日本人女性における切迫早産予測のための腟分泌物pHと腟分泌物緩衝能に関する研究

OBJECTIVE: To determine the relationship between preterm labor and delivery, and the pH and buffer capacity of vaginal secretions. METHODS: Between January 1, 2009 and March 31, 2012, two cohorts of patients at 22-36weeks of pregnancy were enrolled in a prospective cohort study at Nara Medical University Hospital, Japan. Patients experiencing preterm contractions and a control group of patients experiencing normal pregnancies were included. The pH and buffer capacity of vaginal secretions were measured and compared. RESULTS: Of the 237 patients enrolled, 48 (20.3%) were experiencing symptoms of preterm labor and 189 (79.7%) were included in the control group. The pH was higher (P<0.001) and the buffer capacity was lower (P=0.0135) in the vaginal secretions of the patients experiencing preterm contractions compared with the control group. There was no difference in the pH and buffer capacity of the vaginal secretions of symptomatic patients who would experience preterm delivery and those who would not. Receiver operating characteristic curve analyses demonstrated that vaginal-secretion pH and buffer capacity could differentiate between patients experiencing preterm contractions and those not, but could not differentiate between patients who would experience preterm delivery and those who would not. CONCLUSION: Vaginal-secretion pH and buffer capacity could be useful in diagnosing preterm labor; further studies are needed to determine potential practical diagnostic criteria.博士（医学）・乙第1383号・平成28年9月28日Copyright © 2016 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd. All rights reserved

Appendiceal Mucocele Detected under Treatment of Ulcerative Colitis

A 33-year-old female patient with ulcerative colitis was referred to our outpatient clinic in January 2008 with right lower abdominal pain without bloody diarrhea. Colonoscopy found mild proctosigmoiditis and a submucoal tumor with a maximal diameter of 5 cm in the cecum. Computed tomography revealed a large, hypodense, cystic cylindrical structure extending to the pelvic space. For severe pain, she underwent partial resection of the cecum including the tumor in March 2008. Intraoperatively, the vermiform appendix was swollen like a sausage and compressing the cecum, which accounted for what appeared to be a submucosal tumor like a volcano by endoscopy. Lymphadenectomy was not performed because malignancy was not suspected. In the surgical specimen, the vermiform appendix was spindle-shaped and contained a large quantity of viscous liquid. Postoperative pathological diagnosis was mucinous cystadenoma, and no cancer cells were present in the viscous liquid within the vermiform appendix. The patient left the hospital 7 days postoperatively, and her colitis remains in remission without any complications

Exploration of Genes Associated with Sponge Silicon Biomineralization in the Whole Genome Sequence of the Hexactinellid Euplectella curvistellata.

Silicatein is the first protein isolated from the silicon biominerals and characterized as constituent of the axial filament in the silica spicules of the demosponge Tethya aurantia, by significant sequence similarity with cathepsin L, an animal lysosomal protease, and as a catalyst of silica polycondensation at neutral pH and room temperature. This protein was then identified in a wide range of the class Demospongiae and in some species of the class Hexactinellida. Our attempt to isolate silicatein from the silica skeleton of Euplectella was unsuccessful, but instead we discovered glassin, a protein directing acceleration of silica polycondensation and sharing no significant relationship with any proteins including silicatein. The present study aims to verify the existence of silicatein by exploring the whole genome DNA sequence database of E. curvistellata with the sequence similarity search. Although we identified the sequences of glassin, cathepsin L and chitin synthetase, an enzyme synthesizing chitin, which has already been found in the silicon biominerals in E. aspergillum, silicatein failed to be identified. Our result indicates that silicatein is not essential for poriferan silicon biomineralization in the presence of glassin

One pot synthesis of optically active 4-isoxazolines by asymmetric addition of alkynylzinc reagents to nitrones followed by cyclization

