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Biomedical subjects

S Winkler

Publications and source records attributed to S Winkler.

At least 37 records · Page 2Linked to original sources
PubMed2003

Cellular profile of cytokine production in a patient with visceral leishmaniasis: gammadelta+ T cells express both type 1 cytokines and interleukin-10.

The cytokine profile of CD4+, CD8+ T cells, gammadelta+ T cells and natural killer (NK) cells (CD94+CD3-) was studied in a patient with visceral leishmaniasis (VL). The otherwise healthy, human immunodeficiency virus-negative patient acquired the disease in Tuscany, Italy. Diagnosis was made by demonstration of high concentrations of antibodies against Leishmania antigens in serum. Flow cytometry for the detection of intracellular interferon-gamma (IFN-gamma), interleukin (IL)-2, IL-4, IL-6, IL-10, IL-13 and tumour necrosis factor (TNF)-alpha expression in peripheral blood mononuclear cells stimulated with phorbol 12-myristate 13-acetate and ionomycin was performed, followed by treatment with liposomal amphotericin B. CD4+ cells were identified as major cytokine-expressing cells, capable of producing both type 1 and type 2 cytokines. A high frequency of IL-4- and IL-13-expressing CD8+ cells was noted. NK cells and gammadelta+ T cells, thought to be involved in innate host defences against Leishmania, expressed IFN-gamma and TNF-alpha. Ten per cent of gammadelta+ T cells expressed IL-10, predominantly together with IFN-gamma, suggesting additional immune-regulatory roles for this T-cell subset in VL.

Amphotericin B↗
PubMed2003

In vitro activity and interaction of clindamycin combined with dihydroartemisinin against Plasmodium falciparum.

Combination regimens are considered a valuable tool for the fight against drug-resistant falciparum malaria. This study was conducted to evaluate the antimalarial potential of clindamycin in combination with dihydroartemisinin in continuously cultured and in freshly isolated Plasmodium falciparum parasites, measuring the inhibition of Plasmodium falciparum histidine-rich protein II synthesis. Interaction analysis revealed a synergistic or additive mode of interaction at various concentration ratios in all continuously cultured parasites at the 50% effective concentration (EC(50)) level. Antagonism was not found for any of the culture-adapted parasites. In fresh P. falciparum isolates, a fixed clindamycin-dihydroartemisinin combination exhibited additive activity at the EC(50) and EC(90) levels. The drug mixture showed no significant activity correlation to other commonly used antimalarials. The clindamycin-dihydroartemisinin combination appears to be a promising candidate for clinical investigation.

Animals↗
PubMed2003

Influence of changes of the wastewater composition on the applicability of UV-absorption measurements at combined sewer overflows.

The applicability of UV-absorption measurements at combined sewer overflows was investigated under different storm water conditions. Three specific rainfall events of different intensity, different duration and different intervals between the events were investigated. An individual evaluation of each single event resulted in an acceptable correlation between the UV absorption and the pollution measured as COD. A combined evaluation of the different events exhibited a very poor correlation which could not be used as pollution control parameter. Since the calibration procedure of the spectrometer used was not flexible enough to distinguish between different wastewater matrices from the different storm events the applicability of this type of spectrometer for the control of storm water overflows is questionable.

Adsorption↗
PubMed2003

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↗
PubMed2003

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↗
PubMed2003

Optimum aerobic volume control based on continuous in-line oxygen uptake monitoring.

