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Anneke Geurts-Moespot

Publications and source records attributed to Anneke Geurts-Moespot.

17 recordsLinked to original sources
PubMed2006

MIF production by dendritic cells is differentially regulated by Toll-like receptors and increased during rheumatoid arthritis.

Macrophage migration inhibitory factor (MIF) is clearly associated with rheumatoid arthritis (RA) disease severity. However, the regulation of MIF during the course of RA has not been subjected to similar scientific scrutiny. The aim of our study was to investigate the role of various Toll-like receptors (TLRs) and inflammatory mediators on MIF production by dendritic cells (DCs) in healthy controls and RA patients. DCs were cultured from 12 healthy donors and 12 RA patients. Triggering via TLR mediated pathways was achieved using various TLR specific ligands alone or in combination: Pam3Cys for TLR2, LPS and recombinant extra domain A containing fibronectin for TLR4 and Poly(I:C) and R848 for TLR3 and TLR7, respectively. In addition, iDCs from healthy controls were incubated with various cytokines, RANKL and CD40L for 48 h. MIF levels were measured using an ELISA assay. Stimulation of DCs by TLR4 ligands resulted in higher MIF production compared to immature DCs from healthy controls (p<0.002) and RA patients (p<0.002). DCs from RA patients produced higher MIF levels than healthy controls both at the immature stage (p<0.04) as well after full maturation via TLR2 (p<0.04) and TLR4 (p<0.001) triggering. Incubation with TLR3 and TLR7 ligands resulted in a significantly decreased secretion of MIF in RA patients and controls. Simultaneous incubation of TLR4 with either TLR3 or TLR7 ligands resulted in a decrease of MIF secretion when compared to TLR4 stimulation alone. The secretion of MIF increased when DCs were stimulated with TNF-alpha, RANKL and CD40L. The secretion of MIF by dendritic cells is differentially regulated by TLRs. In addition, TNF-alpha, RANKL, and CD40L augment MIF production by DCs and thus play a potential role in the amplification of the inflammatory loop in RA.

Arthritis, Rheumatoid↗
PubMed2006

Complex congenital malformations and the impact of the plasminogen activator system and beta-hCG in amniotic fluid.

OBJECTIVE: The plasminogen activator system and beta-hCG may affect neural crest cells and angiogenesis, and thereby embryogenesis. Therefore, we investigated these parameters in amniotic fluids of pregnancies with a complex congenital malformation. STUDY DESIGN: In a case-control study amniotic fluid samples were collected from 62 pregnancies with a complex congenital malformation and from 110 healthy control pregnancies at an obstetric department of a large university hospital in the Netherlands. We determined concentrations of tissue-type plasminogen activator (tPA), urokinase-type plasminogen activator (uPA), plasminogen activator inhibitors (PAI-1, PAI-2), tPA approximately PAI-1 and uPA approximately PAI-1 complexes, and beta-hCG with enzyme-linked immunosorbent assays. Mann-Whitney U-tests and analysis of covariance, adjusting for gestational and maternal age, were performed for data comparisons. RESULTS: Compared with controls, cases demonstrated significantly lower adjusted geometric mean levels of uPA (24%), tPA (> or =19%) and tPA approximately PAI-1 (35%). Cases showed significantly higher adjusted mean levels of beta-hCG (> or =48%) and PAI-2 (10 ng/mL) than controls. Mean PAI-1 and uPA approximately PAI-1 levels were comparable between both groups. CONCLUSIONS: Disturbances in the plasminogen activator system and beta-hCG levels are suggested to be involved in the pathogenesis of complex congenital malformations by affecting neural crest cell migration and angiogenesis.

Adult↗
PubMed2006

Possible role of the plasminogen activation system in human subfertility.

