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Uterine arteriovenous fistula (AVF) is a rare entity, but may lead to life-threatening hemorrhage. Although transcatheter embolization, surgical ligation, or hysterectomy would be considered for treatment of uterine AVF, there is poor knowledge as to how gynecologists can manage the uterine AVF with multiple large inflow arteries. Herein we report a uterine AVF successfully treated using multiple-step transcatheter embolization. The patient, a 58-year-old postmenopausal woman with a history of dilation and curettage, had intermittent massive uterine bleeding. Radiologic imaging revealed the presence of a large vasculature mass. The mass occupied the entire pelvis, and the source of hemorrhage was identified as an accompanying AVF. We thought that surgical intervention was contraindicated because of the potential risk of uncontrollable intraoperative bleeding. Multiple-step transcatheter embolization was performed, with complete resolution of the AVF. Thereafter, the patient had no further uterine bleeding. Multiple-step transcatheter embolization might be the most beneficial and efficient treatment option for a uterine AVF with multiple large inflow arteries. [ABSTRACT FROM AUTHOR]

Abstract: Intrapericardial diaphragmatic hernia is a very rare phenotype of neonatal diaphragmatic hernia which is thought to be caused by the developmental failure of the septum transversum. There have been only 10 cases reported since 1980, and among them, only 2 cases were diagnosed in fetal life. We herein report a new case that was diagnosed in fetal life, and pericardiocentesis was performed at 27 weeks of gestation. This is the first case to undergo a fetal interventional therapy. After birth, the patient successfully underwent closure of the hernia, despite severe pulmonary hypoplasia. [Copyright &y& Elsevier]

Abstract: Glutamate-induced excitotoxicity has been implicated in the pathogenesis of various neurological damages and disorders. In the brain damage of immature animals such as neonatal hypoxic-ischemic brain injury, the excitotoxicity appears to be more intimately involved through apoptosis. Bax, a member of the Bcl-2 family proteins, plays a key role in the promotion of apoptosis by translocation from the cytosol to the mitochondria and the release of apoptogenic factors such as cytochrome c. Recently, Bax-inhibiting peptide (BIP), a novel membrane-permeable peptide which can bind Bax in the cytosol and inhibit its translocation to the mitochondria, was developed. To investigate the possibility of a new neuroprotection strategy targeting Bax translocation in glutamate-induced neuronal cell death, cerebellar granule neurons (CGNs) were exposed to glutamate with or without BIP. Pretreatment of CGNs with BIP elicited a dose-dependent reduction of glutamate-induced neuronal cell death as measured by MTT assay. BIP significantly suppressed both the number of TUNEL-positive cells and the increase in caspases 3 and 9 activities induced by glutamate. In addition, immunoblotting after subcellular fractionation revealed that BIP prevented the glutamate-induced Bax translocation to the mitochondria and the release of cytochrome c from the mitochondria. These results suggest that agents capable of inhibiting Bax activity such as BIP might lead to new drugs for glutamate-related diseases in the future. [Copyright &y& Elsevier]

Problem: Our previous studies have demonstrated that a subclass of soluble human leukocyte antigen-G1 protein (sub-sHLA-G1), that has α1 to α3 extra-cellular portion but lacks C-terminus of authentic soluble HLA-G1 secreted by trophoblasts, fine-tunes the release of cytokines from peripheral blood mononuclear cells (PBMCs) chiefly by counterbalancing membrane-bound HLA-G1 (mHLA-G1), and thereby may play a role in maintaining pregnancy. In this study, we investigated whether the presence of sHLA-G1 protein altered the release of cytokines from decidual mononuclear cells (DMCs) which are localized at the interface of feto–maternal interaction and whose cell population is completely different from PBMCs. Method of study: We cultured peripheral DMCs with either HLA-A and -B lacking B lymphoblast cell line (721.221 cells) or the cells transfected with mHLA-G1 (721.221-G1 cells) with or without sub-sHLA-G1. Cytokines concentrations in the culture media were determined by an enzyme-linked immunosorbent assay. Results: Regardless of the presence of mHLA-G1 expressing cells, the addition of the recombinant sub-sHLA-G1 protein in the DMC culture media decreased the amounts of tumor necrosis factor (TNF)-α and interferon (IFN)-γ, with the release of IL-4 from DMCs being unchanged. Conclusion: The sub-sHLA-G1 protein modulates the release of cytokines from DMCs additively to mHLA-G1 expressing cells. In view of the distinct fetomaternal interaction during implantation, it appears that sHLA-G1 might play a role in the establishment of pregnancy by regulating cytokine release in concert with mHLA-G1. [Copyright &y& Elsevier]

