Direct Observation of Microphase-separated Structure of Polyurethane by Temperature Dependent Atomic Force Microscopy

Nagasaki Symposium on Nano-Dynamics 2008 (NSND2008) 平成20年1月29日(火)於長崎大学 Poster Presentatio

Epigenetic-scale comparison of human iPSCs generated by retrovirus, Sendai virus or episomal vectors

Human induced pluripotent stem cells (iPSCs) are established by introducing several reprogramming factors, such as OCT3/4, SOX2, KLF4, c-MYC. Because of their pluripotency and immortality, iPSCs are considered to be a powerful tool for regenerative medicine. To date, iPSCs have been established all over the world by various gene delivery methods. All methods induced high-quality iPSCs, but epigenetic analysis of abnormalities derived from differences in the gene delivery methods has not yet been performed. Here, we generated genetically matched human iPSCs from menstrual blood cells by using three kinds of vectors, i.e., retrovirus, Sendai virus, and episomal vectors, and compared genome-wide DNA methylation profiles among them. Although comparison of aberrant methylation revealed that iPSCs generated by Sendai virus vector have lowest number of aberrant methylation sites among the three vectors, the iPSCs generated by non-integrating methods did not show vector-specific aberrant methylation. However, the differences between the iPSC lines were determined to be the number of random aberrant hypermethylated regions compared with embryonic stem cells. These random aberrant hypermethylations might be a cause of the differences in the properties of each of the iPSC lines

A PERIOD3 variant causes a circadian phenotype and is associated with a seasonal mood trait.

In humans, the connection between sleep and mood has long been recognized, although direct molecular evidence is lacking. We identified two rare variants in the circadian clock gene PERIOD3 (PER3-P415A/H417R) in humans with familial advanced sleep phase accompanied by higher Beck Depression Inventory and seasonality scores. hPER3-P415A/H417R transgenic mice showed an altered circadian period under constant light and exhibited phase shifts of the sleep-wake cycle in a short light period (photoperiod) paradigm. Molecular characterization revealed that the rare variants destabilized PER3 and failed to stabilize PERIOD1/2 proteins, which play critical roles in circadian timing. Although hPER3-P415A/H417R-Tg mice showed a mild depression-like phenotype, Per3 knockout mice demonstrated consistent depression-like behavior, particularly when studied under a short photoperiod, supporting a possible role for PER3 in mood regulation. These findings suggest that PER3 may be a nexus for sleep and mood regulation while fine-tuning these processes to adapt to seasonal changes

Efficacy and safety of temporary biliary stent for prevention of post-ERCP cholangitis after endoscopic common bile duct stone removal: a retrospective study

　Although post-endoscopic retrograde cholangiopancreatography (ERCP) cholangitis (PEC) is not as severe as post-ERCP pancreatitis, this complication should not be disregarded. The aim of the present study was to evaluate the efficacy of a temporary biliary stent for prevention of PEC. Between April 2011 and May 2017, 190 patients underwent complete stone removal in a first session of ERCP at our hospital. Using propensity score matching, 72 pairs were enrolled in this study. After common bile duct (CBD) stone removal, the endoscopists decided to insert a temporary biliary stent if necessary. The incident rate of PEC was significantly lower in the stent group than the no-stent group (1% vs. 11%, p = 0.03). The length of hospital stay was also significantly shorter in the stent group than the no-stent group (5 days vs. 7 days, p < 0.01). In the stent group, one case had stent migration into the bile duct and two cases had a mooring stent at the papilla after 1 month. Multivariate analysis identified the pancreatic guide wire technique as a risk factor for PEC. We demonstrated that a temporary biliary stent reduced the incidence of PEC significantly and the outcome of its placement contributed to shortening the hospital stay. Furthermore, the placement of a temporary biliary stent caused fewer adverse effects than expected. Mooring stents were noted in three cases, which were confirmed by plain abdominal X-ray, but the patients had no symptoms. In two cases, the stent remained in the orifice of the papilla, and in one case it migrated into the CBD. All three stents were retrieved by elective endoscopic procedures. In conclusion, a temporary biliary stent can reduce the incidence of PEC and shorten the length of hospital stay without severe adverse outcomes