OBJECTIVE: To correlate components of the plasminogen activator (PA) system with fertility outcome parameters in participants in an IVF/intracytoplasmic sperm injection (ICSI) procedure. DESIGN: Case-control study. SETTING: Outpatient clinic for IVF/ICSI treatment at the Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands. PATIENT(S): One hundred and fifty-six couples undergoing an IVF/ICSI procedure. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Urokinase-type plasminogen activator (u-PA), tissue-type plasminogen activator (t-PA), plasminogen activator inhibitor 1 (PAI-1), and t-PA-PAI-1 complex concentrations in the ejaculate, spermatozoa, and follicular fluid (FF). RESULT(S): Concentrations of t-PA were higher in spermatozoa of the male factor subfertility group (geometrical mean, 77.1 pg/million spermatozoa; 25th-75th percentiles, 31.8-211.2), compared to fertile men (geometrical mean, 1.91; 25th-75th percentiles, 0.74-5.79) and idiopathic subfertile men (geometrical mean, 3.14; 25th-75th percentiles, 0.97-9.97). Furthermore, the concentration of t-PA in spermatozoa was significantly associated with pregnancy (odds ratio [OR], 0.995). Likewise, a trend was shown for higher t-PA concentrations in the FF of women with fallopian-tube pathology (geometrical mean, 18.5 pg t-PA/mg protein; 25th-75th percentiles, 11.4-25.7) or endometriosis (geometrical mean, 18.8; 25th-75th percentiles, 11.4-27.1), compared to fertile women (geometrical mean, 14.3; 25th-75th percentiles, 10.3-17.6) and idiopathic subfertile women (geometrical mean, 13.9; 25th-75th percentiles, 9.5-17.8). Also, t-PA in FF is associated with the proportion of cleaved embryos (regression coefficient, 0.16). The concentrations of u-PA, PAI-1, and t-PA-PAI-1 complex were comparable between diagnostic subgroups in both men and women. CONCLUSION(S): The t-PA concentrations in spermatozoa and FF tend to be higher in human subfertility, and seem to be associated with some fertility outcome parameters.

Adult↗
PubMed2006

Concentrations of plasminogen activators and their inhibitors in blood preconceptionally, during and after pregnancy.

BACKGROUND: Haemostasis is a complex balance of activating and inhibitory pathways resulting in coagulation and lysis. Normal pregnancy is associated with hypercoagulation that is even more profound in complicated pregnancies. OBJECTIVE: To study the role of the plasminogen-activator system in complicated pregnancy with regard to haemostasis, it is essential to have reference values of components of this system during uneventful pregnancy. In this study we investigated the concentrations of six different components of the plasminogen-activator system preconceptionally, during and after uncomplicated pregnancies. MATERIAL AND METHODS: Tissue-type and urokinase-type plasminogen activator (tPA and uPA), plasminogen inhibitor type-1 and -2 (PAI-1 and-2), and the complexes between tPA and PAI-1, and between uPA and PAI-1 (tPA-PAI-1, uPA-PAI-1) were measured by ELISAs in blood obtained preconceptionally, at 6, 10, 20, 32 weeks of gestation, and 6 weeks after delivery in uncomplicated pregnancies (n=41; all six parameters n=22). RESULTS: tPA and uPA concentrations decreased in the first 10 weeks of pregnancy and subsequently increased in the third trimester. PAI-1 concentrations increased in the third trimester and PAI-2 concentrations increased throughout pregnancy (preconception versus 32 weeks of gestation; 38.73 versus 102.23ng/ml, and 0.024 versus 151.06ng/ml, respectively). tPA-PAI-1 and uPA-PAI-1 complex concentrations decreased in the first trimester, followed by an increase in the third trimester. The concentrations of all components returned to the preconception values 6 weeks after delivery. CONCLUSION: This study provides longitudinal data on activating and inhibitory components of the plasminogen-activator system during pregnancy. Insight in the longitudinal changes in these concentrations may be of help in the understanding of the thrombotic tendency in pregnancy complications such as preeclampsia.

