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Focuses on protease inhibitor, Bikunin. Potential to suppress tumor cell invasion and metastasis; Impact of bikunin overexpression on the down regulation in uPA and uPAR gene expression; Use of cDNA microarray hybridization screening with mRNA to identify bikunin regulated genes; Identification of 11 bikunin-stimulated and -repressed genes; Subsets which the identified genes can be classified.

Studies how Kunitz-type protease inhibitor, Bikunin, inhibits ovarian cancer cell invasion. Blocking of the calcium-dependent transforming growth factor-beta1 (TGF-beta1) signaling cascade; Production of secreted and cell-associated urokinase-type plasminogen activator (uPA) by the human ovarian cancer cell line; Inhibition of the constitutive expression of TGF-beta1 and TGF-beta1-mediated PA system signaling cascade.

The aim of the present study was to elucidate functions of the interleukin (IL)-8 at ovulation and luteinization in vivo. To compare the morphological differences between human chorionic gonadotropin (hCG) and IL-8 stimulation, scanning electron microscopy was employed to study rat ovarian vascular corrosion casts. Follicular growth and increased capillary vessel densities around the follicles were seen in vascular corrosion casts after IL-8 injection, similar to the result of hCG administration. This result indicated that exogenous IL-8 could play a role in the neovascularization during follicular development as an angiogenetic factor. Many fenestrations were observed in the vascular endothelium by hCG administration. In contrast, no fenestrations were observed with IL-8 injection, indicating that IL-8 may not be sufficient to increase the vascular permeability directly. Although germinal vesicle breakdown (GVBD) occurred at rates of 82% after the hCG injection, only 20% GVBD was observed after the IL-8 injection. The present study indicated that IL-8 might have important effects on rat follicles at ovulation and luteinization via vascularization in a similar manner to hCG. However, IL-8 was not effective on vascular permeability and oocyte maturation, which were different from hCG. Thus, we can conclude that IL-8 can participate in follicular development in part and may play important roles in ovulation and luteinization as one of some mediators induced by endogenous luteinizing hormone. [ABSTRACT FROM AUTHOR]

Summary Macrophages are multifunctional cells that participate in numerous biological processes; they actively phagocytose foreign particles and cell debris. Embryonic tissue macrophages are present at early stages of mammalian development; their ontogeny and function is still under investigation. Our study used immunohistochemistry and electron microscopy to investigate early rat yolk sac macrophages using mouse antirat macrophage monoclonal antibodies (mAb) March 1 and March 3 produced by our laboratory. March 3 mAb revealed the first emergence of immature macrophages in the rat yolk sac at fetal day nine coinciding with the beginning of yolk sac haemopoiesis that consisted mainly of erythropoiesis, while Mar 1 mAb detected specifically rat yolk sac macrophages at about the 13th to 14th day of gestation. Immunoreactivity against Mar mAbs was mainly located in the yolk sac endodermal cell layer, which may signify endodermal origin of the yolk sac macrophages. Ultrastructurally mature yolk sac macrophages contained numerous endocytic vesicles or vacuoles, well-developed Golgi saccules and many electron dense granules in their cytoplasm and a number of microvillous projections from the cell surface. After establishment of the circulation between yolk sac and embryo, Mar 3 positive cells were also demonstrated inside fetal undifferentiated mesenchymal tissue at fetal day 12. The study demonstrated the first emergence of immature yolk sac macrophages being among the earliest haemopoietic cells formed in mammalian development. Thus, Mar mAbs managed to detect macrophage differentiation antigens through their development early in the rat yolk sac. [ABSTRACT FROM AUTHOR]

Key Clinical Message We present the successful application of C1 esterase inhibitor (C1 INH) concentrate to a patient with clinical amniotic fluid embolism ( AFE). [ABSTRACT FROM AUTHOR]

Preeclampsia is a leading cause of maternal and perinatal morbidity and mortality. Several studies have demonstrated the beneficial effects of antithrombin replacement in patients with preeclampsia. Here, we describe the study protocol of KOUNO-TORI (K W-3357 rand O mized, m U lti-center, double-bli N d, placeb O -controlled phase 3 s T udy in patients with early O nset p R eeclamps I a) to evaluate recombinant human antithrombin gamma (rhAT-gamma) for the treatment of early-onset severe de novo preeclampsia. Patients with early-onset severe de novo preeclampsia who are ≥24 to <32 weeks pregnant at the time of registration and have an antithrombin activity of ≤100% at screening are included. The target population is selected based on a reanalysis of the data of a previous plasma-derived antithrombin phase 3 study. Primary endpoint is the prolongation of pregnancy from the initiation of rhAT-gamma treatment to the pregnancy termination. Secondary endpoints include gestational age in terms of achievement of 32- and 34-weeks'gestation, and gestational age in terms of achievement of 28 weeks' gestation for patients enrolled at <28 weeks' gestation. Maternal, fetal, and neonatal outcomes will be assessed. As we have selected a specifically defined target population based on reanalysis of data of a previous plasma-derived antithrombin phase 3 study, the results of our study are expected to provide efficacy and safety data concerning rhAT-gamma treatment in Japanese patients. This study could help identify an effective novel treatment for such patients with early-onset severe preeclampsia for whom appropriate treatment is unavailable. [ABSTRACT FROM AUTHOR]

