Maternal Blood Serum and Plasma Human Tumor-Associated Antigen RCAS1 During the Course of Uncomplicated Pregnancies: A Prospective Study.

in American Journal of Reproductive Immunology (2010), 64(3), 218-24

Citation Tskitishvili E, Sharentuya N, Tsubouchi H, Kinugasa-Taniguchi Y, Kanagawa T, Shimoya K, Tomimatsu T, Kimura T. Maternal blood serum and plasma human tumor-associated antigen RCAS1 during the ... [more ▼]

Citation Tskitishvili E, Sharentuya N, Tsubouchi H, Kinugasa-Taniguchi Y, Kanagawa T, Shimoya K, Tomimatsu T, Kimura T. Maternal blood serum and plasma human tumor-associated antigen RCAS1 during the course of uncomplicated pregnancies: a prospective study. Am J Reprod Immunol 2010; 64: 218-224 Problem We aimed to investigate the expression of the tumor-associated RCAS1 protein in maternal blood of uncomplicated pregnancies. Method of study Maternal blood was obtained from women with uncomplicated pregnancies (N = 43) at 11-13, 20-22, 32-34, 37-38 weeks of gestation, and immediately after delivery. Serum RCAS1 concentration was studied by ELISA, and plasma mRNA was subjected to real-time (RT)-PCR. Results Serum RCAS1 protein concentration was significantly up-regulated at 11-13 and 20-22 weeks than that at 32-34 weeks and after delivery. RCAS1 mRNA level was significantly increased at 11-13 weeks than that at 37-38 weeks. A significant positive correlation was defined between RCAS1 serum concentration at 11-13 weeks and gestational age at delivery and that between plasma RCAS1 mRNA levels at 37-38 weeks and umbilical cord blood base excess. A significant negative correlation was found between RCAS1 serum concentration at 37-38 weeks and umbilical cord blood pH at delivery. Conclusions RCAS1 protein might have importance in the development of uncomplicated pregnancies and for the prediction of pregnancy outcome. [less ▲]

Oxidative stress-induced S100B protein from placenta and amnion affects soluble Endoglin release from endothelial cells.

in Molecular Human Reproduction (2010), 16(3), 188-99

Oxidative stress with elevated intracellular Ca(2+) concentration as well as endothelial dysfunction is a component of pre-eclampsia. Our aim was to investigate the oxidative stress-dependent expression ... [more ▼]

Oxidative stress with elevated intracellular Ca(2+) concentration as well as endothelial dysfunction is a component of pre-eclampsia. Our aim was to investigate the oxidative stress-dependent expression of Endoglin and Ca(2+)-binding S100B protein from villous and amniotic tissue cultures, and to assess sEng expression from S100B protein-stimulated endothelial cells. We initially examined Endoglin and Hydroxy-nonenal-(HNE)-modified proteins in the placentas and amnion obtained from women with pre-eclampsia (n = 8), and healthy controls (n = 8) by immunohistochemistry. To examine oxidative stress and the S100B protein effect on sEng expression from endothelial cells, normal villous and amniotic tissue cultures were stimulated by 4-HNE, sodium fluoride and xanthine/xanthine oxidase, whereas human umbilical vein endothelial cell cultures were treated with S100B protein in a dose- and time-dependent manner at 37 degrees C in an environment of 95% air and 5% of CO(2). Culture supernatants were assessed using ELISA. Cell viability was determined using MTS assay. The concentrations of sEng and S100B protein were significantly increased in the villous and amniotic tissue culture supernatants under oxidative stress. S100B protein-stimulated endothelial cells released sEng into conditioned media with a significantly higher expression levels at a concentration of 200 pM-20 nM S100B by 2 h, whereas treated with 200 nM of S100B endothelial cells significantly expressed sEng by 12 h and stimulated the cell proliferation by the same period of time. Our findings show that oxidative stress affects sEng and S100B protein expression from villous and amniotic tissues, and picomolar and low nanomolar concentrations of S100B protein significantly up-regulate sEng release from endothelial cells leading to endothelial dysfunction. [less ▲]

The human tumor-associated antigen RCAS1 in pregnancies complicated by pre-eclampsia.

in Journal of Reproductive Immunology (2008), 77(1), 100-8

The human tumor-associated antigen RCAS1 (receptor-binding cancer antigen expressed on SiSo cells) is considered to play a role in the escape of tumor cells from immune surveillance and, at the same time ... [more ▼]

The human tumor-associated antigen RCAS1 (receptor-binding cancer antigen expressed on SiSo cells) is considered to play a role in the escape of tumor cells from immune surveillance and, at the same time, participates in the inhibition of the maternal immune response during pregnancy. The aim of our study was to investigate the expression of tumor-associated RCAS1 protein in the placenta and amniotic membranes and to assess and compare its concentration in amniotic fluid, maternal and cord blood sera in pregnancies complicated by pre-eclampsia. Samples were obtained from women with pre-eclampsia (N=9), pre-eclampsia with IUGR (N=4), normotensive IUGR (N=7) and healthy term controls (N=25) after delivery. Placentas were studied by immunohistochemistry, Western blot analysis and real-time (RT)-PCR. For assessment of RCAS1 protein concentrations in biological fluids, ELISA was performed. RCAS1 mRNA expression in the placentas of pre-eclamptic patients was significantly lower than in controls (p<0.01). The maternal blood serum RCAS1 protein concentration in the pre-eclampsia cases was also significantly lower than in controls (p=0.0207). The other study groups did not differ significantly. This study reveals the possible role of the RCAS1 protein in the development of pre-eclampsia through an immunological pathway. [less ▲]