Adult↗
PubMed2006

Protein chip based miniaturized assay for the simultaneous quantitative monitoring of cancer biomarkers in tissue extracts.

A multiplexed fluorescence immunoassay using a novel planar waveguide technology-based microarray system, ZeptoMARK (Zeptosens), was developed to detect simultaneously urokinase-type plasminogen activator (uPA), plasminogen activator inhibitor-1 (PAI-1), and vascular endothelial growth factor (VEGF) in extracts of breast cancer tissues. The three analytes assay was cross-validated with single-analyte ELISA/chemiluminescence immunosorbent assay tests, revealing good correlations and enhanced assay sensitivities (LODs) of 1 pg/mL for uPA, 33 pg/mL for PAI-1, and 1 pg/mL for VEGF. Values were well within the 80-120% limits for assay recovery and within the +/-20% limits for assay precision. The uPA, PAI-1, and VEGF results obtained from 50 breast cancer cytosols using the protein array system demonstrated that the microarray-based multiplexed assay is a sensitive and robust tool to be used for the simultaneous quantification of cancer markers in small breast cancer tissue samples (core biopsies). The miniaturized, multiplexed assay format has a potential to be used for the quantitative analysis of a larger set of validated markers with significance in disease management.

Biomarkers, Tumor↗
PubMed2005

Correlation of rheumatoid arthritis severity with the genetic functional variants and circulating levels of macrophage migration inhibitory factor.

OBJECTIVE: To study whether genetic variants of macrophage migration inhibitory factor (MIF), the MIF -173G>C and CATT(5-8) alleles, are associated with disease severity and levels of circulating MIF in patients with rheumatoid arthritis (RA). METHODS: Genotyping was performed in patients with early RA and in healthy controls. Demographic data, disease activity, and outcome measurements were compared between patients with and without the MIF variants. MIF -173G>C and CATT(5-8) polymorphisms were genotyped, and a newly developed enzyme-linked immunosorbent assay for human MIF was used. Allele and genotype distributions of the MIF -173G>C and CATT(5-8) polymorphisms were compared between patients and controls by chi-square test. Multiple regression analysis was performed to assess the independence of the MIF functional genetic variants as risk factors for radiologic joint damage. RESULTS: Genotyping of the -173G>C and CATT(5-8) polymorphisms of MIF in RA patients and healthy individuals (n = 277 each) revealed similar frequencies of genotypes and haplotypes in both groups. No significant differences in demographic or clinical features were observed between RA patients carrying the MIF -173C allele or the MIF CATT7 allele or both and non-carrier RA patients. Radiologic joint damage was significantly higher in patients carrying risk alleles of the MIF -173G>C or the MIF CATT(5-8) functional variants. No synergistic effects between both genetic variants were observed. Multivariate regression analysis revealed that presence of the MIF -173C/C and MIF CATT(7/7) genotypes and having 1 MIF -173C allele were independent prognostic variables. Carriership of the MIF -173C allele (P = 0.002) or MIF CATT7 allele (P = 0.004) was associated with significantly higher circulating MIF levels compared with those in subjects having none of the risk-conferring alleles, and greater circulating MIF levels correlated with more severe radiologic joint damage (r = 0.64, P = 0.001). CONCLUSION: The MIF polymorphisms are not associated with RA susceptibility but are associated with high levels of radiologic joint damage. High circulating MIF levels were shown to correlate strongly with radiologic joint damage, suggesting that MIF expression is genetically determined and can be used as a novel prognostic tool in RA.

Adult↗
PubMed2005

Development of a sensitive ELISA for the quantification of human tumour necrosis factor-alpha using 4 polyclonal antibodies.

