Search

Immediately after the initial methionine codon, the PABPN1 gene encodes a stretch of 10 alanines, 1 glycine, and 2 alanines. Oculopharyngeal muscular dystrophy (OPMD) is caused by the expansion of the first 10 alanine stretches. The only exception is the missense mutation of glycine at the 12th residue into alanine, which elongates the stretch to 13 alanines by connecting the first and second stretch with the addition of one alanine in between, indicating that the expansion or elongation of the alanine stretch results in OPMD. We report a 77-year-old man with the novel missense mutation c.34G > T (p.Gly12Trp) in PABPN1 gene whose clinicopathological findings were compatible with OPMD. He presented with slowly progressive bilateral ptosis, dysphagia, and symmetrical proximal dominant muscle weakness. Magnetic resonance imaging revealed selective fat replacement of the tongue, bilateral adductor magnus, and soleus muscles. Immunohistochemistry studies of the muscle biopsy sample revealed PABPN1-posibive aggregates in the myonuclei which have been reported to be specific to OPMD. This is the first OPMD case caused by neither the expansion nor the elongation of alanine stretch. The present case suggests that OPMD may be caused not only by triplet repeats but also by point mutations.

INTRODUCTION: From previous research, an emerging material composed of gelatin hydrogel nonwoven fabric (Genocel) has shown potential as a skin substitute, by improving neovascularization promotion in the early phase of wound healing. However, Genocel was inferior in terms of granulation formation compared to Pelnac. To solve this problem, we modified the manufacturing process of Genocel to reduce its water content, extend the degradation time (Genocel-L), and evaluate its healing process as a skin substitute. METHODS: Genocel with a low water content (Genocel-L) was prepared and the difference in water content compared to that of the conventional Genocel was confirmed. Degradation tests were performed using collagenase and compared among Genocel-L, Genocel, and Pelnac sheets. In the in vivo study, sheets of Genocel-L or Pelnac were applied to skin defects created on the backs of C57BL/6JJcl mice. On days 7, 14, and 21, the remaining wound area was evaluated and specimens were harvested for Hematoxylin and Eosin, Azan, anti-CD31, CD68, and CD163 staining to assess neoepithelialization, granulation tissue, capillary formation, and macrophage infiltration. RESULTS: Genocel-L had a lower water content than the conventional Genocel and a slower degradation than Genocel and Pelnac. In the in vivo experiment, no significant differences were observed between Genocel-L and Pelnac in relation to the wound area, neoepithelium length, granulation formation, and the number of newly formed capillaries. The area of newly formed capillaries in the Pelnac group was significantly larger than that in the Genocel-L group on day 21 (p

AIMS: Several studies demonstrated that tricuspid regurgitation (TR) is associated with poor clinical outcomes. However, data on patients with TR who experienced acute heart failure (AHF) remains scarce. The purpose of this study is to evaluate the association between TR and clinical outcomes in patients admitted with AHF, using a large-scale Japanese AHF registry. METHODS AND RESULTS: The current study population consisted of 3735 hospitalized patients due to AHF in the Kyoto Congestive Heart Failure (KCHF) registry. TR grades were assessed according to the routine clinical practice at each participating centre. We compared the baseline characteristics and outcomes according to the severity of TR. The primary outcome was all-cause death. The secondary outcome was hospitalization for heart failure (HF). The median age of the entire study population was 80 (interquartile range: 72-86) years. One thousand two hundred five patients (32.3%) had no TR, while mild, moderate, and severe TR was found in 1537 patients (41.2%), 776 patients (20.8%), and 217 patients (5.8%), respectively. Pulmonary hypertension, significant mitral regurgitation, and atrial fibrillation/flutter were strongly associated with the development of moderate/severe of TR, while left ventricular ejection fraction

The UV light densitometer was developed to measure concentration of gases having absorption in the ultraviolet region using UV absorption method. The developed densitometer was applied to monitor temporal variation of concentration of ALD precursor TEMAZ introduced into a chamber, where TEMAZ was introduced alternately with purge Ar gas to simulate ALD process. We could successfully capture temporal variation of gas concentration such as time delay in arrival of gas in the chamber due to presence of gas flow. Such phenomenon cannot be measured by the pressure gauge.

