Biomedical subjects

L Rieger

Publications and source records attributed to L Rieger.

34 records · Page 2Linked to original sources

PubMed2002

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↗

PubMed2002

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↗

PubMed2002

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↗

PubMed2001

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↗

PubMed2001

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↗

PubMed2001

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↗

PubMed2001

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↗

PubMed2000

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↗

PubMed2000

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↗

PubMed1999

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↗

PubMed1998

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↗

PubMedDate not supplied

[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↗

PubMedDate not supplied

[Reversible loss of vision in severe preeclampsia: case report and review of the literature].

Visual disturbances occur in up to 25 % of the patients with preeclampsia. However, blindness remains a rare phenomenon. A 39 year old primigravida was admitted for observation at 30 weeks gestation with signs of preeclampsia. After 11 days she suffered a complete loss of vision. The blindness reversed completely after cesarean section and antihypertensive treatment. Blindness in preeclamptic patients is mostly caused by hypertensive encephalopathy. We discuss pathophysiological aspects as well as diagnostic approaches and therapeutic options with respect to the available literature.

Adult↗

PubMedDate not supplied

Heat-shock protein 70 as a prognostic marker in node-negative breast cancer.

BACKGROUND: Heat-shock proteins (hsp) are involved in processes which are associated with tumour neogenesis and the biological behaviour of tumours. The object of our study was to investigate the significance of the 70 kDa hsp for the outcome of women with node-negative breast cancer. PATIENTS AND METHODS: Paraffin sections of 191 patients with operated breast cancer and a median follow-up of 177 months were stained immunohistochemically with a commercially available antibody against hsp70. RESULTS: We found a statistically significant correlation of the nuclear staining pattern with tumour size (> or < or = 2 cm; p = 0.046) and with a low tumour grading (G1 and G2 versus G3; p = 0.029). Patients showing a cytoplasmatic staining for hsp70 had a statistically significantly decreased overall survival [OS] (p = 0.04) and a shorter survival after recurrence [SR] (p = 0.026). CONCLUSION: The nuclear share of hsp70 is associated with various biological characteristics of malignant breast tumours, while the occurrence of cytoplasmatic hsp70 influences OS and SR.

Adult↗

PubMedDate not supplied

Brain metastases in breast cancer--an in vitro study to evaluate new systemic chemotherapeutic options.

BACKGROUND: Fifteen-30% of breast cancer patients develop central nervous system (CNS) metastases. The most potent drugs for the treatment of breast cancer like taxanes, anthracyclines and trastuzumab have limited efficacy for brain metastases. No standardized therapy has yet been established for this condition. Drugs with proven efficacy in the CNS and which are commonly used for primary brain tumors were applied. We evaluated the capacity of these drugs to inhibit breast tumor cell growth in vitro. MATERIALS AND METHODS: Twelve primary cell cultures of pulmonary/pleural metastases of breast cancer and 3 commercially available cell lines were used for non-radioactive cytotoxicity assays to evaluate the efficacy of 3 different concentrations of Topotecan, Cisplatin, Nimustine, Vincristine, Irinothecan, Caelyx (pegylated liposomal Doxorubicin) and Etoposide. RESULTS: Topotecan, Cisplatin, Caelyx and Vincristine showed significantly higher cytostatic activity in vitro than Irinotecan, Etoposide and Nimustine. With regard to the median cytotoxicity, the order of drugs in our assays was Topotecan, Cisplatin, Vincristine, Caelyx, Irinotecan, Etoposide and Nimustine. Nimustine showed almost no efficacy against breast cancer cells. CONCLUSION: Topotecan, Cisplatin, Vincristine and Caelyx seem to be suitable candidates for further clinical evaluation. The data and the "liposomal packaging" suggest that Caelyx might be effective in the CNS. Since pulmonary metastases are often associated with brain metastases, evaluatingprimary cell cultures from malignant pleural effusions could be a valuable approach for the testing of new cytostatic drugs for brain metastases.

Adult↗

PubMedDate not supplied

Heat shock protein 27 is associated with decreased survival in node-negative breast cancer patients.

BACKGROUND: Heat shock protein 27 (hsp27) is a molecular chaperone which supports cells to keep their homeostasis under stressful conditions. It is associated with resistance to chemotherapeutics, radiation and hyperthermia. The aim of this retrospective study was to investigate the prognostic value of hsp27 for patients with node-negative breast cancer. MATERIALS AND METHODS: Paraffin sections of 191 patients were stained immunohistochemically with a monoclonal antibody against hsp27. Median follow-up was 177 months. The results were correlated with clinical and histopathological parameters using the Chi-square test. RESULTS: There was no significant correlation between hsp27 expression and standard histopathological features or the proliferation marker ki-67. Disease-free survival (DFS) was not altered for patients expressing hsp27-positive tumors, whereas overall survival (OS) [p=0. 02] and survival after first recurrence (SR) [p=0.01] were significantly decreased. CONCLUSION: The expression of hsp27 in primary breast cancers is associated with a short survival for node-negative patients.

Adult↗