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Biomedical subjects

G Schwarz

Publications and source records attributed to G Schwarz.

At least 37 records · Page 2Linked to original sources
PubMed2001

Airborne surveys of Swiss nuclear facility sites.

Annually since 1989, biannually since 1994, the environs (approximately 50 km2) of the Swiss nuclear facilities are surveyed (by helicopters) flying the same survey lines. The equipment and the data processing software used for these surveys were built and developed at the Institute of Geophysics, ETH Zurich. For mapping of man-made radiation at or around nuclear facility sites a pixel representation and the MMGC (man-made gross count) ratio is used. So far no artificial radioactivity that could not be explained by the Chernobyl event (1986) or by earlier nuclear weapon tests was detected outside the fenced sites of the nuclear facilities.

Air Pollution, Radioactive↗
PubMed2001

Effects of QiGong on brain function.

QiGong is an ancient and widely practiced Chinese meditation exercise. We studied the effects of QiGong on brain function with modern neuromonitoring tools in two subjects. In a male QiGong master (extremely trained practitioner), the technique induced reproducible changes in transcranial Doppler sonography, EEG, stimulus-induced 40 Hz oscillations, and near-infrared spectroscopy findings. Similar effects were seen after the application of multimodal stimuli and when the master concentrated on intense imagined stimuli (e.g. 22.2% increase in mean blood flow velocity (vm) in the posterior cerebral artery, and a simultaneous 23.1% decrease of vm in the middle cerebral artery). Similar effects were seen in the female subject. Neuromonitoring during QiGong appears able to objectify accompanied cerebral modulations surrounding this old Chinese meditation exercise.

Acoustic Stimulation↗
PubMed2001

Interleukin 16 expression in relation to disease activity in rheumatoid arthritis.

OBJECTIVE: Rheumatoid arthritis (RA) is a chronic inflammatory disease of unknown etiology characterized by an infiltration of CD4+ T lymphocytes within the rheumatoid synovium. Cytokines have been shown to play a modulatory role in the pathogenesis of RA. We analyzed the expression of a T cell derived cytokine. interleukin 16 (IL-16), in relation to disease activity to characterize its biologic function in RA. METHODS: Secreted IL-16 was measured by enzyme immunoassay in sera and synovial fluids (SF) from 25 patients with RA in comparison to 20 control samples from patients with osteoarthritis (OA). IL-16 expression in peripheral blood mononuclear cells (PBMC) was characterized by flow cytometric analysis after intracellular cytokine staining for IL-16. In synovial tissue specimens, IL-16 mRNA expression was analyzed by real-time quantitative reverse transcriptase polymerase chain reaction (RT-PCR). In parallel, expression of IL-16 was localized in synovial tissues by in situ hybridization and immunohistochemistry. Results were analyzed in relation to disease activity. RESULTS: IL-16 was detected at significantly higher levels in sera and SF of patients with RA in comparison to OA (p < 0.001). Flow cytometry of PBMC showed that a great proportion of both CD4+ and CD8+ T cells constitutively expressed the IL-16 protein. In synovial tissues, IL-16 mRNA levels were significantly elevated in comparison to OA controls (p < 0.001). In situ hybridization for IL-16 producing cells revealed a predominant accumulation of IL- 16 positive cells within the inflammatory infiltrates. A significant correlation between IL- 16 expression and local inflammatory activity could not be established (r = 0.27, p = 0.19) by microscopic analysis of the synovial cell infiltrate. In addition, no significant association was observed between serum, SF, and synovial tissue expression of IL-16 and clinical disease activity in RA. CONCLUSION: These data suggest IL-16 might play a role in the pathogenesis of chronic inflammation in RA. The lack of significant correlation between IL-16 expression, clinical disease activity, and local inflammatory activity suggests a regulatory rather than a proinflammatory function for IL-16 in the pathogenesis of chronic synovial inflammation in RA.

