Kazuyo Kakui

Differential expression and the anti-apoptotic effect of human placental neurotrophins and their receptors

Neurotrophin (NT) is important in the survival, maintenance and differentiation of neuronal tissue, and functions in follicle maturation, tumor growth, angiogenesis and immunomodulation; however, the expression of NT and its receptors (NTR) in human placenta and their influence on fetal growth are unclear. Here we investigated the correlation of NT and NTR in human placenta with uterine environment and fetal growth. TrkB, a NTR, mRNA was expressed on decidual and villous tissue and increased with gestational age, localizing in the trophoblast layer and endothelium by immunohistochemistry. Villous TrkB mRNA was significantly increased in preeclampsia (PE) than in controls and was higher in the normotensive small for gestational age (SGA) placenta, although it was not significant. It was also significantly increased in the small twin of discordant twin pregnancies. Brain-derived neurotrophic factor (BDNF), the main ligand of TrkB, was expressed in membranous chorion and villous tissue and was significantly higher in maternal plasma in normotensive SGA and PE than in controls. TrkB mRNA expression was up-regulated on cultured villous tissue explants and on JEG-3, a choriocarcinoma cell line, by H(2)O(2) treatment. BDNF decreased apoptotic cells in H(2)O(2)-treated JEG-3, indicating that BDNF/TrkB signaling had anti-apoptotic effects against oxidative stress in JEG-3, suggesting a protective role of BDNF/TrkB in human villous tissue under unfavorable conditions in utero.

Site-Specific Augmentation of Amnion Cyclooxygenase-2 and Decidua Vera Phospholipase-A2 Expression in Labor: Possible Contribution of Mechanical Stretch and Interleukin-1 to Amnion Prostaglandin Synthesis

Objective: To investigate a possible site-specific augmentation of prostaglandin (PG) synthesis in the fetal membranes during labor. Methods: We used reverse transcriptase-polymerase chain reaction or Western blot analysis to evaluate the expression of cytosolic phopholipase A2 (cPLA2) and cyclooxygenase-1, -2 (COX-1, -2), in both the upper and lower parts of the amnion, chorion laeve, and decidua vera tissues from term pregnant women before (n = 8) and after labor (n = 24). Prostaglandin E2 (PGE2) secretion from amnion-derived WISH cells was assessed using enzyme-linked immunosorbent assay after stimulation by cyclic mechanical stretching and interleukin-1 (IL-1). Results: The expression of cPLA2 and COX-1 and COX-2 mRNAs was detected in all samples examined. Western blot analysis revealed that COX-2 expression in the upper part of the amnion, chorion laeve, and decidua vera tissues after labor was 4.7-, 4.9-, and 3.7-fold higher than that before labor, respectively (P < .05 for all). The cPLA2 protein expression in the upper part of the amnion and chorion laeve tissues after labor was 14.0- and 8.8-fold higher than that before labor, respectively (P < .05 for both). Moreover, in specimens obtained after labor, the amnion COX-2 expression and the decidua vera cPLA2 expression in the lower part of the fetal membrane was 1.9- and 2.6-fold higher than the respective levels in the upper part (P < .05 for both). In an in vitor study, cyclic mechanical stretching significantly enhanced IL-1-augmented PGE2 secretion from WISH cells. Conclusion: In the lower part of the amnion and decidua vera tissues, adjacent to the dilating cervical canal, PG synthesis was upregulated site specifically after labor. Such enhancement of amnion PG synthesis might be regulated at least partly by IL-1 and cyclic distension.