Abstract: In human pregnancy, CD14+ decidual macrophages (DMs) are the dominant professional antigen-presenting cells in the decidua, comprising 20–30% of the local leukocyte population. Although the relevance of DMs to feto-maternal immune tolerance has been described, the molecular mechanisms underlying these functions have not been fully elucidated. B7-H1, a costimulatory ligand in the B7 family, negatively modulates T cell activity by binding to its corresponding receptor, PD-1. The present study aimed to investigate the functional significance of costimulatory interactions between DMs and T cells, with a particular focus on B7-H1:PD-1 signaling. An analysis of the expression profile of B7 ligands on human DMs revealed that B7-H1 was present on DMs isolated from early but not term pregnancies. B7-H1 was not expressed on the peripheral monocytes (PMs) of pregnant women. In response to IFN-γ, B7-H1 expression was induced on PMs and was enhanced on DMs, suggesting that this cytokine might be a key factor in the control of B7-H1 expression in the decidua. The majority of decidual T cells were noted to exhibit robust expression of PD-1, whereas the expression was limited to a small subpopulation of circulating T cells. Functional assays demonstrated that DMs are able to suppress T cell IFN-γ production via B7-H1:PD-1 interactions. This suppressive property was not observed for PMs, which lack B7-H1. B7-H1 on DMs may function as a key regulator of local IFN-γ production and thereby contribute to the development of appropriate maternal immune responses to the fetus in early pregnancy. [Copyright &y& Elsevier]

Abstract: Objective: To study the recurrence rate and predictive factors for recurrence after surgical excision of ovarian mature cystic teratomas (MCT). Study design: Retrospective study of 382 patients who underwent surgical excision of MCT and whose post-surgical follow-up data were available over six months. Patients who underwent concomitant oophorectomy or had a history of oophorectomy were excluded. Medical records were reviewed for evidence of recurrence. The Cox-hazard model was used for the estimation of predictive factors for recurrence. Categorical data were compared using the Chi-square and Fisher's exact tests. Results: There were 16 recurrences within a mean follow-up period of 43.0 months, with a recurrence rate of 4.2%. Young age (<30 years old, Y) (hazard ratio (HR) 2.98; 95% confidence interval (CI) 1.04–8.62, P =0.043), large cyst (≥8cm in diameter, L) (HR 2.75; 95% CI 1.03–7.37, P =0.044), and bilaterality (B) (HR 2.88; 95% CI 1.07–7.76, P =0.036) were shown to be significant predictive factors. When a patient had all these three factors, the recurrence rate was 21.0%, otherwise 3.4% (P <0.01). Patients with Y+L, Y+B, and B+L also showed significantly higher recurrence rate (21.4%, 15.9%, and 11.4%, respectively). Conclusion: The long-term recurrence rate after surgical excision of MCT in this study is 4.2%. A patient with young age (<30 years old) or large cyst (≥8cm in diameter) or bilateral cysts is at high risk of recurrence, which is even higher when a patient has more than one of these factors. [Copyright &y& Elsevier]