Background: Due to clinicoradiological similarities, including amnestic cognitive impairment and limbic atrophy, differentiation of argyrophilic grain disease (AGD) from Alzheimer’s disease (AD) is often challenging. Minimally invasive biomarkers, especially magnetic resonance imaging (MRI), are valuable in routine clinical practice. Although it is necessary to explore radiological clues, morphometry analyses using new automated analytical methods, including whole-brain voxel-based morphometry (VBM) and surface-based morphometry (SBM), have not been sufficiently investigated in patients with pathologically confirmed AGD and AD. Objective: This study aimed to determine the volumetric differences in VBM and SBM analyses between patients with pathologically confirmed AGD and AD. Methods: Eight patients with pathologically confirmed AGD with a lower Braak neurofibrillary tangle stage (

Genetic conflicts shape the genomes of prokaryotic and eukaryotic organisms. Here, we argue that some of the key evolutionary novelties of adaptive immune systems of vertebrates are descendants of prokaryotic toxin-antitoxin (TA) systems. Cytidine deaminases and RAG recombinase have evolved from genotoxic enzymes to programmable editors of host genomes, supporting the astounding discriminatory capability of variable lymphocyte receptors of jawless vertebrates, as well as immunoglobulins and T cell receptors of jawed vertebrates. The evolutionarily recent lymphoid lineage is uniquely sensitive to mutations of the DNA maintenance methylase, which is an orphaned distant relative of prokaryotic restriction-modification systems. We discuss how the emergence of adaptive immunity gave rise to higher order genetic conflicts between genetic parasites and their vertebrate host.

A 52-year-old male was carried to hospital by ambulance, because of an abrupt abnormal behavior and impaired consciousness. Soon after the arrival, the patient started a generalized seizure. Although the seizure was stopped by Midazolam, amnesia were observed. With meningeal irritation signs, in addition to the clinical course, the patient was thought to develop limbic encephalitis. The cause of the encephalitis was diagnosed as neurosyphilis because of the positive serum and CSF syphilis reactions, and the patient was treated with penicillin G from the first admission day on. Steroid pulse therapy was also conducted, followed by acyclovir since herpes encephalitis could not be ruled out; the brain MRI showed left-side dominant T

in press

Gastrointestinal stromal tumors (GIST) with KIT exon 11 deletions involving in codons 557–558 (KIT Δ557–558) exhibit higher proliferation rates and shorter disease-free survival times compared with GISTs with other KIT exon 11 mutations. We analyzed 30 GIST cases and observed genomic instability and global DNA hypomethylation only in high-risk malignant GISTs with KIT Δ557–558. Whole-genome sequencing revealed that the high-risk malignant GISTs with KIT Δ557–558 (12 cases) had more structural variations (SV), single-nucleotide variants, and insertions and deletions compared with the low-risk, less malignant GISTs with KIT Δ557–558 (six cases) and the high-risk (six cases) or low-risk (6 cases) GISTs with other KIT exon 11 mutations. The malignant GISTs with KIT Δ557–558 showed higher frequency and significance in copy number (CN) reduction on chromosome arms 9p and 22q, and 50% of them had LOH or CN-dependent expression reduction in CDKN2A. In addition, SVs with driver potential were detected in 75% of them, in which AKT3 and MGMT were recurrently identified. Genome-wide DNA methylation and gene expression analyses showed global intergenic DNA hypomethylation, SNAI2 upregulation, and higher expression signatures, including p53 inactivation and chromosomal instability, as characteristics of malignant GISTs with KIT Δ557–558 that distinguished them from other GISTs. These genomic and epigenomic profiling results revealed that KIT Δ557–558 mutations are associated with increased genomic instability in malignant GISTs. Significance: We present genomic and epigenomic insights into the malignant progression of GISTs with KIT exon 11 deletions involving in 557–558, demonstrating their unique chromosomal instability and global intergenic DNA hypomethylation.