金沢大学理工研究域物質化学系One pot synthesis of optically active 4-isoxazolines was achieved by asymmetric addition of alkynylzinc reagents to nitrones utilizing di(t-butyl) (R,R)-tartrate as a chiral auxiliary followed by cyclization. By addition of dimethylzinc, the cyclization step was accelerated to afford the corresponding 4-isoxazolines with up to 93% ee. Furthermore, a cyclized zinc intermediate could be trapped with formaldehyde to give the corresponding 2,3,4,5-tetrasubstituted 4-isoxazoline with 85% ee. © 2009 The Japan Institute of Heterocyclic Chemistry All rights reserved

Auto-Luminescent Genetically-Encoded Ratiometric Indicator for Real-Time Ca2+ Imaging at the Single Cell Level

Background: Efficient bioluminescence resonance energy transfer (BRET) from a bioluminescent protein to a fluorescent protein with high fluorescent quantum yield has been utilized to enhance luminescence intensity, allowing single-cell imaging in near real time without external light illumination. Methodology/Principal Findings: We applied BRET to develop an autoluminescent Ca2+ indicator, BRAC, which is composed of Ca^[2+]-binding protein, calmodulin, and its target peptide, M13, sandwiched between a yellow fluorescent protein variant, Venus, and an enhanced Renilla luciferase, RLuc8. Adjusting the relative dipole orientation of the luminescent protein's chromophores improved the dynamic range of BRET signal change in BRAC up to 60%, which is the largest dynamic range among BRET-based indicators reported so far. Using BRAC, we demonstrated successful visualization of Ca2+ dynamics at the single-cell level with temporal resolution at 1 Hz. Moreover, BRAC signals were acquired by ratiometric imaging capable of canceling out Ca^[2+]-independent signal drifts due to change in cell shape, focus shift, etc. Conclusions/Significance: The brightness and large dynamic range of BRAC should facilitate high-sensitive Ca2+ imaging not only in single live cells but also in small living subjects

Chemokine and Free Fatty Acid Levels in Insulin-Resistant State of Successful Pregnancy: A Preliminary Observation

Increased insulin resistance and inflammatory action are observed in pregnancy-induced hypertension (PIH), but similar insulin resistance is observed also in successful pregnancy. To estimate insulin resistance and inflammatory activity in normal pregnancy and PIH, serum concentrations of free fatty acids (FFA; corrected with albumin to estimate unbound FFA), monocyte chemoattractant protein (MCP)-1, and high-molecular weight (HMW) adiponectin were measured in severe PIH patients with a BMI less than 25 kg/m2 and were measured 3 times during the course of pregnancy in women with normal pregnancies. FFA/albumin, MCP-1, and HMW adiponectin concentrations were significantly higher in PIH patients than in women with normal pregnancies. The 3 measurements of FFA/albumin showed a significant increase through the course of uncomplicated pregnancies. In contrast, MCP-1 and HMW adiponectin were significantly decreased during the course of pregnancy. These results suggest that the reduced MCP-1 concentration in normal pregnancy may be a pathway to inhibit the induction of pathological features from physiological insulin resistance and homeostatic inflammation

卵巣明細胞腺癌における転写因子HNF-1βはDNA損傷チェックポイント機構の一つであるCHK1タンパクを制御し、抗癌剤耐性を獲得する

Objective Appropriate cell cycle checkpoints are essential for the maintenance of normal cells and chemosensitivity of cancer cells. Clear cell adenocarcinoma (CCA) of the ovary is highly resistant to chemotherapy. Hepatocyte nuclear factor-1β (HNF-1β) is known to be overexpressed in CCA, but its role and clinical significance is unclear. We investigated the role of HNF-1β in regulation of the cell cycle in CCA. Methods To clarify the effects of HNF-1β on cell cycle checkpoints, we compared the cell cycle distribution and the expression of key proteins involved in CCA cells in which HNF-1β had been stably knocked down and in vector-control cell lines after treatment with bleomycin. HNF-1β (+) cells were arrested in G2 phase because of DNA damage. Results HNF-1β (−) cells died because of a checkpoint mechanism. G2 arrest of HNF-1β (+) cells resulted from sustained CHK1 activation, a protein that plays a major role in the checkpoint mechanism. HNF-1β (+) cells were treated with a CHK1 inhibitor after bleomycin treatment. Flow cytometric analysis of the cell cycle demonstrated that DNA damage–induced G2-arrested cells were released from the checkpoint and killed by a CHK1 inhibitor. Conclusions The chemoresistance of CCA may be due to aberrant retention of the G2 checkpoint through overexpression of HNF-1β. This is the first study demonstrating cell cycle regulation and chemosensitization by a CHK1 inhibitor in CCA.博士（医学）・乙第1345号・平成26年12月3日© 2014 by the International Gynecologic Cancer Society and the European Society of Gynaecological Oncology

