ブドウ球菌の表皮ケラチノサイトからの選択的抗菌ペプチドの誘導

Staphylococcus aureus (S. aureus) is one of the most clinically important inflammation-inducing pathogens, while Staphylococcus epidermidis (S. epidermidis) is nonpathogenic and hardly causes inflammation on skin. β-defensins, antimicrobial peptides, are secreted from keratinocytes constitutively or upon induction by various microorganisms. However, the difference between S. aureus and S. epidermidis is still unclear in terms of their influences on the production of β-defensins. In this study, we focused on the influences of S. aureus and S. epidermidis on the keratinocyte innate immune response. Pathogenic S. aureus mainly induced human β-defensin (hBD) 1 and hBD3, but not hBD2, and nonpathogenic S. epidermidis mainly induced hBD2 from human keratinocytes. Molecular weight fractions of >10 kDa prepared from S. aureus supernatants induced the production of hBD1 and hBD3. On the other hand, molecular weight fraction of >100 kDa prepared from S. epidermidis supernatants induced the production of hBD2.Furthermore, the secreted products of S. epidermidis used the toll-like receptor (TLR) 2 pathway in the induction of hBD2 production. The secreted products of S. aureus and S. epidermidis differentially induced subtypes of hBD through different receptors, which may be associated with the difference in virulence between these two bacteria.博士（医学）・甲第643号・平成28年3月15日Copyright © 2012 Elsevier Ltd. All rights reserved

Post-fracture Rehabilitation Effects on Brain Function in Older People

[Background] Deterioration of cognitive function is an underlying cause of older people’s fractures. The purpose of this study was to evaluate electroencephalogram and cognitive function in patients hospitalized with fractures, both at admission (before intervention) and at the time of discharge (after intervention), to investigate the effects of rehabilitation on brain function. [Methods] A total of 24 patients hospitalized with fracture due to a fall were enrolled in this study. All the subjects received 140 minutes of rehabilitation every day during hospitalization. Touch Panel-type Dementia Assessment Scale (TDAS) was used to test their cognitive function. In electroencephalography (EEG), the Neuronal Activity Topography (NAT) system was used to calculate the “Alzheimer’s disease (AD) - normal controls (NLc) differential similarity” in sNAT, ie, a numerical index to show the proximity to AD or normal NLc. [Results] There was no significant difference in the total TDAS score among subjects who were examined before and after intervention, but 12 subjects who were observed with deterioration of cognitive functionat at before intervention had a significant improvement in “word-recognition,” a sub-item in TDAS (P < 0.05). In addition, the NAT analysis findings showed that the differential similarity in sNAT significantly approached the NLc pattern (P < 0.05). [Conclusion] EEGs in patients with fractures resulting from a fall became more similar to NL patterns at the time of discharge. In addition, recent-memory function of patients who had decline in cognitive function improved

Emotional Experiences of Skin Markings Among Patients Undergoing Radiotherapy and Related Factors: A Questionnaire-Based Cross-Sectional Study

Purpose: Patients undergoing radiotherapy often have their skin marked. Previous studies on skin markings examined the durability and physical effects of the markings, but no study has focused on patients' emotional experiences toward the markings. This study aimed to clarify how patients undergoing radiotherapy feel about skin markings, as well as factors that affect patients' emotional experiences. Patients and Methods: We conducted a cross-sectional study using a self-administered questionnaire and medical records. Participants were patients aged ≥20 years undergoing cancer radiotherapy at a designated cancer care hospital. The primary outcome was the level of uncomfortable emotions toward skin markings, and the secondary outcome was the level of favorable ratings on skin markings. To examine factors related to uncomfortable emotions, ordinal logistic regression analysis was performed. Results: Questionnaire forms were distributed to 153 patients, and responses were collected from 132 (86%). Among 108 patients included in the analysis, 56% (59/105, excluding 3 who did not answer this question) responded that they were uncomfortable with skin markings. The proportion of patients who favorably rated skin markings was 63% (59/93, excluding 15 who did not answer this question). No factors were significantly associated with the primary outcome. Conclusion: Many patients accepted skin markings with resignation, as they understood the necessity of the markings in their treatment. Medical staff should understand the emotional experiences of patients toward skin markings and take sufficient care to ensure that they are provided with explanations, including the impact of skin markings on their daily lives, as well as a sense of security that treatment is being performed in a precise manner

Deregulation of the Histone Lysine-Specific Demethylase 1 Is Involved in Human Hepatocellular Carcinoma

Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer and is a leading cause of cancer-related death worldwide. Given that the standard-of-care for advanced liver cancer is limited, there is an urgent need to develop a novel molecular targeted therapy to improve therapeutic outcomes for HCC. In order to tackle this issue, we conducted functional analysis of the histone lysine-specific demethylase (LSD1) to explore the possibility that this enzyme acts as a therapeutic target in HCC. According to immunohistochemical analysis, 232 of 303 (77%) HCC cases showed positive staining of LSD1 protein, and its expression was correlated with several clinicopathological characteristics, such as female gender, AFP (alpha-fetoprotein) levels, and HCV (hepatitis C virus) infectious. The survival curves for HCC using the Kaplan–Meier method and the log-rank test indicate that positive LSD1 protein expression was significantly associated with decreased rates of overall survival (OS) and disease-free survival (DFS); the multivariate analysis indicates that LSD1 expression was an independent prognostic factor for both OS and DFS in patients with HCC. In addition, knockout of LSD1 using the CRISPR/Cas9 system showed a significantly lower number of colony formation units (CFUs) and growth rate in both SNU-423 and SNU-475 HCC cell lines compared to the corresponding control cells. Moreover, LSD1 knockout decreased cells in S phase of SNU-423 and SNU-475 cells with increased levels of H3K4me1/2 and H3K9me1/2. Finally, we identified the signaling pathways regulated by LSD1 in HCC, including the retinoic acid (RA) pathway. Our findings imply that deregulation of LSD1 can be involved in HCC; further studies may explore the usefulness of LSD1 as a therapeutic target of HCC