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Epithelial borderline ovarian tumor (BOT) frequently occurs in young women. Because progression-free survival, overall survival, and reproductive function are important outcomes, BOT is often treated by fertility-sparing surgery (FSS). We conducted a Japan-wide study to understand post-FSS prognosis in relation to clinical characteristics and types of FSS performed.We analyzed clinical and outcome data pertaining to 531 adolescent and young adult (AYA) patients (aged 15-39 years) who underwent FSS for BOT between 2009 and 2013.Median (range) age was 30 (15-39) years, and median observation time was 70 (2-120) months. The disease was of FIGO stage I in 492 (93%) patients. Histopathologically, tumors were of the mucinous (n = 372, 70%), serous (n = 120, 23%), seromucinous (n = 23, 4%), and other (n = 16, 3%) types. Five-year overall survival was 99.5% among patients with stage I and 100% among those with stage II-IV. Five-year progression-free survival was 96.7% and 69.3%, respectively. Multivariate analysis in cases of stage I showed a positive peritoneal cytology to be a significant risk factor for recurrence (HR, 5.199; p = 0.0188). The post-FSS pregnancy rate was relatively low for patients aged ≥30 years (OR, 0.868; 95% CI, 1.16-3.00; p = 0.0090).Post-FFS outcomes in terms of overall and progression-free survival are favorable, especially for AYA patients with stage I BOT. However, the relapse rate is high for patients with FIGO stage II-IV and for those with stage I but a positive peritoneal cytology. A long-term prospective observation is needed before reproductive outcomes can be fully established.

We present a case of hemorrhagic shock occurred during dienogest therapy for uterine adenomyosis which necessitated an emergency hysterectomy. The patient was a 45-year-old woman with adenomyosis. Magnetic resonance imaging showed type I adenomyosis measuring 10 cm. She had a history of intimal thrombectomy of pulmonary embolism and had been receiving warfarin and aspirin until the onset of the hemorrhagic shock. Following 6-month of gonadotropin-releasing hormone analogue, dienogest was commenced. Nine months after switching to dienogest, the patient experienced a persistent abnormal uterine bleeding for 2 weeks, eventually causing a massive bleeding and was transferred to our emergency room. A diagnosis of hemorrhagic shock with a severe anemia (hemoglobin 3.6 g/dL) was made. Despite blood transfusion and warfarin antagonization, continuous bleeding ≥150 g/h was not controlled. Emergent hysterectomy was opted and enabled hemostasis. Although the number of patients with adenomyosis who can avoid surgery by dienogest is increasing, care must be taken during dienogest therapy, especially in patients with anticoagulants and after gonadotropin-releasing hormone analogue treatment. To prevent such a critical event, careful management including patient education should be carried out.

BACKGROUND Approximately 10% of female athletes have a history of stress fractures, which most commonly occur between the ages of 16 and 17 years old. PURPOSE We investigated whether tartrate-resistant acid phosphatase 5b (TRACP-5b), which is a bone resorption marker, can serve as a valid predictor of stress fractures in female athletes in their teens and 20s. METHODS Three hundred and sixteen elite female athletes were recruited between 2013 and 2015. Serum TRACP-5b and various hormones were examined in blood samples. The serum TRACP-5b level was compared between athletes with and without stress fractures within 3 months after the initial collection of their blood samples. RESULTS The 316 athletes were divided into two age groups: 13-19 years old and 20-29 years old. Thirty-six athletes (11.4%) experienced new stress fractures within 3 months after the initial collection of their blood samples. The median serum TRACP-5b level was significantly higher in teenage athletes with new stress fractures than in teenage athletes without new stress fractures. In univariate logistic regression analysis, the Z-score of serum TRACP-5b was a significant predictive factor of stress fractures in teenage athletes only (odds ratio: 1.87; 95% CI: 1.31-2.66; P

Purpose The Japan Society of Obstetrics and Gynecology (JSOG) has collected cycle‐based assisted reproductive technology (ART) data in an online registry since 2007. Herein, we present the characteristics and treatment outcomes of ART cycles registered during 2017. Methods We collected cycle‐specific information for all ART cycles implemented at participating facilities and performed descriptive analysis. Results In total, 448,210 treatment cycles and 56,617 neonates (1 in 16.7 neonates born in Japan) were reported in 2017, increased from 2016; the number of initiated fresh cycles decreased for the first time ever. The mean patient age was 38.0 years (standard deviation 4.6). A total 110,641 of 245,205 egg retrieval cycles (45.1%) were freeze‐all cycles; fresh embryo transfer (ET) was performed in 55,720 cycles. A total 194,415 frozen‐thawed ET cycles were reported, resulting in 66,881 pregnancies and 47,807 neonates born. Single ET (SET) was performed in 81.8% of fresh transfers and 83.4% of frozen cycles, with singleton pregnancy/live birth rates of 97.5%/97.3% and 96.7%/96.6%, respectively. Conclusions Total ART cycles and subsequent live births increased continuously in 2017, whereas the number of initiated fresh cycles decreased. SET was performed in over 80% of cases, and ET shifted from using fresh embryos to frozen ones.

