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Biomedical subjects

L Rieger

Publications and source records attributed to L Rieger.

At least 19 recordsLinked to original sources

[Placenta praevia percreta--a serious complication after previous cesarean section].

A 36-year-old G4P1 presented at 20 weeks gestation with vaginal bleeding. Her obstetrical history was significant for two first-trimester spontaneous abortions requiring curettage and a cesarean section. On admission placenta praevia was suspected by ultrasound. A placenta percreta was suspected by ultrasound follow-up at 30 weeks. At 33 weeks she underwent cesarean section because of serious vaginal bleeding. The profound blood loss with consecutive coagulopathy required an emergency hysterectomy and multiple blood transfusions. Placenta percreta is a rare but dramatic complication after previous cesarean section. This should be kept in mind as the rate of elective cesarean sections is rising continuously.

Abortion, Spontaneous↗

Immunocompetent cells in the endometrium of fetuses and children.

BACKGROUND: Although the immunocompetent cells of the adult human endometrium are well characterized, there is little information about these cells in the developing uterus. This study was undertaken to investigate the distribution of leukocyte subpopulations in the endometrium of fetuses and children. METHODS: Uterine tissue obtained at autopsy from fetuses (n = 11) and neonates/children (n = 9) between 17 weeks gestation and 5(1/2) years of age was investigated with antibodies against various leukocyte subsets by immunohistochemical staining techniques. RESULTS: The densities of CD45+ and CD68+ cells were significantly higher in the endometrium of neonates/children than in that of fetuses. CD14+ monocytes represented the largest leukocyte subpopulation in both groups. CD56+ natural killer cells and HLA-DR+ antigen-presenting cells were absent from fetal endometrium. There were no differences in density of CD3+ T cells between the two groups, but CD4+ T helper cells were found only in fetal endometrium. CONCLUSIONS: The endometrial leukocyte population of fetuses and small children is different from that seen in adult women. The appearance of CD56+ and HLA-DR+ cells in endometrium seems to be a post-natal event, which may be induced by the changes in hormone levels and/or the adaptation of the local immune system to the changing microenvironment.

Antigen-Presenting Cells↗

Progress in sensor technology--progress in process control? Part 1: sensor property investigation and classification.

To ensure correctly operating control systems, the measurement and control equipment in WWTPs must be mutually consistent. The dynamic simulation of activated sludge systems could offer a suitable tool for designing and optimising control strategies. Ideal or simplified sensor models represent a limiting factor for comparability with field applications. More realistic sensor models are therefore required. Two groups of sensor models are proposed on the basis of field and laboratory tests: one for specific sensors and another for a classification of sensor types to be used with the COST simulation benchmark environment. This should lead to a more realistic test environment and allow control engineers to define the requirements of the measuring equipment as a function of the selected strategy.

Environmental Monitoring↗

Progress in sensor technology--progress in process control? Part II: results from a simulation benchmark study.

To show the impact of sensor behaviour on the control result, four strategies for aeration control are tested using different sensor characteristics. It is demonstrated, on the one hand, how an increasing response time will limit the achievable control quality and, on the other hand, how a given sensor characteristic can be taken into account for the controller design. The presented tests show that an improvement potential by control for WWTPs is available but this potential is limited compared to proper DO control with fixed set-points. To activate this control potential, sufficient control authority must be available and a careful control design is required. It can be shown that using feedback control, sensors with a small response time have significant advantages compared to conventional sensors. Using feed forward control, the improvement potential by control is considerably higher and additionally, the sensor delay can be integrated into the controller design. The presented discussion is based on simulation studies performed on a standardised benchmark case. For these tests it was necessary to include sensor models into the simulation model. It can be stated that the usage of sensor models is necessary for the application of dynamic simulation for the design and evaluation of WWTP control and in general to achieve realistic results.

Automation↗

[Expression of the molecules HLA-G and HLA-E modulates cytokine production of monocyte generated dendritic cells].