17β-Estradiol Up-Regulates Prostacyclin Production in Cultured Human Uterine Myometrial Cells Via Augmentation of Both Cyclooxygenase-1 and Prostacyclin Synthase Expression

Objective: To investigate whether 17β-estradiol elevates prostacyclin (PGI2) production in human myometrial cells in the middle of gestation. Methods: The concentration of 6-keto-PGF1α, a stable metabolite of PGI2, in the culture medium was assessed using enzyme-linked immunosorbent assay (ELISA). Western blot analysis and quantitative reverse-transcriptase polymerase chain reaction (RT-PCR) using TaqMan (Applied Biosystems, Foster City, CA) technology were performed to evaluate the expression of cytosolic phospholipase A2 (cPLA2), cyclooxygenase-1 (COX-1), COX-2, and prostacyclin synthase (PGIS) in cultured human myometrial cells prepared from second trimester pregnant women (n = 3) after stimulation with 17β-estradiol. Results: Treatment with 17β-estradiol (4-400 nM) dose-dependently elevated PGI2 secretion from cultured human myometrial cells. Western blot analysis detected cPLA2 and COX-1 and PGIS protein expression in the cultured human myometrial cells; however, COX-2 protein expression was below the detection sensitivity. Stimulation with 40-nM 17β-estradiol significantly up-regulated protein and mRNA expression of both COX-1 and PGIS. Conclusion: 17βEstradiol from placenta may contribute to the augmentation of PGI2 production in the human myometrium in the middle of gestation via up-regulation of both COX-1 and PGIS expression.

Deciduosis can cause remarkable leukocytosis and obscure abdominal pain

Remarkable leukocytosis with obscure abdominal pain during pregnancy is clinically challenging for obstetricians. A 31‐year‐old pregnant woman developed persistently elevated white blood cell (approximately 30 000/µL) and C‐reactive protein (3.0 mg/dL) with occasional moderate abdominal pain. At 29 gestational weeks, she underwent emergency cesarean section due to suspected abruptio placentae. Hemoperitoneum was observed with extensive hemorrhagic nodules on the peritoneal and omental surfaces. White blood cells rose 87 200/µL, and C‐reactive protein peaked at 44.9 mg/dL after surgery. Pathologically, biopsies showed deciduosis, and decidual cells on the omental surface showed immunohistochemical staining for granulocyte colony‐stimulating factor (G‐CSF). Serum G‐CSF concentration was 339 pg/mL at 28 weeks, and that of ascites was 312 000 pg/mL at cesarean section. G‐CSF‐producing deciduosis can induce leukocytosis as well as abdominal pain during pregnancy and postpartum.

A case of peripartum cardiomyopathy with a transient increase of plasma interleukin-6 concentration occurred following mirror syndrome.

Abstract Peripartum cardiomyopathy (PPCM) is an unusual heart failure of unknown etiology that occurs during pregnancy or postpartum. Mirror syndrome is a characteristic of maternal edema subsequent to fetal and/or placental edema. We report a case of PPCM with a transient increase of interleukin-6 concentration occurring in the postpartum period of mirror syndrome.

Advanced papillary serous carcinoma of the uterine cervix: a case with a remarkable response to paclitaxel and carboplatin combination chemotherapy

Papillary serous carcinoma of the uterine cervix (PSCC) is a very rare, recently described variant of cervical adenocarcinoma. This review, describes a case of stage IV PSCC whose main tumor existed in the uterine cervix and invaded one third of the inferior part of the anterior and posterior vaginal walls. Furthermore, it had metastasized from the para-aortic lymph nodes to bilateral neck lymph nodes. Immnoreactivity for CA125 was positive, whereas the staining for p53 and WT-1 were negative in both the original tumor and the metastatic lymph nodes. Six cycles of paclitaxel and carboplatin combination chemotherapy were administered and the PSCC dramatically decreased in size. The main tumor of the uterine cervix showed a complete response by magnetic resonance imaging (MRI), and on rebiopsy, more than 95% of the tumor cells in the cervix had microscopically disapperared. This is the first report of PSCC in which combination chemotherapy was used and showed a remarkable response.

Prenatal Findings in Congenital Leukemia: A Case Report

We here describe a case of congenital leukemia that ended in intrauterine fetal demise at 30 weeks of gestation. Acute enlargement of the fetal trunk, elevated pulsatility index of the umbilical artery with concomitant decline of pulsatility index of the middle cerebral artery, pleural effusion, and polyhydramnios preceded the fetal death. Diagnosis of congenital myeloid leukemia was suggested by microscopic examination of the placental tissue, revealing immature myeloid precursors filling the lumina of fetal vessels in the umbilical cord and chorionic villi. Extensive vascular involvement of the placenta by leukemic cells was considered to be a primary cause of the fetal death.