Dynamic adaptation of the aerated volume to changing load conditions is essential to maximise the nitrogen removal performance and to minimise energy consumption. A control strategy is presented which provides optimum aerobic volume control (OAV-control concept) based on continuous in-line oxygen uptake monitoring. For ammonium concentrations below 1 mg/l the oxygen uptake rate shows a strong and almost linear dependency on the ammonium concentration. Therefore, the oxygen uptake rate is an ideal indicator for the nitrification performance in activated sludge systems. The OAV-control concept provides dynamic variation of the minimum aerobic volume required for complete nitrification and therefore maximises the denitrification performance. In-line oxygen uptake monitoring is carried out by controlling the oxygen concentration in a continuous aerated zone of the aeration tank and measuring the total air flow to the aeration tank. The total air flow to the aeration tank is directly proportional to the current oxygen uptake rate and can therefore be used as an indicator for the required aerobic volume. The instrumentation requirements for installation of the OAV-control are relatively low, oxygen sensors in the aeration tank and an on-line air flow measurement are needed. This enables individual control of aeration tanks operated in parallel at low investment costs. The OAV-control concept is installed at the WWTP Linz-Asten (1 Mio PE) and shows very good results. Full scale results are presented.

Air Movements↗
PubMed2002

Thoracoscopic fluorescence diagnosis (TFD) of pleural malignancies: experimental studies.

BACKGROUND: Fluorescence diagnosis (FD) using the photosensitiser 5-aminolaevulinic acid (ALA) was experimentally combined with conventional video assisted thoracic surgery (VATS) to improve tumour staging in advanced lung cancer with pleural tumour spread. METHODS: A disseminated pleural carcinosis affecting the entire pleural cavity was induced by inoculation of human adenocarcinoma cells in nude rats. After 5-7 weeks of tumour growth the animals were randomised into six groups with different photosensitisation parameters. Pleural lavage was performed either with 1.5% or 3.0% ALA solution. Photosensitisation times varied were 2, 4, or 6 hours. Conventional white light VATS was first performed to evaluate tumour growth in the pleural cavity. Fluorescence illumination of the light source, the D-light, was then used to examine the site for additional tumours which were previously invisible. The tumour fluorescence intensity was measured spectrometrically and compared with normal tissue. RESULTS: Compared with conventional white light VATS alone, thoracoscopic fluorescence diagnosis (TFD) detected up to 30% additional pleural malignant lesions. The highest diagnostic sensitivity was reached 6 hours after 3.0% ALA pleural lavage. Photosensitiser accumulation in the tumour, measured indirectly by spectrometry, was up to 11 times higher than in normal tissue. CONCLUSIONS: TFD increases sensitivity of VATS for tumour staging. It may prevent unnecessary thoracotomies in cancer patients and facilitate surgical planning.

Adenocarcinoma↗
PubMed2002

Serum thrombopoietin levels and anti-thrombopoietin antibodies in systemic lupus erythematosus.

Thrombocytopenia is a common phenomenon in patients suffering from systemic lupus erythematosus (SLE). The cause of thrombocytopenia in SLE, however, is poorly understood. In this study, 100 patients with SLE were evaluated for serum thrombopoietin levels, anti-thrombopoietin antibodies and routine laboratory parameters such as peripheral blood counts, parameters of blood chemistry and immunologic parameters of SLE. The median platelet count of SLE patients was 230 g/l and 19 were thrombocytopenic (range 8-148 g/l). Thrombopoietin levels in SLE patients were found to be significantly higher than in healthy controls (n = 96; median, 117 pg/ml vs 64 pg/ml, P < 0.01). When excluding thrombocytopenic SLE patients, thrombopoietin levels in SLE were still above controls (111 pg/ml, P < 0.01). The thrombopoietin levels were correlated to erythrocyte sedimentation rate and ECLAM score of disease activity, and inversely correlated to complement factor C4, but not to the platelet count. Anti-thrombopoietin antibody reactivity was found in 23% of SLE patients. Interestingly, these patients had lower platelet counts than SLE patients without anti-thrombopoietin antibodies (median 174 g/l and 253 g/l, respectively, P < 0.01), but thrombopoietin levels were not significantly different. Taken together, thrombopoietin levels are significantly higher in the sera of SLE patients than in healthy controls and anti-thrombopoietin antibodies are frequently found.

Adolescent↗
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

Two stage activated sludge plants--influence of different operational modes on sludge bulking and nitrification.

