老化細胞が分泌する細胞外小胞の機能解析

内容の要約広島大学(Hiroshima University)博士(薬学)Doctor of Philosophy in Pharmaceutical Sciencedoctora

CENP-B box is required for de novo centromere chromatin assembly on human alphoid DNA

Centromere protein (CENP) B boxes, recognition sequences of CENP-B, appear at regular intervals in human centromeric α-satellite DNA (alphoid DNA). In this study, to determine whether information carried by the primary sequence of alphoid DNA is involved in assembly of functional human centromeres, we created four kinds of synthetic repetitive sequences: modified alphoid DNA with point mutations in all CENP-B boxes, resulting in loss of all CENP-B binding activity; unmodified alphoid DNA containing functional CENP-B boxes; and nonalphoid repetitive DNA sequences with or without functional CENP-B boxes. These four synthetic repetitive DNAs were introduced into cultured human cells (HT1080), and de novo centromere assembly was assessed using the mammalian artificial chromosome (MAC) formation assay. We found that both the CENP-B box and the alphoid DNA sequence are required for de novo MAC formation and assembly of functional centromere components such as CENP-A, CENP-C, and CENP-E. Using the chromatin immunoprecipitation assay, we found that direct assembly of CENP-A and CENP-B in cells with synthetic alphoid DNA required functional CENP-B boxes. To the best of our knowledge, this is the first reported evidence of a functional molecular link between a centromere-specific DNA sequence and centromeric chromatin assembly in humans

Sunlight Photocatalyzed Regioselective β‐Alkylation and Acylation of Cyclopentanones.

Visible light induced direct β-C–H/C–C conversion of cyclopentanones was accomplished by using tetrabutylammonium decatungstate, TBADT, as the photocatalyst

Evaluation of vascular quality of life questionnaire in dialysis patients with peripheral arterial disease treated by low-density lipoprotein apheresis

Background: Peripheral arterial disease (PAD) is a common complication in dialysis patients. Early diagnosis and treatment are recommended. Low-density lipoprotein apheresis (LDL-A) is a potential therapy to improve PAD. However, the mechanism has yet to be fully clarified due to lack of established quantitative methods to assess the therapeutic effects of LDL-A treatment. Improvement of skin perfusion pressure (SPP) or ankle brachial index (ABI) is a representative therapy goal, but clinical symptoms were not always consistent with the values of SPP/ABI. Vascular quality of life questionnaire (VascuQOL) was proposed as a disease-specific QOL score, getting validated recently. The possibility of VascuQOL to reflect the severity of PAD in dialysis patients and evaluate the therapeutic effects of LDL-A has yet to be elucidated. Methods: This is an observational study. LDL-A treatment was performed in 32 dialysis patients with PAD. They were divided to critical limb ischemia (CLI) group (17 subjects) and non-CLI group (15 subjects) according to their clinical manifestations. We examined the relationship of PAD severity with SPP, ABI, VascuQOL, and lipid profile such as apoB/apoA-I ratio, malondialdehyde-modified LDL, and remnant-like particles cholesterol. Furthermore, we evaluated these parameters successively to find out a suitable therapeutic marker just after the first LDL-A, at tenth LDL-A, and 1 month after completion of LDL-A treatment. Results: All of the lipid markers were higher in CLI patients, but not significantly different from those in the non-CLI group. They decreased significantly just after LDL-A, although no changes were observed 1 month after completion of LDL-A treatment. ABI was significantly different between the CLI and non-CLI groups, but did not improve by LDL-A treatment. By contrast, SPP was ameliorated significantly and the peak was at tenth LDL-A. Among VascuQOL domains, “Symptom” and “Emotional” domains were significantly different between the CLI and non-CLI groups. The average score of VascuQOL increased successively until 1 month after completion of LDL-A treatment. Conclusions: Several domains of VascuQOL can reflect the severity of PAD in dialysis patients. VascuQOL was a useful marker to show the prolonged therapeutic effects of LDL-A treatment in dialysis patients with PAD, independent of SPP

Maggot debridement therapy for a patient with critical limb ischaemia and severe cardiac dysfunction: possibility of limb salvage

Ischaemic skin ulcer occurred on the foot of a 73-year-old man who had a history of fulminant myocarditis with severe cardiac dysfunction. We attempted wound bed preparation by maggot debridement therapy and salvaged his limb. It can be one of the adjuvant treatment strategies for critical limb ischaemia

Catheter ablation of non-inducible atrial tachycardia after surgical repair of heart disease

We present a patient with non-inducible atrial tachycardia (AT) after atriotomy for surgical repair of heart disease who underwent ablation successfully. Using a 3-D mapping system, we presumed the atriotomy site on the lateral right atrial wall by searching for linear double potentials (DP) during sinus/paced rhythm from the coronary sinus, but it was evaluated incompletely. We could verify the edges of the atriotomy scar precisely by pacing from close to the linear DP lesion and the opposite site. After ablation between the presumed atriotomy scar and the inferior vena cava and cavotricuspid isthmus, no AT recurred without anti-arrhythmic drugs.ArticleHEART AND VESSELS. 27(1):114-118 (2012)journal articl