Biomedical subjects

Yeon Mee Kim

Publications and source records attributed to Yeon Mee Kim.

28 records · Page 2Linked to original sources

PubMed2004

Toll-like receptor-2 and -4 in the chorioamniotic membranes in spontaneous labor at term and in preterm parturition that are associated with chorioamnionitis.

OBJECTIVE: The Toll-like receptor-2 and -4 recognize microbial products that are associated with gram-positive and gram-negative bacteria, respectively. This study examined Toll-like receptor-2 and -4 expression in fetal membranes in response to labor at term and histologic chorioamnionitis. STUDY DESIGN: Immunohistochemistry and real-time quantitative reverse transcriptase-polymerase chain reaction were used to examine the chorioamnion from patients with (1) preterm labor and intact membranes, (2) preterm premature rupture of membranes who were delivered < or =34 weeks of gestation, and (3) women at term with or without labor. All groups were stratified on the basis of the presence of histologic chorioamnionitis. RESULTS: Toll-like receptor-2 expression was significantly higher in patients with chorioamnionitis than in patients without this condition (all P < .05). The Toll-like receptor-2 and -4 messenger RNA amounts were significantly higher in membranes from women at term with spontaneous labor than women who were not in labor ( P = .001 and .002, respectively). Toll-like receptor-2 expression was polarized to the basal surface of amniotic epithelial cells in patients without chorioamnionitis, but this distribution was lost in the presence of inflammation. CONCLUSION: Spontaneous labor at term and preterm delivery with histologic chorioamnionitis, regardless of the membrane status (intact or ruptured), are associated with an increased expression of Toll-like receptor-2 and -4 in the chorioamniotic membranes. These observations have implications for understanding the biologic nature of innate immunity.

Amnion↗

PubMed2004

Genome-wide expression profiling of fetal membranes reveals a deficient expression of proteinase inhibitor 3 in premature rupture of membranes.

OBJECTIVE: We used a genome-wide approach to identify differentially expressed genes in patients with preterm premature rupture of membranes to improve the understanding of underlying molecular mechanisms. STUDY DESIGN: RNA was isolated from the fetal membranes of patients with preterm labor with intact membranes and preterm premature rupture of membranes and was stratified according to the presence or absence of histologic chorioamnionitis. Microarray experiments were used to identify differentially expressed genes, and real-time quantitative reverse transcriptase-polymerase chain reaction and immunohistochemistry were used in follow-up experiments. RESULTS: Microarray experiments identified decreased expression of proteinase inhibitor 3 in the preterm premature rupture of membranes cases. Quantitative reverse transcriptase-polymerase chain reaction confirmed these results. Immunohistochemistry demonstrated decreased proteinase inhibitor 3 protein expression in preterm premature rupture of membranes. CONCLUSION: A genome-wide approach identified deficient expression of proteinase inhibitor 3 in preterm premature rupture of membranes, which demonstrated the usefulness of functional genomics for the dissection of mechanisms of disease and identification of differentially regulated genes that were not suspected previously to play a role in parturition.

Acute Disease↗

PubMed2004

Macrophages and apoptotic cell clearance during pregnancy.

BACKGROUND: During implantation, apoptosis is critical for the appropriate tissue remodeling of the maternal decidua and invasion of the developing embryo, yet the regulation of apoptosis is also imperative for a successful pregnancy. The quick and effective removal of apoptotic cells by tissue macrophages represents an essential process, which prevents the release of self-antigens, and in the case of pregnancy, paternal alloantigens. METHODS OF STUDY: Recent studies have shown that the process of apoptotic cell clearance is not a neutral event, but rather an active one that induces macrophage production of anti-inflammatory cytokines and survival factors. Apoptotic cell clearance is, therefore, necessary for the resolution of inflammatory conditions, which during pregnancy could have lethal consequences. CONCLUSIONS: The function of the maternal immune system during implantation and throughout pregnancy is, therefore, an important area of investigation. This review will discuss the role of decidual macrophages in apoptotic cell clearance during pregnancy.

Apoptosis↗

PubMed2003

Promyelocytic leukaemia (PML) protein expression in human placenta and choriocarcinoma.

