Joonho Lee

Eunice Kennedy Shriver National Institute of Child Health and Human Development, Rockville, MD, USA

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Publications (25)60.83 Total impact

  • Article: Methylome of fetal and maternal monocytes and macrophages at the feto-maternal interface.
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    ABSTRACT: Decidual macrophages (dMφ) of the mother and placental macrophages (Hofbauer cells, HC) of the fetus are deployed at a critical location: the feto-maternal interface. This study was conducted to compare the DNA methylome of maternal and fetal monocytes, dMφ, and HC and thereby to determine the immunobiological importance of DNA methylation in pregnancy. Paired samples were obtained from normal pregnant women at term not in labor and their neonates. Maternal monocytes (MMo) and fetal monocytes (FMo) were isolated from the peripheral blood of mothers and fetal cord blood, respectively. dMφ and HC were obtained from the decidua of fetal membranes and placentas, respectively. DNA methylation profiling was performed using the Illumina Infinium Human Methylation27 BeadChip. Quantitative real-time PCR and Western Blot were performed for validation experiments. (i) Significant differences in DNA methylation were found in each comparison (MMo versus FMo, 65 loci; dMφ versus HC, 266 loci; MMo versus dMφ, 199 loci; FMo versus HC, 1030 loci). (ii) Many of the immune response-related genes were hypermethylated in fetal cells (FMo and HC) compared to maternal cells (MMo and dMφ). (iii) Genes encoding markers of classical macrophage activation were hypermethylated, and genes encoding alternative macrophage activation were hypomethylated in dMφ and HC compared to MMo and FMo, respectively. (iv) mRNA expressions of DNMT1, DNMT3A, and DNMT3B were significantly lower in dMφ than in HC. (v) 5-azacytidine treatment increased expression of INCA1 in dMφ. The findings herein indicate that DNA methylation patterns change during monocyte-macrophage differentiation at the feto-maternal interface. It is also suggested that DNA methylation is an important component of the biological machinery conferring an anti-inflammatory phenotype to macrophages at the feto-maternal interface.
    American Journal Of Reproductive Immunology 03/2012; 68(1):8-27. · 2.17 Impact Factor
  • Article: Glycogen phosphorylase isoenzyme BB plasma concentration is elevated in pregnancy and preterm preeclampsia.
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    ABSTRACT: Glycogen phosphorylase is a key enzyme in glycogenolysis. Released with myocardial ischemia, blood concentration of glycogen phosphorylase isoenzyme BB (GPBB) is a marker of acute coronary syndromes. Pregnancy imposes metabolic stress, and preeclampsia is associated with cardiac complications. However, plasma GPBB concentration during pregnancy is unknown. This study was conducted to determine maternal plasma GPBB concentration in normal pregnancy and in preeclampsia. Plasma samples from 6 groups (n=396) were studied: nonpregnant and pregnant women with normal term delivery, term and preterm preeclampsia, and term and preterm small-for-gestational-age neonates. GPBB concentration was measured with a specific immunoassay. Placental tissues (n=45) obtained from pregnant women with preterm and term preeclampsia, spontaneous preterm delivery, and normal term delivery were analyzed for potential GPBB expression by immunoblotting. Median plasma GPBB concentration was higher in pregnant women than in nonpregnant women (38.7 versus 9.2 ng/mL; P<0.001), which remained significant after adjusting for age, race, and parity. Maternal plasma GPBB concentrations did not change throughout gestation. Cases of preterm (but not term) preeclampsia had higher median plasma GPBB concentrations than gestational age-matched normal pregnancy cases (72.6 versus 26.0 ng/mL; P=0.001). Small-for-gestational-age neonates did not affect plasma GPBB concentration. GPBB was detected in the placenta and was less abundant in preterm preeclampsia than in preterm delivery cases (P<0.01). There is physiological elevation of plasma GPBB concentration during pregnancy; an increase in maternal plasma GPBB is a novel phenotype of preterm preeclampsia. It is strongly suggested that these changes are attributed to GPBB of placental origin.
    Hypertension 01/2012; 59(2):274-82. · 6.21 Impact Factor
  • Article: Peripheral CD300a+CD8+ T lymphocytes with a distinct cytotoxic molecular signature increase in pregnant women with chronic chorioamnionitis.