Aim This study aimed to describe the clinical presentation, diagnostic evaluation, and operative or medical management of inguinal endometriosis. Methods In this study, we retrospectively reviewed 20 cases of inguinal endometriosis in our facility, particularly on the clinical characteristics, diagnosis, and surgical and medical treatment. Results We retrospectively investigated the following items for each patient: age at diagnosis, surgical history, presence of extragenital endometriosis, symptoms, imaging modalities, surgical therapy, hormonal therapy, follow-up period, postoperative recurrence and time to recurrence. We identified 20 cases of inguinal endometriosis in our facility. First, 75% of the patients had right inguinal endometriosis. Second, T1-weighted or fat-saturated T1-weighted images showed hyperintensity in the lesions in 17 patients (17/18 patients, 94.4%). Third, in 5 of 6 patients who underwent surgical therapy, we performed radical surgery to excise the inguinal lesion including the round ligament. One patient had disease relapse. Fourth, in 6 of 7 cases, dienogest effectively improved pain without significant adverse effects, but oral contraceptive was effective in 1 of 4 patients without significant adverse effects. Conclusion We retrospectively reviewed 20 patients with inguinal endometriosis in our facility. We have shown that magnetic resonance imaging can be a useful imaging modality to obtain a specific diagnosis of this disease. In addition, inguinal endometriosis can be managed with radical surgery to resect lesions including the round ligament and with hormonal treatment. In particular, dienogest ameliorated symptoms, which can be an option for patients who do not want surgery.

Aim The cryopreservation of embryos is essential for assisted reproductive technology field. The aim of the present study is to examine the efficacy and ease of use of a new vitrification device, Kitasato Vitrification System (KVS), in cryopreservation of human embryos. Methods Human embryos at the cleavage or blastocyst stage were vitrified and warmed by KVS or Cryotop (control device). The survival of cleavage- and blastocyst-stage embryos and the developmental competence of cleavage-stage embryos were evaluated. Four individuals inexperienced in vitrification and warming embryos tested both KVS and Cryotop. The vitrification time and the detachment time of the embryos were evaluated. Results At the cleavage stage, there were no significant differences in the survival rate and the development rate to the blastocyst stage between KVS and Cryotop (100 vs 96.8% and 63.3 vs 61.3%, respectively). At the blastocyst stage, there was no significant difference in the re-expansion rate between KVS and Cryotop (100 vs 88.9%). The vitrification time was shorter for KVS than Cryotop. There was no significant difference in the detachment time between KVS and Cryotop. Conclusion Kitasato Vitrification System is easy to operate, even for inexperienced users, and the viability of human embryos vitrified by KVS is comparable to that of Cryotop, a widely used vitrification device.

Aim To determine the efficacious treatment for infertile couples, we assessed the impact of infertility factors including endometriosis on assisted reproductive technology (ART) and non-ART treatment, and the effect of age in infertility treatment outcomes was also investigated. Methods The medical records of 1864 females, infertile patients from January 2000 to December 2015 at our hospital, were retrospectively reviewed under the approval of the Institutional Review Board. We extracted 10 representative factors and calculated the cumulative live birth rate (CLBR) in these patients. Multivariate analysis of ART and non-ART treatment was performed to assess the impact of infertility factors, and the age-related decline in cumulative live birth rate was calculated by creating eight age-stratified subgroups. Results In total, 21.9% and 49.4% of the patients conceived after being treated with non-ART and ART, respectively. Multivariate analysis revealed that age > 35, advanced endometriosis defined by the revised American Society for Reproductive Medicine classification system stages III to IV, and the past history or current presence of uterine fibroid had significantly negative impact on the outcome of non-ART. Age stratification revealed that advanced endometriosis adversely affected the outcome of non-ART, especially for patients in their 30s. Assisted reproductive technology treatment for patients with advanced endometriosis was shown to be efficacious because the negative impact had been diminished. Conclusion Considering that non-ART treatment had limited role in patients with advanced endometriosis, prompt initiation of ART in these patients aged as young as 30 years can be recommended to achieve conception.

Aim Adenomyosis is a common gynecological disorder that causes dysmenorrhea, hypermenorrhea and metrorrhagia. Previously, we reported that 24 weeks of dienogest treatment is highly effective for pain in symptomatic adenomyosis. Up to present, there is no report that describes treatment of adenomyosis with long-term dienogest administration for more than 2 years. In this retrospective cohort study, we investigated the course of long-term dienogest treatment in patients with symptomatic adenomyosis. Methods This is a retrospective cohort study. Dienogest was continuously administered at a dose of 2 mg daily for patients with symptomatic adenomyosis. The outcome of long-term administration of dienogest was investigated, and the characteristics of patients were compared between discontinued cases and long-term administration cases. Results Two patients were excluded from this study because of transfer to another hospital or discontinuation due to infertility treatment. Twelve of 18 patients (66.7%) received dienogest until menopause or for a period of >80 months. Four cases (22.2%) discontinued dienogest treatment because of severe metrorrhagia. In the discontinued cases because of severe metrorrhagia, the pain score for dysmenorrhea and serum CA125 level at baseline significantly elevated, and the hemoglobin level at baseline and the frequency of type 2 adenomyosis significantly decreased, compared to those with long-term use. Moreover, long-term dienogest use did not decrease the serum estradiol level. Conclusion Our report suggests that dienogest is tolerable for long-term use until menopause and can be an alternative treatment option in some patients, especially those with type 2 adenomyosis, to avoid hysterectomy.