Promyelocytic leukaemia (PML) protein, the product of the pml gene, is heterogeneously expressed in various normal and neoplastic tissues, and the fusion of the pml gene with retinoic acid receptor-alpha is believed to be a central mechanism in acute PML tumourigenesis. As PML is important for controlling major cellular processes, such as growth and differentiation, it is believed that it plays an important role during human gestation. The human placenta is a critical organ for the maintenance of gestation, but the expression pattern and functional significance of PML in the placenta have not been documented. The present study has therefore investigated the expression of PML in the human placenta and in choriocarcinoma, and has observed the biological effects following the overexpression of PML in choriocarcinoma cell lines (BeWo and JEG-3). In the human placenta, PML expression was readily found in villous stromal fibroblasts, capillary endothelial cells, Hofbauer cells, and occasionally in amnion cells. Moreover, immunoblotting of placental lysates demonstrated increased PML expression with increasing gestation. Interestingly, PML expression was confined to intermediate trophoblasts and syncytiotrophoblastic giant cells at the placental site (placental site giant cells) in the trophoblastic cell population. Intermediate trophoblasts at non-placental sites, and villous cytotrophoblasts and syncytiotrophoblasts consistently did not express PML. Further screening of PML expression in hydatidiform moles (n = 4) and choriocarcinomas (n = 7) also revealed selective PML expression in intermediate trophoblastic cells and syncytiotrophoblastic cells, but not in the cytotrophoblastic populations, which corresponds well with observations in the placental bed. Adenoviral transduction of PML resulted in a marked reduction in cell growth in both choriocarcinoma cell lines, which was associated with increased apoptosis. The findings of the present study strongly suggest that PML plays an important role in human placental development and growth, and in the pathobiology of trophoblasts and trophoblastic neoplasia.

Choriocarcinoma↗

PubMed2003

Failure of physiologic transformation of the spiral arteries in patients with preterm labor and intact membranes.

OBJECTIVE: The purpose of this study was to determine whether abnormal placentation (defined as the failure of physiologic transformation of spiral arteries) is present in patients with preterm labor and intact membranes who delivered a preterm neonate. STUDY DESIGN: A cross-sectional study was conducted to examine the histopathologic findings in the placental bed and placenta of patients with preterm labor and intact membranes (n=27), preeclampsia (n=43), and healthy pregnant women at term (n=103). Immunohistochemistry studies with cytokeratin 7 and periodic acid-Schiff were used to detect trophoblast and fibrinoid, respectively, and diagnose the failure of physiologic transformation of the spiral arteries. RESULTS: The mean percentage of spiral arteries with failure of physiologic transformation in the myometrium was significantly higher in patients with preterm labor and preeclampsia than in normal pregnant women at term (P=.0004 and P<.0001, respectively). Similar findings were observed in the decidual segment of spiral arteries within the placental bed (P=.001 and P<.0001). In contrast, the mean percentage of the spiral arteries with failure of physiologic transformation in the decidua of the basal plate was not significantly different between patients with preterm labor and normal pregnant women (P=.17). CONCLUSION: Failure of physiologic transformation of the spiral arteries in the myometrial and decidual segments of the placental bed is frequent in patients with preterm labor and intact membranes.

Adult↗

PubMed2003

Matrix metalloproteinase 3 in parturition, premature rupture of the membranes, and microbial invasion of the amniotic cavity.

