体の痛み、社会的支援、抑うつ状態、脳血管疾患は独立して高齢者の睡眠障害と関連する : 藤原京スタディ横断解析

OBJECTIVE: To investigate independent effects of various factors associated with sleep disturbance among community-dwelling elderly individuals. METHODS: We analyzed data obtained from 3732 individuals aged ≥65 years who responded to a self-administered questionnaire and participated in a structured interview which assessed the Pittsburgh Sleep Quality Index (PSQI), subjective bodily pain, the Jichi Medical School Social Support Scale, the Geriatric Depression Scale (GDS-15), health status, and demographic characteristics. Sleep disturbance was defined as a global PSQI score >5.5, which was used as a dependent variable in multiple logistic regression analysis to determine adjusted odds ratios (ORs) and 95 % confidence intervals (CIs) of related factors. RESULTS: We identified a significant increase in the adjusted ORs for female (OR 1.56, 95 % CI 1.34-1.83), age ≥80 years (1.31, 1.01-1.69), history of stroke (1.44, 1.08-1.92), and a GDS-15 score ≥6 as compared to 0-2 (2.29, 1.86-2.81), with regard to sleep disturbance. Participants with severe or very severe bodily pain had the highest adjusted OR (3.00, 2.15-4.19), and those with very mild bodily pain also had a relatively high OR (1.30, 1.06-1.60), relative to those without subjective bodily pain. In addition, compared with participants with strong social support from spouse or family, those with weak social support had significantly increased adjusted ORs (1.21, 1.01-1.44, 1.44, 1.23-1.70, respectively). CONCLUSIONS: The present study indicates that sleeping disturbances among the elderly are closely associated with social support from a spouse and family. They are also associated with pain, even at stages in which subjective bodily pain is very mild.博士（医学）・乙第1381号・平成28年9月28日© The Japanese Society for Hygiene 2016The final publication is available at Springer via http://dx.doi.org/10.1007/s12199-016-0529-

spERt Technology: A novel strategy to improve productivity through enhanced polyribosome assembly on the endoplasmic reticulum in CHO cells

In cell line development process, it is frequently observed that increased mRNA levels do not always correlate with protein expression levels in CHO cells. In line with this gap, the endoplasmic reticulum (ER) in CHO cells is much less proliferated as compared with that in terminally differentiated (i.e., professional) secretory cells, suggesting that there is still room to improve their specific productivity if translational efficiency on the ER can be up-regulated. Here we present a novel engineering approach (spERt Technology) to improve specific production rates by mimicking the ER translational apparatus of professional secretory cells. In spERt Technology, we exploit the unique factors that are required for translationally active polyribosome formation on the ER to directly enhance the translational efficiency (1, 2). A high antibody (Ab) producing clone generated by a novel screen using flow cytometry (3) was used as a model cell line. The factors were introduced into the high producer and a series of the spERt Technology - introduced cell lines were generated Among these cell lines, we selected one of the best clones (spERt-f9) having stable and high productivity. Polyribosome analysis of these cell lines revealed that enhanced assembly of the ER polyribosomes as expected (1). Consistent with the highly developed polyribosomes, the spERt-introduced cell lines produced higher levels of Ab than that of parental cells, and showed prominent increase of specific production rates. Further optimization of feeding process resulted in remarkable increase of productivity in spERt-f9 cells: Ab titers of 7.6 g/L and 9.5 g/L on day 14 and 17, respectively, were achieved in shake flask fed-batch cultures by using chemically defined media. Importantly, high cell viabilities were maintained in spERt-f9 cells throughout the culture periods. In addition, lower glucose consumption and reduced accumulation of ammonia were observed. Product quality in these cells were analyzed and compared with that in the parental cells. In conclusion, spERt Technology enables to improve productivity of high Ab producers, associated with reduced accumulation of waste metabolites and high cell viabilities

Epidermal growth factor receptor mutation in combination with expression of MIG6 alters gefitinib sensitivity

<p>Abstract</p> <p>Background</p> <p>Epidermal growth factor receptor (EGFR) signaling plays an important role in the regulation of cell proliferation, survival, metastasis, and invasion in various tumors. Earlier studies showed that the EGFR is frequently overexpressed in non-small-cell lung cancer (NSCLC) and EGFR mutations at specific amino acid residues in the kinase domain induce altered responsiveness to gefitinib, a small molecule EGFR tyrosine kinase inhibitor. However, the mechanism underlying the drug response modulated by EGFR mutation is still largely unknown. To elucidate drug response in EGFR signal transduction pathway in which complex dynamics of multiple molecules involved, a systematic approach is necessary. In this paper, we performed experimental and computational analyses to clarify the underlying mechanism of EGFR signaling and cell-specific gefitinib responsiveness in three H1299-derived NSCLC cell lines; H1299 wild type (H1299WT), H1299 with an overexpressed wild type EGFR (H1299EGFR-WT), and H1299 with an overexpressed mutant EGFR L858R (H1299L858R; gefitinib sensitive mutant).</p> <p>Results</p> <p>We predicted and experimentally verified that Mig6, which is a known negative regulator of EGFR and specifically expressed in H1299L858R cells, synergized with gefitinib to suppress cellular growth. Computational analyses indicated that this inhibitory effect is amplified at the phosphorylation/dephosphorylation steps of MEK and ERK.</p> <p>Conclusions</p> <p>Thus, we showed that L858R receptor mutation in combination with expression of its negative regulator, Mig6, alters signaling outcomes and results in variable drug sensitivity.</p