Abstract: The Japanese herbal medicines, Juzen-taiho-to (JTT) and Hochu-ekki-to (HET), have been shown to enhance humoral immune responses to vaccine antigen when used as adjuvants for prophylactic vaccines. However, their adjuvant effect on mucosal cellular immune responses remains unstudied. The precursor lesion of cervical cancer, high-grade CIN that expresses HPV E7 oncoprotein ubiquitously is a target for HPV therapeutic vaccines that elicit mucosal E7-specific type 1 T cell responses. We have demonstrated that oral immunization with recombinant Lactobacillus casei expressing HPV16 E7 (LacE7) is more effective in eliciting mucosal E7-specific IFNγ-producing cells than subcutaneous or intramuscular antigen delivery. Here we report the synergistic effect of an oral Lactobacillus-based vaccine and Japanese herbal medicines on mucosal immune responses. Oral immunization of mice with LacE7 plus either a Japanese herbal medicine (JTT or HET) or a mucosal adjuvant, heated-labile enterotoxin T subunit (LTB), promotes systemic E7-specific type 1 T cell responses but not mucosal responses. Administration of LacE7 plus either Japanese herbal medicine and LTB enhanced mucosal E7-specific type 1 T cell response to levels approximately 3-fold higher than those after administration of LacE7 alone. Furthermore, secretion of IFNγ and IL-2 into the intestinal lumen was observed after oral administration of LacE7 and was enhanced considerably by the addition of Japanese herbal medicines and LTB. Our data indicated that Japanese herbal medicines, in synergy with Lactobacillus and LTB, enhance the mucosal type 1 immune responses to orally immunized antigen. Japanese herbal medicines may be excellent adjuvants for oral Lactobacillus-based vaccines and oral immunization of LacE7, HET and LTB may have the potential to elicit extremely high E7-specific mucosal cytotoxic immune response to HPV-associated neoplastic lesions. [Copyright &y& Elsevier]

Abstract: Although many clinical trials on human papillomavirus (HPV) therapeutic vaccines have been performed, clinical responses have not been consistent. We have addressed mucosal cytotoxic cellular immune responses to HPV16 E7 after oral immunization of mice with recombinant Lactobacillus casei expressing HPV16 E7 (LacE7). C57BL/6 mice were orally exposed to 0.1–100mg/head of attenuated LacE7 or vehicle (Lac) vaccines at weeks 1, 2, 4, and 8. Responses to subcutaneous or intramuscular injection of an HPV16 E7 fusion protein using the same timing protocol were used for comparison. Oral immunization with LacE7 elicited E7-specific IFNγ-producing cells (T cells with E7-type1 immune responses) among integrin α4β7+ mucosal lymphocytes collected from gut mucosa. An induction of E7-specific granzyme B-producing cells (E7-CTL) exhibiting killer responses toward HPV16 E7-positive cells was also observed. The induction of T cells with specific mucosal E7-type1 immune responses was greater after oral immunization with LacE7 when compared to subcutaneous or intramuscular antigen delivery. Oral immunization with Lactobacillus-based vaccines was also able to induce mucosal cytotoxic cellular immune responses. This novel approach at a therapeutic HPV vaccine may achieve more effective clinical responses through its induction of mucosal E7-specific CTL. [Copyright &y& Elsevier]

Abstract: The balance of inhibitory and activating natural killer (NK) receptors on maternal decidual NK cells, most of which are CD56bright, is thought to be crucial for the proper growth of trophoblasts in placenta. A lectin-like NK receptor, CD94/NKG2, is the receptor for human leukocyte antigen (HLA)-E, which is expressed on trophoblasts. To clarify the mechanism regulating the activity of decidual NK cells during pregnancy, we investigated the expression patterns of inhibitory NK receptor, CD94/NKG2A, and activating receptor, CD94/NKG2C, on decidual NK cells in an early stage of normal pregnancy and compared them with those on peripheral NK cells, most of which are CD56dim. The rate of NKG2A-positive cells was significantly higher for decidual CD56bright NK cells than for peripheral CD56dim NK cells, but the rates of NKG2C-positive cells were comparable between the two cell types. Interestingly, peripheral CD56dim NK cells reciprocally expressed inhibitory NKG2A and activating NKG2C, but decidual CD56bright NK cells that expressed activating NKG2C simultaneously expressed inhibitory NKG2A. The co-expression of inhibitory and activating NKG2 receptors may fine-tune the immunoregulatory functions of the decidual NK cells to control the trophoblast invasion in constructing placenta. [Copyright &y& Elsevier]

