A CASE OF DIABETES INSIPIDUS ACCOMPANYING THIRST DISORDER ASSOCIATED WITH HYPEROSMOLAR DIABETIC COMA

The case of a 14-year-old female who suffered from hyperosmolar diabetic coma (HODC) after resection of craniopharyngioma and during treatment for hypopituitarism and diabetes insipidus is presented. In Aug. 1989, craniopharyngioma was diagnosed and she underwent resection surgery and radiotherapy. Since then, she had been on supplemental therapy with hydrocortisone and thyroxin and desmopressin (DDAVP). On Jan. 17, 1992, she fell into HODC upon ingesting a large amount of soft drink to supplement water due to persistent polyuria. She improved quickly when supplementary fluids and insulin were administered. She had demonstrated no abnormality in glucose tolerance prior to this manifestation. Insulin therapy was deemed unnecessary after her recovery from HODC. Because of a disorder in the central nervous thirst mechaninm, she lacked the sense of thirst and concomitantly the thirst-mediated water intake in spite of elevated plasma osmolarity due to dehydration and hyperglycemia. This seemed to be the cause of her accelerating dehydration. The resulting insulin resistance then brought about her HODC. Thus, it is difficult to consider such a case of HODC as symptomatic of diabetes when no abnormality in glucose tolerance either before manifestation or after restoration can be found. It should rather be considered as a case of “dehydration hyperglycemia" and be treated as such

Involvement of resistin-like molecule β in the development of methionine-choline deficient diet-induced non-alcoholic steatohepatitis in mice

Resistin-like molecule β (RELMβ) reportedly has multiple functions including local immune responses in the gut. In this study, we investigated the possible contribution of RELMβ to non-alcoholic steatohepatitis (NASH) development. First, RELMβ knock-out (KO) mice were shown to be resistant to methionine-choline deficient (MCD) diet-induced NASH development. Since it was newly revealed that Kupffer cells in the liver express RELMβ and that RELMβ expression levels in the colon and the numbers of RELMβ-positive Kupffer cells were both increased in this model, we carried out further experiments using radiation chimeras between wild-type and RELMβ-KO mice to distinguish between the contributions of RELMβ in these two organs. These experiments revealed the requirement of RELMβ in both organs for full manifestation of NASH, while deletion of each one alone attenuated the development of NASH with reduced serum lipopolysaccharide (LPS) levels. The higher proportion of lactic acid bacteria in the gut microbiota of RELMβ-KO than in that of wild-type mice may be one of the mechanisms underlying the lower serum LPS level the former. These data suggest the contribution of increases in RELMβ in the gut and Kupffer cells to NASH development, raising the possibility of RELMβ being a novel therapeutic target for NASH

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

The Biosynthesis of Astaxanthin—VIII: The Conversion of Labelled β-carotene-15,15\u27-\u3csup\u3e3\u3c/sup\u3eh2 into Astaxanthin in Prawn, Penaeus japonicus Bate

To clarify the metabolic pathway from β-carotene to astaxanthin which was proposed in this thesis series, the present investigation was undertaken. Astaxanthin is the dominant pigment in prawn, Penaeus japonicus Bate. Prawn were cultured in the laboratory for 21 days by feeding artificial food containing labelled β-carotene-15, 15\u27-3H2 dissolved in plant oil. In prawn, β-carotene-15,15\u27-3H2 was converted to labelled astaxanthin via echinenone, canthaxanthin and phoenicoxanthin. The metabolic pathway fromβ-carotene to astaxanthin in prawn is as follows: β-carotine--►echinenone-►canthaxanthin -►phoenicoxanthin-►astaxanthin chichesteret al.12)recently found that in a Californian strain of Artemia salina, the two step conversion of β-carotene into canthaxanthin was the apparent pathway as follows: This was achieved by feeding [14C] labelled β-carotene. /9-carotene-——^echinenone-^canthaxanthin 1 t T. t isocryptoxanthin-risozeaxanthin ^hydroxy-T-ketO\u27/S-carotene. © 1972, The Japanese Society of Fisheries Science. All rights reserved