Despite the availability of many assays to measure concentrations of tumour necrosis factor alpha (TNF-alpha) in body fluids, these assays often lack specificity or sensitivity and are often of questionable reliability, resulting in inconsistent results. Therefore, we have developed an ELISA that is sensitive, reliable and not susceptible to disturbances by interfering substances such as heterophilic antibodies. The assay involves a combination of four polyclonal antibodies. The antibodies, which capture the analyte, were raised in chicken and the trapping anti-analyte antibodies were raised in rabbit. The immobilization of capture antibodies was achieved via a coating antibody raised in a duck against chicken IgY and the recognition of trapping antibodies was achieved by a detection antibody raised in a goat against rabbit IgG and labelled with HRP. The analytical and functional sensitivities of the ELISA are 8 pg/mL and 13 pg/mL, respectively. The assay showed good precision and, in contrast to our in-house RIA, excellent parallelism in serial dilutions. The recovery of TNF-alpha spiked to plasma samples ranged from 97% to 119%. Comparison of the newly developed, sensitive ELISA with our in-house RIA showed that the median TNF-alpha value obtained by RIA (range: 0.095-10.0, median 0.578 ng/mL) was found to be 1.5-2 times higher than that obtained with the ELISA (range 0.008-5.84, median 0.213 ng/mL). Spearman correlation was 0.755 (p < 0.0001). In addition, analysis of the TNF-alpha concentrations in blood from healthy individuals and from patients suffering from tuberculosis, with RIA and ELISA, showed the same differences although TNF-alpha levels obtained with ELISA were lower. We feel that this ELISA is a major improvement compared to the currently available assays for TNF.

Animals↗
PubMed2004

The prognostic value of BCAR1 in patients with primary breast cancer.

PURPOSE: BCAR1, the human homologue of the rat p130Cas protein, was identified in a functional screen for human breast cancer cell proliferation resistant to antiestrogen drugs. Here, we study the prognostic value of quantitative BCAR1 levels in a large series of breast cancer specimens. EXPERIMENTAL DESIGN: A specific ELISA was developed to measure BCAR1 protein levels in 2593 primary breast tumor cytosols. Tumor levels of BCAR1 were correlated with relapse-free survival (RFS) and overall survival (OS) and compared with collected data on urokinase-type plasminogen activator (uPA) and plasminogen activator inhibitor 1 (PAI-1). RESULTS: In tumor cytosols, BCAR1 protein levels varied between 0.02 and 23 ng/mg protein. BCAR1 levels exhibited a positive correlation with steroid hormone receptor levels, age and menopausal status, and uPA and PAI-1 levels. The level of BCAR1 (continuous or categorized as low, intermediate, or high) was inversely related with RFS and OS time. Multivariate analysis showed that BCAR1 levels contributed independently to a base model containing the traditional prognostic factors for both RFS and OS (both P < 0.0001). When added together with uPA and PAI-1 in the multivariate model, BCAR1 contributed independently of PAI-1 and was favored over uPA. Interaction tests allowed for additional analyses of BCAR1 protein levels in clinically relevant subgroups stratified by nodal and menopausal status. CONCLUSIONS: The quantitative BCAR1 protein level represents a prognostic factor for RFS and OS in primary breast cancer, independent of the traditional prognostic factors and the other novel marker PAI-1.

Adult↗
PubMed2004

Complex of urokinase-type plasminogen activator with its type 1 inhibitor predicts poor outcome in 576 patients with lymph node-negative breast carcinoma.

