33 research outputs found
Aberrant DNA methylation patterns in microsatellite stable human colorectal cancers define a new marker panel for the CpG island methylator phenotype
No full textA distinct group of colorectal carcinomas (CRCs) referred to as the "CpG island methylator phenotype" (CIMP) shows an extremely high incidence of de novo DNA methylation and may share common pathological, clinical or molecular features. However, there is limited consensus about which CpG islands (CGIs) define a CIMP, particularly in microsatellite stable (MSS) carcinomas. To study this phenotype in a systematic manner, we analyzed genome-wide CGI DNA methylation profiles of 19 MSS CRC using methyl-CpG immunoprecipitation (MCIp) and hybridization on 244K CGI oligonucleotide microarrays, determined KRAS and BRAF mutation status and compared disease-related DNA methylation changes to chromosomal instability as detected by microarray-based comparative genomic hybridization. Results were validated using mass spectrometry analysis of bisulfite-converted DNA at a subset of 76 individual CGIs in 120 CRC and 43 matched normal tissue samples. Both genome-wide profiling and CpG methylation fine mapping segregated a group of CRC showing pronounced and frequent de novo DNA methylation of a distinct group of CGIs that only partially overlapped with previously established classifiers. The CIMP group defined in our study revealed significant association with colon localization, either KRAS or BRAF mutation, and mostly minor chromosomal losses but no association with known histopathological features. Our data provide a basis for defining novel marker panels that may enable a more reliable classification of CIMP in all CRCs, independently of the MS status
HIV-1 Seroprevalence among Pregnant Women in Rural Uganda: A Longitudinal Study over Fifteen Years
No full textIntroduction: In order to determine the development of the prevalence of HIV infection in rural Western Uganda, data of epidemiological studies conducted in 2001 and 2007 were compared to study data from 1993. Methods: In 2001 (n = 466) and in 2007 (n = 486), one group each of clinically healthy pregnant women of a local prenatal care department were enrolled in the study and anonymously screened for HIV-1. For both groups, informed consent was obtained prior to enrolment. Testing for HIV was done by enzyme-linked immunosorbent assay (ELISA) and confirmed by Western blot. In addition, age and antibodies against syphilis were determined as risk factors of HIV infection. Results: The seroprevalence of HIV-1 infection did not decrease significantly over this time period, dropping from 28.3 to 25.1% between 2001 and 2007, but the prevalence of syphilis antibodies decreased from 27.9 to 11.1%. The data of 2001 and 2007 were compared to a third cohort from 1993, in which 21.5% of pregnant women were HIV-1-positive and 31.1% were Treponema pallidum hemagglutination assay (TPHA)-positive. Conclusion: The current prevalence of HIV-1 infection in Uganda is still high and there is a need for further promotion of HIV prevention and control services. Copyright (C) 2013 S. Karger AG, Base
Usage of the wearable cardioverter-defibrillator during pregnancy.
No full textBackground
Pregnancy can trigger or aggravate the risk for life-threating arrhythmias in cardiac diseases. Pregnancy is associated with reluctance for implantable cardioverter-defibrillators (ICD) due to concerns about radiation. Thus, the wearable cardioverter-defibrillator (WCD) might be an option during pregnancy. Aim of the study was to collect experiences about the use of WCD in pregnancy.
Methods and results
This study retrospectively included eight women who received a WCD during pregnancy. They suffered from ventricular tachycardia (VT) without known cardiac disease (n = 3), Brugada syndrome (n = 1), hypertrophic cardiomyopathy (n = 1), dilated cardiomyopathy (n = 1), non-compaction (n = 1), and survived sudden cardiac arrest during a preceding pregnancy (n = 1). WCD usage was started between 13 and 28 weeks of gestation. WCD wearing period ranged from 3 days to 30.9 weeks, WCD wearing time ranged from 13.0 to 23.7 h per day. Two women (25%) abandoned WCD already during pregnancy. Neither appropriate nor inappropriate WCD shocks were recorded. Antiarrhythmic management included beta-blockers (n = 5) and flecainide (n = 2). After delivery, ICD were implanted (n = 4), refused (n = 2) and estimated not necessary after successful catheter ablation (n = 2).