A Novel Method for the Deprotection of Phenylcarbamoyl Group

講演番号：4 G3 16 日本化学会第72春季年会, 平成9年3月27日～3月30日, 東

Rad9 modulates the P21WAF1 pathway by direct association with p53

<p>Abstract</p> <p>Background</p> <p>Previous studies suggest that human <it>RAD9 </it>(hRad9), encoding a DNA damage checkpoint molecule, which is frequently amplified in epithelial tumor cells of breast, lung, head and neck cancer, participates in regulation of the tumor suppressor p53-dependent transactivation of pro-survival <it>P21</it>^{<it>WAF1</it>}. This study examined the exact mechanism of the hRad9 function, especially through the phosphorylation of the C-terminus, in the transcription regulation of <it>P21</it>^{<it>WAF1</it>}.</p> <p>Results</p> <p>The transfection of phosphorylation-defective <it>hRAD9 </it>mutants of C-terminus resulted in reduction of the p53-dependent <it>P21</it>^{<it>WAF1 </it>}transactivation; the knockdown of total hRad9 elicited an increased <it>P21</it>^{<it>WAF1 </it>}mRNA expression. Immunoprecipitation and a ChIP assay showed that hRad9 and p53 formed a complex and both were associated with two p53-consensus DNA-binding sequences in the 5' region of <it>P21</it>^{<it>WAF1 </it>}gene. The association was reduced in the experiment of phosphorylation-defective <it>hRAD9 </it>mutants.</p> <p>Conclusion</p> <p>The present study indicates the direct involvement of hRad9 in the p53-dependent <it>P21</it>^{<it>WAF1 </it>}transcriptional mechanism, presumably via the phosphorylation sites, and alterations of the hRad9 pathway might therefore contribute to the perturbation of checkpoint activation in cancer cells.</p

Life-Threatening Infantile Diarrhea from Fluoroquinolone-Resistant Salmonella enteric Typhimurium with Mutations in Both gyrA and parC

Salmonella Typhimurium DT12, isolated from a 35-day-old infant with diarrhea, was highly resistant to ampicillin, tetracycline, chloramphenicol, streptomycin, gentamycin, sulfamethoxazole/trimethoprim, nalidixic acid, and fluoroquinolones. The patient responded to antibiotic therapy with fosfomycin. Multidrug-resistance may become prevalent in Salmonella infections in Japan, as shown in this first case of a patient infected with fluoroquinolone-resistant Salmonella

Multicenter questionnaire survey for sporadic inclusion body myositis in Japan

Background: Sporadic inclusion body myositis (sIBM) is the most prevalent acquired muscle disease in the elderly. sIBM is an intractable and progressive disease of unknown cause and without effective treatment. The etiology of sIBM is still unknown; however, genetic factors, aging, lifestyles, and environmental factors may be involved. The purpose of this study is to elucidate the cross-sectional profile of patients affected by sIBM in Japan. Methods: We surveyed patient data for 146 cases diagnosed at a number of centers across Japan. We also issued a questionnaire for 67 patients and direct caregivers to further elucidate the natural history of the disease. Results: The mean age at the onset was 63.4 ± 9.2 years. The mean length of time from the onset to diagnosis was 55.52 ± 49.72 months, suggesting that there is a difficulty in diagnosing this disease with long-term consequences because of late treatment. 73 % described the psychological/mental aspect of the disease. The most popular primary caregiver was the patient’s spouse and 57 % patients mentioned that they were having problems managing the finances. Conclusions: Through these surveys, we described the cross-sectional profiles of sIBM in Japan. Many patients described psychological/mental and financial anxiety because of the aged profile of sIBM patients. The profiles of sIBM patients are similar to those in Western countries