OBJECTIVE: Preferential secretion of Th1-like cytokine is mainly a property of monocyte derived dendritic cells (DC). Since normal early pregnancy is characterized by a shift towards a Th2-like cytokine pattern, it may be assumed that cytokine secretion by DC during early pregnancy could be modulated by the non-classical HLA molecules G and E present on invasive trophoblast. MATERIAL AND METHODS: DC were cultivated from monocytes isolated from peripheral blood mononuclear cells. DC were cocultured with K-562 leukemia cells lacking the class I and II HLA antigens transfected with either HLA-G or HLA-E or ultratransfected cells (controls) and the concentrations of IL-8, IL-10, IL-12p70, IL-18 and TNF-alpha were measured in the supernatants by ELISA. RESULTS: Coculture with ultratransfected cells resulted in a significant increase of the production of IL-8 and TNF-alpha by mature and immature DC and of IL-10 by immature DC (p < 0.01). When cocultured with HLA-G and HLA-E transfected K-562 cells, the secretion of IL-8 by immature and mature DC and that of IL-10 and TNF-alpha by immature DC was significantly (p < 0.01) decreased. The contact with HLA-G and HLA-E transfected cells had no effect on the production of IL-12p70 and IL-18 by DC. CONCLUSIONS: These results show that DC react with an increased cytokine release upon contact with cells lacking HLA class I and II antigens. The suppressive effect of HLA-G and HLA-E on the secretion of TNF-alpha (Th1 cytokine), IL-10 (Th2 cytokine) and IL-8 (chemokine) by immature DC could be interpreted as further evidence for the central immunotolerance role of HLA-G and HLA-E during early pregnancy.

Cells, Cultured↗

Th1- and Th2-like cytokine production by first trimester decidual large granular lymphocytes is influenced by HLA-G and HLA-E.

During normal early pregnancy, a particular immune environment in the decidua and the expression of non-classical HLA-G and HLA-E molecules on the invading trophoblast are assumed to be essential for the tolerance of the fetus. To assess whether HLA-G and HLA-E influence the cytokine production of their putative target cells [large granular lymphocytes (LGL)], we analysed the concentrations of tumour necrosis factor (TNF-alpha), interferon (IFN)-gamma, interleukin (IL)-10, IL-13 and granulocyte-macrophage colony stimulating factor (GM-CSF) in supernatants of isolated first trimester LGL co-cultured with HLA-G or HLA-E transfected K-562 leukaemia cells lacking the classical HLA class I and II molecules. In comparison with that observed with untransfected K-562 cells, co-culture of LGL with HLA-G-expressing cells significantly reduced the concentration of all cytokines investigated (TNF-alpha, IL-10 and GM-CSF, P < 0.01; IFN-gamma and IL-13, P < 0.05). In contrast, co-culture of LGL with HLA-E-expressing cells significantly (P < 0.01) decreased only IL-10 production, although a strong tendency towards reduced IL-13 levels was also observed. In the co-culture system presented, membrane-bound HLA-G and, to a lesser extent, HLA-E expression affected cytokine release by decidual LGL in a manner not consistent with the Th1/Th2 paradigm. In conclusion, our data are indicative of a general immune-suppressive effect of HLA-G on LGL activity.

Cells, Cultured↗

In-situ measurement of ammonium and nitrate in the activated sludge process.

A new in-situ probe is presented for the continuous measurement of ammonium and nitrate in wastewater. It requires no sample preparation and is installed directly in the process liquid. This new low-cost probe significantly reduces investment and operating costs and requires minimum maintenance. The paper describes the sensor principle and test results from three different probe locations: the primary clarifier effluent, the activated sludge tank and the nitrifying biofilter influent. Reference measurements were carried out by means of conventional analyzers with ultrafiltration, an in-situ UV spectrometer for the nitrate and laboratory analysis of spot and 2h-composite samples. The aim of the study was to investigate the operational reliability and accuracy of the new probe and the expenditure required for its maintenance and calibration. The tests showed that the new probe performed very well overall and required minimum maintenance. Some problems were observed during the biofilter plant test. They are assumed to be related to substantial changes in the wastewater composition.

Calibration↗

The EAWAG Bio-P module for activated sludge model No. 3.

An additional module for the prediction of enhanced biological phosphorus removal is presented on the basis of a calibrated version of ASM3. The module uses modified processes from ASM2d but neglects the fermentation of readily degradable substrate. Biomass decay is modeled in the form of endogenous respiration as in ASM3. The glycogen pool and biologically induced P-precipitation is not taken into account. The module was systematically calibrated with experimental data from various batch experiments, a full-scale WWTP and a pilot plant treating Swiss municipal wastewater. A standard parameter set allowed all data to be simulated.

Calibration↗

An efficient monitoring concept with control charts for on-line sensors.