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    ABSTRACT:   CD300a is an immunomodulatory molecule of the immunoglobulin receptor superfamily expressed in the leukocytes of myeloid and lymphoid lineages. However, its biological function on CD8+ T lymphocytes remains largely unknown. This study was conducted to assess the biological significance of CD300a expression in T lymphocytes and to determine whether its expression in peripheral T lymphocytes changes in pregnant women presenting with antifetal rejection. Microarray analysis was performed using total RNA isolated from peripheral CD300a+ and CD300a- T lymphocytes. Flow cytometric analysis of the peripheral blood samples of pregnant women and pathologic examination of the placentas were conducted.   A large number of genes (N = 1245) were differentially expressed between CD300a- and CD300a+ subsets of CD8+ T lymphocytes, which included CCR7, CD244, CX3CR1, GLNY, GZMB, GZMK, IL15, ITGB1, KLRG1, PRF1, and SLAMF7. Gene ontology analysis of differentially expressed genes demonstrated enrichment of biological processes such as immune response, cell death, and signal transduction. CD300a expression in CD8+ T lymphocytes was coupled to a more cytotoxic molecular signature. Of note, the proportion of CD300a+CD8+ T lymphocytes increased in pregnant women with chronic chorioamnionitis (antifetal rejection of the chorioamniotic membranes; P < 0.05).   The findings of this study strongly suggest an increase in systemic T-lymphocyte-mediated cytotoxicity in pregnant women with chronic chorioamnionitis as a manifestation of maternal antifetal rejection.
    American Journal Of Reproductive Immunology 11/2011; 67(3):184-97. · 2.17 Impact Factor
  • Article: Unexplained fetal death has a biological signature of maternal anti-fetal rejection: chronic chorioamnionitis and alloimmune anti-human leucocyte antigen antibodies.
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    ABSTRACT: Chronic chorioamnionitis is a histological manifestation of maternal anti-fetal cellular rejection. As failure of graft survival is the most catastrophic event in organ transplantation, we hypothesized that fetal death could be a consequence of maternal rejection. The aim of this study was to assess whether there is evidence of cellular and antibody-mediated rejection in fetal death. Placental histology was reviewed for the presence of chronic chorioamnionitis in unexplained preterm fetal death (n=30) and preterm live birth (n=103). Amniotic fluid CXCL10 concentrations were measured with a specific immunoassay. Chronic chorioamnionitis was more frequent in fetal death than in live birth (60.0% versus 37.9%; P<0.05) and fetal death had a higher median amniotic fluid CXCL10 concentration than live birth (2.0 versus 1.8 ng/ml, P<0.05), after adjusting for gestational age at amniocentesis. Maternal anti-human leucocyte antigen class II panel-reactive seropositivity determined by flow cytometry was higher in fetal death compared to live birth (35.7% versus 10.9%; P<0.05). Chronic chorioamnionitis is a common pathologic feature in unexplained preterm fetal death. This novel finding suggests that cellular and antibody-mediated anti-fetal rejection of the mother is associated with fetal death (graft failure) in human pregnancy.
    Histopathology 11/2011; 59(5):928-38. · 3.08 Impact Factor
  • Article: The frequency and clinical significance of intra-amniotic inflammation in women with preterm uterine contractility but without cervical change: do the diagnostic criteria for preterm labor need to be changed?
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    ABSTRACT: The objective of this study was to determine the frequency and clinical significance of intra-amniotic inflammation in patients with preterm increased uterine contractility with intact membranes but without cervical change. Amniocentesis was performed in 132 patients with regular uterine contractions and intact membranes without cervical change. Amniotic fluid was cultured for bacteria and mycoplasmas and assayed for matrix metalloproteinase-8 (MMP-8). Intra-amniotic inflammation was defined as an elevated amniotic fluid MMP-8 concentration (>23 ng/mL). (1) Intra-amniotic inflammation was present in 12.1% (16/132); (2) Culture-proven intra-amniotic infection was diagnosed in 3% (4/132) of patients without demonstrable cervical change on admission or during the period of observation; and (3) Patients with intra-amniotic inflammation had significantly higher rates of preterm delivery and adverse outcomes, and shorter amniocentesis-to-delivery intervals than those without intra-amniotic inflammation (P < 0.05 for each). Adverse outcomes included chorioamnionitis, funisitis, and neonatal death. Intra-amniotic inflammation was present in 12% of patients with regular uterine contractions without cervical change, while culture-proven intra-amniotic infection was present in 3%. The presence of intra-amniotic inflammation was a significant risk factor for adverse neonatal outcomes. These observations question whether cervical changes should be required for the diagnosis of preterm labor, because patients without modifications in cervical status on admission or during a period of observation are at risk for adverse pregnancy outcomes.