BACKGROUND: The ability of a solid tumor to grow and metastasize has a significant dependence on protease systems, such as the plasminogen activation system. The plasminogen activation system includes the urokinase-type plasminogen activator (uPA) and plasminogen activator inhibitor type 1 (PAI-1), among other molecules. Both uPA and PAI-1 are established prognostic factors for patients with breast carcinoma. In the current study, the authors investigated whether the complex of uPA with PAI-1 is also associated with the natural course of this malignancy. METHODS: Cytosolic levels of uPA, PAI-1, and the uPA:PAI-1 complex were measured in tumor tissue from 576 patients with lymph node-negative invasive breast carcinoma using quantitative enzyme-linked immunosorbent assays. Patients did not receive adjuvant systemic therapy, and the median follow-up duration was 61 months (range, 2-187 months) after primary diagnosis. Correlations with well known clinicopathologic factors were assessed, and univariate and multivariate survival analyses were performed. RESULTS: uPA:PAI-1 complex levels were positively associated with adverse histologic grade and inversely correlated with estrogen and progesterone receptor status. On univariate analysis, increased levels of the uPA:PAI-1 complex were found to be associated with reduced recurrence-free survival (RFS) and overall survival (OS) rates. On multivariate analysis, uPA:PAI-1 complex levels were found to be an independent predictor of OS (P = 0.039), but not RFS (P = 0.240). When uPA and PAI-1 levels were not included in the multivariate analysis, uPA:PAI-1 complex levels became a significant predictor of both RFS and OS (P = 0.029 and P = 0.007, respectively). CONCLUSIONS: The results of the current study demonstrate that uPA:PAI-1 complex levels have prognostic value on univariate analysis. In addition, increased uPA:PAI-1 complex levels were significantly associated with poor OS on multivariate analysis. Increased uPA:PAI-1 complex levels were also significantly associated with reduced RFS rates after the exclusion of uPA and PAI-1 levels from the multivariate analysis model.

Adult↗
PubMed2004

Development of an ELISA for measurement of BCAR1 protein in human breast cancer tissue.

BACKGROUND: High concentrations of breast cancer anti-estrogen resistance 1 (BCAR1) protein measured by Western blotting in primary breast tumor cytosols are associated with early disease progression and failure of tamoxifen therapy. The aim of the present study was to develop an ELISA to measure BCAR1 quantitatively in extracts of human breast cancer tissue. METHODS: A recombinant fragment of BCAR1 (the human homolog of murine p130Cas) was produced in bacterial M15 cells, purified, and injected into chickens and rabbits. The generated antibodies were affinity-purified and used for the construction of an ELISA. After validation, the results obtained with the ELISA were compared with Western blot findings on primary breast tumors. RESULTS: The detection limit the BCAR1 ELISA was 0.0031 microg/L, and the within-run imprecision (CV) was <20% at concentrations down to 0.004 microg/L. The within-run imprecision (CV) was 1.0-7.2%, and the between-run CV was 3.6-5.4%. There was no cross-reactivity with family member HEF1. The assay exhibited parallelism of results between serial dilutions and a mean recovery (range) of 96 (79-118)%. CONCLUSIONS: The ELISA measures BCAR1 in human breast cancer cytosols with high sensitivity and specificity. The assay can be used to confirm and to quantitatively extend previous semiquantitative Western blot data on the prognostic and predictive value of BCAR1 in human breast cancer; it can also be applied for other diseases.

Animals↗
PubMed2003

Vascular endothelial growth factor independently predicts the efficacy of postoperative radiotherapy in node-negative breast cancer patients.

PURPOSE: Vascular endothelial growth factor (VEGF) is a mediator of angiogenesis and is up-regulated under hypoxic conditions. Hypoxic tumors are known to exhibit resistance to radiotherapy. We investigated the association between VEGF levels in tumor tissue and the effect of radiotherapy for relapse-free survival (RFS) and overall survival (OS) in node-negative breast cancer. EXPERIMENTAL DESIGN: The study was performed on 489 patients; 221 patients received postoperative radiotherapy as part of the breast-conserving therapy (BCT), and 268 patients were treated by mastectomy only. VEGF levels were measured using a quantitative ELISA. None of the patients received adjuvant systemic therapy. The median follow-up was 64 months (range, 2-149) after BCT and 59 months (range, 2-117) after mastectomy. Correlations with well-known prognostic factors were studied, and univariate and multivariate survival analyses were performed. RESULTS: Only in the BCT group, high VEGF levels (equal or above the median level) predicted a reduced RFS and OS in univariate survival analysis (P = 0.004 and P = 0.028, respectively), implying that patients with high VEGF levels have less benefit from BCT. This was seen as a significant interaction between local treatment and VEGF for the total population for RFS (P = 0.012) and OS (P = 0.004). The interaction between local treatment and tumor size was also significant for both RFS (P = 0.046) and OS (P = 0.019) in the multivariate analysis. CONCLUSIONS: These results show that, in node-negative patients, both tumor size and VEGF content predict for a reduced efficacy of postoperative radiotherapy as part of BCT, indicating that the choice of local treatment of these patients can also be modified based on tumor VEGF content.