A monitoring concept for on-line sensors will be discussed which helps the WWTP staff to detect drift-, shift- and outlier effects as well as unsatisfactory calibration curves. The approach is based on the analysis of comparative measurements between the sensor and a reference method. It combines statistical analysis such as control charts and regression analysis with decision support rules. The combination of two different detection levels in the selected Shewhart control charts with additional criteria allows one to detect 'out-of-control' situations early with an optimized measurement effort. Beside the statistical analysis the concept supports the operator with a graphical analysis to monitor the accuracy of on-line measurements efficiently. The widely applicable monitoring concept will be illustrated with examples for an ion-sensitive NH4+- and a MLSS-sensor.

Automation↗

SALL1, the gene mutated in Townes-Brocks syndrome, encodes a transcriptional repressor which interacts with TRF1/PIN2 and localizes to pericentromeric heterochromatin.

The Townes-Brocks syndrome (TBS) is an autosomal dominantly inherited malformation syndrome presenting as an association of imperforate anus, triphalangeal and supernumerary thumbs, malformed ears and sensorineural hearing loss. Mutations in SALL1, a gene mapping to 16q12.1, were identified as a cause for TBS. To elucidate how SALL1 mutations lead to TBS, we have performed a series of functional studies with the SALL1 protein. Using epifluorescence and confocal microscopy it could be shown that a GFP-SALL1 fusion protein localizes to chromocenters and smaller heterochromatin foci in transiently transfected NIH-3T3 cells. Chromocenters consist of clustered pericentromeric heterochromatin and contain telomere sequences. Indirect immunofluorescence revealed a partial colocalization of GFP-SALL1 with M31, the mouse homolog of the Drosophila heterochromatic protein HP1. It was further demonstrated that SALL1 acts as a strong transcriptional repressor in mammalian cells. Transcriptional repression could not be relieved by the addition of the histone deacetylase inhibitor Trichostatin-A. In a yeast two-hybrid screen we identified PIN2, an isoform of telomere-repeat-binding factor 1 (TRF1), as an interaction partner of SALL1, and showed that the N-terminus of SALL1 is not necessary for the interaction with PIN2/TRF1. The interaction was confirmed in vitro in a GST-pulldown assay. The association of the developmental regulator SALL1 with heterochromatin is striking and unexpected. Our results propose an involvement of SALL1 in the regulation of higher order chromatin structures and indicate that the protein might be a component of a distinct heterochromatin-dependent silencing process. We have also provided new evidence that there is a close functional link between the centromeric and telomeric heterochromatin domains not only in Drosophila and yeast, but also in mammalian cells.

3T3 Cells↗

Calibration and validation of an ASM3-based steady-state model for activated sludge systems--part II: Prediction of phosphorus removal.

An ASM3-based steady-state model which can be used for estimating the average nitrogen-removal, sludge-production and phosphorus-removal rates of different biological phosphorus-removing systems (AAO, UCT, intermittent processes) is developed. It considers the wastewater composition, the oxygen and nitrate input in the anaerobic compartment and the interaction between biological phosphorus removal and denitrification for different operating conditions. The model is calibrated and validated with data from a number of long-term pilot and full-scale experiments for Swiss municipal wastewater. The steady-state model is adequate for a comparison of different BPR process configurations or for a first estimation of the nutrient-removal efficiency. It allows the plant performance and key parameters to be determined very quickly. Excel spreadsheets of the model for different flow schemes are available from the corresponding author.

Anaerobiosis↗

The EAWAG Bio-P module for activated sludge model No. 3.

An additional module for the prediction of enhanced biological phosphorus removal is presented on the basis of a calibrated version of ASM3. The module uses modified processes from ASM2d but neglects the fermentation of readily degradable substrate. Biomass decay is modeled in the form of endogenous respiration as in ASM3. Moreover, an additional glycogen pool and biologically induced P-precipitation were not taken into account. The module was systematically calibrated with experimental data from various batch experiments, a full-scale WWTP and a pilot plant treating Swiss municipal waste water. A standard parameter set allowed all data to be simulated.

Biomass↗

Choriocarcinoma cells modulate the cytokine production of decidual large granular lymphocytes in coculture.