The female athlete triad (FAT) is defined by the American College of Sports Medicine (ACSM) as low energy availability (low EA), functional hypothalamic amenorrhoea and osteoporosis. In low EA, lutein dysfunction first develops, followed by anovulation and, subsequently, oligomenorrhea, leading to amenorrhea. Moreover, low estradiol concentrations due to amenorrhea decrease bone mineral density (BMD). In athletes with one of the factors of FAT, the risk of a stress fracture is 2.4-4.9 times higher and may increase the risk of fracture throughout the lifespan. Low EA is the starting point of FAT, and the FAT concept emphasizes the importance of energy intake that is commensurate with exercise energy expenditure in athletes. In amenorrheic athletes who undergo gynecological examination, it is important to appropriately evaluate whether the cause is low EA and to review exercise energy expenditure and energy intake. It remains difficult even for experts to calculate available energy using the ACSM definition formula when evaluating energy deficiency. Moreover, performing early FAT screening during teenage years and cooperation between the department of obstetrics and gynecology and sports dietitians are also issues. The aim of this paper is to review the management of FAT from the viewpoint of gynecologists.

AIM Our objective was to determine the preoperative factors associated with difficulty in total laparoscopic hysterectomy (TLH). METHODS This retrospective clinical study included 157 patients who underwent TLH for leiomyoma or adenomyosis between 2009 and 2013. All patients underwent magnetic resonance imaging (MRI) before surgery. We categorized patients as 'difficult' if the operation time was > 243 min, if total blood loss was > 500 mL, or if conversion to laparotomy was necessary. Preoperative information, including MRI findings, was compared between the difficult and 'other' patients. Stepwise logistic regression analysis was used to control for covariates that were significant on univariate analysis (P

AIM: Recent investigations have demonstrated that athletes with high relaxin-2 levels have a high risk of anterior cruciate ligament injuries while athletes taking oral contraceptives (OC) have low relaxin-2 levels. It has not yet been clarified whether taking OC reduces relaxin-2 levels. The purpose of this study was to investigate changes in relaxin-2 levels in athletes taking OC. METHODS: Levels of relaxin-2 estradiol progesterone luteinizing hormone and follicle-stimulating hormone were measured in serum samples (n = 183) from 106 elite female athletes. Five athletes with serum relaxin-2 concentrations > 6 pg/mL during the luteal phase were recruited to assess the effect of OC therapy. RESULTS: Serum relaxin-2 concentrations were significantly higher during the luteal phase (n = 57) than in the follicular phase (n = 72) or in athletes on OC therapy (n = 10) (P 6 pg/mL. In 23 athletes serum relaxin-2 concentrations were measured during both the follicular and luteal phases revealing that relaxin-2 levels were significantly higher in the luteal phase compared with the follicular phase. In 5 out of 23 athletes serum relaxin-2 concentrations were > 6 pg/mL in the luteal phase and during the second cycle of OC therapy relaxin-2 concentrations decreased dramatically to below the detection limit (0.26 pg/mL). CONCLUSIONS: High serum relaxin-2 concentrations were only detected during the luteal phase. In athletes with high relaxin-2 concentrations during the luteal phase OC therapy decreased serum relaxin-2 levels. (c) 2016 Japan Society of Obstetrics and Gynecology.

Problem Neutrophils are known to be accumulated in endometriosis; however, direct evidence of the impact of neutrophils in the development of endometriosis was lacking. To clarify the importance of neutrophils, we examined the effect of neutrophil depletion on the development of endometriosis. Method of study Ovariectomized, estradiol-replaced, 8-week-old, female BALB/c mice were injected with endometrial fragments (Day 0). Neutrophils were depleted by anti-Gr-1 antibody, either in the early stage (from Day 1 to Day 3, group E) or late stage (from Day 8 to Day 12, group L). Control mice (group C) did not receive antibodies. On Day 14, mice were killed and the number and weight of endometriotic lesions were counted and weighed. Results The number of endometriotic lesions was significantly less in group E in comparison with Group C and Group L. Weight per lesion did not differ between groups. Conclusion Neutrophils are essential for the initial formation of endometriosis.

Aim The aim of this study was to investigate the prevalence of hypointensity on T2 star-weighted imaging (T2*WI), which is useful for detecting hemosiderin, in endometriomas and other ovarian tumors. The efficacy of detecting adhesions around ovarian tumors was also investigated. Methods Pelvic magnetic resonance (MR) examinations, including T2*WI, were carried out. The inclusion criteria were female patients with ovarian surgical treatments. One hundred seventeen patients with a total of 147 lesions were enrolled. Two radiologists retrospectively evaluated MR imaging (MRI) to predict ovarian pathology and the presence of adhesions. T2*WI hypointensity of the inside and outside along ovarian cysts/tumors was utilized to predict pathological diagnoses and the presence of adhesions, respectively. The kappa scores were calculated to measure interobserver agreement on MRI findings. The MRI interpretations were compared with the results of pathological investigation and surgical observations. Results Hypointensity inside along the cyst walls on T2*WI was observed in 100 out of 106 lesions of endometriomas (94.3%), and three out of 41 non-endometrial ovarian cysts/tumors (7.3%). Four different patterns of T2*WI were observed in ovarian cysts/tumors. The kappa score regarding T2*WI hypointensity inside along the cyst walls was 0.633. Using conventional routine pelvic MRI, the sensitivity for detecting adhesions around ovarian cysts was 84.5%. By adding T2*WI, the sensitivity improved to 91.4% (P < 0.01). With conventional methods to predict adhesions, the kappa score was 0.660. After adding T2*WI to the conventional methods, the kappa score was 0.767. Conclusion Hypointensity on T2*WI was observed frequently in endometrioma. T2*WI also improved the sensitivity for detecting adhesions around ovarian cysts/tumors.