Adult↗
PubMed2003

Ethnic variations in uterine leiomyoma biology are not caused by differences in myometrial estrogen receptor alpha levels.

OBJECTIVE: Uterine leiomyomas develop in women of reproductive age and regress after menopause, suggesting that they grow in a steroid hormone-dependent fashion. Furthermore, it is widely accepted that symptomatic uterine leiomyomas occur at a twofold to threefold higher frequency in black women than in white women. The present study was designed to investigate a possible physiologic role of racial differences in the myometrial estrogen receptor alpha in this phenomenon. METHODS: We compared the expression of the estrogen receptor and progesterone receptor in myometrium by ligand-binding assay and the estrogen receptor alpha by real-time polymerase chain reaction in women from different ethnic backgrounds who have uterine leiomyoma. RESULTS: Estrogen receptor and progesterone receptor concentrations and estrogen receptor alpha transcription levels were not statistically different between ethnic backgrounds. CONCLUSION: Neither on a transcriptional nor on a protein level were there statistically relevant differences in steroid hormone receptor levels. A causative role for these receptors in the ethnic variation of leiomyoma biology seems unlikely.

Adult↗
PubMed2003

Combined vascular endothelial growth factor and TP53 status predicts poor response to tamoxifen therapy in estrogen receptor-positive advanced breast cancer.

PURPOSE: In recent studies, we showed that TP53 gene mutation or high levels of cytosolic vascular endothelial growth factor (VEGF) in estrogen receptor (ER)-alpha-positive primary breast tumors predict a poor disease outcome for patients treated with first-line tamoxifen for advanced disease. Mutant TP53 may up-regulate VEGF, whereas, on the other hand, wild-type TP53 may decrease VEGF production. EXPERIMENTAL DESIGN: In the present study, we aimed to assess the combined predictive value of TP53 gene mutation and VEGF status of 160 advanced breast cancer patients with ER-positive tumors who were treated with tamoxifen (median follow-up from start of tamoxifen treatment, 64 months). To assess TP53 gene mutation status, the entire open reading frame was sequenced; for VEGF status, an ELISA was used. RESULTS: In univariate analysis, both TP53 gene mutation (28% of the tumors) and a VEGF level above the median value were significantly associated with a short progression-free survival, post-relapse overall survival, and a poor rate of response to tamoxifen. In Cox multivariate regression analysis including the traditional predictive factors, the addition of TP53 gene mutation and VEGF status, alone or in combination, significantly predicted a poor efficacy of tamoxifen treatment. When the two factors were combined, a significantly decreased odds ratio was seen for the rate of response (odds ratio, 0.27). Similarly, an increased hazard ratio (HR) was seen for progression-free survival (HR, 2.32) and post-relapse overall survival (HR, 1.68) in the group with mutant TP53 and high VEGF compared with the group with both risk factors absent. CONCLUSIONS: Combined TP53 gene mutation status and high VEGF levels of ER-positive primary breast tumors independently predict a poor course of the disease of patients with advanced breast cancer treated with tamoxifen. These patients, having unfavorable tumor characteristics, might benefit more from other types of (individualized) treatment protocols.

Antineoplastic Agents, Hormonal↗
PubMed2002

Evaluation of the efficiency of chemotherapy in in vivo orthotopic models of human glioma cells with and without 1p19q deletions and in C6 rat orthotopic allografts serving for the evaluation of surgery combined with chemotherapy.

