Protective effects of cold spinoplegia with fasudil against ischemic spinal cord injury in rabbits

ObjectiveParaplegia remains a serious complication after surgical repair of thoracoabdominal aortic aneurysms. The aim of this study was to evaluate the neuroprotective efficacy of fasudil, a Rho kinase (ROCK) inhibitor, by reducing the number of infiltrating cells in the ventral horn and increasing the induction of eNOS against ischemic spinal cord injury in rabbits.MethodsEighteen Japanese white rabbits were divided into three groups: saline (group 1, n = 7, 4°C) and fasudil (group 2, n = 6, 4°C) were immediately infused into the isolated segmental lumbar arteries over 30 seconds after aortic clamping. Group 3 (n = 5) was the sham-operated group. Hind limb function was evaluated 4 and 8 hours, and 1 and 2 days after 15 minutes of transient ischemia. Cell damage was analyzed by hematoxylin and eosin staining and temporal profiles of endothelial nitric oxide synthase immunoreactivity were performed. The number of intact motor neuron cells and infiltrating cells in the ventral horn were compared.ResultsTwo days after reperfusion, group 2 and group 3 showed better neurologic function, a greater number of intact motor neuron cells, and a smaller number of infiltrating cells in the ventral horn than group 1. The induction of endothelial nitric oxide synthase (eNOS) was prolonged up to 2 days after reperfusion in group 2.ConclusionThese results indicate that fasudil has neuroprotective effects against ischemic spinal cord injury in rabbits by reducing the number of infiltrating cells in the ventral horn and prolonging the expression of eNOS.Clinical RelevanceParaplegia or paralysis caused by spinal cord ischemia remains a devastating and unpredictable complication after descending and thoracoabdominal aortic surgery. This study has revealed that fasudil has a neuroprotective effect against ischemic spinal cord injury in rabbits. Inhibition of the Rho/Rho kinase pathway by fasudil reduces the number of infiltrating cells in the ventral horn and prolongs the expression of eNOS. In the near future, Rho kinase may be an important therapeutic target for paraplegia induced by spinal cord ischemia

Bryosphere within an Antarctic moss pillar

第6回極域科学シンポジウム分野横断セッション：[IB2] 地球環境変動の解析と地球生命システム学の構築11月19日（木）　統計数理研究所 セミナー室1（D305

極限環境適応における微生物ゲノムの生命情報学

第6回極域科学シンポジウム分野横断セッション：[IB2] 地球環境変動の解析と地球生命システム学の構築11月19日（木）　統計数理研究所 セミナー室1（D305

Protective effects of glycoglycerolipids extracted from spinach on 5-fluorouracil induced intestinal mucosal injury

Glycoglycerolipids are mostly found in plants, however the beneficial effects of the glycoglycerolipids on mammalian body have not been understood. In this study, we investigated the effects of glycolipid extracts from spinach, which highly contained glycoglycerolipids, on mucosal injury induced by 5-fluorouracil (5-FU) in rats. Preadministration of glycolipid extracts from spinach (20 mg/kg body weight) prevented villous atrophy, misaligned crypts, and increased inflammatory cytokines in rat jejunum treated with 5-FU (300 mg/kg body weight) compared with the extracts from soybean. The glycolipid extracts from spinach highly contained monogalactosyl-diacylglycerol (MGDG) and diglactosyl-diacylglycerol (DGDG). In Caco-2 cells, MGDG and DGDG inhibited the production of reactive oxygen species induced by phorbol ester. We concluded that glycolipid extracts from spinach has anti-oxidative and anti-inflammatory effects, and the extract may be useful for prevention of drug-induced mucosal injury and other inflammatory diseases

Two cases of multiple infarctions due to vertebral arterial occlusion associated with atlantoaxial subluxation caused by rheumatoid arthritis

Case 1: A 58-year-old woman with rheumatoid arthritis (RA) suffered from pontine and cerebellar infarctions and underwent three-dimensional computed tomography angiography (3D-CTA) of the vertebral artery (VA) with left-sided rotation of the head. This revealed a destroyed right atlantoaxial (AA) joint and right VA occlusion, which had caused the infarction. No recurrent infarctions have been observed after transarticular screw fixation (Magerl technique) was performed. Case 2: A 68-yearold woman with RA also suffered from pontine and cerebellar infarctions and underwent 3D-CTA of the VA with right-sided rotation of the head. This revealed a destroyed left AA joint and left VA occlusion, which had caused the infarction. No recurrentinfarctions have been observed after posterior fusion between the occiput and 3rd cervical vertebra was performed. In both cases of RA, who had multiple infarctions due to VA occlusion and a temporary thrombus formation, 3D-CTA in a rotated position helped to diagnose arterial occlusion. In addition, posterior fusion of the AA joint was a useful surgical technique

The case of double primary lung adenocarcinomas with an EGFR mutation and ALK translocation successfully treated with alectinib at the post-surgicalrecurrence