Aim The objective of this study is to determine the factors associated with successful pregnancy in women of late reproductive age with uterine fibroids who undergo embryo cryopreservation before surgery (ECBS). Methods Patients who underwent in vitro fertilization treatment with controlled ovarian stimulation from November 2010 to January 2017 in our university hospital were included. Twenty-two patients older than 35 years of age at the first visit with cavity-distorting uterine fibroids underwent ECBS, a three-step therapeutic approach consisting of oocyte pick-up, myomectomy and embryo transfer (ET), which are performed in this order. We retrospectively calculated the pregnancy rate and determined the factors associated with successful pregnancy. Results The mean age at ET of the patients who underwent ECBS was 40.9 years, with a pregnancy rate per ET of 36.8% (21/57). Of 22 patients, 10 (45.5%) successfully continued pregnancy beyond 12 weeks of gestation (ongoing pregnancy). An ongoing pregnancy was observed only among the patients with more than three frozen embryos. The ongoing pregnancy rates of patients with ≤five fibroids and ≤5 cm in the maximal diameter were significantly higher compared to the respective remaining group (90.0% vs 14.3% and 87.5% vs 33.3%). Conclusion ECBS is an effective strategy for infertile women of late reproductive age with cavity-distorting uterine fibroids, especially when it is applied to the patients who can freeze at least three embryos before myomectomy, with five or less fibroids smaller than 5 cm in the maximal diameter.

Problem Immune tolerance to endometriotic cells is important to promote endometriosis. Tryptophan 2,3-dioxygenase (TDO) enhances immune tolerance by catabolizing tryptophan to kynurenine. We studied whether interleukin-1β (IL-1β), a typical endometriosis-associated cytokine, affects the expression of TDO and the catabolism of tryptophan in endometrioma stromal cells (ESCs). We also studied whether the expression of TDO is involved in IL-1β-induced secretion of IL-6 and IL-8 in ESCs. Method of study Nineteen endometriotic patients of reproductive age with normal menstrual cycles were recruited. Primary cultures of ESCs were treated with IL-1β and TDO siRNA. TDO mRNA was measured using quantitative PCR. TDO protein was measured using Western blotting. Concentrations of kynurenine in condition media were measured using Ehrlich reagent. Concentrations of tryptophan in conditioned media were measured using tryptophan detection kit. Concentrations of IL-6 and IL-8 in conditioned media were measured using ELISA kits. Results IL-1β (1 ng/mL) increased the expression of TDO mRNA and TDO protein in ESCs. IL-1β-treated ESCs increased the production of kynurenine and the effect was inhibited by TDO siRNA. Treatment with the siRNA also decreased IL-1β-induced secretion of IL-6 and IL-8 from ESCs. Conclusion IL-1β is suggested to stimulate tryptophan catabolism and production of IL-6 and IL-8 by increasing TDO expression in endometriosis.

Aim The aim of this study was to review diagnostic/therapeutic strategies of umbilical endometriosis managed in our department and evaluate the effectiveness of these strategies. Methods Medical records for patients with diagnosis of endometriosis managed from 1999 through 2011 in the University of Tokyo Hospital were retrospectively reviewed. Cases with diagnosis of umbilical endometriosis were identified. Clinical information of age, gravida, parity, histories of surgery and oral contraceptive (OC), management for the disease prior to the first visit, symptoms, patients' desire for pregnancy, diagnostic/therapeutic methods and prognosis were reviewed and summarized. Results During the period, 2530 patients with diagnosis of endometriosis were identified. Seven patients had diagnosis of umbilical endometriosis, giving an incidence of 0.29% of all endometriosis cases and 5.6% of extragenital endometriosis cases. A definitive diagnosis was made by histological examination following a biopsy (two cases) or a resection (three cases). A clinical diagnosis was made by empirical treatment with OC (one case) or dienogest (one case). With regard to therapy, three patients chose expectant management and did not require therapeutic intervention. Three patients began OC and symptoms were well controlled in all patients. One patient who wished to conceive chose a wide resection followed by umbilical reconstruction. She became pregnant afterwards and recurrence was not reported. Conclusion There are various options of diagnostic/therapeutic strategies, such as empirical treatments and OC that can provide individualized management of umbilical endometriosis, congruent with the severity of patient symptoms, age and desire for pregnancy.

