The Constrained Maximal Expression Level Owing to Haploidy Shapes Gene Content on the Mammalian X Chromosome.

X chromosomes are unusual in many regards, not least of which is their nonrandom gene content. The causes of this bias are commonly discussed in the context of sexual antagonism and the avoidance of activity in the male germline. Here, we examine the notion that, at least in some taxa, functionally biased gene content may more profoundly be shaped by limits imposed on gene expression owing to haploid expression of the X chromosome. Notably, if the X, as in primates, is transcribed at rates comparable to the ancestral rate (per promoter) prior to the X chromosome formation, then the X is not a tolerable environment for genes with very high maximal net levels of expression, owing to transcriptional traffic jams. We test this hypothesis using The Encyclopedia of DNA Elements (ENCODE) and data from the Functional Annotation of the Mammalian Genome (FANTOM5) project. As predicted, the maximal expression of human X-linked genes is much lower than that of genes on autosomes: on average, maximal expression is three times lower on the X chromosome than on autosomes. Similarly, autosome-to-X retroposition events are associated with lower maximal expression of retrogenes on the X than seen for X-to-autosome retrogenes on autosomes. Also as expected, X-linked genes have a lesser degree of increase in gene expression than autosomal ones (compared to the human/Chimpanzee common ancestor) if highly expressed, but not if lowly expressed. The traffic jam model also explains the known lower breadth of expression for genes on the X (and the Z of birds), as genes with broad expression are, on average, those with high maximal expression. As then further predicted, highly expressed tissue-specific genes are also rare on the X and broadly expressed genes on the X tend to be lowly expressed, both indicating that the trend is shaped by the maximal expression level not the breadth of expression per se. Importantly, a limit to the maximal expression level explains biased tissue of expression profiles of X-linked genes. Tissues whose tissue-specific genes are very highly expressed (e.g., secretory tissues, tissues abundant in structural proteins) are also tissues in which gene expression is relatively rare on the X chromosome. These trends cannot be fully accounted for in terms of alternative models of biased expression. In conclusion, the notion that it is hard for genes on the Therian X to be highly expressed, owing to transcriptional traffic jams, provides a simple yet robustly supported rationale of many peculiar features of X's gene content, gene expression, and evolution

常用量アセトアミノフェンによる昏睡型急性肝不全の一例

アセトアミノフェン（acetaminophen:AAP）は，一般に非ステロイド性抗炎症薬（non-steroidal anti-inflammatory drugs:NSAIDs）と比較して副作用が少ない解熱鎮痛薬として，高齢者や肝腎機能障害を有する患者にも頻用されている。一方で肝障害の副作用が知られ，肝疾患のある患者では1,500 mg/日以下とすべきであると記載されている。今回，常用量AAPによる昏睡型肝不全の一例を経験したので報告する。症例は意識障害を主訴に当院へ救急搬送された73歳の女性。左変形性膝関節症に対して，左膝関節全置換術施行後もAAP 1,200 mg/日の内服を2カ月間継続していた。搬送時にJapan Coma Score （JCS） 200の意識障害と黄疸，全身性浮腫を認めた。高度の肝機能障害と凝固障害，肝萎縮があり，昏睡型急性肝不全と診断し加療を開始した。集学的に加療を行ったものの，第7病日に痙攣が出現し呼吸状態悪化に伴い亡くなった。本症例はAAPによる薬物性肝障害（drug-induced liver injury:DILI） であったと判断した。以前より指摘されていた非アルコール性脂肪性肝疾患（nonalcoholic fatty liver disease:NAFLD）と高齢により，DILIのリスクが高かったと考えた。本症例のようにDILIの危険性のある症例では，定期的な肝機能検査の施行や，症状改善に伴う頓服への変更または減量が推奨される。Acetaminophen (AAP) is an antipyretic and analgesic drug with fewer side effects than NSAIDs, and is frequently prescribed for the elderly and patients with hepatic and renal dysfunction. On the other hand, known side effects of AAP include hepatic damage, for which reason its dose is recommended to be less than 1,500 mg/day in patients with hepatic disease. Herein, we describe a case of acute hepatic failure with hepatic coma attributed to regular doses of AAP. A 73-year-old woman in a coma was brought to our hospital. She had been taking 1,200 mg/day of AAP for 2 months after a total knee arthroplasty for left knee osteoarthritis. At the time of admission, the patient’s Japan Coma Scale (JCS) score was 200; she had jaundice and generalized edema. With severe liver dysfunction, coagulopathy, and hepatic atrophy, she was diagnosed with acute hepatic failure and hepatic coma. Despite aggressive multidisciplinary treatment, the patient died on the seventh day of hospitalization, with convulsions and worsening of respiratory status. We concluded that this was a case of drug-induced liver injury (DILI) caused by AAP. The risk of DILI was considered to be high due to the presence of nonalcoholic fatty liver disease (NAFLD), previously diagnosed, and advanced age. In patients at risk of DILI, as in the present case, periodic liver function tests should guide the cessation or dose reduction of AAP to minimize risks of hepatic dysfunction and possible mortality

Usefulness of intraoperative esophagogastroduodenoscopy in a patient with lupus enteritis

A 19-year-old Japanese woman had melena 2 months after systemic lupus erythematosus was diagnosed. Colonoscopy showed diffuse ulceration with bleeding in the ileum, suggesting that the melena was due to ischemic enteritis associated with lupus enteritis. Because treatment with high doses of steroid, anticoagulants, and cyclophosphamide pulse was ineffective, surgical intervention was planned. On exploration, it was impossible to determine the extent of resection visually. Intraoperative esophagogastroduodenoscopy clearly revealed the border between the ulcer and normal area, permitting successful resection of the ileum and ileostomy. This is the first report to document the usefulness of esophagogastroduodenoscopy in surgical treatment of ischemic enteritis in a patient with systemic lupus erythematosus