Ligand-Specific c-Fos Expression Emerges from the Spatiotemporal Control of ErbB Network Dynamics

SummaryActivation of ErbB receptors by epidermal growth factor (EGF) or heregulin (HRG) determines distinct cell-fate decisions, although signals propagate through shared pathways. Using mathematical modeling and experimental approaches, we unravel how HRG and EGF generate distinct, all-or-none responses of the phosphorylated transcription factor c-Fos. In the cytosol, EGF induces transient and HRG induces sustained ERK activation. In the nucleus, however, ERK activity and c-fos mRNA expression are transient for both ligands. Knockdown of dual-specificity phosphatases extends HRG-stimulated nuclear ERK activation, but not c-fos mRNA expression, implying the existence of a HRG-induced repressor of c-fos transcription. Further experiments confirmed that this repressor is mainly induced by HRG, but not EGF, and requires new protein synthesis. We show how a spatially distributed, signaling-transcription cascade robustly discriminates between transient and sustained ERK activities at the c-Fos system level. The proposed control mechanisms are general and operate in different cell types, stimulated by various ligands

Antisynthetase syndrome: Pulmonary computed tomography findings of adult patients with antibodies to aminoacyl-tRNA synthetases

AbstractObjectivesTo describe the pulmonary CT findings in patients with anti-ARS-antibody-positive interstitial lung disease (anti-ARS-ILD)MethodsThe CT findings of 64 patients with anti-ARS-ILD were retrospectively reviewed. The images were retrospectively reviewed independently by 2 chest radiologists, and the final decision on the CT findings was made by a third chest radiologist.ResultsThere were 16 male and 48 female patients, aged 54.2±13.4 years. Sixteen patients had anti Jo-1, 24 had anti-EJ, 9 had anti-PL-7, 7 had anti-PL-12, 5 had anti-KS, and 3 had anti-OJ antibodies. Overall, 63 patients (98.4%) had CT findings predominantly in the lower lobe; 61 patients (95.3%) showed peripheral opacities, and 47 patients (73.4%) showed peribronchovascular opacities. Ground-glass attenuation, consolidation, and reticulation showed similar distribution patterns. Regarding detailed CT findings, 89.1% of patients had lower volume loss, 76.6% had interlobular septal thickening, and 67.2% had thickening of bronchovascular bundles. The final radiologic diagnoses were as follows: inconsistent with usual interstitial pneumonia (UIP) in 63 patients (98.4%), which included nonspecific interstitial pneumonia (NSIP) in 35 patients (55.6%), organizing pneumonia (OP) in 4 patients (6.3%), and OP with fibrosis in 22 patients (34.9%).ConclusionsThe characteristic CT findings of patients with anti-ARS-ILD were areas of ground-glass attenuation and reticulation, predominantly distributed as lower and peribronchovascular lesions, which is compatible with NSIP. One-third of patients showed OP with fibrosis

Postoperative assessment after AVR and TAVI

Background and aims : Severe aortic stenosis (AS) has been normally treated with surgical aortic valve replacement (AVR) whereas recently, transcatheter aortic valve implantation (TAVI) has been introduced as a minimally invasive operation for patients with high surgical risk and frailty. In this study, we have evaluated postoperative physical function and nutrition intake in the patients following AVR and TAVI. Methods : This prospective observational study involved 9 patients with surgical aortic valve replacement (AVR) and 7 patients with transcatheter aortic valve implantation (TAVI). Body composition was measured one day prior surgery, postoperative day (POD) 1, POD 3, POD 5 and POD 7. Hand grip strength, calf circumference and gait speed were measured one day before surgery and on the day of discharge. Results : Skeletal muscle was significantly decreased in AVR patients at postoperative day 3 and 7, while there was no change in TAVI patients. Patients with TAVI showed higher dietary intake after surgery compared to patients with AVR, and they maintained hand grip strength and calf circumference at discharge. Conclusions : In elderly patients with AS, TAVI can improve post-operative recovery maintaining nutritional status and physical function even