    The journal of maternal-fetal & neonatal medicine: the official journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstetricians 10/2011; 25(8):1212-21. · 1.36 Impact Factor
  • Article: Maternal HLA panel-reactive antibodies in early gestation positively correlate with chronic chorioamnionitis: evidence in support of the chronic nature of maternal anti-fetal rejection.
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    ABSTRACT: Maternal tolerance of the fetus is essential for viviparity, yet anti-fetal rejection occurs in several pregnancy complications. Chronic chorioamnionitis is a feature of anti-fetal cellular rejection. There is a robust association between chronic chorioamnionitis and maternal seropositivity for anti-human leukocyte antigen (HLA) panel-reactive antibodies (PRA) at the time of delivery. This longitudinal study was performed to assess maternal HLA PRA status in early gestation and the temporal evolution of maternal HLA PRA in the context of chronic chorioamnionitis and, thereby, to determine whether HLA PRA during the course of pregnancy is useful for the detection of anti-fetal rejection. Maternal sera obtained before 16 weeks of gestation and at delivery were analyzed for HLA PRA in cases with (N = 100) and without (N = 150) chronic chorioamnionitis. IgG (but not IgM) HLA class I and II PRA positivity at delivery was higher in cases with chronic chorioamnionitis than in those without chronic chorioamnionitis. IgG HLA class I PRA positivity before 16 weeks of gestation was higher in cases with chronic chorioamnionitis than in those without (30.3 versus 13.3%; P = 0.001). Positive conversion (negative HLA PRA before 16 weeks of gestation but positive at delivery) of IgG HLA class I and II PRA was significantly associated with chronic chorioamnionitis. Fetal HLA class I antigen-specific antibodies were confirmed in 12 of 16 mothers tested who were sensitized to HLA class I antigens before 16 weeks of gestation. Positive maternal HLA PRA before 16 weeks of gestation and the temporal evolution of maternal HLA PRA are associated with the presence of chronic chorioamnionitis at the time of delivery. Maternal IgG HLA PRA has the potential to be a monitoring tool of anti-fetal rejection. Furthermore, the findings herein indicate that subsets of fetuses are exposed to alloimmune HLA antibodies for months, especially in cases with chronic chorioamnionitis.
    American Journal Of Reproductive Immunology 09/2011; 66(6):510-26. · 2.17 Impact Factor
  • Article: miR-210 targets iron-sulfur cluster scaffold homologue in human trophoblast cell lines: siderosis of interstitial trophoblasts as a novel pathology of preterm preeclampsia and small-for-gestational-age pregnancies.
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    ABSTRACT: This study was performed to assess the biological significance of miR-210 in preeclampsia and small-for-gestational-age (SGA) pregnancies. Placental miR-210 expression was evaluated by quantitative RT-PCR (RT-qPCR) in the following groups: i) appropriate-for-gestational-age pregnancies (n = 72), ii) preeclampsia (n = 52), iii) SGA (n = 66), and iv)preeclampsia with SGA (n = 31). The effects of hypoxia (1% O(2)) on miR-210 and iron-sulfur cluster scaffold homologue (ISCU) expressions and miR-210 binding to ISCU 3' UTR were examined in Swan 71 and BeWo cell lines. Perls' reaction (n = 229) and electron microscopy (n = 3) were conducted to verify siderosis of trophoblasts. miR-210 expression was increased in preeclampsia and SGA cases and was decreased with birth weight and gestational age. In both cell lines, miR-210 was induced by hypoxia, whereas ISCU expression was decreased. The luciferase assay confirmed miR-210 binding to ISCU mRNA 3' UTR. RNA interference knockdown of ISCU expression in Swan 71, but not in BeWo, cells resulted in autophagosomal and siderosomal iron accumulation and a fourfold decrease of Matrigel invasion (P = 0.004). Placental ISCU expression was decreased in preeclampsia (P = 0.002) and SGA (P = 0.002) cases. Furthermore, hemosiderin-laden trophoblasts were more frequent in the placental bed of preterm preeclampsia and/or SGA births than in control cases (48.7% versus 17.9%; P = 0.004). Siderosis of interstitial trophoblasts is a novel pathological feature of preeclampsia and SGA. The findings herein suggest that ISCU down-regulation by miR-210 perturbing trophoblast iron metabolism is associated with defective placentation.
