Sequence divergence and retrotransposon insertion underlie interspecific epigenetic differences in primates

内在性レトロウイルス配列によってヒトのエピゲノムが変化してきたことを発見！ --ヒトとチンパンジーのiPS細胞の比較解析から--. 京都大学プレスリリース. 2022-10-12.Changes in the epigenome can affect the phenotype without the presence of changes in the genomic sequence. Given the high identity of the human and chimpanzee genome sequences, a substantial portion of their phenotypic divergence likely arises from epigenomic differences between the two species. In this study, the transcriptome and epigenome were determined for induced pluripotent stem cells (iPSCs) generated from human and chimpanzee individuals. The transcriptome and epigenomes for trimethylated histone H3 at lysine-4 (H3K4me3) and lysine-27 (H3K27me3) showed high levels of similarity between the two species. However, there were some differences in histone modifications. Although such regions, in general, did not show significant enrichment of interspecies nucleotide variations, gains in binding motifs for pluripotency-related transcription factors, especially POU5F1 and SOX2, were frequently found in species-specific H3K4me3 regions. We also revealed that species-specific insertions of retrotransposons, including the LTR5_Hs subfamily in human and a newly identified LTR5_Pt subfamily in chimpanzee, created species-specific H3K4me3 regions associated with increased expression of nearby genes. Human iPSCs have more species-specific H3K27me3 regions, resulting in more abundant bivalent domains. Only a limited number of these species-specific H3K4me3 and H3K27me3 regions overlap with species-biased enhancers in cranial neural crest cells, suggesting that differences in the epigenetic state of developmental enhancers appear late in development. Therefore, iPSCs serve as a suitable starting material for studying evolutionary changes in epigenome dynamics during development

乳腺腺様嚢胞癌においてサイトケラチン5/6の腺腔形成細胞の染色性は類似病変との鑑別に有用である

Adenoid cystic carcinoma (AdCC) of the breast is an uncommon but distinct neoplasm composed of a dual cell population polarized around true glandular (luminal) spaces and pseudolumina. The aim of this study was to clarify whether various immunohistochemical markers (CK7, EMA, CD117, p63, calponin, CD10, S100, CK5/6, CK14, vimentin, and type IV collagen) can distinguish between the two cell types in classical AdCC (n = 14) and in collagenous spherulosis (n = 5). The sensitivity and specificity of these 11 markers to distinguish luminal from abluminal cells were evaluated using a curve created by plotting the true-positive rate (sensitivity) against the false-positive rate (1 - specificity) at threshold settings of 0, 10, 50, and 70 %. The most sensitive and specific markers for luminal cells in AdCC were CK7 and EMA; those for abluminal cells were type IV collagen, p63, and vimentin. CD10 and S100 did not act as abluminal markers in AdCC. CK5/6, one of the basal/myoepithelial markers, was expressed more frequently in luminal than in abluminal cells of AdCC. Thus, CK5/6 immunostaining resulted in a reverse expression pattern, analogous to what we recently documented in clear cells in mammary adenomyoepithelioma. In conclusion, compared with myoepithelial/abluminal cells of normal breast or collagenous spherulosis, the neoplastic abluminal cells of classical AdCC are characterized by enhanced vimentin and attenuated CD10 and S100. Furthermore, the luminal cells of AdCC show a unique aberrant staining pattern for CK5/6 that may aid in the differential diagnosis.博士（医学）・乙第1389号・平成28年11月24日© Springer-Verlag Berlin Heidelberg 2016The final publication is available at Springer via http://dx.doi.org/10.1007/s00428-016-1963-

内視鏡超音波ガイド下穿刺吸引の液状検体の残余を用いたK-ras 遺伝子検査は正診率を高める

Background: Endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) technology is widely used for the diagnosis of pancreatic masses. However, in some cases, inadequate tissue volume or difficulty of morphological diagnosis are constraining factors for adequate cytopathological evaluation. K-ras mutation is the most frequently acquired genetic abnormality, occurring in approximately 90% of all patients with pancreatic ductal adenocarcinoma (PDAC). In the present study, the clinical utility of residual liquid-based cytology (LBC) specimens obtained using EUS-FNA for K-ras mutation analysis was evaluated. Methods: In this study, 81 patients with pancreatic lesions were examined. The cell block (CB) specimens separated from EUS-FNA samples were morphologically evaluated by hematoxylin-eosin (HE) staining. Final diagnoses were confirmed by CB specimens, surgical resection specimens, diagnostic imaging, and clinical follow-up. Genomic DNA of residual LBC specimens stored at 4°C for several months were extracted and assessed for K-ras mutations using a fluorescence resonance energy transfer-based preferential homoduplex formation assay. Results: K-ras mutation analysis using residual LBC samples was successful in all cases. The sensitivity, specificity, and accuracy of CB examination alone were 77.4%, 100%, and 81.3%, respectively, and those of the combination of CB examination and K-ras mutation analysis were 90.3%, 92.3%, and 90.7%, respectively. Furthermore, K-ras mutations were detected in 8 (57.1%) of 14 PDAC samples for which the CB results were inconclusive. Conclusion: These findings suggest that K-ras mutation analysis using residual LBC specimens improves the diagnostic accuracy of EUS-FNA.博士（医学）・乙第1492号・令和2年12月24日Copyright: © 2018 Sekita-Hatakeyama et al. This is an open access article distributed under the terms of the Creative Commons Attribution License(https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

Exhaustion of nucleus pulposus progenitor cells with ageing and degeneration of the intervertebral disc.