PROBLEM: How do major histocompatibility complex (MHC) I positive/negative choriocarcinoma (CC) cells affect the production of tumor necrosis factor-alpha (TNF-alpha), interferon-gamma (IFN-gamma), interleukin-10 (IL-10), interleukin-4 (IL-4), and granulocyte-macrophage colony-stimulating factor (GM-CSF) by decidual CD56++ cells (large granular lymphocytes [LGL]), LGL-depleted decidual cells (WASH) and unseparated decidual cells (DEC) in cocultures? METHOD OF STUDY: Decidual tissue was obtained by legal abortions. CD 56++ LGL were isolated in a magnetic cell separator. Cytokines were measured by ELISA. Differences were analyzed for significance by Wilcoxons test. RESULTS: We found a significant increase of IL-10 in LGL/JEG-3 and of TNF-alpha in LGL/JAR cocultures compared to noncocultured decidual cells. There was a significant increase of IL-10 and TNF-alpha and a significant decrease of GM-CSF in WASH and DEC cocultures with both JEG-3 and JAR. IFN-gamma was only found in 3/11 cases of LGL/JAR cocultures. No IL-4 was found in any experiment. CONCLUSION: MHC class I positive/negative CC modulate the cytokine production of decidual LGL in different ways.

Cell Fractionation↗

Evidence for a constitutive, verapamil-sensitive, non-P-glycoprotein multidrug resistance phenotype in malignant glioma that is unaltered by radiochemotherapy in vivo.

Human malignant gliomas are commonly resistant to chemotherapy. Here, we examined the role of the multidrug resistance (mdr) mechanism in the chemo-resistance of these tumors, using a twofold approach: (i) by assessing a possible mdr phenotype before and after chronic drug exposure of glioma cells in vitro, and (ii) by assessing the modulation of expression of the mdr-associated P-glycoprotein (Pgp) using radiotherapy and serial cycles of chemotherapy in human glioblastoma patients in vivo. T98G, and to a lesser degree, LN-229 human malignant glioma cells exhibit a constitutive mdr phenotype as determined by the modulation of dye transport and by the augmentation of chemosensitivity by the mdr antagonist, verapamil. Thus, coexposure to verapamil enhances the cytotoxicity of vincristine, doxorubicin and VM26 in T98G cells and that of vincristine in LN-229 cells. Chronic exposure of the cells to low concentrations of vincristine and doxorubicin, but not VM26, topotecan or BCNU, moderately enhances the mdr-like phenotype, as assessed by drug expulsion assays. However, chronic exposure to increasing drug concentrations does not significantly alter the sensitivity to the respective drugs. These data are consistent with a constitutive, but not drug-inducible, mdr-like drug resistance in glioma cells in vitro. Immunocytochemical analysis of human malignant gliomas in vivo reveals that Pgp expression is more abundant in endothelial cells within the gliomas, than in the glioma cells proper. Importantly, Pgp expression is unaltered by radiochemotherapy, assessed by comparative immunocytochemistry of glioma specimens obtained serially before and after radiochemotherapy. We conclude that (i) glioma cells exhibit constitutive mdr-like drug resistance that is not significantly altered by chronic drug exposure in vitro; (ii) endothelial cells may play an important role in Pgp-mediated drug resistance of gliomas in vivo; (iii) radiotherapy and repeated chemotherapy cycles do not modulate Pgp expression in human malignant gliomas in vivo; (iv) there is preliminary evidence for a non-Pgp, verapamil-sensitive drug transport activity in glioma cells.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Bag-1 and Bcl-2 gene transfer in malignant glioma: modulation of cell cycle regulation and apoptosis.

Bag-1 is a heat shock 70 kDa (Hsp70)-binding protein that can collaborate with Bcl-2 in suppressing apoptosis under some conditions. Here, we report that 11 of 12 human glioma cell lines express Bag-1 protein in vitro. Moreover, 15 of 19 human glioblastomas expressed Bag-1 as assessed by immunohistochemistry in primary tumor specimens. To examine the biological effects of Bag-1 in glioma cells, we expressed Bag-1 or Bcl-2 transgenes in 2 human malignant glioma cell lines, LN-18 and LN-229. Bag-1 significantly slowed glioma cell growth and reduced clonogenicity of both cell lines in vitro. Coexpressed Bcl-2 abrogated these effects of Bag-1. Intracranial LN-229 glioma xenografts implanted into nude mice revealed a substantial growth advantage afforded by Bcl-2. Bag-1 had no such effect, either in the absence or presence of Bcl-2. Upon serum starvation in vitro, Bcl-2 prevented cell death whereas Bag-1 did not. Both Bcl-2 and Bag-1 slowed proliferation of serum-starved cells when expressed alone. Importantly, coexpression of Bcl-2 and Bag-1 provided a distinct growth advantage under conditions of serum starvation that is probably the result of (i) the death-preventing activity of Bcl-2 and (ii) the property of Bag-1 to overcome a Bcl-2-mediated enhancement of exit from the cell cycle. In contrast to these Bcl-2/Bag-1 interactions observed under serum starvation conditions, Bag-1 did not further enhance the strong protection from staurosporine-, CD95 (Fas/Apo1) ligand-, Apo2 ligand (TRAIL)- or chemotherapeutic drug-induced apoptosis afforded by Bcl-2. Taken together, these results indicate a role for Bag-1/Bcl-2 interactions in providing a survival advantage to cancer cells in a deprived microenvironment that may be characteristic of ischemic/hypoxic tumors such as human glioblastoma multiforme, and suggest that Bcl-2/Bag-1 interactions also modulate cell proliferation.