Problem The purpose of this study was to evaluate the impact of mechanical stretch caused by uterine contraction and progesterone (P4) on decidual cells (DC), neutrophil chemokines, and MMP-1 expression. Method of study DC were cultured, and cyclic stretch was applied using a computer-operated cell stretch system. Interleukin (IL)-8, growth-regulated oncogene (GRO) α, matrix metalloproteinase (MMP)-1, and mRNA and/or protein expression/activity was measured using RT-PCR and ELISA. Neutrophil chemotactic activity in conditioned media was evaluated using migration assays. The effect of P4 was also studied. Results Cyclic mechanical stretch increased IL-8, GROα, mRNA and protein, and MMP-1 production and activity level. Supernatant from stretched cells induced neutrophil chemotactic activity significantly. P4 suppressed the effect of stretch. Conclusion The current study demonstrates that cyclic mechanical stretch stimulates the production of neutrophil chemokines and MMP-1 from human decidual cells, and the production was reduced by progesterone. These findings suggest that decidual cells are responding to mechanical and endocrine signals and induce biochemical factors and thereby contribute to the regulation of human labor.

A mesogenic epoxy resin (DGETAM) was cured with a series of curing agents having different lengths of long alkyl chain (nBAB, n = 4, 8, 12). Properties of the curings were compared with those of the DGEBA cured with the same curing agents revealing the achievement of a balance between certain levels of thermal properties and excellent mechanical properties. Moreover, some curing systems were prepared with twin mesogenic type epoxy resins (DGEnMA, n = 4, 6, 8, 10, 12) having different lengths of alkyl chain as a flexible spacer and the same curing agents (n′BABs). Combinations of the same concentrations of chemical structures in the basic units of the network structure were applied, and the thermal and mechanical properties of their curing systems were investigated. The fracture energy of each system increased considerably with the increase of the alkyl chain length that adjoins the two mesogenic groups in the epoxy resins. © 2016 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2016, 133, 44244.

Problem The aim of this study was to investigate the impact of uterine contraction on the immune environment within the uterus during parturition. Method of study Uterine smooth muscle cells (USMC) were isolated from uterine myometrial tissues and cultured. The effects of cyclic stretch on mRNA and/or protein expression of IL-8, Groα, and pro-MMP-1 by USMC were measured using RT-PCR and ELISA. Neutrophil chemotactic activity in conditioned media was evaluated using migration assays. To evaluate the effect of progesterone (P4), USMC were pretreated with P4 for 24 hr. Results Cyclic stretch increased IL-8 and Groα mRNA and protein and pro-MMP-1 production significantly. Supernatants from stretched cells induced neutrophil chemotactic activity significantly; these effects were abrogated by anti-IL-8 or Groα neutralizing antibodies. Stretch effects were reduced by P4. Conclusion These results suggest that uterine contraction may induce neutrophil infiltration and MMP-1 production, which may contribute to cervical ripening and rupture of membrane. The inhibitory effects of P4 may explain the mechanism by which progestin prevents preterm labor.

Problem The aim of this study is to evaluate the expression and regulation of proprotein convertase subtilisin/kexin (PCSK) 6, which is known to be an important factor in the production of bone morphogenetic protein (BMP) cytokines in human ovary. Method of study The localization of PCSK 6 protein in normal human ovaries was examined by immunohistochemistry. Human granulosa cells (GC), obtained from 34 patients undergoing ovarian stimulation for in vitro fertilization, were cultured with BMP-2, BMP-6, BMP-7, BMP-15, growth differentiation factor (GDF)-9, and activin-A with or without FSH. PCSK 6 mRNA expression level was evaluated by quantitative real-time reverse transcription and polymerase chain reaction (RT-PCR). Results An immunohistochemistry study revealed that GC expressed PCSK 6 throughout follicular development, beginning in the primary follicle stage, while oocytes expressed PCSK 6 from the primordial follicle stage onwards. An in vitro study demonstrated that BMP-2, BMP-6, BMP-7, and BMP-15, not activin-A and GDF-9, decreased PCSK 6 gene expression in human GC. FSH induced PCSK 6 mRNA in the presence of activin-A or GDF-9. GDF-3, which is an inhibitor of BMP cytokines, also induced PCSK 6 mRNA expression. Conclusions PCSK 6, which is a critical factor to produce BMP cytokines, was suppressed with BMP stimulation in human GC, suggesting the presence of a negative feedback system in the follicular development process.

Effects of addition of nano-sized and micro-sized fillers into epoxy resin on its mechanical and dielectric relaxation phenomena were examined. The glass transition temperature (Tg) decreased when a small content of nanoclay modified by octadecylamine was added, but the decrease in Tg was suppressed when the nanoclay was modified by dimethyldodecylamine. On the other hand, Tg increased when an abundant amount of microsilica was added. At temperatures above Tg, both mechanical and dielectric relaxations were accelerated in samples with octadecylamine-modified nanoclay, while the acceleration did not occur in samples with nanoclay modified by dimethyldodecylamine. Both relaxations were restricted in composites with abundant microsilica. Therefore, co-addition of dimethyldodecylamine-modified nanoclay and abundant microsilica is adequate in order to make an epoxy resin composite with a high Tg and low dielectric loss. ©2012 Wiley Periodicals, Inc. Electron Comm Jpn, 95(9): 1–9, 2012; Published online in Wiley Online Library (wileyonlinelibrary.com). DOI 10.1002/ecj.11420