Conventional two stage activated sludge plants often lack sufficient nutrient removal performance due to substrate limitation for denitrification in the second stage. For the extension of the Vienna Main WWTP a two stage concept has been developed and tested by means of a pilot plant (scale 1:10.000). The new concept enables the operation of two different modes: In BYPASS-mode a portion of the primary clarifier effluent is fed directly to the second stage; the HYBRID-mode includes the exchange of mixed liquor between the two stages; over the course of the pilot plant investigations it turned out that nutrient removal is strongly increased in comparison to conventional two stage mode, but the two modes of operation lead to different results with regard to the sludge quality and the nitrification performance. BYPASS mode yields a higher SVI in both stages and a lower nitrification performance in comparison to HYBRID mode. This is caused by the negative influence of the primary effluent on the biocoenosis of the second stage. Additionally, the reduced sludge loading of the first stage in this mode results in a higher sludge age which favours the growth of filaments (Microthrix and Nocardia). In HYBRID-mode the higher load of the first stage results in a lower sludge age, fatty components are metabolized and incorporated in the sludge, thus, the growth of filaments is significantly reduced. Additionally, nitrification inhibiting substances are degraded in the first stage, which results in a higher nitrification performance in the second stage.

Actinobacteria↗
PubMed2002

Treatment of easily biodegradable wastewater avoiding bulking sludge.

The presence of easily degradable compounds from food industries frequently leads to bulking problems. The paper describes a new process that has been developed for a dairy in Austria. Because of the increase in production the treatment plant receiving the wastewater up to now was not able to handle the increased loads. Therefore detailed studies for treatment alternatives have been undertaken which led to a completely new concept. The excess sludge of the urban treatment plant is contacted with the concentrated dairy waste in a separate contact tank. In this tank the easily degradable substrate from the industrial waste is mainly adsorbed to the biological sludge and after a mechanical dewatering transferred to the anaerobic digester where it yields an increased gas production. The filtrate of the dewatering process is completely free from biodegradable material and can without danger of bulking be fed to the aeration tank. The process has been in operation for more than one year and has fulfilled all expectations.

Adsorption↗
PubMed2001

Photosynthetic water oxidation in Synechocystis sp. PCC6803: mutations D1-E189K, R and Q are without influence on electron transfer at the donor side of photosystem II.

The oxygen-evolving manganese cluster (OEC) of photosynthesis is oxidised by the photochemically generated primary oxidant (P(+*)(680)) of photosystem II via a tyrosine residue (Y(Z), Tyr161 on the D1 subunit of Synechocystis sp. PCC6803). The redox span between these components is rather small and probably tuned by protonic equilibria. The very efficient electron transfer from Y(Z) to P(+*)(680) in nanoseconds requires the intactness of a hydrogen bonded network involving Y(Z), D1-His190, and presumably D1-Glu189. We studied photosystem II core particles from photoautotrophic mutants where the residue D1-E189 was replaced by glutamine, arginine and lysine which were expected to electrostatically differ from the glutamate in the wild-type (WT). Surprisingly, the rates of electron transfer from Y(Z) to P(+*)(680) as well as from the OEC to Y(ox)(Z) were the same as in the WT. With the generally assumed proximity between D1-His190 (and thus D1-Glu189) and Y(Z), the lack of any influence on the electron transfer around Y(Z) straightforwardly implies a strongly hydrophobic environment forcing Glu (acid) and Lys, Arg (basic) at position D1-189 into electro-neutrality. As one alternative, D1-Glu189 could be located at such a large distance from the OEC, Y(Z) and P(+*)(680) that a charge on D1-189X does not influence the electron transfer. This seems less likely in the light of the drastic influence of its direct neighbour, D1-His190, on Y(Z) function. Another alternative is that D1-Glu189 is negatively charged, but is located in a cluster of acid/base groups that compensates for an alteration of charge at position 189, leaving the overall net charge unchanged in the Gln, Lys, and Arg mutants.