    American Journal Of Pathology 08/2011; 179(2):590-602. · 4.89 Impact Factor
  • Article: Chronic chorioamnionitis displays distinct alterations of the amniotic fluid proteome.
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    ABSTRACT: Acute chorioamnionitis of infectious origin and chronic chorioamnionitis of immunological origin are two major placental lesions of spontaneous preterm birth with elevated amniotic fluid interleukin-6 and CXCL10 concentrations, respectively. The changes in the amniotic fluid proteome associated with intra-amniotic infection and acute chorioamnionitis are well defined, yet alterations unique to chronic chorioamnionitis remain to be elucidated. This study was conducted to determine those amniotic fluid proteins changing specifically in the presence of chronic chorioamnionitis. Amniotic fluid obtained from acute chorioamnionitis, chronic chorioamnionitis and gestational age-matched controls were analysed by two-dimensional (2D) difference in gel electrophoresis and MALDI-TOF analyses. The type of histological inflammation was used to define each condition in preterm labour cases (n = 125) and term not in labour cases (n = 22), and the amniotic fluid concentrations of interleukin-6, CXCL8, CXCL10 and prostaglandin F(2α) were also measured by specific immunoassays. Among preterm labour cases, 31 differentially expressed proteins were identified in chronic chorioamnionitis cases as compared to both acute chorioamnionitis and control cases. Importantly, glycodelin-A, which maintains maternal tolerance against an allogeneic fetus, was decreased in chronic chorioamnionitis, while haptoglobin was increased. We report the amniotic fluid proteome of chronic chorioamnionitis for the first time, and the findings herein strongly suggest that there is a pathophysiological association between the changes of immunomodulatory proteins in the amniotic fluid and chronic chorioamnionitis, a histological manifestation of maternal anti-fetal allograft rejection.
    The Journal of Pathology 03/2011; 223(4):553-65. · 6.32 Impact Factor
  • Article: Fragmented forms of insulin-like growth factor binding protein-1 in amniotic fluid of patients with preterm labor and intact membranes.
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    ABSTRACT: To determine the clinical significance of an increase in various fragmented forms of insulin-like growth factor binding protein-1 (IGFBP-1) in amniotic fluid (AF), a retrospective cohort study was conducted in 103 consecutive patients with preterm labor and intact membranes. Amniotic fluid samples were cultured for aerobic and anaerobic bacteria, and mycoplasmas, and then assayed for matrix metalloproteinase-8. Fragmented-to-intact IGFBP-1 ratios were evaluated by densitometric analysis of Western blot assays. Intact IGFBP-1 (30 kDa) and 21, 17, and 12 kDa fragments were detected in AF. Median ratios of fragmented-to-intact IGFBP-1 were higher in patients whose neonates had significant morbidity than in those whose neonates did not (P < .05), in patients spontaneously delivered within 2 and 7 days from amniocentesis than in those delivered after 2 and 7 days (P < .05), and in patients with intra-amniotic infection/inflammation than in those without (P < .001). Collectively, fragmented IGFBP-1 in AF may be indicators for adverse perinatal outcomes.
    Reproductive sciences (Thousand Oaks, Calif.) 03/2011; 18(9):842-9. · 2.31 Impact Factor
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    Article: A signature of maternal anti-fetal rejection in spontaneous preterm birth: chronic chorioamnionitis, anti-human leukocyte antigen antibodies, and C4d.