The maternal blood serum human tumor-associated protein RCAS1 in pregnancies complicated by gestational diabetes mellitus

Poster (2007)

Level of S100B protein expression in the amnion at various gestational ages in the third trimester of normal pregnancies.

in Acta Obstetricia et Gynecologica Scandinavica (2007), 86(8), 915-20

BACKGROUND: S100B protein is a unique calcium-binding protein. Its biological role within the cell populations is not completely defined. Some pathological conditions that develop during pregnancy could ... [more ▼]

BACKGROUND: S100B protein is a unique calcium-binding protein. Its biological role within the cell populations is not completely defined. Some pathological conditions that develop during pregnancy could affect S100B concentrations in the amniotic fluid, cord blood, and maternal serum. The aim of our study was to assess the correlation between S100B protein expression in the amnion, amniotic fluid and gestational age in the third trimester of uncomplicated pregnancies. METHODS: Amnion, amniotic fluid, maternal peripheral and umbilical cord blood samples were collected from healthy women who delivered at 31-36 weeks (n=17), 37-40 weeks (n=22), and 41-42 weeks (n=21). The expression of S100B in the amnion was assessed by immunohistochemistry and real-time (RT)-PCR, and its concentrations in amniotic fluid, maternal and cord blood sera were determined by ELISA. RESULTS: The S100B protein expression in the amnion and its concentrations in amniotic fluid, maternal and cord blood sera of patients in the third trimester were not significantly different at various gestational ages. CONCLUSIONS: The S100B protein expression in the amnion and the S100B protein concentrations in amniotic fluid, maternal and cord blood do not vary significantly in the third trimester of uncomplicated pregnancies. [less ▲]

S100B protein expression in the amnion and amniotic fluid in pregnancies complicated by pre-eclampsia.

in Molecular Human Reproduction (2006), 12(12), 755-61

Our aim was to investigate the expression of S100B protein in the amnion and to assess the amniotic fluid concentration in pregnancies complicated by pre-eclampsia. Samples were obtained from women who ... [more ▼]

Our aim was to investigate the expression of S100B protein in the amnion and to assess the amniotic fluid concentration in pregnancies complicated by pre-eclampsia. Samples were obtained from women who developed pre-eclampsia (n = 7), pre-eclampsia with intrauterine growth retardation (IUGR) (n = 4), normotensive IUGR (n = 7) and gestational hypertension (n = 4) during pregnancy and healthy controls who delivered at term (n = 35). To determine the difference in the expression of S100B in the amnion, we performed immunohistochemistry, western blot analysis and RT-PCR. Using enzyme-linked immunosorbent assay (ELISA), we assessed the S100B concentration in amniotic fluid. The S100B mRNA expression in the amnion of pre-eclamptic patients and patients with pre-eclampsia with IUGR was significantly higher than that in the control. The amniotic fluid S100B protein concentration of the pre-eclampsia and normotensive IUGR cases was significantly higher than that of the control. This study shows that amnion could be a source responsible for the increased concentration of S100B in amniotic fluid. In pre-eclampsia, reactive oxygen species (ROS) are generated by oxidative stress. Some pathological conditions that develop during pregnancy and are related to hypoxic stress can affect the elevation of S100B concentration in the amnion. [less ▲]

Post-ischemic hypothermia reduced IL-18 expression and suppressed microglial activation in the immature brain.

in Brain Research (2006), 1121(1), 35-45

Inflammation is an important factor for hypoxia-ischemia (HI) brain injury. Interleukin (IL)-18 is a proinflammatory cytokine which may be a contributor to injury in the immature brain after HI. To ... [more ▼]

Inflammation is an important factor for hypoxia-ischemia (HI) brain injury. Interleukin (IL)-18 is a proinflammatory cytokine which may be a contributor to injury in the immature brain after HI. To investigate the effects of post-HI hypothermia on IL-18 in the developing brain, 7-day-old rats were subjected to left carotid artery ligation followed by 8% oxygen for 60 min and divided into a hypothermia group (rectal temperature 32 degrees C for 24 h) and a normothermia group (36 degrees C for 24 h). The IL-18 mRNA was analyzed with real-time RT-PCR, and the protein level was analyzed by Western blot, and the location and source of IL-18 were assessed by immunohistochemistry. The significant increase of the IL-18 mRNA was observed in the ipsilateral hemispheres of the normothermia group at 24 h and 72 h after HI compared with controls, but the level in the ipsilateral hemispheres of the hypothermia group was significantly reduced at both time points, compared with the normothermia group, respectively. The IL-18 protein level in the ipsilateral hemispheres of the normothermia group significantly increased at 72 h after HI compared with controls, however, the protein level of the hypothermia group was significantly decreased, compared with the normothermia group. IL-18-positive cells were observed throughout the entire cortex, corpus callosum (CC) and striatum in the ipsilateral hemispheres of normothermia group at 72 h after HI, however, little positive cells were observed in the hypothermia group. Double labeling immunostaining found that most of the IL-18-positive cells were colocalized with lectin, which is a marker of microglia. The number of ameboid microglia (AM) in the normothermia group was significantly increased in cortex and CC, compared with the number in controls, but there were very few ramified microglia (RM) in these areas. In contrast, the number of AM in the hypothermia group was significantly decreased in cortex and CC, compared with the number in the normothermia group, and there were no significant differences in the number of AM and RM between the hypothermia group and controls. In conclusion, we found that IL-18 mRNA and the protein level were attenuated by post-HI hypothermia and that post-HI hypothermia may decrease microglia activation in the developing brain. [less ▲]

Association between S100B protein levels in the amniotic fluid and preeclampsia

Poster (2005)