Conclusion
Uneventful pregnancy is possible in women at risk for sudden cardiac death by interdisciplinary monitoring and diligent pharmacotherapy protected by the WCD. Since no WCD shocks were recorded, the effectiveness of WCD during pregnancy is still unclear. However, arrhythmia detection by WCD was very good despite the changed anatomy in pregnancy. Nevertheless, further studies are necessary to assess effectiveness of WCD in pregnant women. Furthermore, efforts should be made to increase the wearing adherence of WCD during pregnancy
Changes in Maternal Body Mass Index, Weight Gain and Outcome of Singleton Pregnancies from 2000 to 2015
No full textIntroduction Maternal obesity and excessive gestational weight gain (GWG) affect the outcomes of women and their offspring. Our aim was to evaluate population-based data from Germany. Material and Methods Data from 583633/791514 mother-child pairs obtained from the perinatal database in Hesse for the period from 2000 to 2015 were used after excluding incomplete or non-plausible datasets. Early-stage pregnancy maternal body mass index (BMI) and GWG were evaluated. Significant outcome changes were calculated using linear or logistic regression models. Results The mean maternal age increased from 29.9 to 31.28 years; GWG increased from 445.1 to 457.2 g/week (p < 0.01). Similarly, rates for both overweight and obesity rose from 31.5 to 37.5% (p < 0.001). Cesarean section rates rose from 22.8 to 33.2% (p < 0.001) and rates of postpartum hemorrhage increased from 0.6 to 1% (p < 0.001). There was no significant change in the rates for stillbirth or perinatal mortality (p = 0.92 and p = 0.53 respectively), but there was an increase in the rates of admissions to neonatal intensive care units from 7.8 to 9.5% (p < 0.0001). The percentage of newborns with an Apgar score of < 7 at 5 minutes increased from 1 to 1.1% (p < 0.01) and the rate of neonates with an umbilical artery pH of < 7.1 rose from 1.7 to 2.4% (p < 0.01). Conclusions In just 15 years, pre-pregnancy BMI and GWG rates of women with singleton pregnancies have increased, and this increase has been accompanied by a significant rise in the rate of cesarean sections and a significant worsening of short-term maternal and neonatal outcomes. It is time to discuss the risks and the short-term and more worrying long-term consequences for mothers and their offspring and the future impact on our healthcare system
Cytokine profiles of umbilical cord blood mononuclear cells upon in vitro stimulation with lipopolysaccharides of different vaginal gram-negative bacteria
No full textInflammatory immune responses induced by lipopolysaccharides (LPS) of gram-negative bacteria play an important role in the pathogenesis of preterm labor and delivery, and in neonatal disorders. To better characterize LPS-induced inflammatory response, we determined the cytokine profile of umbilical cord blood mononuclear cells (UBMC) stimulated with LPS of seven vaginal gram-negative bacteria commonly found in pregnant women with preterm labor and preterm rupture of membrane. UBMC from ten newborns of healthy volunteer mothers were stimulated with purified LPS of Escherichia coli, Enterobacter aerogenes, Klebsiella pneumoniae, Proteus mirabilis, Acinetobacter calcoaceticus, Citrobacter freundii, and Pseudomonas aeruginosa. UBMC supernatants were tested for the presence of secreted pro-inflammatory cytokines (IL-6, IL-1β, TNF), anti-inflammatory cytokine (IL-10), TH1-type cytokines (IL-12, IFN-γ), and chemokines (IL-8, MIP-1α, MIP-1β, MCP-1) by Luminex technology. The ten cytokines were differentially induced by the LPS variants. LPS of E. coli and E. aerogenes showed the strongest stimulatory activity and P. aeruginosa the lowest. Interestingly, the ability of UBMC to respond to LPS varied greatly among donors, suggesting a strong individual heterogeneity in LPS-triggered inflammatory response
Perinatal Gram-Positive Bacteria Exposure Elicits Distinct Cytokine Responses In Vitro