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    ABSTRACT: Chronic chorioamnionitis is found in more than one-third of spontaneous preterm births. Chronic chorioamnionitis and villitis of unknown etiology represent maternal anti-fetal cellular rejection. Antibody-mediated rejection is another type of transplantation rejection. We investigated whether there was evidence for antibody-mediated rejection against the fetus in spontaneous preterm birth. This cross-sectional study included women with (1) normal pregnancy and term delivery (n = 140) and (2) spontaneous preterm delivery (n = 140). We analyzed maternal and fetal sera for panel-reactive anti-HLA class I and class II antibodies, and determined C4d deposition on umbilical vein endothelium by immunohistochemistry. Maternal anti-HLA class I seropositivity in spontaneous preterm births was higher than in normal term births (48.6% vs. 32.1%, p = 0.005). Chronic chorioamnionitis was associated with a higher maternal anti-HLA class I seropositivity (p<0.01), significant in preterm and term birth. Villitis of unknown etiology was associated with increased maternal and fetal anti-HLA class I and II seropositivity (p<0.05, for each). Fetal anti-HLA seropositivity was closely related to maternal anti-HLA seropositivity in both groups (p<0.01, for each). C4d deposition on umbilical vein endothelium was more frequent in preterm labor than term labor (77.1% vs. 11.4%, p<0.001). Logistic regression analysis revealed that chronic chorioamnionitis (OR = 6.10, 95% CI 1.29-28.83), maternal anti-HLA class I seropositivity (OR = 5.90, 95% CI 1.60-21.83), and C4d deposition on umbilical vein endothelium (OR = 36.19, 95% CI 11.42-114.66) were associated with preterm labor and delivery. A major subset of spontaneous preterm births has a signature of maternal anti-fetal cellular and antibody-mediated rejections with links to fetal graft-versus-host disease and alloimmune reactions.
    PLoS ONE 01/2011; 6(2):e16806. · 4.09 Impact Factor
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    Article: miR-143 regulation of prostaglandin-endoperoxidase synthase 2 in the amnion: implications for human parturition at term.
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    ABSTRACT: The human amnion plays a pivotal role in parturition. Two of its compartments, the placental amnion and the reflected amnion, have distinct transcriptome and are functionally coordinated for parturition. This study was conducted to determine the microRNA (miRNA) expression pattern and its significance in the placental amnion and the reflected amnion in association with labor at term. MicroRNA microarray, real-time quantitative RT-PCR (qRT-PCR), and miRNA in situ hybridization analyses of the placental amnion and the reflected amnion (n = 20) obtained at term were conducted. Luciferase assay, transfection, and qRT-PCR analyses of primary amnion epithelial cells (AECs) and amnion mesenchymal cells (AMCs) were performed. MicroRNA microarray analysis demonstrated differential expression of 32 miRNAs between the placental amnion and the reflected amnion after labor. Thirty-one (97%) miRNAs, which included miR-143 and miR-145, a cardiovascular-specific miRNA cluster, were down-regulated in the reflected amnion. Analyses of miR-143 and miR-145 by qRT-PCR confirmed microarray results, and further demonstrated their decreased expression in the reflected amnion with labor. Interestingly, expression of miR-143 and miR-145 was higher in AMCs than in AECs (p<0.05). Luciferase assay and transfection confirmed miR-143 binding to 3' UTR of prostaglandin-endoperoxidase synthase 2 (PTGS2) mRNA and miR-143 regulation of PTGS2 in AMCs. We report region-specific amniotic microRNAome and miR-143 regulation of PTGS2 in the context of human labor at term for the first time. The findings indicate that miRNA-mediated post-transcriptional regulation of gene expression machinery in the amnion plays an important role in the compartments (placental amnion vs reflected amnion) and in a cell type-specific manner (AECs vs AMCs) for parturition.
    PLoS ONE 01/2011; 6(9):e24131. · 4.09 Impact Factor
  • Article: Evidence for a spatial and temporal regulation of prostaglandin-endoperoxide synthase 2 expression in human amnion in term and preterm parturition.