Citation Wang B, Koga K, Osuga Y, Hirata T, Saito A, Yoshino O, Hirota Y, Harada M, Takemura Y, Fujii T, Taketani Y. High mobility group Box 1 (HMGB1) levels in the placenta and in serum in preeclampsia. Am J Reprod Immunol 2011; 66: 143–148 Problem Preeclampsia is a pregnancy disorder characterized by systemic inflammation. High mobility group box 1 (HMGB1) is a molecule known to act as a ‘danger signal’ by participating in various inflammatory processes, but data in regard to preeclampsia are sparse. The aim of this study was to analyze placental and serum HMGB1 levels in normal pregnancy and preeclampsia. Method of study Sera were collected from women with preeclampsia soon after the manifestation of the disease and before commencing any medication. Placental samples were collected immediately after delivery. Expressed isoforms of HMGB1 (28- and 30-kDa) in the placenta were evaluated by Western blot analysis. Serum HMGB1 concentrations were measured using enzyme-linked immunosorbent assays (ELISA). Results Two isoforms of HMGB1 are expressed by the human placenta. The 28- and 30-kDa HMGB1 isoforms were expressed highly in preeclamptic placental tissue; however, compared with normotensive control tissue, differences in detected expression levels did not reach statistical significance. No significant difference was observed in serum HMGB1 levels between control and preeclampsia. Conclusion Inflammation provoked by HMGB1 is likely to be involved in the proinflammatory process in preeclamptic placenta. Further studies are needed to elucidate the precise role of HMGB1 in preeclampsia.

The gonadotropins, follicle‐stimulating hormone (FSH), and luteinizing hormone (LH), are of particular importance in ovarian physiology. However, FSH receptors and LH receptors are not expressed until the secondary follicle stage, indicating that initiation of follicular growth is independent of the gonadotropins. Among many intra‐ovarian growth factors, many studies have shown that bone morphogenetic proteins (BMPs) play pivotal roles in regulating the early phases of follicular growth. The BMP system induces the gonadotropin system by modulating gonadotropin receptors in early‐stage follicles. Interestingly, the BMP system also prevents precocious maturation of the follicle by suppressing luteinization. Signals provoked by the preovulatory LH surge eliminate BMPs, enabling luteinization to progress. Thus, the BMP system and the gonadotropin system seem to cooperate in regulating follicular development, maturation, and luteinization.

Liquid-crystalline (LC) epoxy resins were cured at different temperatures to obtain polydomain LC phase-cured resins. The cured resins had polydomain structures with a nematic LC phase and their domain diameters differed depending on the curing temperatures. The relationship between the domain diameter and fracture toughness of the diglycidyl ether of terephthalylidene-bis-(4-amino-3-methylphenol) (DGETAM)/ m-phenylenediamine (m-PDA) systems with the nematic phase and the previously reported smectic LC phase structures was investigated. It was clarified that the highly ordered LC structure (smectic phase) in each domain could improve the fracture toughness. In addition, the changes in the network orientation of the DGETAM/m-PDA systems were evaluated by a mapping of the microscopic infrared dichroism in the fracture process and their toughening mechanism was suggested.

Preoperative diagnosis of chronic ectopic pregnancy is often difficult because of the high incidence of negative results on pregnancy tests as a consequence of the very small amount of live villi, subtle symptoms, and the poor specificity of ultrasonographic patterns. A 45-year-old woman was referred to our department for evaluation of a mass 8 cm in diameter with solid parts in the right adnexal area. Transvaginal ultrasonography showed a mass consisting of a cystic part with an irregular thick capsule distinct from the right ovary. In the center of the cystic part, a fetus-like image, 20 mm in length was seen. Preoperative diagnosis was confirmed by the laparoscopy, which revealed a swollen right tube containing a fetus with highly necrotic changes. This case was unique because chronic ectopic pregnancy was detected at an early stage before absorption of the conceptus occurred, which coincidentally is an appropriate time for morphological diagnosis.

The bisphenol-F type flexible epoxy resin, having a good flexibility, was combined with an organo- and slurry-clay. The clay dispersions in the obtained epoxy/clay systems are significantly different depending on the type of clay. Particularly, the epoxy/slurry-clay system showed a high clay dispersibility into the epoxy matrix and was transparent in spite of the addition of 10 wt % clay. This result means that the swelling of the clay with formamide is effective for the expansion of the basal spacing of the clay. The slurry-clay nanocomposite (clay content: 5 wt %) showed a 4 times higher fracture energy than the neat epoxy system in the tensile test, though the organo-clay system (clay content: 5 wt %) was 1.5 times higher. © 2009 Wiley Periodicals, Inc. J Appl Polym Sci, 2009

The bisphenol-A type epoxy resin was combined with layered clays. Three types of epoxy/clay nanocomposites were prepared by different clay pretreatment methods, that is, the slurry (clay swelling with polar solvent), organo, and solubilization (organoclay swelling with polar solvent) methods. The organo and solubilization systems showed good dispersibility. The basal spacing of the layered clays in the obtained nanocomposites was evaluated by XRD and TEM observations. The basal spacing of the nanoclay in the solubilization system drastically increased. The mechanical properties were improved with the increase in the clay dispersion. A high modulus and fracture toughness were obtained by improvement of the clay dispersion into the matrix. © 2009 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 47: 1753–1761, 2009