Animals↗

p27 modulates cell cycle progression and chemosensitivity in human malignant glioma.

The cell cycle regulatory protein p27, an inhibitor of cyclin-dependent kinases (CDK), has been attributed a role in (i) prognosis in breast and colon cancer, (ii) induction of apoptosis in cancer cells, and (iii) resistance to cancer chemotherapy. Here we report that p27 is widely expressed in human malignant gliomas in vivo and in glioma cell lines in vitro. Serum deprivation or confluency promotes p27 protein accumulation in vitro. Neither baseline p27 levels nor p27 levels induced by confluency or serum deprivation correlate with p53 status or drug sensitivity of human glioma cell lines. Expression of antisense p27 mRNA increased the doubling times in T98G glioma cells, whereas sense p27 mRNA had no such effect. There was a density-dependent and drug-specific modulation of chemosensitivity by sense or antisense mRNA expression in T98G cells. Taken together, these data define a strong p27 response to altered growth conditions and suggest a role for p27 in modulating response to chemotherapy in human malignant glioma cells.

Antineoplastic Agents↗

BCL-2 family protein expression in human malignant glioma: a clinical-pathological correlative study.

Malignant gliomas are rather refractory to current therapeutic approaches including surgery, radiotherapy, chemotherapy and immunotherapy. Acquired alterations in the pathways required for apoptotic cell death are thought to be responsible to the failure of glioma to respond to therapy. Here we have examined the expression of several proteins involved in the susceptibility to apoptosis in 20 human gliomas, including the BCL-2 family proteins BCL-2, BCL-X, BAX and MCL-1, as well as p53 and RB. Most gliomas expressed several BCL-2 family proteins. There was good correlation between expression of the functional antagonists, BCL-2/BCL-X and BAX, suggesting that changes in the BCL-2+BCL-X/BAX ratio are not responsible for the differential response of glioma patients to chemotherapy. The immunochemistry data were also analysed in regard to response to therapy and clinical outcome. All patients had cytoreductive surgery and received radiotherapy and nitrosourea-based adjuvant chemotherapy. There was no prominent association of outcome with the expression patterns of p53, RB, BCL-2, BCL-X or BAX. We find, however, that expression of the MCL-1 protein is associated with early tumour recurrence and shorter survival in this group of glioma patients. This preliminary observation will have to be confirmed in a larger independent sample of glioma patients.

Adolescent↗

[Plasma VEGF levels are increased in women with severe preeclampsia or HELLP syndrome].

AIM: To investigate vascular endothelial growth factor (VEGF) serum levels in severe preeclampsia (PE) and HELLP syndrome. PATIENTS AND METHODS: Serum concentrations of VEGF, progesterone, estradiol and estriol were measured in 16 patients with PE and 14 patients with HELLP syndrome and in 30 well-matched normotensive pregnant controls. Determination of VEGF was performed by a commercially available immunoassay (Quantikine(R), R&D Systeme, Wiesbaden), those of sex steroids by a radioimmunoassay (Fa. Biermann, Bad Nauheim). RESULTS: Serum VEGF levels were significantly higher in the study than in the control group (172.0 +/- 98.9 pg/ml versus 41.4 +/- 30.5 pg/ml, U-Test: p < 0.001). In patients with HELLP syndrome mean serum VEGF concentrations were increased when compared with healthy controls but serum levels were significantly lower than in patients with PE (109.2 +/- 68.5 pg/ml versus 219.0 +/- 72.9, U-Test: p < 0.05). We could demonstrate a positive correlation between VEGF and estradiol serum concentrations in the study and control patients (Spearman rang correlation: p < 0.05). CONCLUSIONS: It is concluded that patients suffering from PE or HELLP syndrome have either an increased placental expression of VEGF as a result of hypoxia or show an increased extraplacental production of this growth factor such as in maternal or fetal endothelial cells, macrophages or smooth muscle tissue.

Adult↗