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

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

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

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/)

Evidence for Activation of Toll-Like Receptor and Receptor for Advanced Glycation End Products in Preterm Birth

Objective. Individuals with inflammation have a myriad of pregnancy aberrations including increasing their preterm birth risk. Toll-like receptors (TLRs) and receptor for advanced glycation end products (RAGE) and their ligands were all found to play a key role in inflammation. In the present study, we reviewed TLR and RAGE expression, their ligands, and signaling in preterm birth. Research Design and Methods. A systematic search was performed in the electronic databases PubMed and ScienceDirect up to July 2010, combining the keywords “preterm birth,” “TLR”, “RAGE”, “danger signal”, “alarmin”, “genomewide,” “microarray,” and “proteomics” with specific expression profiles of genes and proteins. Results. This paper provides data on TLR and RAGE levels and critical downstream signaling events including NF-kappaB-dependent proinflammatory cytokine expression in preterm birth. About half of the genes and proteins specifically present in preterm birth have the properties of endogenous ligands “alarmin” for receptor activation. The interactions between the TLR-mediated acute inflammation and RAGE-mediated chronic inflammation have clear implications for preterm birth via the TLR and RAGE system, which may be acting collectively. Conclusions. TLR and RAGE expression and their ligands, signaling, and functional activation are increased in preterm birth and may contribute to the proinflammatory state

NBRP databases: databases of biological resources in Japan

The National BioResource Project (NBRP) is a Japanese project that aims to establish a system for collecting, preserving and providing bioresources for use as experimental materials for life science research. It is promoted by 27 core resource facilities, each concerned with a particular group of organisms, and by one information center. The NBRP database is a product of this project. Thirty databases and an integrated database-retrieval system (BioResource World: BRW) have been created and made available through the NBRP home page (http://www.nbrp.jp). The 30 independent databases have individual features which directly reflect the data maintained by each resource facility. The BRW is designed for users who need to search across several resources without moving from one database to another. BRW provides access to a collection of 4.5-million records on bioresources including wild species, inbred lines, mutants, genetically engineered lines, DNA clones and so on. BRW supports summary browsing, keyword searching, and searching by DNA sequences or gene ontology. The results of searches provide links to online requests for distribution of research materials. A circulation system allows users to submit details of papers published on research conducted using NBRP resources

Squamous cell carcinoma antigenは羊水塞栓症診断の新しいマーカーとなり得る

AIM: We aimed to evaluate the clinical usefulness of serum squamous cell carcinoma (SCC) antigen for the diagnosis of amniotic fluid embolism (AFE). METHODS: Sera and information of 20 patients with AFE (autopsy-proven AFE, four cases; clinical AFE, 16 cases) were obtained from the Japan Amniotic Fluid Embolism Registration Center at Hamamatsu University School of Medicine. As controls, we included 74 gestational-age-matched healthy women who gave birth to healthy newborns during the period from December 2012 to January 2014. Receiver-operator curves (ROC) were used to evaluate the diagnostic performance of SCC levels for prediction of AFE. RESULTS: Serum SCC antigen levels in women with autopsy-proven AFE (112.0 ± 169.4 ng/mL, P = 0.001) and clinical AFE (9.5 ± 10.3 ng/mL, P = 0.004) were significantly higher than those in healthy controls with normal delivery (4.4 ± 2.2 ng/mL). On ROC analysis, the optimal cut-off value for SCC antigen levels was 7.15 ng/mL, for which the sensitivity and specificity for AFE prediction was 60.0% and 89.2%, respectively (area under the ROC, 0.785; 95% confidence interval, 0.663-0.908; P < 0.001). CONCLUSION: Serum SCC antigen may be a promising predictor of the entry of amniotic fluid into the maternal circulation, potentially serving as a candidate marker for noninvasive diagnosis of AFE.博士（医学）・乙第1436号・令和元年9月27日© 2017 Japan Society of Obstetrics and GynecologyThis is the peer reviewed version of the following article: [https://obgyn.onlinelibrary.wiley.com/doi/full/10.1111/jog.13453], which has been published in final form at [https://doi.org/10.1111/jog.13453]. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions

A Case of Phosphoglyceride Crystal Deposition Disease in the Pelvic Soft Tissues Recurring after Initial Surgery

Phosphoglyceride crystal deposition disease (PGDD) is a rare disease entity that is characterized by phosphoglyceride crystal deposition that stimulates the formation of masses in soft tissue scars or bones. We report a case of PGDD in the pelvic soft tissues that recurred after initial surgical treatment. A 50-year-old woman was referred to our hospital for the evaluation of pelvic masses that were observed on an abdominal ultrasound. Magnetic resonance imaging (MRI) revealed masses in the pelvic region, with the largest being 10 cm in diameter. The masses were diagnosed as ovarian malignant tumors, and an exploratory laparotomy was performed. Operative findings revealed them to be foreign body granulomas, and the patient was diagnosed with PGDD. The patient had a history of cesarean delivery at the age of 24 years. PGDD is extremely rare, but it should be considered in the differential diagnosis of abdominal masses in patients with a history of abdominal surgery

Anastomosis Procedure through an Inguinal Hernia Incision in Simultaneous Laparoscopic Anterior Resection and Inguinal Hernia Repair

For laparoscopic anterior resection, an additional small incision is usually placed in the left lower quadrant or the suprapubic portion. As a left inguinal hernia incision is close to both the left lower quadrant and the suprapubic portion, such an incision can be used for anastomosis in laparoscopic anterior resection, without additional incisions. We report a laparoscopic anterior resection using a left inguinal hernia incision for colorectal anastomosis, in a patient who underwent concomitant left inguinal hernia repair. After a total mesorectal excision was performed laparoscopically, the distal portion of the rectum was transected by a stapler. A 4 cm skin incision was made in the left inguinal region and carried down to the peritoneum through the hernia sac. The bowel resection was performed extracorporeally, and an anvil was placed at the proximal end of the colon over a purse-string suture. After colorectal anastomosis was performed using a circular stapler inserted through the anus, the inguinal hernia was repaired with a mesh. The inguinal wound healed without surgical site infection, and the patient was discharged ten days after surgery