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    ABSTRACT: Prostaglandin-endoperoxide synthase 2 (PTGS2) is a key enzyme involved in parturition. PTGS2 mRNA was found to be differentially expressed between placental amnion (amnion overlying the placental disc) and reflected amnion (amnion of the extraplacental chorioamniotic membranes) in term placentas. The aim was to evaluate the spatial and temporal regulation of PTGS2 expression in the amnion and the chorion-decidua. PTGS2 expression was analyzed in the amnion and chorion-decidua obtained from 32 women: term not in labor (n = 12), term in labor (n = 12), and preterm labor (n = 8), by immunoblotting and densitometry. Prostaglandin E(2) (PGE(2)) in the amnion and chorion-decidua was measured by a specific immunoassay. Compared to preterm labor cases, PTGS2 expression increased at term before the onset of labor far more prominently in placental amnion (4.5-fold; P = 0.002) than in reflected amnion (1.4-fold; P = 0.007). There was a significant increase in PTGS2 expression in reflected amnion (2.9-fold; P < 0.01) but not in placental amnion with labor at term. PTGS2 expression was higher in reflected amnion than in chorion-decidua in labor at term (2.9-fold; P < 0.01). PTGS2 was barely detected in amnion and chorion-decidua with preterm labor. Expression of PGE(2) showed a good correlation with PTGS2 expression (r = 0.722; P < 0.001). PTGS2 expression in the amnion shows a distinct spatial and temporal regulation. Spontaneous labor at term and pathological preterm labor clearly differ in amniotic PTGS2 and PGE(2) abundance. Our observations underscore the biological significance of the amnion and amniotic fluid in human parturition.
    The Journal of clinical endocrinology and metabolism 09/2010; 95(9):E86-91. · 6.50 Impact Factor
  • Article: Surfactant protein-A as an anti-inflammatory component in the amnion: implications for human pregnancy.
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    ABSTRACT: The mechanism of mouse parturition is thought to involve myometrial infiltration by amniotic fluid (AF) macrophages, activated by surfactant protein-A (SP-A). In humans, the concentration of AF SP-A decreases during labor, and no fetal macrophages are found in the myometrium after labor. Therefore, it appears that the mechanisms of labor in mice and humans are different. We investigated a potential role for SP-A in human pregnancy and parturition by examining SP-A expression patterns in AF and amnion. High molecular mass (>250 kDa) oligomeric SP-A was increased in AF with advancing gestation. Interestingly, these oligomers were more abundant in placental amnion before labor at term, while they increased primarily in reflected amnion during labor (p < 0.05). Immunoblotting showed a binding of high molecular mass SP-A in AF to amnion. In C57BL/6 mice, oligomeric SP-A was also readily detected in AF from E15 onwards, but not in amnion. Macrophage density in mice myometrium did not change with advancing gestational age. Microarray analysis of human amnion explants incubated with SP-A revealed a molecular signature of inhibited cytokine-cytokine receptor interaction with downregulation of IL-1beta, CXCL2, and CXCL5 mRNA expression. The findings in this study strongly suggest that SP-A signals amniotic anti-inflammatory response via AF during pregnancy. We propose that an SP-A interaction among AF, placental amnion, and reflected amnion is a unique mechanism for immunoregulation in human pregnancy akin to that established in lung biology. However, AF SP-A and fetal macrophages by themselves do not seem to be exclusive effectors of parturition in humans.
    The Journal of Immunology 06/2010; 184(11):6479-91. · 5.79 Impact Factor
  • Article: Identification and characterization of proteins in amniotic fluid that are differentially expressed before and after antenatal corticosteroid administration.
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    ABSTRACT: We sought to examine changes in the intraamniotic proteomic environment after the administration of antenatal corticosteroids to women with impending preterm delivery. Amniotic fluid samples were collected at the time of clinically indicated amniocentesis before and within 7 days of administration of antenatal corticosteroids for impending preterm delivery (n = 12). Proteins differentially expressed before and after corticosteroids were identified by surface-enhanced laser desorption/ionization time-of-flight mass spectrometry. They were isolated, characterized, and quantified by fast protein liquid chromatography, sodium dodecyl sulfate-polyacrylamide gel electrophoresis, in-gel tryptic digestion, immunodepletion assays, enzyme-linked immunosorbent assay, and electrospray ionization tandem mass spectrometry. Five protein peaks of interest were identified and characterized, all of which were significantly decreased after antenatal corticosteroid administration. These included 2 isoforms of transthyretin, albumin, prothrombin fragment 2, and lumican. Four proteins, identified and characterized in amniotic fluid, were differentially expressed with antenatal corticosteroid administration. These data may provide additional insight into the molecular mechanisms by which antenatal corticosteroids prevent neonatal complications.