A liquid-crystalline (LC) epoxy resin was cured at different temperatures and some types of curing systems having different phase structures (isotropic or polydomain, which have a microscopically ordered LC network structure) were obtained. The diameters of each domain in the polydomain system changed from the small to the larger size. The diameters of the LC domains were evaluated using a polarized optical microscope and the polarized microscopy FTIR mapping method. These systems were used to investigate the relationship between the network arrangement and mechanical properties. The fracture toughness of the cured systems was related to the enlargement of the ordered area in the network structures. With the toughness improvement, the meandering cracks were observed at the fracture surfaces. © 2008 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 47: 156–165, 2009

Polyglycidyloxypropyl silsesquioxane, which has an excellent heat resistance, was combined with sheet-like and spherical titanate as nano-fillers. The burning property of the composites was related to the shape of the dispersed titanate. A burning test was carried out according to the UL-94 test method. As a result, though the test specimen burned from one end to the other in the spherical titanate filled composite system, a fire extinguishing property was observed in the sheet-like titanate filled composite system. The extinguishing time of the latter system classified V-0 in the specification test. © 2008 Wiley Periodicals, Inc. J Appl Polym Sci, 2008

Poly-(glycidyloxypropyl) phenyl silsesquioxane (PGPSQ) was combined with an organo-layered titanate filler. The phase structure of the obtained composite was evaluated by XRD and TEM observations. Moreover, a burning test was carried out according to the UL-94 test method. The extinguishing time of the nanocomposites was classified V-0 even for the 1 wt % layered titanate content. Based on the results, it was clarified that the frame retardancy of the PGPSQ/organo-layered titanate system was superior to the poly-(glycidyloxypropyl) silsesquioxane (PGSQ)/organo-layered titanate system, which was reported in a previous paper. In addition, the layered titanate as a filler also improved the ductility of the PGPSQ. © 2007 Wiley Periodicals, Inc. J Appl Polym Sci 2007

A mesogenic-type curing agent was synthesized to introduce a mesogenic group not only into epoxy resin backbones but also into the crosslink units. In the mesogenic curing agent system, the domain size became larger, and the network arrangement in each domain existed to a greater extent than that in a system cured with the ordinary diamine curing system according to the evidence from polarized optical micrographs and polarized Fourier transform infrared mapping measurements. Moreover, the fracture toughness of the system was considerably improved. © 2006 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 44: 2486–2494, 2006

Problem Adiponectin is a novel adipocytokine of extreme importance for the metabolism. Recent studies have indicated that adiponectin suppresses inflammation, angiogenesis, and fibrosis, which are central pathogenic factors for endometriosis. We addressed the possibility that adiponectin is implicated in endometriosis. Method of study We measured concentrations of adiponectin in peritoneal fluid (PF) of women with (n = 54) or without (n = 26) endometriosis using specific enzyme-linked immunosorbent assay. Results Adiponectin concentrations in PF of women with endometriosis were significantly lower than those of women without endometriosis. With respect to the stages of the disease, the concentrations of adiponectin in women with stage III/IV endometriosis were significantly lower compared to those in women without endometriosis and with stage I/II endometriosis. Body mass index were comparable among the groups. Conclusions These findings imply that adiponectin may be an anti-endometriotic factor, possibly due to its anti-inflammatory, anti-angiogenic, and anti-fibrotic properties.

The fracture toughness of liquid-crystalline epoxy systems, which had a nematic polydomain structure (domain size about 40 μm), with an increasing loading rate was evaluated. In this system, the fracture toughness dramatically decreased from 1.96 to 0.22 MN/m3/2 with an increasing loading rate (0.1–5 mm/min). The network orientation near the fracture surface of different loading rate systems was investigated with polarized optical microscopy and polarized infrared spectroscopy. As a result, a large oriented region of mesogenic groups was observed near the fracture surface in the relatively low loading rate (0.1 and 0.5 mm/min) systems, but such a phenomenon was not observed in the high loading rate (2 and 5 mm/min) systems. These results showed that the high fracture toughness of the system at the low loading rate was due to the magnitude and region of the reorientation of the mesogenic groups in the fracture process and that high toughness could not be achieved at a high loading rate because the loading rate was too fast to allow orientation of the networks containing the mesogenic groups. © 2005 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 43: 1296–1302, 2005

Problem Endometriosis accompanies local inflammatory reactions in the peritoneal cavity. We examined the phosphorylation of mitogen-activated protein kinases (MAPKs), i.e. extracellular signal-regulated kinase (ERK), p38 MAPK (p38) and c-Jun N-terminal kinase (JNK) in endometriotic stromal cells, and their possible pathophysiological roles in endometriosis in relation to proinflammatory substances. Method of study Endometriotic stromal cells were isolated from endometriomas and were cultured for the experiments. Phosphorylation of MAPKs in endometriotic stromal cells treated with interleukin (IL)-1beta, tumor necrosis factor (TNF)alpha and H(2)O(2) were examined by Western blot analysis. Effects of PD98059, SB202190 and SP600125 (inhibitors of ERK, p38 and JNK, respectively) on IL-1beta-induced secretion of IL-6 and IL-8, and on IL-1beta-induced expression of cyclo-oxygenase-2 (COX-2) in endometriotic cells were studied. In addition, eutopic endometrial tissues were collected, and the phosphorylation rate of p38 in eutopic endometrial tissues and endometriotic tissues were determined. Results IL-1beta, TNFalpha and H(2)O(2) stimulated the phosphorylation of ERK, p38 and JNK, while the total amounts of proteins of the respective MAPKs were virtually the same compared with those in the unstimulated controls. Both SB202190 and SP600125 suppressed IL-1beta-induced secretion of IL-6 and IL-8, and PD98059 suppressed IL-1beta-induced secretion of IL-8. Both SB202190 and PD98059 suppressed IL-1beta-induced expression of COX-2 in endometriotic cells. The p38 phosphorylation rates in the endometriotic tissues were significantly higher than those in the eutopic endometrial tissues of the same patients. Conclusions Given the current theory that inflammatory changes are involved in the progression of endometriosis, MAPKs could play as pivotal intracellular signal transducers in endometriotic cells, and thus have a pathophysiological role in the disease.

