionospheric Wind at Kyoto

This paper describes the results of meteor radar observations which have been carried out at Kyoto University since December, 1977. The radar, a coherent pulse doppler radar with a transmitting frequency of 31.57 MHz and a nominal peak power of 10 kW, is able to detect wind fields at meteor regions of 80-110 km. The solar semidiurnal tide generally dominates the wind oscillations at these heights, while a diurnal tide of comparable magnitude reveals itself in a less regular manner. Some anomalies in the amplitude and phase characteristics of the tides are shown, which might be related to a possible interaction with winds and waves, or to some disturbed conditions in the earth's atmosphere. Also planetary scale waves such as quasi-2-day oscillations and resonantly magnified gravity-mode waves have also been found there. Hence, the meteor radar, together with its cooperation with other observations, will helps us understand the dynamical process of atmospheric waves on a global scale

Juvenile Granulosa Cell Tumor with Elevated Peripheral Interleukin-6 Level Shows Prolonged Fever and Delayed Puberty

Juvenile granulosa cell tumor (JGCT), classified as a sex cord-stromal tumor, is a rare neoplasm. This is an instructive case report of JGCT accompanied by augmented interleukin (IL)-6 secretion. A 13-year-old girl with prolonged fever and delayed puberty was diagnosed with JGCT of the left ovary based on an imaging study and pathological investigation. Although it was not clear whether IL-6 was secreted from the tumor cells, her serum level of IL-6 was very high. After tumorectomy, the patient’s symptoms immediately disappeared, her IL-6 level decreased, and she entered puberty. Therefore, augmented IL-6 secretion production induced by tumors should be considered a potential cause of prolonged fever and/or delayed puberty

Aesthetic pectoral muscle flap repair for refractory enterocutaneous fistula after salvage esophagectomy in a female patient

Anastomotic leakage is a severe complication of esophagectomy. Development of an enterocutaneous fistula after anastomotic leakage often occurs after subcutaneous-route reconstruction at esophagectomy. Pectoralis myocutaneous flap (PMCF) repair has recently been performed when an enterocutaneous fistula was refractory to conservative treatment. However, this procedure requires a conspicuous incision and results in deformity of the breast especially in female patient. We performed pectoralis muscle flap (PMF) repair for a 50-year-old woman with a refractory enterocutaneous fistula after salvage esophagectomy. We made an oblique incision along the inframammary crease in order to avoid a conspicuous scar and moved the PMF under the mammary gland to the site of anastomosis. This method was effective for repairing a refractory enterocutaneous fistula, with especially good aesthetic results in a female patient

Surgical assessment system reflexes and facilitates the developing the surgical skills of trainees for the Laparoscopic Distal Gastrectomy

Background: To assess laparoscopic distal gastrectomy (LDG) for gastric cancer (GC), the Japanese Operative Rating Scale (JORS) for LDG has been developed. This study evaluated the learning curve of the initial experience of LDG for GC using JORS-LDG.Methods: Thirty-one cases of LDG were performed by a trainee. The trainee and an instructor scored the surgical performance using JORS-LDG immediately after LDG. The 31 cases were evenly divided into early phase (EP), middle phase (MP), and late phase (LP).Results: The trainee successfully completed all cases of LDG without any complications. There were also no severe postoperative complications with Clavien–Dindo classification grade III or higher. The average JORS-LDG points were stable after 24 cases of experience in the CUSUM analysis. The median JORS-LDG points in EP were significantly lower than those in LP (EP: MP: LP = 43.5: 44.3: 45.5, P = 0.02). In operative data, procedure time, bleeding, and the drain fluid amylase level were correlated with the JORS-LDG points.Conclusion: The JORS-LDG scoring system is a practical tool to evaluate surgical performance in the initial LDG experience

Effect of human airway trypsin-like protease on intracellular free Ca2+ concentration in human bronchial epithelial cells

It has been shown that human airway trypsin-like protease (HAT) is localized in human bronchial epithelial cells (HBEC), and trypsin activates protease-activated receptor-2(PAR-2). Activation of PAR-2 activates G-protein followed by an increase of intracellular free Ca2+, [Ca2+]in. This study was undertaken to clarify whether HAT can activate PAR-2in HBEC or not. RT-PCR showed that HAT mRNA is expressed in HBEC, and PAR-2 mRNA is the most strongly expressed of the known PARs in HBEC. Both PAR-2 agonist peptide (PAR-2 AP) and HAT increased [Ca2+]in in HBEC in a biphasic fashion a prompt, sharp increase (peak I) and a sustained low plateau (peak II). PAR-2 AP over 100-200 μM and HAT over 200-300 mU/ml (0.08-0.12 μM) induced both peak I and II, and PAR-2 AP below100 μM and HAT below 200 mU/ml induced only peak II. Both PAR-2 AP-induced and　HAT-induced peak I were induced by Ca2+ mobilization from intracellular stores, because　they appeared even in Ca2+-free medium. Both PAR-2 AP-induced and HAT-induced peak II were induced by an influx of extracellular Ca2+, because they were abolished in Ca2+-free medium. The Ca2+ response to HAT was desensitized by exposure of HBEC to PAR-2 AP. These results indicate that HBEC have a functional PAR-2, and HAT regulates cellular functions of HBEC via activation of PAR-2

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