Biomedical subjects

Michael Kersten

Publications and source records attributed to Michael Kersten.

7 recordsLinked to original sources

PubMed2005

Storm disturbance of sediment contaminants at a hot-spot in the Baltic Sea assessed by 234Th radionuclide tracer profiles.

Fly ash sludges from an abandoned metal smelter were dumped into the shallow inner part of the Mecklenburg Bay until 1971, representing the most severe heavy metal contamination hot-spot along the German coast. Half of the dumped Zn (455 t) and Pb (173 t) inventory was found to be spread from the originally 0.5 km2 hot-spot site to a now 360 km2 affected adjacent area. Wave-driven resuspension during gale events produced large pulses of contaminated sediments from this hot-spot due to the only 23 m water depth. Instantaneous sediment mixing down to 10 cm occurs during such a wave event as evidenced by activity profiles of the short-lived radionuclide 234Th in sediment cores. According to these estimated sediment exchange fluxes in the transport bottom area, each wave event may have mobilized Zn and Pb pulses on the order of several hundreds of kilograms from the dump site, sufficient to build up a plume in sediments of the outer bay area. With each centimeter (approximately 5 yr) of additional natural sediment capping, however, the amount of metal remobilization would decrease by about 50%.

Environmental Monitoring↗

PubMed2005

Identification of fatty acid binding proteins as markers associated with the initiation and/or progression of renal cell carcinoma.

Renal cell carcinoma (RCC) representing the most common neoplasia of the kidney in Western countries is a histologic diverse disease with an often unpredictable course. The prognosis of RCC is worsened with the onset of metastasis, and the therapies currently available are of limited success for the treatment of metastatic RCC. Although gene expression analyses and other methods are promising tools clarifying and standardizing the pathological classification of RCC, novel innovative molecular markers for the diagnosis, prognosis, and for the monitoring of this disease during therapy as well as potential therapeutic targets are urgently needed. Using proteome-based strategies, a number of RCC-associated markers either over-expressed or down-regulated in tumor lesions in comparison to the normal epithelium have been identified which have been implicated in tumorigenesis, but never linked to the initiation and/or progression of RCC. These include members of the fatty acid binding protein family, which have the potential to serve as diagnostic or prognostic markers for the screening of RCC patients.

Biomarkers, Tumor↗

PubMed2004

Ecotoxicity assessment of natural attenuation effects at a historical dumping site in the western Baltic Sea.

During the late 1950s and early 1960s of the past century, industrial waste material highly enriched in various contaminants (heavy metals, PAHs) was dumped in the inner Mecklenburg Bay, western Baltic Sea. Large-scale shifts in the spatial distribution of heavy metals in surface sediments were mapped by geochemical monitoring in the mid-1980s and 12 years later in 1997. A further study in 2001 was designed to investigate the small-scale spatial distribution of contaminants inside, on top of, and around the historical dumping ground and to examine possible effects to benthic organisms (Arctica islandica, microbiological toxicity tests). The site is located within an area characterized by a discontinuous deposition of fine sediments, but net sedimentation rate of about 3mm/y led ultimately to a gradual coverage of the dumped material. During the first decades after the dumping, about half of the originally dumped material was already spread over the surrounding area as a result of sediment dynamics and re-suspension processes. Recent sediments of the historical dump site are still significantly enriched in heavy metals and PAHs. Microbiological toxicity test results were positive, though uptake of contaminants in mussels was found to deviate only slightly from that of a non-contaminated reference station due to a gradual dilution and decrease in bioavailability of the contaminants.

Animals↗

PubMed2004

Three-dimensional trace element analysis by confocal X-ray microfluorescence imaging.

A three-dimensional (3D) variant of scanning micro X-ray fluorescence (XRF) is described and evaluated at the ID18F instrument of the European Synchrotron Radiation Facility (ESRF). The method is based on confocal excitation/detection using a polycapillary half-lens in front of the energy-dispersive detector. The experimental arrangement represents a significant generalization of regular two-dimensional (2D) scanning micro-XRF and employs a detector half-lens whose focus coincides with that of the focused incoming beam. The detection volume defined by the intersection of the exciting beam and the energy-dependent acceptance of the polycapillary optics is 100-350 mum(3). Minimum detection limits are sub-ppm, and sensitivities are comparable with regular scanning XRF. Next to the reduction of in-sample single/multiple scattering, the setup provides the possibility of sample depth scans with an energy-dependent resolution of 10-35 mum in the energy range of 3-23 keV and the possibility of performing 3D-XRF analysis by simple XYZ linear scanning. This provides a suitable alternative to X-ray fluorescence tomography. The method is illustrated with results of the analysis of solid inclusions in diamond and fluid inclusions in quartz.

Journal Article↗

PubMed2004

The subunit b dimer of the FOF1-ATP synthase: interaction with F1-ATPase as deduced by site-specific spin-labeling.