Adult↗
PubMed2000

A mutation in the gene for the neurotransmitter receptor-clustering protein gephyrin causes a novel form of molybdenum cofactor deficiency.

Gephyrin was originally identified as a membrane-associated protein that is essential for the postsynaptic localization of receptors for the neurotransmitters glycine and GABA(A). A sequence comparison revealed homologies between gephyrin and proteins necessary for the biosynthesis of the universal molybdenum cofactor (MoCo). Because gephyrin expression can rescue a MoCo-deficient mutation in bacteria, plants, and a murine cell line, it became clear that gephyrin also plays a role in MoCo biosynthesis. Human MoCo deficiency is a fatal disease resulting in severe neurological damage and death in early childhood. Most patients harbor MOCS1 mutations, which prohibit formation of a precursor, or carry MOCS2 mutations, which abrogate precursor conversion to molybdopterin. The present report describes the identification of a gephyrin gene (GEPH) deletion in a patient with symptoms typical of MoCo deficiency. Biochemical studies of the patient's fibroblasts demonstrate that gephyrin catalyzes the insertion of molybdenum into molybdopterin and suggest that this novel form of MoCo deficiency might be curable by molybdate supplementation.

Base Sequence↗
PubMed2000

Structure of a fusion peptide analogue at the air-water interface, determined from surface activity, infrared spectroscopy and scanning force microscopy.

We have investigated a point mutant of the HIV-1 fusion peptide in a compressed monolayer at the air-water interface. A variety of surface sensitive techniques were applied to study structural features under conditions mimicking the hydrophobic/hydrophilic environment of a biomembrane. Possible partitioning into the aqueous bulk phase and molecular areas were examined by surface activity based mass conservation plots. This shows that the peptide is practically fully accumulated in the interface. Secondary structure and orientation was analyzed by means of polarized infrared reflectivity. Brewster angle microscopy and scanning force microscopy contributed nanostructural images. At low surface pressures the molecules form anti-parallel beta-sheets lying flat on the interface. Upon a moderate increase of the lateral pressure a flat beta-turn structure appears with inter- and intramolecular H-bonds. We also observed aggregates forming fingerprint-like structures with a diameter of approximately double the hydrophobic length of a beta-turn conformation. Beyond approximately 18 mN m(-1) the beta-turns straighten up. The lowest measured tilt angle was 45 degrees at 36 mN m(-1).

Air↗
PubMed2000

A universal thermodynamic approach to analyze biomolecular binding experiments.

Binding processes of any kind can be characterized as an association of a given ligand with some binding factor. This includes macromolecules as well as supramolecular aggregates such as micelles or membranes. The underlying molecular binding mechanism may be more or less complicated due to various intermediate steps (involving for instance conformational changes, aggregation, cooperativity, etc.). A sensible discussion of possible binding models naturally calls for a model-independent access to basic thermodynamic properties. The present contribution will demonstrate how this can quite generally be accomplished by a pertinent processing of properly selected experimental data. The method requires a series of titration measurements comprising the use of variable amounts of both the ligand and the binding factor. It leads to a linear mass conservation plot (i.e. amount of the ligand vs. a matching amount of the binding factor) whose slope and ordinate intercept are equal to the binding ratio (i.e. bound ligand per binding factor) and the free ligand concentration, respectively. This establishes the specific binding isotherm. The approach also reveals latent structurally determined features of the applied physical measuring signal. A number of examples including specific binding, unspecific adsorption and insertion in two-dimensional molecular films will illustrate the methodology.

Alamethicin↗
PubMed2000

Symmetric versus nonsymmetric structure of the phosphorus vacancy on InP(110).

The atomic and electronic structure of positively charged P vacancies on InP(110) surfaces is determined by combining scanning tunneling microscopy, photoelectron spectroscopy, and density-functional theory calculations. The vacancy exhibits a nonsymmetric rebonded atomic configuration with a charge transfer level 0.75+/-0.1 eV above the valence band maximum. The scanning tunneling microscopy (STM) images show only a time average of two degenerate geometries, due to a thermal flip motion between the mirror configurations. This leads to an apparently symmetric STM image, although the ground state atomic structure is nonsymmetric.