Total uterine rupture during pregnancy after an adenomyomectomy

Summary Background: Adenomyomectomy and myomectomy are treatment options to reduce dysmenorrhea and to preserve fertility. Recently, the number of adenomyomectomies and myomectomies performed has gradually increased. On the other hand, an increased risk of uterine rupture during pregnancy is associated with the thinned uterine scar after these surgeries. Case Report: We encountered a 39-year-old nulliparous woman who experienced a spontaneous uterine rupture at an early stage of the 29 th week of gestation after an adenomyomectomy. The adenomyomectomy method created a deep and wide wedge-shaped excision. Pathologically, the main reason for the rupture was thought to be the uterine scar with the residual adenomyotic fragments, which was very vulnerable to pregnant decidualization and thus ruptured. Conclusions: It should be emphasized that a woman who becomes pregnant after undergoing an adenomyomectomy needs very careful management throughout all gestational periods.

Cyclic mechanical stretching and interleukin-1α synergistically up-regulate prostacyclin secretion in cultured human uterine myometrial cells

Prostacyclin (PGI2), a potent uterine smooth muscle relaxant, is postulated to be a major prostaglandin (PG) secreted from the human myometrium. PGI2metabolite concentrations in the maternal plasma were reported to be elevated during pregnancy, especially during labor. Recently, we developed cultured human myometrial cells from pregnant women and reported that cyclic mechanical stretching mimicking labor increased PGI2secretion from these cells by up-regulating PGI2synthase promoter activities. Since elevation of cervical/vaginal interleukin-1α (IL-1α) concentrations is also a characteristic feature of delivery, and IL-1α is a known stimulator of PGsynthesis, we investigated a possible synergistic effect of cyclic mechanical stretching and IL-1α on PGI2production in cultured human myometrial cells. Treatment with IL-1α (10 ng/ml) significantly augmented (4- to 60-fold) the secretion of PGI2, prostaglandin E2(PGE2), prostaglandin F2α(PGF2α) and thromboxane A2(TXA2) from cultured human myometrial cells obtained from non-pregnant and pregnant women as well as in cultured human umbilical artery and cultured human coronary artery smooth muscle cells (p<0.05 for all comparisons). However, labor-like cyclic mechanical stretching up-regulated IL-1α-augmented PGI2secretion from myometrial cells obtained from nonpregnant and pregnant women 2.1- to 2.8-fold (p<0.05 for all comparisons), but not PGE2, PG F2αnor TXA2. Moreover, such an augumentation of PGI2secretion by cyclic mechanical stretching was not observed in cultured human umbilical artery nor in cultured human coronary artery smooth muscle cells. These results suggest that cyclic mechanical stretching by labor, in concert with IL-1α stimulation, contributes to the increase in myometrial PGI2secretion during delivery.

Secondary postpartum hemorrhage due to uterine artery pseudoaneurysm rupture in von Willebrand disease.

We here report a case of a 33‐year‐old woman who experienced secondary postpartum hemorrhage (PPH) due to uterine artery pseudoaneurysm rupture. She had intrauterine balloon tamponade for unexplained primary PPH after spontaneous vaginal delivery, and subsequent angiography showed no abnormal contrast extravasation. However, profuse vaginal bleeding occurred 22 days postpartum. Color Doppler ultrasonography demonstrated an anechoic mass with turbulent flow in the lower uterine segment, corresponding to uterine artery pseudoaneurysm. She was successfully treated with selective uterine arterial embolization. Decreased levels of von Willebrand factor and factor VIII led to the diagnosis of von Willebrand disease. When it is determined that a patient has unexplained PPH or uterine artery pseudoaneurysm, a high index of suspicion and further investigation for underlying bleeding disorders is warranted.