We have used site-specific spin-labeling of single cysteine mutations within a water-soluble mutant of subunit b of the ATP synthase and employed electron spin resonance (ESR) spectroscopy to obtain information about the binding interactions of the b dimer with F1-ATPase. Interaction of b2 with a delta-depleted F1 (F1-delta) was also studied. The cysteine mutations used for spin-labeling were distributed throughout the cytosolic domain of the b subunit. In addition, each position between residues 101 and 114 of b was individually mutated to cysteine. All mutants were modified with a cysteine-reactive spin label. The room temperature ESR spectra of spin-labeled b2 in the presence of F1 or F1-delta when compared with the spectra of free b2 indicate a tight binding interaction between b2 and F1. The data suggest that b2 packs tightly to F1 between residues 80 and the C terminus but that there are segments of b2 within that region where packing interactions are quite loose. Two-dimensional gel electrophoresis confirmed binding of the modified b mutants to F1-ATPase as well as to F1-delta. Subsequent addition of delta to F1-delta.b2 complex resulted in changes in the ESR spectra, indicating different binding interactions of b to F1 in the presence or absence of delta. The data also suggest that the reconstitution of the ATP synthase is not ordered with respect to these subunits. Additional spectral components observed in b preparations that were spin-labeled between amino acid position 101 and 114 are indicative of either two populations of b subunits with different packing interactions or to helical bending within this region.

Adenosine Triphosphatases↗

PubMed2003

Identification of markers for the selection of patients undergoing renal cell carcinoma-specific immunotherapy.

Renal cell carcinoma (RCC) represents the most common malignant tumor in the kidney and is resistant to conventional therapies. The diagnosis of RCC is often delayed leading to progression and metastatic spread of the disease. Thus, validated markers for the early detection of the disease as well as selection of patients undergoing specific therapy is urgently needed. Using treatment with the monoclonal antibody (mAb) G250 as a model, proteome-based strategies were implemented for the identification of markers which may allow the discrimination between responders and nonresponders prior to application of G250-mediated immunotherapy. Flow cytometry revealed G250 surface expression in approximately 40% of RCC cell lines, but not in the normal kidney epithelium cell lines. G250 expression levels significantly varied thereby distinguishing between low, medium and high G250 expressing cell lines. Comparisons of two-dimensional gel electrophoresis expression profiles of untreated RCC cell lines versus RCC cell lines treated with a mAb directed against G250 and the characterization of differentially expressed proteins by mass spectrometry and/or Edman sequencing led to the identification of proteins such as chaperones, antigen processing components, transporters, metabolic enzymes, cytoskeletal proteins and unknown proteins. Moreover, some of these differentially expressed proteins matched with immunoreactive proteins previously identified by proteome analysis combined with immunoblotting using sera from healthy donors and RCC patients, a technique called PROTEOMEX. Immunohistochemical analysis of a panel of surgically removed RCC lesions and corresponding normal kidney epithelium confirmed the heterogeneous expression pattern found by proteome-based technologies. In conclusion, conventional proteome analysis as well as PROTEOMEX could be successfully employed for the identification of markers which may allow the selection of patients prior to specific immunotherapy.

Antibodies, Monoclonal↗

PubMed2002

Aqueous solubility diagrams for cementitious waste stabilization systems. 4. A carbonation model for Zn-doped calcium silicate hydrate by Gibbs energy minimization.

A thermodynamic Gibbs energy minimization (GEM) solid solution-aqueous solution (SSAS) equilibrium model was used to determine the solubility of Zn from calcium silicate hydrate (CSH) phases doped with 0, 0.1, 1, 5, and 10% Zn at a unity (Ca+Zn)/Si molar ratio. Both the stoichiometry and standard molar Gibbs energy (G(o)298) of the Zn-bearing end-member in the ideal ternary Zn-bearing calcium silicate hydrate (CZSH) solid solution were determined by a "dual-thermodynamic" (GEM-DT) estimation technique. The SSAS model reproduces a complex sequence of reactions suggested to occur in a long-term weathering scenario of cementitious waste forms at subsurface repository conditions. The GEM model of CZSH leaching at several Zn loadings and solid/water (s/w) ratios in a C02-free system showed that, upon complete dissolution of portlandite and calcium zincate phases at decreasing s/w < 0.01 mol x kg(H2O)(-1), the total dissolved concentrations Si(aq), Ca(aq), and Zn(aq) are controlled by a CZSH solid solution of changing composition, with a trough-like Znaq drop by 2-3 orders of magnitude. Carbonation was simulated in another GEM model run series by CO2 titration of the system with initial s/w approximately 0.9 mol/kg(H2O). Formation of (Ca,Zn)-CO3 nonideal solid solution was predicted already at early reaction stage in the presence of both portlandite and calcium zincate hydrate phases. Upon their disappearance, pH, Zn(aq), C(aq), and fCO2 were predicted to change due to the incongruent dissolution of two concurrent CZSH-I and CZSH-II solid solutions, until the total re-partitioning of Ca and Zn into a carbonate solid solution coexisting with amorphous silica at fCO2 > 0.1 bar. Along this solid-phase transition, dissolved Zn(aq) concentrations follow a highly nonlinear trend. The model results predict that at low to moderate Zn loading (< or = 1% per mole Si), CZSH-type compounds can efficiently immobilize Zn in the near field of a cement-stabilized waste repository.

Calcium Compounds↗