    American journal of obstetrics and gynecology 04/2010; 202(4):388.e1-388.e10. · 3.28 Impact Factor
  • Article: "Early rupture of membranes" after the spontaneous onset of labor as a risk factor for cesarean delivery.
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    ABSTRACT: The objective of this study was to examine if patients with "early rupture of membranes (ROM)" after spontaneous onset of labor are at increased risk of cesarean section. The rate of cesarean section was examined in 447 term singleton nulliparas who were admitted after the spontaneous onset of labor. The cases were divided into 2 groups: (1) "early ROM", defined as ROM at a cervical dilatation <4 cm (n=109); and (2) "late ROM", ROM at a cervical dilatation >or=4 cm (n=338). (1) "Early ROM" occurred in 24.4% of the cases and the overall cesarean section rate was 5.6%; (2) there were no significant differences in the clinical characteristics including prepregnancy BMI, proportion of complicated pregnancies, total duration of labor, proportion of regional anesthesia, gestational age at delivery, and birthweight between the two groups of cases. However gravidas with "early ROM" were of advanced maternal age and had less cervical dilation on admission, shorter duration of 1st stage of labor, and more frequent use of oxytocin augmentation; (3) patients with "early ROM" had a threefold higher rate (11.9% vs. 3.6%) of cesarean section and a fourfold higher rate (11.9% vs. 3.0%) of cesarean section due to failure of progress than did those with "late ROM" (p<0.005 for each); (3) 92% (23/25) of cesarean sections were performed due to failure to progress; and (4) there was no significant difference in the rate of histologic chorioamnionitis between the two groups of cases. "Early ROM" after the spontaneous onset of labor is a risk factor for cesarean section in term singleton nulliparas.
    European journal of obstetrics, gynecology, and reproductive biology 12/2009; 148(2):152-7. · 1.97 Impact Factor
  • Article: The importance of intra-amniotic inflammation in the subsequent development of atypical chronic lung disease.
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    ABSTRACT: To examine whether the intra-amniotic inflammation is a risk factor for the development of atypical chronic lung disease (CLD). A retrospective cohort study was undertaken in 72 patients who delivered preterm neonates (gestational age: 24-32 weeks) within 5 days of amniocentesis and whose neonates subsequently developed CLD. Atypical CLD was defined as CLD without respiratory distress syndrome (RDS). Intra-amniotic inflammation was defined as an elevated amniotic fluid (AF) concentration of matrix metalloproteinase-8 (MMP-8) (>23 ng/ml). (1) Atypical CLD was identified in 54.2% (39/72) of cases with CLD; (2) there were no significant differences in the median gestational age at birth and the rate of antenatal corticosteroid use between infants with atypical CLD and CLD with RDS; (3) preterm newborns with atypical CLD had a significantly higher median AF MMP-8 concentration (median 373.1 ng/ml vs. 8.6 ng/ml, p = 0.003) and median AF white blood cell count (median 450.0/mm(3)vs. 5.5/mm(3), p = 0.009), and a higher rate of intra-amniotic inflammation (74.4%vs. 45.5%, p = 0.012) than those with CLD with RDS. Intra-amniotic inflammation confers a greater risk for atypical CLD than for typical CLD with initial RDS. This novel observation strengthens the importance of prenatal inflammation as a mechanism of lung injury.
    The journal of maternal-fetal & neonatal medicine: the official journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstetricians 08/2009; 22(10):917-23. · 1.36 Impact Factor
  • Article: The clinical significance of a positive Amnisure test in women with term labor with intact membranes.
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    ABSTRACT: The Amnisure ROM test is approved for the diagnosis of rupture of membranes (ROM). Yet, a fraction of patients with a positive test have intact membranes by sterile speculum examination. The objective of this study was to determine the clinical significance of this finding. The study population consisted of four groups of nulliparous women at term: (1) not in labor without clinical evidence of ROM (n = 125); (2) in labor without clinical ROM with a negative Amnisure test (n = 56); (3) in labor without clinical ROM with a positive Amnisure test (n = 25); and (4) in labor with clinical ROM (n = 30). The Amnisure test was performed in cases without clinical ROM (Groups 1, 2 and 3). (1) The Amnisure test was positive more frequently in women in labor with intact membranes than in patients not in labor at term without ROM (30.9% (25/81 women) vs. 4.8% (6/125 women); p < 0.001); (2) patients in labor without clinical ROM with a positive Amnisure test had a significantly shorter admission-to-delivery interval than those in labor without clinical ROM with a negative Amnisure test (p < 0.05). (1) A positive Amnisure test is present in about one-third nulliparous women at term presenting in labor with intact membranes; (2) patients with a positive Amnisure test had a shorter admission-to-delivery interval than those with a negative test.