Despite the high prevalence of intervertebral disc disease, little is known about changes in intervertebral disc cells and their regenerative potential with ageing and intervertebral disc degeneration. Here we identify populations of progenitor cells that are Tie2 positive (Tie2+) and disialoganglioside 2 positive (GD2+), in the nucleus pulposus from mice and humans. These cells form spheroid colonies that express type II collagen and aggrecan. They are clonally multipotent and differentiated into mesenchymal lineages and induced reorganization of nucleus pulposus tissue when transplanted into non-obese diabetic/severe combined immunodeficient mice. The frequency of Tie2+ cells in tissues from patients decreases markedly with age and degeneration of the intervertebral disc, suggesting exhaustion of their capacity for regeneration. However, progenitor cells (Tie2+GD2+) can be induced from their precursor cells (Tie2+GD2-) under simple culture conditions. Moreover, angiopoietin-1, a ligand of Tie2, is crucial for the survival of nucleus pulposus cells. Our results offer insights for regenerative therapy and a new diagnostic standard

Public health expenditure, governance and health outcomes in Malaysia

According to the World Health Organization (WHO), government plays a crucial role in providing quality life for its citizens through good health system. There has been less attention given in analysing the relationship between government expenditure, governance and health outcomes particularly in developing countries. This paper aims to study the impact of public health expenditure and governance on health outcomes in Malaysia. An Autoregressive Distributed Lag (ARDL) cointegration framework has been used to analyse data from 1984 to 2009. The results based on the bounds testing procedure show that a stable, long-run relationship exists between health outcomes and their determinants; namely income level, public health expenditure, corruption and government stability. The results also reveal that public health expenditure and corruption affect long- and short run health outcomes in Malaysia. The findings are important to the policy makers in making decisions to improve the citizens’ quality of life. We suggest the Ministry of Health of Malaysia to conduct more consultations with other ministries and other stakeholders in health services as to identify the needs and emphasize on the importance of health program to the society. At the same time, attention should be given to reduce or eliminate the corruption rate as it has adverse effects on the country

Influence of primary and secondary prevention indications on anxiety about the implantable cardioverter-defibrillator

AbstractBackgroundImplantable cardioverter-defibrillators (ICDs) have been established for primary and secondary prevention of fatal arrhythmias. However, little is known about the influence of ICD indications on quality of life (QOL) and psychological disturbances. This study aimed to examine whether there were differences in QOL and psychological distress in patients that have an ICD for primary or secondary prevention of fatal arrhythmias.MethodsA multicenter survey of 179 consecutive outpatients (29.1% primary prevention) with ICD implantations completed the Short Form-8 (SF-8), Beck Depression Inventory (BDI), Impact of Event Scale-Revised (IES-R), State-Trait Anxiety Inventory (STAI), and Worries about ICD (WAICD).ResultsPatients with an ICD for primary prevention had a higher trait anxiety score and worries about ICD score than patients with an ICD for secondary prevention (41.7±12.4 vs. 34.7±12.3, p=0.001 and 39.6±18.0 vs. 30.0±18.9, p=0.002, respectively), even after adjusting for demographic and clinical characteristics. In multivariable analysis of variance, primary prevention ICD recipients reported a poorer QOL on the vitality subscale of the SF-8.ConclusionsIn our study population, which mostly consisted of New York Heart Association (NYHA) class I and II subjects, primary prevention ICD recipients were more prone to experience worries about their ICD, anxiety, and a poorer QOL compared to secondary prevention ICD recipients. In clinical practice, primary prevention ICD patients should be closely monitored. If warranted, they should be offered psychological intervention, as anxiety and low QOL were predictors of mortality

B ビョウイン ノ サンゴ ケアニュウイン ノ カダイ ニ ツイテ ノ イチコウサツ : -サンゴ 4カゲツ マデノ ハハオヤ ノ イクジ サポート ジョウキョウ ノ チョウサケッカ カラ -

背景 近年, 乳幼児虐待予防の観点から産後ケア事業が注目されている. A県のB病院は, 産後ケア入院事業を開設したが, 利用者が少なく事業目的が果たせていない現状である.目的 産後4ヶ月までの育児サポート状況を明確化し, A県B病院の産後ケア入院の課題について考察することを目的とする.方法 産後4ヶ月から1年未満の母親37名を対象に, 産後4ヶ月までのサポート状況と満足度, 専門家に望むサポート, 産後ケア入院に関する質問紙調査を行った.結果および考察 産後1ヶ月までの主な育児サポート者は実母82.9%, 夫68.6%で, 満足群は95.1%であった. 産後1ヶ月以降は, 夫85.7%, 実母94.3%で, サポート者なしが2.9%で, 満足群は82.9%であったが, 不満足群が2.9%から17.1%に増加したことから, この時期の育児サポートは必要性が高いと考える. 産後ケア入院について 「知らない」 者は62.9%であった. 「知らない」 者のうち50%は 「事前に知っていたら利用した」 と回答しており, 効果的な広報活動が必要である.Background The postpartum care enterprise attracts attention. Although B hospital of A prefecture established the postpartum care hospitalization enterprise, a user is the present condition that the business purpose cannot be achieved few.Objective The childcare support situation by four months of postpartum is clarified, and it aims at considering the subject of postpartum care hospitalization of an A prefectural B hospital.Methods Candidates are 37 mothers for less than one year from four months of postpartum.Results/Discussion The main support persons by one month of postpartum were 82.9% of a biological mother, and 68.6% of a husband, and the satisfactory group was 95.1%. The support persons after one month of postpartum were 85.7% of a husband, and 94.3% of a biological mother, those without a support person were 2.9%, and the satisfactory group was 82.9%. However, the dissatisfied group to child-rearing increased to 17.1% from 2.9%.Therefore, I think that the childcare support after one month of postpartum has high necessity. Next, those who "do not know" postpartum care hospitalization were 62.9%.Since 50% of those who "do not know" postpartum care hospitalization answered, "It used when knowing in advance", it thinks that effective publicity work is required