Journal Article↗
PubMed2000

Mutations in the molybdenum cofactor biosynthetic protein Cnx1G from Arabidopsis thaliana define functions for molybdopterin binding, molybdenum insertion, and molybdenum cofactor stabilization.

The molybdenum cofactor (Moco), a highly conserved pterin compound coordinating molybdenum (Mo), is required for the enzymatic activities of molybdoenzymes. In all organisms studied so far Moco is synthesized by a unique and evolutionary old multistep pathway that requires the activities of at least six gene products. In eukaryotes, the last step of Moco synthesis, i.e., transfer and insertion of Mo into molybdopterin (MPT), is catalyzed by the two-domain proteins Cnx1 in plants and gephyrin in mammals. Both domains (E and G) of these proteins are able to bind MPT in vitro. Here, we show the identification and mutational dissection of functionally important regions within the Cnx1 G domain that are essential for MPT binding, the conversion of MPT to Moco, and Moco stabilization. By functional screening for mutants in the Cnx1 G domain that are no longer able to complement Escherichia coli mogA mutants, we found two classes of mutations in highly conserved amino acid residues. (i) The first class affects in vitro binding of MPT to the protein and the stabilization of Moco, the product of the G domain. (ii) The second class is represented by two independent mutations in the aspartate 515 position that is not affected in MPT binding and Moco stabilization; rather the conversion of MPT to Moco by using bound MPT and a yet unknown form of Mo is completely abolished. The results presented here provide biochemical evidence for a purified Cnx1 G domain catalyzing the insertion of Mo into MPT.

Amino Acid Sequence↗
PubMed2000

Sulfite:Cytochrome c oxidoreductase from Thiobacillus novellus. Purification, characterization, and molecular biology of a heterodimeric member of the sulfite oxidase family.

Direct oxidation of sulfite to sulfate occurs in various photo- and chemotrophic sulfur oxidizing microorganisms as the final step in the oxidation of reduced sulfur compounds and is catalyzed by sulfite:cytochrome c oxidoreductase (EC ). Here we show that the enzyme from Thiobacillus novellus is a periplasmically located alphabeta heterodimer, consisting of a 40.6-kDa subunit containing a molybdenum cofactor and an 8.8-kDa mono-heme cytochrome c(552) subunit (midpoint redox potential, E(m8.0) = +280 mV). The organic component of the molybdenum cofactor was identified as molybdopterin contained in a 1:1 ratio to the Mo content of the enzyme. Electron paramagnetic resonance spectroscopy revealed the presence of a sulfite-inducible Mo(V) signal characteristic of sulfite:acceptor oxidoreductases. However, pH-dependent changes in the electron paramagnetic resonance signal were not detected. Kinetic studies showed that the enzyme exhibits a ping-pong mechanism involving two reactive sites. K(m) values for sulfite and cytochrome c(550) were determined to be 27 and 4 micrometer, respectively; the enzyme was found to be reversibly inhibited by sulfate and various buffer ions. The sorAB genes, which encode the enzyme, appear to form an operon, which is preceded by a putative extracytoplasmic function-type promoter and contains a hairpin loop termination structure downstream of sorB. While SorA exhibits significant similarities to known sequences of eukaryotic and bacterial sulfite:acceptor oxidoreductases, SorB does not appear to be closely related to any known c-type cytochromes.

Amino Acid Sequence↗
PubMed2000

[Calciphylaxis: ischemic tissue necrosis in chronic renal failure. Case report and review of the literature].