Phylogenetic analysis of lichen-associated bacteria from Antarctica

第3回極域科学シンポジウム/第34回極域生物シンポジウム 11月27日（火） 国立極地研究所 ３階ラウン

妊娠高血圧症候群におけるRAGEの関与

Preeclampsia/hypertensive disorders of pregnancy (PE/HDP) is a serious and potentially life-threatening disease. Recently, PE/HDP has been considered to cause adipose tissue inflammation, but the detailed mechanism remains unknown. We exposed human primary cultured adipocytes with serum from PE/HDP and healthy controls for 24 h, and analyzed mRNA expression of several adipokines, cytokines, and ligands of the receptor for advanced glycation endproducts (RAGE). We found that the mRNA levels of interleukin-6 (IL-6), C-C motif chemokine ligand 2 (CCL2), high mobility group box 1 (HMGB1), and RAGE were significantly increased by the addition of PE/HDP serum. Among RAGE ligands, advanced glycation endproducts (AGE) and HMGB1 increased mRNA levels of IL-6 and CCL2 in SW872 human adipocytes and mouse 3T3-L1 cells. The introduction of small interfering RNA for RAGE (siRAGE) into SW872 cells abolished the AGE- and HMGB1-induced up-regulation of IL-6 and CCL2. In addition, lipopolysaccharide (LPS), a ligand of RAGE, increased the expression of IL-6 and CCL2 and siRAGE attenuated the LPS-induced expression of IL-6 and CCL2. These results strongly suggest that the elevated AGE, HMGB1, and LPS in pregnant women up-regulate the expression of IL-6 and CCL2 via the RAGE system, leading to systemic inflammation such as PE/HDP.博士（医学）・乙第1451号・令和2年3月16日© 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/)

Underlying Histological Activity of Hepatitis Plays an Important Role for Tumor Recurrence After Curative Resection of Hepatocellular Carcinoma

Background: Hepatocellular carcinoma (HCC) commonly develops in patients with chronic hepatitis. This situation is one of the reasons why intrahepatic recurrence frequently occurs even after curative resection. There are two different components of such recurrences, which occurs within 12 months (the early recurrence group) and at more than 12 months after resection (the late recurrence group). The present study was conducted to clarify the factors contributing to these different types of HCC recurrence. Methods: Ninety seven patients who underwent curative resection for HCCs were followed for initial recurrence, and predictive factors of recurrence were examined. Results: Early and late intrahepatic recurrences developed in 30 and 42 patients, respectively. In the former group, univariate analyses showed the serum AFP level (>100ng/ml, P=0.045), higher inflammatory activity (Grading) (p=0.048) and status of fibrosis (Staging) (p=0.027) in non-cancerous liver tissues to be significant risk factors, while the serum AFP level (>100ng/ml) was the only independent risk factor based on a multivariate analysis (RR: 2.78). In the latter group, only the presence of hyperplastic foci (HPF) was found to be a significant risk factor (p=0.005). Higher Grading tended to be linked to shorter disease-free survival time, although not significant. In the non-cancerous liver tissues with HPF, the level of Grading, Staging, and PCNA labeling index was significantly higher (p=0.033, 0.003, 0.040, respectively).Conclusion: Not only the tumor factors but also the underlying hepatic status including HPF, Grading, and Staging were significant risk factors for intrahepatic recurrence after curative resection for HCC