Regulatory T cells (Tregs) are produced in the thymus to establish self-tolerance, and agonistic stimuli by self-Ags play a pivotal role in this process. Although two types of APCs, medullary thymic epithelial cells (mTECs) and dendritic cells (DCs), are responsible for presenting self-Ags together with costimulatory/cytokine signals, the distinct role of each APC in producing Tregs remains enigmatic. We have approached this issue by depleting the mTECs and DCs using mice expressing diphtheria toxin receptors driven by Aire and CD11c promoters, respectively. Depletion of mTECs showed an effect on Treg production quantitatively and qualitatively more profound than that of DCs followed by the development of distinct organ-specific autoimmune lesions in the hosts. Because self-Ags produced by mTECs are transferable to DCs through a process known as Ag transfer, we monitored the process of Ag transfer using mice expressing GFP from TECs. Although GFP expressed from total TECs was effectively transferred to DCs, GFP expressed from cortical TECs was not, suggesting that mTECs are the predominant source of self-Ags. We also found that GFP expressed not only from mature mTECs but also from immature mTECs was transferred to DCs, suggesting that a broad spectrum of molecules were subjected to Ag transfer during mTEC development. Interestingly, the numbers of recirculating non-Tregs producing IL-2, an important source for Treg expansion in the thymus, were reduced only in the mTEC-depleted mice. These results suggested the cooperative but distinct role of mTECs and DCs in the production of Tregs to avoid autoimmunity.

A 46-year-old woman with lung cancer who received chemotherapy was admitted to our hospital for lower-lobe bilateral ground-glass opacity (GGO). GGO developed after the lung cancer diagnosis, deteriorated after the initiation of osimertinib, and incompletely decreased after interrupting osimertinib; therefore, flexible bronchoscopy was performed. Transbronchial lung biopsy histology and anti-granulocyte/macrophage colony-stimulating factor autoantibody positivity revealed autoimmune pulmonary alveolar proteinosis (aPAP) that did not require treatment. This rare case of aPAP comorbid with lung cancer suggested that using PAP findings to differentiate from drug-induced lung injury or lymphangitis is difficult and that osimertinib was suspected to exacerbate aPAP.

BACKGROUND: Intravascular ultrasound (IVUS) was only rarely used in landmark trials comparing percutaneous coronary intervention (PCI) with coronary artery bypass grafting (CABG) in patients with multivessel disease. OBJECTIVES: The authors aimed to evaluate clinical outcomes after optimal IVUS-guided PCI in patients undergoing multivessel PCI. METHODS: The OPTIVUS (OPTimal IntraVascular UltraSound)-Complex PCI study multivessel cohort was a prospective multicenter single-arm study enrolling 1, 021 patients undergoing multivessel PCI, including left anterior descending coronary artery using IVUS, aiming to meet the prespecified criteria (OPTIVUS criteria: minimum stent area > distal reference lumen area [stent length≥28mm], and minimum stent area >0.8× average reference lumen area [stent length

特集 「ムハンマドの血筋」とムスリム : アリー一族をめぐる多様な語りと語り手たち, Special issue on Muslims, Islam, and the Kinfolk of ʿAlī: Discourses on the “Family of Prophet Muhammad” and Their Proponents