Abstract: Background: Many studies on the physiology of the cardiovascular system reported that nonlinear chaotic dynamics may govern the generation of the heart rate signal. Objective: To examine whether the heart rate dynamics of an intrauterine growth restricted (IUGR) fetus is different from a healthy normal fetus by nonlinear methods of time series analysis. Design of the study: One hundred nineteen fetal heart rate (FHR) recordings from healthy normal fetuses, and 69 recordings from IUGR fetuses were analyzed. Nonlinear analyses included attractor reconstruction, calculation of the largest Lyapunov exponents using the Wolf algorithm, and estimation of correlation dimension. The largest Lyapunov exponents from normal fetuses were checked by means of surrogate-data test. Results: Abnormal FHR patterns of IUGR fetuses such as decreased variability and repetitive late decelerations presented a remarkably different structure in the reconstructed attractor. Surrogate data suggest that the FHR of healthy normal fetuses has unique nonlinear characteristics. The largest Lyapunov exponents were positive for all of 119 healthy normal fetuses, indicating that the FHR control system is sensitive to initial conditions. The values of IUGR fetuses were significantly lower than those of normal subjects. In normal fetuses, significant changes of correlation dimension according to gestational age were observed. In IUGR fetuses, however, such changes were not found. Conclusions: The heart rate dynamics of IUGR fetuses is less chaotic than that of normal fetuses. Decreased system complexity suggested by correlation dimension may limit the IUGR fetuses'' ability to maintain cardiovascular integrity, and therefore, to adapt to the variety of internal and external cardiovascular stresses. [Copyright &y& Elsevier]

Abstract: T helper (Th)1 cytokine-predominating status and compromised placental vasculature is thought to be central to the pathogenesis of preeclampsia. However, it remains to be clarified how these two phenomena relate to each other. We have reported that lymphokine-activated killer (LAK) cells induced from decidual mononuclear cells (DMCs) with interleukin (IL)-2 expressed in preeclamptic placenta reduced the angiogenic activity of cytotrophoblasts (CTs). The objective of this study was to examine how LAK cells reduced the angiogenic activity of CTs. We investigated the angiogenesis-related molecules released from cultured CTs obtained from first trimester placenta that had been pretreated with either non-activated DMCs or LAK cells from DMCs. The amounts of vascular endothelial growth factor (VEGF), placenta growth factor (PlGF) and their antagonist, soluble fms-like tyrosine-kinase-1 (sFlt-1) released in CT culture media were measured using ELISA. CTs pretreated with LAK cells released more sFlt-1 compared with those pretreated with non-activated lymphocytes, and CTs pretreated with non-activated lymphocytes released more sFlt-1 compared with those without pretreatment. The release of total VEGF and free PlGF from CTs was not altered by pretreatment with DMCs. Thus, in preeclamptic placenta, LAK cells induced from DMCs by co-existing IL-2 may react to the invading CTs and enhance the release of sFlt-1 from CTs without any change of VEGF or PlGF secretion. This might result in the reduction of actual angiogenic potential of the VEGF system in decidua and the placental vascular system might be compromised, which may lead to the development of preeclampsia. [Copyright &y& Elsevier]

Abstract: Objective: Our objective was to examine whether heart rate time series of healthy normal fetuses possess fractal properties and, if so, to determine whether consistent changes in fractal features according to gestational age exist. Design of the study: One hundred nineteen fetal heart rate (FHR) recordings in 55 singleton pregnancies between the 22nd and 41st weeks were analyzed. Fractal analysis developed by Higuchi was performed. Changes of fractal dimension were examined according to gestational age. Results: Two characteristic scaling regions were present in each FHR trace. The fractal dimension defined within 500 ms to 5 s (D S; median 1.396, range 1.273–1.642) was lower than that defined longer than 30 s (D L; median 1.933, range 1.492–2.049) in every case. These two values were significantly different (p &#60;0.001). There was a statistically significant difference in the values of D S between (22–29 weeks, mean 1.323), (30–33 weeks, mean 1.443) (p =0.004), (34–35 weeks, mean 1.418) (p =0.002), (36 weeks, mean 1.409) (p =0.030), (37–38 weeks, mean 1.394) (p =0.006), and (40–41 weeks, mean 1.452) (p =0.001), respectively. D S values between (40–41 weeks), (37–38 weeks) (p =0.012), and (39 weeks, mean 1.369) (p =0.030), respectively, were also significantly different. The values of D L decreased from 22–39 weeks (median 1.941) to 40–41 weeks (median 1.891) (p =0.008). Conclusions: Two distinct fractal structures within the FHR variation were identified. Fractal features of heart rate of healthy normal fetuses change significantly during pregnancy period. Fractal analysis may be useful for evaluating FHR variation. [Copyright &y& Elsevier]