Cyanobacteria↗
PubMed2001

F-ATPase: forced full rotation of the rotor despite covalent cross-link with the stator.

In ATP synthase (F(O)F(1)-ATPase) ion flow through the membrane-intrinsic portion, F(O), drives the central "rotor", subunits c(10)epsilongamma, relative to the "stator" ab(2)delta(alphabeta)(3). This converts ADP and P(i) into ATP. Vice versa, ATP hydrolysis drives the rotation backwards. Covalent cross-links between rotor and stator subunits have been shown to inhibit these activities. Aiming at the rotary compliance of subunit gamma we introduced disulfide bridges between gamma (rotor) and alpha or beta (stator). We engineered cysteine residues into positions located roughly at the "top," "center," and "bottom" parts of the coiled-coil portion of gamma and suitable residues on alpha or beta. This part of gamma is located at the center of the (alphabeta)(3) domain with its C-terminal part at the top of F(1) and the bottom part close to the F(O) complex. Disulfide bridge formation under oxidizing conditions was quantitative as shown by SDS-polyacrylamide gel electrophoresis and immunoblotting. As expected both the ATPase activities and the yield of rotating subunits gamma dropped to zero when the cross-link was formed at the center (gammaL262C <--> alphaA334C) and bottom (gammaCys(87) <--> betaD380C) positions. But much to our surprise disulfide bridging impaired neither ATP hydrolysis activity nor the full rotation of gamma and the enzyme-generated torque of oxidized F(1), which had been engineered at the top position (gammaA285C <--> alphaP280C). Apparently the high torque of this rotary engine uncoiled the alpha-helix and forced amino acids at the C-terminal portion of gamma into full rotation around their dihedral (Ramachandran) angles. This conclusion was supported by molecular dynamics simulations: If gammaCys(285)-Val(286) are attached covalently to (alphabeta)(3) and gammaAla(1)-Ser(281) is forced to rotate, gammaGly(282)-Ala(284) can serve as cardan shaft.

Adenosine Triphosphate↗
PubMed2001

CD45 tyrosine phosphatase controls common gamma-chain cytokine-mediated STAT and extracellular signal-related kinase phosphorylation in activated human lymphoblasts: inhibition of proliferation without induction of apoptosis.

The objective of this study was to test whether CD45 signals can influence signaling processes in activated human lymphoblasts. To this end, we generated lymphoblasts which proliferate in response to common gamma-chain cytokines, but readily undergo apoptosis after cytokine withdrawal. In experiments with the CD45R0 mAb UCHL-1, but not control CD45 mAbs, we found significant inhibition of proliferation. Interestingly, the pan-CD45 mAb GAP8.3, which is most effective in inhibition of OKT-3-mediated proliferation in quiescent lymphocytes, was ineffective in lymphoblasts. Addition of CD3 mAb OKT-3 had no influence on IL-2-mediated proliferation (with or without UCHL-1). In contrast, after addition of OKT-3 to IL-4- and IL-7-stimulated proliferation assays, UCHL-1 signals could not significantly alter cellular proliferation. We did not find induction of apoptosis following CD45R0 signaling. In Western blots using mAbs detecting phosphorylated STAT-3, STAT-5, STAT-6, or extracellular signal-related kinase 1/2, we found that CD45R0 signaling could effectively diminish phosphorylation of these intracellular signaling components. Using RT-PCR, we found that CD45R0 signaling inhibited IL-2 mRNA production without major influence on IL-13, IL-5, or IFN-gamma mRNA levels. Costimulation with OKT-3 and IL-2 optimally induced secretion of IFN-gamma, TNF-alpha, and IL-5, which was not decreased by CD45 signals. In conclusion, we illustrate that CD45R0 signals control early cytokine receptor-associated signaling processes and mRNA and DNA synthesis in activated human lymphoblasts. Furthermore, we show the existence of CD45 epitopes (GAP8.3), which are active and critical for signaling in quiescent lymphocytes, but are nonfunctional in activated human lymphoblasts.