• Postpartum acute myometritis (PAM) in uterine body of refractory PPH was reported. • Inflammation of PAM was characterized by anaphylactoid reaction. • Anaphylactoid inflammation in uterine isthmus coincides with PAM in uterine body. Uterine atony is a major cause of postpartum hemorrhage. We recently proposed the new histological concept of postpartum acute myometritis (PAM) for the pathophysiology of refractory uterine atony of unknown etiology, which is characterized by the diffuse activation of mast cells and the complement system as well as the massive infiltration of macrophages and neutrophils into the uterine body. We herein focused on the uterine isthmus just adjacent to the body. The isthmus becomes significantly elongated throughout pregnancy. It is composed of myocytes and fibroblasts with an extracellular matrix that forms a passive lower segment during labor. The aim of this study was to histologically examine the uterine isthmus in cases of PAM in the uterine body. Under the amniotic fluid embolism-registry program in Japan, we selected PAM cases from uterine samples obtained by cesarean hysterectomy and delivered to us for analyses between 2011 and 2017. Control tissues were collected during elective cesarean section. We investigated the isthmus tissues of these cases and performed immunohistochemistry for inflammatory cell markers, i.e. neutrophil elastase, mast cell tryptase, CD68, CD3, and C5a receptor (C5aR). The numbers of tryptase-positive degranulating mast cells, elastase-positive neutrophils, CD68-positive macrophages, and C5aR-positive cells in the isthmus were significantly higher in uteri with PAM in the body than in controls without PAM. CD3 was negative in both groups. In conclusion, inflammation and an anaphylactoid reaction were histologically detected not only in the uterine body, but in the isthmus among cases of refractory PPH of unknown etiology after cesarean section. [ABSTRACT FROM AUTHOR]

Background. In this study, we used an endogenous thrombin potential (ETP)-based assay to examine the response to activated protein C (APC) during early puerperium of 6 Japanese patients of deep vein thrombosis (DVT) and pulmonary embolism (PE) without a history of familial thrombophilia or antiphospholipid syndrome. Methods. The patient group comprised 6 Japanese women diagnosed for DVT or PE at Hamamatsu University School of Medicine, between July 1997 and April 2000. The control group comprised 30 healthy Japanese women in early puerperium. APC-sensitivity ratio (APC-sr), complete blood count (CBC), and other coagulant variables (thrombin- antithrombin-complex (TAT) and fibrin/fibrinogen-degration product (FDP)-D-dimer levels) were determined. Results. Mean APC-sr was 2.0 ± 0.3 in the control group and significantly higher (3.3 ± 1.0) in the patient group (P < 0.05). The FDP-D-dimer level was significantly higher in the patient group than in the control group, but there was no significant difference in the TAT complex level. Conclusions. We conclude that sensitivity to APC is reduced in patients with DVT or PE during early puerperium. Although further clinical studies are needed to confirm, it appears that sensitivity to APC detected by ETP-based assay could become a useful marker to estimate the occurrence of DVT or PE. [ABSTRACT FROM AUTHOR]

Background Ewing sarcoma is considered to have a poor prognosis. Recent advances in multidisciplinary management have resulted in a marked improvement in long-term survival. Case We describe a case of successful pregnancy in a patient who underwent sacrectomy combined with multi-agent chemotherapy and radiotherapy for Ewing sarcoma. The patient was diagnosed with Ewing sarcoma of the sacrum at the age of 16. The ovaries were transposed, the uterus was shielded, and a gonadotropin-releasing hormone agonist was used during treatment to protect ovarian function. The patient spontaneously conceived at the age of 27. After an uneventful pregnancy, the patient delivered a healthy neonate at term by cesarean section. Summary and Conclusions Successful pregnancy and delivery can be achieved after multi-modality treatment with pretreatment intervention for fertility preservation. [ABSTRACT FROM AUTHOR]