Juria Akasaka

Peripheral RAGE (Receptor for Advanced Glycation Endproducts)-ligands in normal pregnancy and preeclampsia: novel markers of inflammatory response

Inflammatory response in preeclampsia (PE) is a key feature in its pathophysiology. Advanced Glycation Endproducts (AGEs), receptors for AGEs (RAGE), and RAGE ligands are involved in systemic inflammation in various pathological conditions. In this study, we measured serum RAGE ligands in normal pregnancy controls and PE patients. Levels of Carboxymethyl Lysine (CML), HMGB1 and S100A12/EN-RAGE were measured in thirty-three normal pregnant women 3 times at 10-12 (1st measurement), 28 (2nd measurement), and 36 (3rd measurement) weeks during gestation for paired analysis. We also measured those in serum samples from 17 severe PE patients at admission using ELISA. Early onset (EO, <32 weeks) and late onset (LO, ≥32 weeks) PE patients were compared with the 2nd and 3rd measurements of normal controls, respectively. CML and HMGB1 did not change during normal pregnancy. However, S100A12/EN-RAGE decreased from the 1st to 2nd measurement (P<0.0001). Across all PE patients, serum CML was unaltered, while HMGB1 significantly increased compared to 2nd (P=0.0002) and 3rd (P<0.0001) measurement as well as individually compared to both EO (P=0.018) and LO groups (P=0.0001). S100A12 in all PE patients increased over 2nd (P=0.0015) and 3rd (P=0.0002) measurements, although only LO was significantly increased compared to the 3rd measurement (P=0.0005). Our data suggest that patterns of serum RAGE ligand concentration indicate different inflammatory pathways in normal pregnancy, EO-PE, and LO-PE.

The biology of uterine sarcomas: A review and update

Uterine sarcoma is a rare neoplasm, accounting for only 5% of uterine malignancies. The pathogenesis of uterine sarcoma remains largely unknown, although recent basic science and pre-clinical animal models have provided a better understanding of tumor biology. The aim of this study was to review the clinical features, imaging characteristics, genetic aberrations and therapeutic approaches in uterine sarcoma. This study reviewed the English-language literature on clinical and basic studies on uterine sarcoma. The common variants of uterine sarcoma are carcinosarcoma, leiomyosarcoma and endometrial stromal sarcoma (ESS). Genetic profiling efforts have identified amplification, overexpression and mutation, while the molecular mechanisms of tumorigenesis driven by these genomic and genetic aberrations have yet to be fully elucidated yet. Recent genome-wide studies have also identified complex chromosomal rearrangements as oncogenic mechanisms. The cell cycle regulators, p16 and p53, are frequently over-expressed and appear to be involved in key modifications of sarcomagenesis. Molecular-targeted therapy has now been evaluated in clinical trials for certain subtypes. In conclusion, aberrations of cell cycle control would be a critical step in the development of uterine sarcoma. This review has provided new areas of study targeting molecular and genetic pathways.

Pathogenesis and malignant transformation of adenomyosis (Review)

The aim of our review was to identify the current information with regard to the pathogenesis and malignant transformation of adenomyosis. The current literature was reviewed by searching MEDLINE/PubMed, using the following keywords: adenomyosis, myometrium, stromal cells, malignant transformation, pathogenesis, etiology, genome-wide and microarray. Early signs of the development of adenomyosis are considered to be the penetration of stromal cells into the inner layer of the myometrium. Adenomyosis smooth muscle cells are developed, possibly, through a remodeling pathway via reactivation of coelomic epithelial cells as a result of estrogen-induced epithelial mesenchymal transition. Smooth muscle cell hyperplasia and hypertrophy are a reflection of a reaction of the surrounding tissue. The development of adenocarcinoma arising from adenomyosis is a relatively rare occurrence. In our literature review, to date, 44 cases of malignant tumors arising from adenomyosis have been documented. Studies reporting results of genetic abnormalities, epigenetic changes, monoclonal expansion, mutational analysis and the inactivation of specific tumor suppressor genes are very few in this field. In conclusion, adenomyosis can be a precursor of some carcinomas. The exact molecular mechanisms that lead to the malignant transformation are poorly understood.

CA-125 cut-off value as a predictor for complete interval debulking surgery after neoadjuvant chemotherapy in patients with advanced ovarian cancer

Objective In the present study, we evaluated changes in CA-125 cut-off values predictive of complete interval debulking surgery (IDS) after neoadjuvant chemotherapy (NAC) using receiver operating characteristic (ROC) analysis. Methods This retrospective single-institution study included patients with International Federation of Gynecology and Obstetrics (FIGO) stage III epithelial ovarian cancer and a pre-NAC serum CA-125 level of greater than 40 U/mL who were treated with neoadjuvant platinum-based chemotherapy followed by IDS between 1994 and 2009. Logistic regression analysis was used to evaluate univariate and independent multivariate associations with the effect of clinical, pathological, and CA-125 parameters on complete IDS, and ROC analysis was used to determine potential cut-off values of CA-125 for prediction of the possibility of complete IDS. Results Seventy-five patients were identified. Complete IDS was achieved in 46 (61.3%) patients and non-complete IDS was observed 29 (38.7%). Median pre-NAC CA-125 level was 639 U/mL (range, 57 to 6,539 U/mL) in the complete IDS group and 1,427 U/mL (range, 45 to 10,989 U/mL) in the non-complete IDS group. Median pre-IDS CA-125 level was 15 U/mL (range, 2 to 60 U/mL) in the complete IDS group and 53 U/mL (range, 5 to 980 U/mL) in the non-complete IDS group (p<0.001). Multivariate analyses performed with complete IDS as the endpoint revealed only pre-IDS CA-125 as an independent predictor. The odds ratio of non-complete IDS was 10.861 when the pre-IDS CA-125 level was greater than 20 U/mL. Conclusion The present data suggest that in the setting of IDS after platinum-based NAC for advanced ovarian cancer, a pre-IDS CA-125 level less than 20 U/mL is an independent predictor of complete IDS.