No full textDuring pregnancy, infections caused by the gram-positive bacteria Enterococcus faecalis (E. faecalis), Streptococcus agalacticae (S. agalacticae), and Staphylococcus aureus (S. aureus) are major reasons for preterm labor, neonatal prematurity, meningitis, or sepsis. Here, we propose cytokine responses to bacterial infections by the immature perinatal immune system as central players in the pathogenesis of preterm birth and neonatal sepsis. We aimed to close the gap in knowledge about such cytokine responses by stimulating freshly isolated umbilical blood mononuclear cells (UBMC) with lysates of E. faecalis, S. agalacticae, and S. aureus collected from pregnant women in preterm labor. Bacterial lysates and, principally, S. aureus and S. agalacticae distinctly triggered most of the eleven inflammatory, anti-inflammatory, TH1/TH2 cytokines, and chemokines quantified in UBMC culture media. Chemokines depicted the most robust induction. Among them, MIP-1β was further enhanced in UBMC from female compered to male newborn infants. Due to its stability and high levels, we investigated the diagnostic value of IL-8. IL-8 was critically upregulated in cord blood of preterm neonates suffering from infections compared to gestational age-matched controls. Our results provide novel clues about perinatal immunity, underscoring a potential value of IL-8 for the timely detection of infections and suggesting that MIP-1β constitutes an early determinant of sex-specific immunity, which may contribute, e.g., to male’s vulnerability to preterm birth
Expression of HBsAg particles by recombinant vaccinia viruses in different cell lines.
No full text(A) The hepatoma cell line HuH-7 was infected with various M.O.I. [multiplicity of infection] of HBsAg-recombinant vaccinia viruses. The expression level of HBsAg was measured from the cell culture supernatant (S/N-value) by an IMx microparticle enzyme immunoassay at indicated time points: 24, 48, 72, and 96 h after infection. (B) HuH-7 hepatoma cells, primary hepatocytes, and HepG2 were comparatively infected with recombinant vaccinia viruses at the indicated M.O.I´s. Four days after infection, cells were harvested, and the expression level of HBsAg was measured in the supernatant by an IMx microparticle enzyme immunoassay.</p
Purification of HBsAg particles by isopycnic kalium bromide (KBr) gradient centrifugation.
No full text(A) Cell culture supernatants of primary hepatocytes, which were infected with recombinant vaccinia viruses, were pre-cleared, and proteins were concentrated by trichloroacetic acid (TCA) precipitation prior to separation by isopycnic ultracentrifugation with KBr. Eleven fractions were collected, and the HBsAg in each fraction was detected by an IMx microparticle enzyme immunoassay. (B) Peak fraction was loaded on SDS-PAGE and immunostained with HBsAg-specific goat polyclonal antibodies: M: Premixed protein low range molecular weight standard marker (Boehringer); Lane 1: KBr gradient peak fraction 8. Sizes of reactive proteins are indicated in kilodaltons (KDa).</p
Summary of the cytokine profiles in UBMC stimulated with LPS of seven gram-negative bacteria.
No full textMedian cytokine levels in LPS-stimulated UBMC isolated from ten uncomplicated deliveries. Median cytokine levels are directly derived from the data presented in Fig 6. Due to log scale representation, values of 0 pg/ml were replaced by 0.1; thus values depicted at 0.1 pg/ml along the x axis are actually equal to zero. IL-8, IL-6, MIP-1α, MIP-1β and MCP-1 showed the highest median level of induction, followed by TNF, IL-1β, IL-10 and IL-12. IFN-γ showed the lowest median level of secretion.</p
Characteristics of the 10 mothers and respective neonates, as well as storage time of umbilical cord blood from collection at delivery until isolation of UBMC<sup>a</sup>.
No full textCharacteristics of the 10 mothers and respective neonates, as well as storage time of umbilical cord blood from collection at delivery until isolation of UBMCa.</p