A liquid-crystalline epoxy resin was cured at two different temperatures. The phases of the cured systems clearly showed isotropic and nematic polydomain structures, which depended on the curing temperature. The fracture toughness of the systems was measured, and the fracture mechanism was investigated with polarized IR measurements. The nematic polydomain structure system showed considerably higher fracture toughness than the isotropic structure. Moreover, both systems exhibited a reorientation of the network chains near the fracture surface during the fracture process, and the region of the network reorientation in the nematic polydomain structure system was larger than that in the isotropic structure system. © 2004 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 42: 4044–4052, 2004

During the curing process of a liquid-crystalline epoxy resin, a relatively strong magnetic field was applied, and the thermomechanical properties of the cured resin were investigated. The network orientation and mechanical properties of the cured system were evaluated with wide-angle X-ray diffraction, dynamic mechanical analysis, and fracture toughness testing. The cured system was found to have an anisotropic network structure, which arranged along the applied field, and the anisotropy was reflected in the thermomechanical properties. In particular, the fracture toughness of the system dramatically increased when the network chains were arranged across the direction of the crack propagation.

A biphenol-type epoxy resin, which had a mesogenic group in the backbone moiety, was modified with carboxy-terminated butadiene acrylonitrile copolymer (CTBN) as a reactive elastomer, and its fracture toughness was measured. With the addition of CTBN, the fracture toughness of the biphenol-type epoxy resin significantly increased and became significantly higher than that of a bisphenol A-type epoxy resin modified with CTBN. The network chain orientation in the cured biphenol-type epoxy resin system was clearly observed during the fracture process with polarized microscopy Fourier transform infrared measurements, although such a phenomenon was not observed in the bisphenol A-type epoxy resin system. The high toughness of the cured biphenol-type system was clearly due to the consumption of the mechanical energy by a large deformation of the matrix resin due to the orientation of the network chains during the fracture process. © 2003 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 41: 1198–1209, 2003

When tensile stress was applied to epoxy resin filled with silica particles, we expected that the stress concentration would occur in the epoxy matrix near the interface between the matrix and the silica particles. We investigated the plastic deformation of the network chains near the interface, which was quantitatively evaluated using a polarized microscope FTIR technique. A biphenol-type epoxy resin, which has a mesogenic group in the backbone moiety, was used as the matrix resin. As a result, reorientation of the network chains along the direction of the tensile stress near the interface with the silica particles was observed. Especially when the silica/matrix interface has good bonding properties, the reorientation of the network chains was observed at a larger area around the silica particles. © 2002 Wiley Periodicals, Inc. J Appl Polym Sci 87: 787–794, 2003

Author(s): Yamada-Nomoto, Kaori; Yoshino, Osamu; Akiyama, Ikumi; Iwase, Akira; Ono, Yosuke; Nakamura, Tomoko; Harada, Miyuki; Nakashima, Akitoshi; Shima, Tomoko; Ushijima, Akemi; Osuga, Yutaka; Chang, Russell Jeffrey; Shimasaki, Shunichi; Saito, Shigeru | Abstract: ProblemPlasminogen activator inhibitor-1 (PAI-1) is elevated in women with polycystic ovary syndrome (PCOS), but the regulation in granulosa cells (GCs) is unclear.Method of studyPAI-1 expression in PCOS ovaries was investigated immunohistologically. PAI-1 expressions in HGrC1, a human GC cell line, were investigated at mRNA and activity levels. The expressions of TGF-β and TNF-α in peritoneal fluid mononuclear cells (PFMCs) were measured with quantitative PCR.ResultsLittle PAI-1 expression is observed in healthy GCs, whereas GCs of PCOS and atretic follicle exhibit distinct expression in vivo. In vitro study using HGrC1 shows that TGF-β and TNF-α increase PAI-1 mRNA and its activity, and both together exhibit a synergistic effect. The expression of PAI-1 mRNA is suppressed by simvastatin. Moreover, insulin-sensitizing drugs (metformin, pioglitazone, and rosiglitazone) suppress LPS-induced TGF-β and TNF-α mRNA expression in PFMC.ConclusionStatin and insulin-sensitizing drugs may provide a potential therapy for PCOS via down-regulation of PAI-1 expression in GCs and down-regulation of TGF-β and TNF-α expression in PFMC, respectively.