Incidence, diagnosis and pathophysiology of amniotic fluid embolism

Abstract Amniotic fluid embolism (AFE) is a rare clinical entity, sometimes fatal. A review was conducted to describe the frequency, diagnosis and pathophysiology of AFE. The reported incidences ranged from 1.9 cases per 100,000 maternities (UK) to 6.1 per 100,000 maternities (Australia), which can vary considerably, depending on the period, region of study and the definition. Although the development of amniotic fluid-specific markers would have an impact on early diagnosis, definition of AFE based on these markers is not widely accepted. To date, immunological mechanisms, amniotic fluid-dependent anaphylactic reaction and complement activation, have been proposed as potential pathogenetic and pathophysiological mechanisms. Immune cell activation induced through complement activation may be associated with the mechanism that immediately initiates maternal death, only in susceptible individuals. This review will focus on advances in the field of AFE biology and discuss the prevalence, diagnosis and pathophysiology of AFE.

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.

Epigenetic dysregulation of endometriosis susceptibility genes (Review)

The aim of the present review was to illustrate how dysregulation of hormonal signaling regulates expressional changes of spatially associated genes in endometriosis. From a multi‑platform endometriosis dataset, an integrated analysis was performed of epigenomic changes of several biologically relevant genes that have been validated in the literature. Estrogen receptor (ER) may act as a direct epigenetic driver for endometriosis establishment, maintenance and progression. A majority of endometriosis susceptibility genes may be present in functional downstream targets of ER and located near the known imprinting genes. Previous studies have shed light on the overlapping genetic signatures between endometriosis development and the defective decidualization process. The steroid hormone‑mediated decidualization signaling pathway was shown to be frequently dysregulated in endometriosis. DNA methylation is associated with various intragenic or intergenic epigenetic modifications of chromatin. Chromatin architecture may be established in temporal and spatial orchestration of the recruitment of genes specifically downregulated in endometriosis. In conclusion, defective chromatin architecture at the ER target locus may have a key role in endometriosis. Endometriosis represents an interesting model to explore the variation of expression of spatially associated genes.

Vaginal delivery after placental abruption and intrauterine fetal death, including failed cases.

pia au to riz ad a p or CD R textmessaging that allows for the recipient to replywill bemore appropriate for future studies. Thirdly, although unlikely to influence the overall study outcome, sociodemographic information for both groups was not available. A randomized control trial on this subject would be beneficial. Further areas of researchwill include the use of text reminders for prenatal clinic appointments, child vaccination programs, and drug compliance. In conclusion, text reminders led to a 50% reduction in failure to attend postnatal clinic appointments. Policymakers should consider its implementation within maternal health services in Sub-Saharan Africa.

Genes Downregulated in Endometriosis Are Located Near the Known Imprinting Genes

There is now accumulating evidence that endometriosis is a disease associated with an epigenetic disorder. Genomic imprinting is an epigenetic phenomenon known to regulate DNA methylation of either maternal or paternal alleles. We hypothesize that hypermethylated endometriosis-associated genes may be enriched at imprinted gene loci. We sought to determine whether downregulated genes associated with endometriosis susceptibility are associated with chromosomal location of the known paternally and maternally expressed imprinting genes. Gene information has been gathered from National Center for Biotechnology Information database geneimprint.com. Several researchers have identified specific loci with strong DNA methylation in eutopic endometrium and ectopic lesion with endometriosis. Of the 29 hypermethylated genes in endometriosis, 19 genes were located near 45 known imprinted foci. There may be an association of the genomic location between genes specifically downregulated in endometriosis and epigenetically imprinted genes.

Evaluation of vaginal fluid squamous cell carcinoma antigen test in diagnosis of premature rupture of membranes

Abstract Objective: Previous studies have reported that concentrations of squamous cell carcinoma (SCC) antigen in amniotic fluid are extremely higher than that in the maternal serum. The aim of this study was to assess the potential clinical utility of vaginal fluid SCC level as a marker for diagnosing premature rupture of membranes (PROM). Methods: A case-control study was performed using patients admitted to Nara Medical University Hospital, delivery ward, from January 2011 to December 2012. The discriminatory potential of SCC assay was determined using 54 PROM and 108 gestational age-matched control vaginal fluid samples, in a 1:2 ratio. Levels of vaginal fluid SCC in patients with PROM and control pregnant women were quantified by an enzyme-linked immunosorbent assay. Results: The statistical results showed no correlation between gestational age and vaginal fluid SCC levels. There was no significant difference in vaginal fluid SCC levels between patients with PROM and those with control pregnant women (16156.5 ± 10495.8 ng/mL versus 15471.9 ± 11362.2 ng/mL, p = 0.467). Conclusion: We conclude that SCC could not be regarded as a potential marker for diagnosis of PROM. SCC may be a physiologic constituent of the vaginal fluid during pregnancy.