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

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

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

Secretion of Angiogenic Growth Factors by Villous Cytotrophoblast and Extravillous Trophoblast in Early Human Pregnancy

Angiogenesis is a key feature of placental and uterine development in early pregnancy. We hypothesized that trophoblast cells produce angiogenic growth factors, and that expression differs between villous cytotrophoblast (CTB) and extravillous trophoblast (EVT) cells. Fourteen angiogenic growth factors were measured by multiplex growth factor analysis or ELISA in tissue culture supernatants from EVT and CTB from pregnancies at 8e10 and 12e14 weeks' gestation. Gestational age and cell type differences were observed. EVT and CTB are major producers of angiogenic growth factors that likely contribute to placental vascular development and spiral artery remodeling.This project was supported by funding from BBSRC (S19967)