OBJECTIVE: Matrix metalloproteinases (MMPs) are a family of zinc-dependent endopeptidases that are expressed in many inflammatory conditions and contribute to connective tissue breakdown. Stromelysin 1 [matrix metalloproteinase 3 (MMP-3)], a novel member of this family, is produced in the context of infection and is able to activate the latent forms of other MMPs. The purpose of this study was to determine if parturition (either term or preterm), premature rupture of the membranes (PROM), and microbial invasion of the amniotic cavity are associated with changes in amniotic fluid concentrations of MMP-3. STUDY DESIGN: A cross-sectional study was conducted, which included women who underwent transabdominal amniocentesis (n = 365) in the following categories: (1) mid-trimester with a subsequent normal pregnancy outcome (n = 84) and a subsequent fetal loss (n = 10); (2) preterm labor with intact membranes without microbial invasion of the amniotic cavity who delivered at term (n = 36), or prematurely (n = 50), and preterm labor with microbial invasion of the amniotic cavity (n = 25); (3) preterm PROM with (n = 25) and without (n = 26) microbial invasion of the amniotic cavity; (4) term with intact membranes in the absence of microbial invasion of the amniotic cavity, in labor (n = 52) and not in labor (n = 31); and (5) term with PROM in the absence of microbial invasion of the amniotic cavity and not in labor (n = 26). MMP-3 concentrations in amniotic fluid were measured by a sensitive and specific immunoassay that was validated for amniotic fluid. MMP-3 concentrations were normalized using logarithmic transformation for statistical analysis. Parametric statistics were used and a p value < 0.05 was considered statistically significant. RESULTS: (1) MMP-3 was detected in 99.5% (363/365) of amniotic fluid samples, and its concentration did not change with advancing gestational age. (2) Spontaneous parturition at term and preterm was associated with a significant increase in amniotic fluid MMP-3 concentrations (p = 0.04 and p = 0.002, respectively). (3) Spontaneous rupture of membranes in term and preterm gestations was not associated with significant changes in amniotic fluid MMP-3 concentrations. (4) Intra-amniotic infection was associated with a significant increase in amniotic fluid MMP-3 concentrations in both women with preterm labor and intact membranes (p = 0.03), and women with preterm PROM (p = 0.02). (5) Subsequent fetal loss after genetic amniocentesis was not associated with significant changes in mid-trimester concentrations of amniotic fluid MMP-3. CONCLUSIONS: (1) MMP-3 is a physiologic constituent of amniotic fluid. (2) MMP-3 may play a role in the mechanisms of human parturition and in the regulation of the host response to intrauterine infection.

Amnion↗

PubMed2002

Pre-eclampsia and expression of heparin-binding EGF-like growth factor.

BACKGROUND: Pre-eclampsia is a disorder of pregnancy associated with poor extravillous cytotrophoblast invasion and above-normal rates of apoptosis in the trophoblast. Heparin-binding epidermal-growth-factor-like growth factor (HB-EGF) has strong cytoprotective activity and is an important signalling protein that regulates trophoblast invasion during early placentation. We aimed to establish whether HB-EGF expression is altered in placentae of pre-eclamptic women. METHODS: We assessed the expression of HB-EGF mRNA and protein by in-situ hybridisation and immunohistochemical techniques, respectively, in archived placental tissues from pregnancies terminated at around 20 weeks of gestation, and from women delivering between weeks 19 and 35 of gestation with preterm labour, small for gestational age infants, or pre-eclampsia. FINDINGS: HB-EGF mRNA and protein were expressed in villous and extravillous cytotrophoblast cells up to week 35 of gestation in placentae from women who delivered preterm. Similar levels of HB-EGF protein were found in the placentae of women who were not in labour. HB-EGF expression was reduced about five-fold (p=0.0001) in pre-eclamptic pregnancies. Fetal growth retardation, which has been linked with shallow trophoblast invasion and moderate apoptosis, was associated with placentae expressing intermediate levels of HB-EGF. INTERPRETATION: In pre-eclampsia, deficient HB-EGF signalling during placental development could impair trophoblast survival, differentiation, and invasion, leading to poor placental perfusion and hypertension.

Adult↗

PubMed2002

Evidence for fetal involvement in the pathologic process of clinical chorioamnionitis.