BACKGROUND: Malignant gliomas of the central nervous system remain associated with dismal prognoses because of their diffuse invasion of the brain parenchyma. Very few experimental models that mimic clinical reality are available today to test potentially new therapies. The authors set up experimental in vivo glioma models of anaplastic astrocytomas of human and rat origins and anaplastic oligodendroglioma of human origin. Standard hospital chemotherapies were employed to test the validity of these models. METHODS: Three glioma cells lines obtained from the American Type Culture Collection (i.e., human Hs683 and U373 cells and rat C6 cells) were implanted into nude mouse brains (Hs683 and U373 cells) and rat brains (C6 cells). The astrocytic nature, as opposed to the oligodendrocytic nature, of the Hs683 and U373 models was investigated by using quantitative (computer-assisted microscopy) immunohistochemical characterizations of nestin, vimentin, glutathione-S-transferase alpha (GSTalpha), GSTmu, GSTpi, and p53 expression. Comparative genomic hybridization (CGH) was employed to investigate 1p19q losses. Chronic administrations of carmustine (BCNU), fotemustin, or temozolomide were assayed in the xenografted U373 and Hs683 models. Both BCNU-related chemotherapy and surgery were assayed in the C6 model. RESULTS: The quantitative phenotypic analyses pointed to the oligodendroglial nature of the Hs683 cell line and the astrocytic nature of the U373 cell line. The Hs683 cells exhibited 1p19q losses, whereas the U373 cells did not. BCNU, fotemustin, and temozolomide dramatically increased the time of survival of the Hs683 oligodendroglioma-bearing mice, whereas temozolomide only induced a weak but nevertheless statistically significant increase in the U373 glioma-bearing mice. In the C6 rat glioma model, surgery and BCNU chemotherapy were more efficient than either treatment alone. CONCLUSIONS: The in vivo models of gliomas of the central nervous system developed in the current work best mimicked clinical reality. They can be used either to identify new therapies against human gliomas or to optimize existing therapies.

Animals↗
PubMed2002

Levels of plasminogen activators and their inhibitors in maternal and umbilical cord plasma in severe preeclampsia.

OBJECTIVE: The purpose of this study was to evaluate the plasminogen activator system in maternal and umbilical cord plasma in patients with severe preeclampsia compared with control subjects with normotensive pregnancies. STUDY DESIGN: Maternal blood was sampled from 42 patients at a median gestational age of 32 weeks; after delivery, arterial and venous umbilical cord blood was sampled from 37 and 36 of these patients, respectively. Maternal blood from women with uncomplicated pregnancies was sampled at the gestational age of 32 weeks (n = 18, group I), and umbilical cord blood was sampled after premature deliveries of normotensive pregnancies (n = 5, group II). Data were analyzed with the use of Mann-Whitney U tests. RESULTS: Patients had significantly higher tissue plasminogen activator (P <.01) and unchanged urokinase plasminogen activator plasma levels compared with control subjects at 32 weeks of gestation; lower plasminogen activator inhibitor type 2 (P < 0.01) and no different plasminogen activator inhibitor type 1 concentrations were observed compared to control subjects at 32 weeks of gestation. In the arterial and venous umbilical cord plasma of patients, plasminogen activator inhibitor type 1 levels were significantly higher(P <.01) compared with control subjects at 32 weeks of gestation, although urokinase plasminogen activator levels in arterial and venous umbilical cord plasma (P < 0.01) were significantly lower. CONCLUSION: Lower plasminogen activator inhibitor type 2 levels are associated with placental insufficiency, and higher tissue plasminogen activator levels are associated with endothelial dysfunction in patients with severe preeclampsia. The higher plasminogen activator inhibitor type 1 levels and lower urokinase plasminogen activator levels in umbilical cord of these patients are suggestive of decreased fibrinolysis in the fetal circulation.

Female↗