ステロイド治療は間葉系幹細胞の組織修復能を低下させる

この博士論文は内容の要約のみの公開（または一部非公開）になっています筑波大学 (University of Tsukuba)201

ステロイド治療は間葉系幹細胞の組織修復能を低下させる

筑波大学 (University of Tsukuba)201

Interdisciplinary Class in Okayama University on the Climate Environment around Japan in Association with the Variety of Seasonal Feeling (with Attention to the Seasonal Cycle of Rainfall in the Warm Season)

The present study is a part of the activity to develop an interdisciplinary class on the climate environment around the Japan Islands in association with the “seasonal feeling”, with attention to the seasonal cycle of the weather systems and the rainfall characteristics during the warm season. Firstly, the school song “Wa-ka-ba” (which means the deep green leaves) was analyzed as a typical song expressing the season just between the spring and the Baiu, for developing study materials for the joint activity of meteorology to music. Next, seasonal difference of the rainfall characteristics around the Japan Islands was reviewed together with the new preliminary analyses, with attention to the contribution of the “heavy rainfall days” to the total precipitation amount. Finally, the joint activity of the art with meteorology for the class at the Faculty of Education, Okayama University was reported, together with the analyses of the students’ works expressing the rainfall event in a specified season by themselves

Correlation between symptomatic improvement and quality of life in patients with reflux and dyspeptic symptoms

We investigated the correlation between symptomatic improvement and quality of life in Japanese gastroesophageal reflux disease patients with PPI. Eighty one patients with reflux and dyspeptic symptom were enrolled. The evaluation of the symptom was used he Frequency Scale for the Symptom of GERD in 3 categories: total score of 12 questions, score related to reflux symptoms, and score related to dyspeptic symptoms and the evaluation of the quality of life was use the 8-item Short Form Health Survey in 2 categories, the physical component summary score and mental component summary score. All patients administered rabeprazole 10 mg/day for 8 weeks. We investigated the correlation between symptomatic improvement with proton pump inhibitor and quality of life. Significant symptomatic improvement was seen in the total score of 12 questions (26.7 ± 8.8 → 17.5 ± 5.9, p<0.0001), score related to reflux symptoms (14.9 ± 5.4 → 9.6 ± 3.6, p<0.0001), and score related to dyspeptic symptoms (11.8 ± 4.3 → 8.0 ± 2.9, p<0.0001). Significant improvement in quality of life was seen in the physical component summary score (47.8 ± 6.6 → 50.0 ± 5.9, p = 0.0209) and mental component summary score (47.4 ± 8.5 → 50.4 ± 5.3, p = 0.0133) with proton pump inhibitor. With proton pump inhibitor, a significant positive correlation was seen between the improvement rates in total score of 12 questions, score related to dyspeptic symptoms and in mental component summary score at 8 weeks (total score of 12 questions: r = 0.275, p = 0.0265, score related to dyspeptic symptoms: r = 0.367, p = 0.0027). In conclusion, quality of life was associated with improvement in dyspeptic symptoms with proton pump inhibitor treatment

Glucocorticoid Impaired the Wound Healing Ability of Endothelial Progenitor Cells by Reducing the Expression of CXCR4 in the PGE2 Pathway

Background: Endothelial progenitor cells (EPCs) can be used to treat ischemic disease in cell-based therapy owing to their neovascularization potential. Glucocorticoids (GCs) have been widely used as strong anti-inflammatory reagents. However, despite their beneficial effects, side effects, such as impairing wound healing are commonly reported with GC-based therapy, and the effects of GC therapy on the wound healing function of EPCs are unclear.Methods: In this study, we investigated how GC treatment affects the characteristics and wound healing function of EPCs.Results: We found that GC treatment reduced the proliferative ability of EPCs. In addition, the expression of CXCR4 was dramatically impaired, which suppressed the migration of EPCs. A transplantation study in a flap mouse model revealed that GC-treated EPCs showed a poor homing ability to injured sites and a low activity for recruiting inflammatory cells, which led to wound healing dysfunction. Impairment of prostaglandin E2 (PGE2) synthases, cyclooxygenase (COX2) and microsomal PGE2 synthase 1 (mPEGS1) were identified as being involved in the GC-induced impairment of the CXCR4 expression in EPCs. Treatment with PGE2 rescued the expression of CXCR4 and restored the migration ability of GC-treated EPCs. In addition, the PGE2 signal that activated the PI3K/AKT pathway was identified to be involved in the regulation of CXCR4 in EPCs under the effects of GCs. In addition, similar negative effects of GCs were observed in EPCs under hypoxic conditions. Under hypoxic conditions, GCs independently impaired the PGE2 and HIF2α pathways, which downregulated the expression of CXCR4 in EPCs. Our findings highlighted the influences of GCs on the characteristics and functions of EPCs, suggesting that the use of EPCs for autologous cell transplantation in patients who have used GCs for a long time should be considered carefully