Apoptosis↗
PubMed2001

Declining chloroquine resistance of Plasmodium falciparum in Lambaréné, Gabon from 1992 to 1998.

Plasmodium falciparum malaria continues to threaten human populations in the tropics and travellers in endemic areas. Drug resistance of the parasite is a major problem in treating this devastating disease. In a prospective trial we investigated the in vitro sensitivity of Plasmodium falciparum to chloroquine, quinine and mefloquine in the Albert Schweitzer Hospital in Lambaréné, Gabon every second year from 1992 to 1998. We used the standard WHO in vitro sensitivity assay. Parasite sensitivity to quinine and mefloquine remained stable over the years. However, parasite resistance to chloroquine decreased highly significantly with the change in local malaria treatment policy. In 1992, 100% of parasite isolates showed resistance to chloroquine, whereas in 1998 only 45% were found resistant.

Animals↗
PubMed2001

Decreased serum erythropoietin and its relation to anti-erythropoietin antibodies in anaemia of systemic lupus erythematosus.

OBJECTIVE: This study was performed to assess erythropoietin levels and anti-erythropoietin antibodies in patients with systemic lupus erythematosus (SLE). METHODS: The sera of 100 patients with SLE were investigated for serum erythropoietin levels and the presence of anti-erythropoietin antibodies by ELISA. Routine laboratory parameters such as peripheral blood count, relevant parameters of blood chemistry, and immunological parameters of SLE were recorded. RESULTS: Erythropoietin levels were significantly decreased in SLE patients when related to individual haemoglobin and haematocrit values (P<0.001), suggesting an inadequate erythropoietin response in SLE. Anti-erythropoietin antibodies were found in 46% of SLE patients, and erythropoietin levels (but not haemoglobin or haematocrit values) were significantly decreased in these patients compared with patients without anti-erythropoietin antibodies. Serum erythropoietin concentration as determined by ELISA was reduced in the presence of anti-erythropoietin antibodies. Furthermore, anti-erythropoietin antibodies also correlated with younger age, decreased serum levels of complement factors C3 and C4 and elevated anti-double-stranded DNA antibodies. CONCLUSIONS: We conclude that the anaemia of SLE is characterized by an inadequate erythropoietin response. Anti-erythropoietin antibodies are frequently present in SLE and interfere with the measurement of serum erythropoietin level. However, these antibodies are not associated with increased severity of SLE-associated anaemia.

Adolescent↗
PubMed2001

Molecular characterization of Bombyx mori cytoplasmic polyhedrosis virus genome segment 4.

The complete nucleotide sequence of the genome segment 4 (S4) of Bombyx mori cytoplasmic polyhedrosis virus (BmCPV) was determined. The 3,259-nucleotide sequence contains a single long open reading frame which spans nucleotides 14 to 3187 and which is predicted to encode a protein with a molecular mass of about 130 kDa. Western blot analysis showed that S4 encodes BmCPV protein VP3, which is one of the outer components of the BmCPV virion. Sequence analysis of the deduced amino acid sequence of BmCPV VP3 revealed possible sequence homology with proteins from rice ragged stunt virus (RRSV) S2, Nilaparvata lugens reovirus S4, and Fiji disease fijivirus S4. This may suggest that plant reoviruses originated from insect viruses and that RRSV emerged more recently than other plant reoviruses. A chimeric protein consisting of BmCPV VP3 and green fluorescent protein (GFP) was constructed and expressed with BmCPV polyhedrin using a baculovirus expression vector. The VP3-GFP chimera was incorporated into BmCPV polyhedra and released under alkaline conditions. The results indicate that specific interactions occur between BmCPV polyhedrin and VP3 which might facilitate BmCPV virion occlusion into the polyhedra.

Amino Acid Sequence↗