OBJECTIVE: Clinical and histologic chorioamnionitis have recently been identified as risk factors for cerebral palsy. Proinflammatory cytokines have been implicated in the mechanisms that are responsible for brain injury in cases of intrauterine infection. The purpose of this study was to determine whether clinical chorioamnionitis, which is a maternal syndrome, is associated with an elevation in the fetal plasma interleukin-6 (IL-6) that is indicative of fetal inflammation. STUDY DESIGN: A cross-sectional study was designed to determine plasma concentrations of IL-6 in umbilical venous blood from patients with clinical chorioamnionitis (n = 26) and a control group (n = 111). Umbilical cord blood was obtained at the time of delivery. Plasma concentrations of IL-6 were measured with a sensitive and specific immunoassay. Nonparametric statistics were used for analysis. RESULTS: Plasma concentrations of IL-6 were detectable in all samples of umbilical venous plasma. The median concentration of plasma IL-6 was higher in neonates born to mothers with clinical chorioamnionitis than in neonates born to mothers in the control group (clinical chorioamnionitis: median, 27.46 pg/mL; range, 1.3-5550.0 pg/mL; vs control: median, 2.13 pg/mL; range, 0.6-812.3 pg/mL; P <.001). Sixty-two percent of neonates (16/26) who were born to women with clinical chorioamnionitis had fetal plasma concentrations of IL-6 >11 pg/mL and 54% (14/26) had fetal plasma concentrations of IL-6 >18 pg/mL (these cutoff points have been used previously to define the fetal inflammatory response syndrome). CONCLUSION: Umbilical vein plasma concentrations of interleukin-6 are elevated in the neonates who were born to mothers with clinical chorioamnionitis, which suggests that the inflammatory process that is responsible for the maternal syndrome of clinical chorioamnionitis frequently involves the human fetus.

Adolescent↗

PubMed2002

Failure of physiologic transformation of the spiral arteries in the placental bed in preterm premature rupture of membranes.

OBJECTIVE: The purpose of this study was to determine whether failure of physiologic transformation of the spiral arteries occurs in patients with preterm premature rupture of membranes (PROM). STUDY DESIGN: A cross-sectional study was designed to examine the histopathologic findings in the placental bed and placenta of patients with preterm PROM, preeclampsia, and normal women at term. Immunohistochemistry with cytokeratin 7 and periodic acid-Schiff (PAS) were used to detect trophoblast and fibrinoid and to diagnose failure of physiologic transformation of the spiral arteries. RESULTS: One hundred thirteen cases met the inclusion criteria, 59 from patients with normal pregnancies, 31 with preterm PROM, and 23 with preeclampsia. The mean number of the spiral arteries with failure of physiologic transformation of the myometrial segment was significantly higher in patients with preterm PROM and preeclampsia than in normal pregnant women at term (P =.006 and P <.0001, respectively). In contrast, the mean number of the spiral arteries with failure of physiologic transformation of the decidual segment of the spiral arteries in the basal plate of the placenta was not significantly different in patients with preterm PROM from that in normal pregnant women (P >.05). Placentas from patients with preterm PROM had a higher frequency of vascular lesions than those from normal pregnant women (P =.02). CONCLUSION: Defective placentation, defined as failure of physiologic transformation of the myometrial segment of the spiral artery, is frequently present in preterm PROM.

Adult↗

PubMed2002

Pregnancy alters glucose-6-phosphate dehydrogenase trafficking, cell metabolism, and oxidant release of maternal neutrophils.

Pregnancy is associated with changes in host susceptibility to infections and inflammatory disease. We hypothesize that metabolic enzyme trafficking affects maternal neutrophil activation. Specifically, immunofluorescence microscopy has shown that glucose-6-phosphate dehydrogenase (G-6-PDase), the rate-controlling step of the hexose monophosphate shunt (HMS), is located near the cell periphery in control neutrophils but is found near the microtubule-organizing centers in cells from pregnant women. Cytochemical studies confirmed that the distribution of the G-6-PDase antigen is coincident with functional G-6-PDase activity. Metabolic oscillations within activated pregnancy neutrophils are higher in amplitude, though lower in frequency, than activated control neutrophils, suggesting limited HMS activity. Analysis of radioisotope-labeled carbon flux from glucose to CO(2) indicates that the HMS is intact in leukocytes from pregnant women, but its level is not enhanced by cell stimulation. Using extracellular fluorescent markers, activated pregnancy neutrophils were found to release reactive oxygen metabolites (ROMs) at a lower rate than activated control neutrophils. However, basal levels of ROM production in polarized pregnancy neutrophils were greater than in control neutrophils. Microtubule-disrupting agents reversed the observed changes in G-6-PDase trafficking, metabolic oscillations, and ROM production by maternal neutrophils. G-6-PDase trafficking appears to be one mechanism regulating ROM production by maternal neutrophils.

Animals↗