Interferon-α/β receptor-mediated selective induction of a gene cluster by CpG oligodeoxynucleotide 2006

BACKGROUND: Oligodeoxynucleotides containing unmethylated CpG motifs (CpG ODN) are known to exert a strong adjuvant effect on Th1 immune responses. Although several genes have been reported, no comprehensive study of the gene expression profiles in human cells after stimulation with CpG ODN has been reported. RESULTS: This study was designed to identify a CpG-inducible gene cluster that potentially predicts for the molecular mechanisms of clinical efficacy of CpG ODN, by determining mRNA expression in human PBMC after stimulation with CpG ODN. PBMCs were obtained from the peripheral blood of healthy volunteers and cultured in the presence or absence of CpG ODN 2006 for up to 24 hours. The mRNA expression profile was evaluated using a high-density oligonucleotide probe array, GeneChip(®). Using hierarchical clustering-analysis, out of a total of 10,000 genes we identified a cluster containing 77 genes as having been up-regulated by CpG ODN. This cluster was further divided into two sub-clusters by means of time-kinetics. (1) Inflammatory cytokines such as IL-6 and GM-CSF were up-regulated predominantly 3 to 6 hours after stimulation with CpG ODN, presumably through activation of a transcription factor, NF-κB. (2) Interferon (IFN)-inducible anti-viral proteins, including IFIT1, OAS1 and Mx1, and Th1 chemoattractant IP-10, were up-regulated predominantly 6 to 24 hours after stimulation. Blocking with mAb against IFN-α/β receptor strongly inhibited the induction of these IFN-inducible genes by CpG ODN. CONCLUSION: This study provides new information regarding the possible immunomodulatory effects of CpG ODN in vivo via an IFN-α/β receptor-mediated paracrine pathway

Thin-film and single-crystal transistors based on a trifluoromethyl-substituted alternating (thiophene/phenylene)-co-oligomer

We demonstrated the performance of thin-film transistors (TFTs) and single-crystal field-effect transistors (FETs) based on a trifluoromethyl-substituted alternating (thiophene/phenylene)-co-oligomer (AC5-CF3), 1,4-bis(5'-(4 ''-trifluoromethylphenyl)thiophene-2'-yl) benzene. An FET with a fine AC5-CF3 single-crystal demonstrated field-effect mobility as high as 3.1 cm(2) V-1 s(-1). This value implies that AC5-CF3 must be a useful n-type organic semiconducting material. The performance of AC5-CF3 TFTs depended on the substrate temperatures at which AC5-CF3 thin films were deposited. From the viewpoint of mobility, threshold voltage and sub-threshold slope, we obtained the highest performance at the substrate temperature of 100 degrees C. This was because a higher substrate temperature for deposition enlarged the size of grains in AC-CF3 thin films and improved the characteristics of grain boundaries. However, 120 degrees C depositions of AC5-CF3 induced deep valley-like cracks in the thin films, probably because of the difference between the coefficients of thermal expansion for AC5-CF3 thin films and silicon wafer substrates, resulting in effects such as worsening mobility. AC5-CF3 TFTs prepared at 100 degrees C deposition showed no channel length dependence of the field-effect mobility, and their average field-effect mobility was 0.55 +/- 0.05 cm(2) V-1 s(-1).ArticleOrganic Electronics. 11(9):1549-1554 (2010)journal articl

Combination of Oxaliplatin and 5-Fluorouracil/Leucovorin for Advanced Esophageal Squamous Cell Carcinoma Refractory or Intolerant to Standard Therapies

Here, we report the four cases with metastatic esophageal squamous cell carcinoma pretreated with standard chemotherapy who then received salvage-line chemotherapy with oxaliplatin and 5-fluorouracil plus l-leucovorin (FOLFOX) at our institution. We identified four men following the mentioned regimen; their median age was 68.5 years (range, 65–76 years). All patients developed disease progression on 5-fluorouracil, cisplatin, and taxanes. Two patients achieved partial response; the other two achieved stable disease on receiving cisplatin-containing regimens as first-line therapy. The Eastern Cooperative Oncology Group performance statuses were 1 in three patients and 2 in one patient. The best response was partial response in one patient, stable disease in one, and progressive disease in two. For the two patients who achieved partial response or stable disease, the times to progression were 5.7 and 5.2 months and the overall survival times were 8.1 and 9.5 months, respectively. A grade 3 encephalopathy in one patient improved soon after chemotherapy discontinuation and supportive therapies. There was no treatment-related death. This is the first report suggesting the potential effectiveness of FOLFOX as salvage chemotherapy for metastatic esophageal cancer