A 36-year-old male was found two nodules in the right lower lobe of the lung. After the surgical resection, both lesions were diagnosed as invasive adenocarcinomas. One lesion was primarily lepidic growth component with EGFR-L858R mutation, and the other was micropapillary component with ALK translocation accompanying mediastinal lymphnode metastases. While he experienced disease recurrence, the disease was controlled by an ALK inhibitor, given based on the findings of surgical specimens. This is the first case who had two simultaneous lung cancers with EGFR mutation and ALK translocation in each respective lesion, and was successfully treated with ALK inhibitor at the post-surgical recurrence

Calaxin is required for cilia-driven determination of vertebrate laterality

Sasaki, K., Shiba, K., Nakamura, A. et al. Calaxin is required for cilia-driven determination of vertebrate laterality. Commun Biol 2, 226 (2019). https://doi.org/10.1038/s42003-019-0462-

An oxyl/oxo mechanism for dioxygen bond formation in PSII revealed by X-ray free electron lasers

Photosynthetic water oxidation is catalyzed by the Mn4CaO5 cluster of photosystem II (PSII) with linear progression through five S-state intermediates (S0 to S4). To reveal the mechanism of water oxidation, we analyzed structures of PSII in the S1, S2, and S3 states by x-ray free-electron laser serial crystallography. No insertion of water was found in S2, but flipping of D1 Glu189 upon transition to S3 leads to the opening of a water channel and provides a space for incorporation of an additional oxygen ligand, resulting in an open cubane Mn4CaO6 cluster with an oxyl/oxo bridge. Structural changes of PSII between the different S states reveal cooperative action of substrate water access, proton release, and dioxygen formation in photosynthetic water oxidation

注意障害事例の行動の特徴と機能評価との関連性：観察記録のテキストマイニングによる分析とTrail Making Test の検討より

研究報告Original Articles　本研究は，注意機能の評価として広く一般的に行われているTrail Making Test（TMT）の評価結果と，日常における行動の特徴との関連性を明らかにすることを目的とした探索的研究である．対象は，日本における医学論文情報のインターネット検索サービスである医中誌WEB に1999 年～2012 年までの13 年間に登録された文献のうち，“ 作業療法” と，“ 注意障害” をキーワードとして検索した（2013 年5 月検索）．その結果31 例の作業療法士が報告する症例を得たが，それらの内でTMT を評価として用いていた17 症例を対象とした．17 症例の報告から，34 組の行動の観察記録とTMT の評価結果を抽出し，行動の観察記録をテキストマイニング手法により分析した後，TMT の結果と照らし合わせて比較検討した．検討の結果，4 段階に分かれたTMT の遂行レベルについて，各々の段階の行動の特徴が明らかとなった．　The present exploratory study was aimed to examine the relationship between the results of the trail-making test (TMT), a common test to assess attentional function, and the behavioral characteristics in people with attentional deficits in daily life. A search of documents for a thirteen-year period, between 1999 and 2012, was conducted in May 2013, using Ichushi-Web, an Internet search service containing information on Japanese medical papers, with the keywords : “occupational therapy” and “attention deficits”. There were 31 papers written by occupational therapists, and 17 which adopted the TMT for assessment were selected. Observation records of the behaviors of 34 subjects and TMT assessment results were extracted from the 17 papers. The observation records were analyzed using text-mining, and the analysis results were compared with those of TMT assessment. The TMT assessment results were classified into four levels, and the characteristics of the behaviors at each level were identified

Evolutionary histories of breast cancer and related clones

乳がん発生の進化の歴史を解明 --ゲノム解析による発がんメカニズムの探索--. 京都大学プレスリリース. 2023-07-28.Tracking the ol' mutation trail: Unraveling the long history of breast cancer formation. 京都大学プレスリリース. 2023-08-31.Recent studies have documented frequent evolution of clones carrying common cancer mutations in apparently normal tissues, which are implicated in cancer development1, 2, 3. However, our knowledge is still missing with regard to what additional driver events take place in what order, before one or more of these clones in normal tissues ultimately evolve to cancer. Here, using phylogenetic analyses of multiple microdissected samples from both cancer and non-cancer lesions, we show unique evolutionary histories of breast cancers harbouring der(1;16), a common driver alteration found in roughly 20% of breast cancers. The approximate timing of early evolutionary events was estimated from the mutation rate measured in normal epithelial cells. In der(1;16)(+) cancers, the derivative chromosome was acquired from early puberty to late adolescence, followed by the emergence of a common ancestor by the patient’s early 30s, from which both cancer and non-cancer clones evolved. Replacing the pre-existing mammary epithelium in the following years, these clones occupied a large area within the premenopausal breast tissues by the time of cancer diagnosis. Evolution of multiple independent cancer founders from the non-cancer ancestors was common, contributing to intratumour heterogeneity. The number of driver events did not correlate with histology, suggesting the role of local microenvironments and/or epigenetic driver events. A similar evolutionary pattern was also observed in another case evolving from an AKT1-mutated founder. Taken together, our findings provide new insight into how breast cancer evolves