    The journal of maternal-fetal & neonatal medicine: the official journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstetricians 04/2009; 22(4):305-10. · 1.36 Impact Factor
  • Article: Evidence to support that spontaneous preterm labor is adaptive in nature: neonatal RDS is more common in "indicated" than in "spontaneous" preterm birth.
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    ABSTRACT: The onset of preterm labor has been proposed to have survival value and to be adaptive in nature. This hypothesis would predict that induced preterm birth may be associated with higher rates of complications than spontaneous preterm birth. The purpose of this study was to determine if there is a difference in the frequency of neonatal respiratory distress syndrome (RDS), the most common neonatal complication, according to the etiology of preterm birth (e.g., preterm labor [PTL], preterm PROM, or pregnancies which ended because of maternal-fetal indications). The relationship between the occurrence of RDS and the obstetrical circumstances leading to preterm birth was examined in 257 consecutive singleton preterm births (gestational age: 24-32 weeks). Cases with major congenital anomalies were excluded. The study population was divided into two groups according to the cause of preterm birth: 1) preterm birth due to PTL with intact membranes or preterm PROM (spontaneous preterm birth group); and 2) preterm birth due to maternal or fetal indications (indicated preterm birth group). 1) RDS was diagnosed in 47% of cases; 2) RDS was more common in patients with indicated preterm birth than in those with spontaneous preterm birth group (58.1% vs. 38.4%, P=0.002); 3) Patients with indicated preterm birth had a significantly higher mean gestational age at birth, but lower mean birth weight, lower rate of histological chorioamnionitis and higher rates of cesarean delivery, 5 min Apgar score of <7, and umbilical arterial blood pH of <7.15 than those with spontaneous preterm birth (P<0.05 for each); 4) Antenatal corticosteroids were used in 73.4% of cases with indicated preterm birth and in 76.9% of those with spontaneous preterm birth; 5) Multivariate analysis demonstrated that indicated preterm birth was associated with an increased risk of RDS after adjusting for confounding variables (OR=2.29, 95% CI 1.22-4.29). 1) The rate of RDS is greater following "indicated" rather than spontaneous preterm birth; 2) This observation supports the view that spontaneous preterm labor is adaptive in nature.
    Journal of Perinatal Medicine 01/2009; 37(1):53-8. · 1.70 Impact Factor
  • Conference Proceeding: Priority-based Routing for Solar-Powered Wireless Sensor Networks
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    ABSTRACT: Rapid advances in wireless sensor networks require routing protocols which can accommodate new types of power source and data of differing priorities. We describe a priority-based geographical routing scheme based on a solar-cell energy model. It exploits an algorithm (APOLLO) that periodically and locally determines the topological knowledge range of each node, based on an estimated energy budget for the following period which includes the current energy, the predicted energy consumption, and the energy expected from the solar cell. The second algorithm (PISA) runs on each node and uses its knowledge range to determine a route which meets the objectives of each priority level in terms of path delay and energy consumption. These algorithms maximize scalability and minimize memory requirements by employing a localized geographical routing method which only uses information about a node and its adjacent neighbors
    Wireless Pervasive Computing, 2007. ISWPC '07. 2nd International Symposium on; 03/2007
  • Conference Proceeding: Low-Latency Routing for Energy-Harvesting Sensor Networks.
    Ubiquitous Intelligence and Computing, 4th International Conference, UIC 2007, Hong Kong, China, July 11-13, 2007, Proceedings; 01/2007

Institutions

  • 2010–2012
    • Eunice Kennedy Shriver National Institute of Child Health and Human Development
      Rockville, MD, USA
  • 2011
    • National Institutes of Health
      Bethesda, MD, USA
  • 2009–2011
    • Seoul National University Hospital
      Seoul, Seoul, South Korea
  • 2005–2007
    • Seoul National University
      • School of Computer Science and Engineering
      Seoul, Seoul, South Korea