Placental hypoxia following the immature remodeling of spiral arteries by extravillous cytotrophoblasts (CTs) is focused on the pathogenesis of pre-eclampsia. At the same time, the expression of human leukocyte antigen (HLA)-G is decreased at the protein and mRNA levels in the pre-eclamptic placenta. In view of the potential function of HLA-G in immunological tolerance in the feto–maternal interface, we were much concerned to find whether the lowered expression of HLA-G in the pre-eclamptic placenta is a precursor or the result of placental hypoxia. The effect of oxygen on the expression of membrane-bound (mb) and soluble (s) HLA-G was investigated in primary cultures of extravillous CTs. The undifferentiated CTs isolated from the first-trimester placenta were cultured with different concentrations of oxygen (20%, 8% and 2%). The protein expression of mbHLA-G and of sHLA-G was assessed using flow cytometry, and mRNA expression was analyzed using real-time PCR. Expression of mbHLA-G and of sHLA-G protein was intensified with time in culture regardless of the oxygen concentration, and the expression intensities were synchronized between the 20% and the 2% oxygen concentrations at each time point. The mRNA expressions of mbHLA-G1 and sHLA-G1 at 2% oxygen were increased to twice those with 20% oxygen.Our findings demonstrate that no reduction of HLA-G was induced in CTs by short-term exposure to hypoxia, although further study may be required to find the effect of chronic hypoxia. [Copyright &y& Elsevier]

The objective of this study was to establish a novel method of preoperative autologous blood donation (PAD) for surgery of gynecologic malignancies, which requires considerable amounts of plasma relative to the red blood cell component. To collect a double volume of plasma over the amount obtained from whole blood without using an aphaeresis system, we first collected 500 ml of whole blood (2.5 units), and centrifuged it. We gave back the resultant red cell component alone, and retained the plasma component. We further collected an additional 500 ml of whole blood, and centrifuged it. The red cell component (2.5 units) was stored in the refrigerator (as a concentrated red cell, CRC). The resultant plasma together with the plasma collected first (5 units) was frozen and stored in the freezer (fresh frozen plasma, FFP), We repeated this procedure at most three times at intervals of 1 week. Erythropoietin was injected once a week and iron tablets were prescribed. Ninety-nine patients undergoing surgery for a gynecological malignancy were subjected to this method and 86 patients without PAD served as a control. We conducted the procedure for PAD without any noticeable side effects. The amount of actual use of allogeneic CRC and FFP were significantly reduced in the PAD group compared with the control group. In particular, 93.6% of the PAD cases who gave 10 or less units of FFP could go without allogeneic FFP. Postoperative serum albumin levels were higher in the PAD group compared with the control. We have established a novel PAD method which can yield a greater volume of FFP relative to CRC, thus meeting requirements for surgery for gynecological malignancies. [Copyright &y& Elsevier]

Objective: To report a case of aberrant implantation and growth of uterine leiomyoma in the abdominal wall after laparoscopically assisted myomectomy. Design: Case report. Setting: University hospital. Patient(s): One 27-year-old woman with a newly developed solid mass in the abdominal wall near the minilaparotomic site of a previous laparoscopically assisted myomectomy. Intervention(s): Surgical removal of the mass. Main Outcome Measure(s): Histologic examination of the mass. Result(s): A newly developed mass measuring approximately 9 cm was surgically removed. The mass was located in the fascial area of abdomen close to the incision site of a previous laparoscopically assisted myomectomy. Histologic diagnosis including Hematoxylin-Eosin staining and immunohistochemistry confirmed that the lesion was compatible with uterine leiomyoma. Conclusion(s): Implantation and growth of uterine leiomyoma fragments after myomectomy is a rare event. However, this complication should be considered as a differential diagnosis when a progressively growing mass is observed at the incision site. [Copyright &y& Elsevier]