Thrombocytopenia in Preterm Infants with Intrauterine Growth Restriction

Sick preterm infants often have thrombocytopenia at birth, and this is often associated with intrauterine growth restriction (IUGR), or birth weights less than the 10th percentile. The pathogenesis of the thrombocytopenia and its importance in IUGR are still unclear. We studied the characteristics of preterm IUGR infants with thrombocytopenia. Twenty-seven singleton Japanese preterm IUGR infants were born between January 2002 and June 2007 at Okayama University Hospital. Infants with malformation, chromosomal abnormalities, alloimmune thrombocytopenia, sepsis, and maternal aspirin ingestion were excluded. The infants were divided into group A (n&#65309;8), which had thrombocytopenia within 72h after birth, and group B (n&#65309;19), which did not. There were significant differences in birth weight, head circumference, umbilical artery (UA)-pulsatility index (PI), middle cerebral artery-PI, UA-pH, UA-pO2, and UA-pCO2. The infants in group A were smaller, had abnormal blood flow patterns, and were hypoxic at birth. We speculate that the infants with thrombocytopenia were more severely growth-restricted by chronic hypoxia. Thrombocytopenia is an important parameter for chronic hypoxia in the uterine.</p

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

Differences in Stream Water Nitrate Concentrations between a Nitrogen-Saturated Upland Forest and a Downstream Mixed Land Use River Basin

Nitrogen (N) saturation of upland forests has been assumed to be a substantial N source downstream. However, removal processes of N, including assimilation and denitrification in the downstream area, have not been clarified. To evaluate the N removal processes, nitrate (NO3−) and organic N concentrations, as well as nitrogen isotope ratio (δ15N) and oxygen isotope ratio (δ18O) of NO3− were measured along three rivers of Tatara River Basin, Japan where upland forests have already been N-saturated. Geographic information system (GIS) based topographical analysis was also conducted to evaluate the land use as urban area in relation to topography. In two of the three rivers, NO3− concentrations did not increase from upstream to downstream, despite the potential non-point N sources of urban areas. In another river, NO3− concentrations rather decreased. The values of δ15N and δ18O of NO3− and organic N concentrations suggested the presence of denitrification and assimilation over N pollutants in the river whose watersheds have a lower percentage of urban area. The lower percentage of urban area could be explained by the lower topographic index. This study concluded that the NO3− leaching from upland N-saturated forests was substantially assimilated or denitrified in the downstream area

Mild encephalopathy with reversible lesions in the splenium of corpus callosum and bilateral cerebral deep white matter in identical twins

Identical twin brothers developed mild encephalopathy at the age of 7.0 and 9.7 years (Patient 1) and 10.7 years (Patient 2). Patient 1 had influenza A at the time of his second episode, but triggering agents were not evident at the first episode. The triggering agents in Patient 2 were unclear. The neurological features of both patients included transient facial numbness, left arm paresis, dysarthria, and gait disturbance. Diffusion-weighted images from magnetic resonance imaging showed high signal levels at the splenium of corpus callosum and in the bilateral cerebral deep white matter. These results are characteristic of mild encephalitis/encephalopathy with a reversible isolated splenium of corpus callosum lesion. All three episodes were treated with a methylprednisolone pulse. Acyclovir was also administered to Patient 2 and to Patient 1 during his first episode. Patient 1 received an anti-influenza agent and intravenous immunoglobulin during his second episode. Both patients recovered completely without sequelae. Genetic factors, which may predispose identical twins to develop encephalopathy, are discussed

Gitelman Syndrome in a School Boy Who Presented with Generalized Convulsion and Had a R642H/R642W Mutation in the SLC12A3 Gene

An 8-year-old Japanese boy presented with a generalized convulsion. He had hypokalemia (serum K 2.4 mEq/L), hypomagnesemia, and metabolic alkalosis (BE 5.7 mmol/L). In addition, his plasma renin activity was elevated. He was tentatively diagnosed with epilepsy on the basis of the electroencephalogram findings and was treated by potassium L-aspartate and carbamazepine to control the hypokalemia and seizure, respectively. However, a year later, the patient continued to have similar abnormal laboratory data. A presumptive diagnosis of Gitelman syndrome (GS) was then made and the patient’s peripheral blood mononuclear cells were subjected to sequence analysis of the SLC12A3 gene, which encodes a thiazide-sensitive sodium-chloride cotransporter. The patient was found to have compound heterozygous mutations, namely, R642H inherited from his father and R642W inherited from his mother. Thus, if a patient shows persistent hypokalemia and metabolic alkalosis, GS must be considered, even if the patient exhibits atypical clinical symptoms

Neonatal Sweet’s syndrome associated with rectovestibular fistula with normal anus

Sweet’s syndrome, characterized by fever and a painful erythematous rash with a dermal neutrophilic infiltrate, develops primarily due to paraneoplastic phenomena in adults. Sweet’s syndrome is very rare in neonates. We report a Japanese female neonate (age &lt;2 months), who developed Sweet’s syndrome with episodes of perineal infection in association with congenital rectovestibular fistula with normal anus. Sweet’s syndrome was diagnosed basing on clinical features and histopathology of biopsied skin tissues. Rectovestibular fistula was confirmed after the signs of inflammation subsided and the rash disappeared. In the literature, we found another case of neonatal Sweet’s syndrome associated with rectovestibular fistula in a Japanese female neonate. The perineal region should be screened for anomalies following diagnosis of Sweet’s syndrome in neonates