Indication for Endoscopic Resection of Submucosal Colorectal Carcinoma: Special Reference to Lymph Node Metastasis

We investigated the relationship between histological factors and lymph node metastasis in 77 lesions with submucosally invasive colorectal carcinomas to establish useful criteria for lesions in which endoscopic treatment alone results in cure of malignancy. There were positive correlations between histological factors, including the level of invasion, the histologic grade, presence or absence of lymphatic invasion, presence or absence of budding, and lymph node metastasis (p < 0.05, p < 0.05, p < 0.005, p < 0.01). The presence or absence of venous invasion did not influence lymph node metastasis. Laparoscopic surgery involving lymph node dissection should be indicated for sm1 carcinoma lesions with unfavorable histological factors. In lesions diagnosed as sm2 or sm3 prior to resection, intestinal resection involving lymph node dissection by laparoscopic surgery should be directly performed without endoscopic resection

Oxytocin Influences Male Sexual Activity via Non-synaptic Axonal Release in the Spinal Cord

Oxytocinergic neurons in the paraventricular nucleus of the hypothalamus that project to extrahypothalamic brain areas and the lumbar spinal cord play an important role in the control of erectile function and male sexual behavior in mammals. The gastrin-releasing peptide (GRP) system in the lumbosacral spinal cord is an important component of the neural circuits that control penile reflexes in rats, circuits that are commonly referred to as the “spinal ejaculation generator (SEG).” We have examined the functional interaction between the SEG neurons and the hypothalamo-spinal oxytocin system in rats. Here, we show that SEG/GRP neurons express oxytocin receptors and are activated by oxytocin during male sexual behavior. Intrathecal injection of oxytocin receptor antagonist not only attenuates ejaculation but also affects pre-ejaculatory behavior during normal sexual activity. Electron microscopy of potassium-stimulated acute slices of the lumbar cord showed that oxytocin-neurophysin-immunoreactivity was detected in large numbers of neurosecretory dense-cored vesicles, many of which are located close to the plasmalemma of axonal varicosities in which no electron-lucent microvesicles or synaptic membrane thickenings were visible. These results suggested that, in rats, release of oxytocin in the lumbar spinal cord is not limited to conventional synapses but occurs by exocytosis of the dense-cored vesicles from axonal varicosities and acts by diffusion—a localized volume transmission—to reach oxytocin receptors on GRP neurons and facilitate male sexual function

Intention to return to the town of Tomioka in residents 7 years after the accident at Fukushima Daiichi Nuclear Power Station: a cross-sectional study

The aim of our study was to identify the factors associated with intention to return (ITR) in residents of Tomioka town, Fukushima Prefecture. We contacted approximated 8000 residents aged 20 years or older who lived in Tomioka. We invited them to take part in a written survey on ITR. In all, 1749 residents\u27 replies were included in the analysis. We asked about ITR in former residents of Tomioka town. We also asked about relevant factors and about risk perception in relation to the health effects of radiation exposure. Of those contacted, 469 (26.8%) had an ITR. Logistic regression analysis revealed that being male (OR = 1.6, 95% Cl: 1.24-1.96, P < 0.001),the anticipation of improving shopping in the town (OR = 1.5, 95% Cl: 1.26-1.67, P < 0.001) and requests for individual consultation with experts on the health effects of radiation (OR = 2.7, 95% Cl: 2.10-3.48, P <0.001) were associated with the ITR (+), and living with children under 18 years of age (OR = 0.7, 95% Cl: 0.51-0.95, P = 0.023), reluctance to drink tap water (OR = 0.5, 95% Cl: 0.36-0.69, P < 0.001) and anxiety regarding genetic effects of radiation in the next generation (OR = 0.6, 95% Cl: 0.45-079, P <0.001) were associated with the ITR (-) to Tomioka town, independent of other covariates. To allay the anxieties of residents who have an ITR to their hometown, careful risk communication, including information on the potential effects of radiation on health, is important

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

Polarizing agents beyond pentacene for efficient triplet dynamic nuclear polarization in glass matrices

Triplet dynamic nuclear polarization (triplet-DNP) is a technique that can obtain high nuclear polarization under moderate conditions. However, in order to obtain practically useful polarization, large single crystals doped with a polarizing agent must be strictly oriented with respect to the magnetic field to sharpen the electron spin resonance (ESR) spectra, which is a fatal problem that prevents its application to truly useful biomolecular targets. Instead of this conventional physical approach of controlling crystal orientation, here, we propose a chemical approach, i.e., molecular design of polarizing agents; pentacene molecules, the most typical triplet-DNP polarizing agent, are modified so as to make the triplet electron distribution wider and more isotropic without loss of the triplet polarization. In fact, the modification of pentacene with thiophene moieties makes the ESR spectrum sharper and stronger than that of pentacene. To elucidate the effect of the substitutions on spin polarization and zero-field splitting parameters, which determine ESR spectrum, state-of-the-art quantum chemical calculations were performed and revealed that the direction of the spin polarization is altered by the modification with thiophene moieties and the size of D and E parameters are reduced from parent pentacene due to the partial delocalization of spin densities on the thiophene moieties. The triplet-DNP with the new polarizing agent successfully exceeds the previous highest 1H polarization of glassy materials by a factor of 5. This demonstrates the feasibility of a polarizing agent that can surpass pentacene, the best polarizing agent for more than 30 years since triplet-DNP was first reported, in the unoriented state. This work provides a pathway toward practically useful high nuclear polarization of various biomolecules by triplet-DNP

Triplet Dynamic Nuclear Polarization of Pyruvate via Supramolecular Chemistry

Dynamic nuclear polarization (DNP) significantly improves the sensitivity of magnetic resonance imaging, and its most important medical application is cancer diagnosis via hyperpolarized 13C-labeled pyruvate. Unlike cryogenic DNP, triplet-DNP uses photoexcited triplet electrons under mild conditions. However, triplet-DNP of pyruvate has not been observed because of incompatibility of the hydrophobic polarizing agent with hydrophilic pyruvate. This work demonstrates that supramolecular complexation with β-cyclodextrin can disperse 4,4′-(pentacene-6,13-diyl)dibenzoate (NaPDBA), a pentacene derivative with hydrophilic substituents, even in the presence of high sodium pyruvate concentrations. The polarization of photoexcited triplet electron spins in NaPDBA was transferred to the 13C spins of sodium pyruvate via triplet-DNP of 1H spins in water and 1H-to-13C cross-polarization. This provides an important step toward the widespread use of ultra-sensitive MRI for cancer diagnosis