特集 「ムハンマドの血筋」とムスリム : アリー一族をめぐる多様な語りと語り手たち, 第一部 サイイド／シャリーフの立場をめぐる語りと語り手たち, Special issue on Muslims, Islam, and the Kinfolk of ʿAlī: Discourses on the “Family of Prophet Muhammad” and Their Proponents, Part I Perspectives on Sayyids and Sharīfs

application/pdf, COVID-19感染拡大予防における自粛生活の長期化は、高齢者の生活機能を低下させ、要介護状態を招く可能性を高める。生活機能は特に前期高齢者と比較して後期高齢者において低下しやすいとされている。しかし、その実態、特に在宅において健康維持に努めている高齢者への影響は十分に明らかにされていない。そこで、運動機能向上を主目的とした通いの場に参加する地域で自立した生活を送る高齢者に対し、COVID-19自粛下の生活の影響を検討するために、COVID-19前と比較して感じる運動量の変化と生活機能の実態を捉え、高齢者が感じる運動量の変化で生活機能にどのような特徴があるのかを明らかとすることを目的とした。, 研究デザインは既存のデータを用いた量的記述的研究であった。対象を、運動機能向上を目的とした通いの場に参加した65歳以上の高齢者とした。また、自粛生活において、運動量が「減ったと感じた者」と「減ったと感じていない者」で分類し、生活機能評価（基本チェックリスト・K6）や客観的評価（1日あたりの歩数・握力）を行った。さらに、前期高齢者、後期高齢者で層化した検討を行った。, 結果は、自粛生活の影響で運動量が「減ったと感じた者」が約25%いたが、実際に歩数や握力といった客観的評価項目に違いを認めなかった。後期高齢者において、運動量が「減ったと感じていない者」に比べて「減ったと感じた者」の該当割合は低栄養状態が有意に高く（p=0.012）、精神機能低下の該当割合に有意傾向がみられた（p=0.049）。, 運動量が「減ったと感じた者」は先行研究と比べて少なく、調査時期や調査地域の活動自粛の影響が軽微であった。また、特に運動量が減ったと感じている後期高齢者には、栄養や精神機能に重点を置いたアプローチの必要性が示唆された。, Prolonged self-quarantine to prevent the spread of COVID-19 infection may reduce activities of daily living (ADL) and function of older adults, and increase the risk of physical dysfunction. However, the effect of self-quarantine on ADL and function in the home-based dwelling of older adults has not been fully clarified. Therefore, this study elucidated whether the ADL and function of the community-dwelling members of the club of ‘Kayoinoba' during the period of self-quarantine. This was a quantitative and descriptive study that used existing data. The participants were 308 older adults who were members of the club of Kayoinoba, where they may improve their physical functions or keep their health. We collected data regarding the exercise (classified into two categories according to the individual's subjective activity levels), and subjective data regarding the ADL and function and objective evaluation., Consequently, approximately 25 % of the respondents felt that their physical activities had decreased because of the COVID-19 self-quarantine, but there was no statistical difference in objective evaluation. Among the late older adults, the proportion of low-level activity was significantly higher among those with malnutrition (p = 0.012) and those with lower mental function (p = 0.049)., The proportion of the older adults who thought that the amount of their physical activities had decreased was smaller than in previous studies, and the influence of the self-quarantine on their ADL and function was limited. The findings suggested that even late oleder adults (≥ 75 yr-old) who could be aware of their sedentary lives might keep their body healthy.

The purpose of this study was to classify patients with severe COVID-19 into more detailed risk groups using coagulation/fibrinolysis, inflammation/immune response, and alveolar/myocardial damage biomarkers, as well as to identify prognostic markers for these patients. These biomarkers were measured every day for eight intensive care unit days in 54 adult patients with severe COVID-19. The patients were classified into survivor (n = 40) and non-survivor (n = 14) groups. Univariate and multivariate analyses showed that the combined measurement of platelet count and presepsin concentrations may be the most valuable for predicting in-hospital death, and receiver operating characteristic curve analysis further confirmed this result (area under the curve = 0.832). Patients were consequently classified into three groups (high-, medium-, and low-risk) on the basis of their cutoff values (platelet count 53 × 103/µL, presepsin 714 pg/mL). The Kaplan–Meier curve for 90-day survival by each group showed that the 90-day mortality rate significantly increased as risk level increased (P