Calciphylaxis is a rare but potentially life-threatening complication in chronic renal failure. It is characterized by ischemic tissue necrosis primarily of the skin. The typical histopathologic finding is microvascular calcification with endovascular fibrosis. Patients typically present with violaceous, mottled and painful lesions which tend to progress to non-healing ulcers and necrosis. Most frequently the lower extremities are involved in a symmetric fashion but the trunk may also be affected. Sepsis from superinfection of the lesions accounts for the high mortality of this disease which is of importance for dermatologists and nephrologists alike. 61-year-old female patient developed lesions of calciphylaxis on both calves two years after beginning hemodialysis to treat renal failure due to diabetic glomerulosclerosis. We discuss aspects of the pathogenesis of calciphylaxis, as well as diagnosis, treatment and means of prevention, and review the current literature.

Biopsy↗
PubMed2000

Characterization of steroid hormone sensitivity in human breast cancers maintained ex vivo under organotypical culture conditions.

PURPOSE: The methodology we propose combines the immunohistochemical determination of the oestrogen and progesterone receptors (ER and PgR) with the characterization of the oestradiol- and progesterone-induced influence on cell proliferation in breast cancers in order to characterize their steroid hormone sensitivity at both the "static" and "dynamic" level. METHODS: ER and PgR have been immunohistochemically quantified by means of computer-assisted microscopy. Cell proliferation has been determined by means of tritiated thymidine autoradiography in tumour samples maintained in vitro as organotypic cultures. A series of 14 patients was investigated. RESULTS: Of the 14 breast cancers under study, one with an unequivocally "very ER-rich"/"very PgR-rich" immunohistochemical phenotype totally failed to exhibit any modification in its cell proliferation level after both oestradiol and progesterone stimulation. Two cases definitively associated with an "ER-poor"/"PgR-poor" immunohistochemical phenotype nevertheless responded noticeably to the dynamic stimulation of their cell proliferation by oestradiol and progesterone. While our series of cases covers 14 patients only, it suffices to demonstrate the limits of ER and PgR determination in characterizing steroid hormone sensitivity in breast cancer. DISCUSSION: The present work therefore presents an in vitro approach to test growth regulation of human breast cancer by steroid hormones. The clinical value of the present approach should be further determined by showing that steroid hormone-induced modifications in cell proliferation level are actually associated with clinical response.

Aged↗
PubMed2000

Equations of state for POPX lipids at the air/water interface. A comprehensive study.

We have investigated monomolecular fluid-like films of palmitoyl oleoylphosphatidyl lipids with choline, glycerol and serine head groups, respectively. Conventional Langmuir trough experiments have been evaluated towards a thermodynamic analysis applying a novel approach that was recently developed in this laboratory. Our work involves elaborate efforts to exclude possible error sources of the basic measuring parameters. By means of pertinent mass conservation plots it could then be shown that the present lipids form a practically insoluble monolayer. Relative deviations of the lateral pressure from its ideal (gaseous) value are seen to be a very pronounced linear function of the surface concentration (between 1 and about 35 mN/m). They reveal a clearly manifested Boyle point around 4 mN/m, indicating formation of aggregates in the very low pressure range. The results are discussed in terms of a rather simple quantitative formulation of the underlying equation of state including fit curves of the related partial molecular area and Gibbs free energy.

Phosphatidylcholines↗
PubMed2000

Two new proteases in the MHC class I processing pathway.

The proteasome generates exact major histocompatibility complex (MHC) class I ligands as well as NH2-terminal-extended precursor peptides. The proteases responsible for the final NH2-terminal trimming of the precursor peptides had, until now, not been determined. By using specific selective criteria we purified two cytosolic proteolytic activities, puromycin-sensitive aminopeptidase and bleomycin hydrolase. These proteases could remove NH2-terminal amino acids from the vesicular stomatitis virus nucleoprotein cytotoxic T cell epitope 52-59 (RGYVYQGL) resulting, in combination with proteasomes, in the generation of the correct epitope. Our data provide evidence for the existence of redundant systems acting downstream of the proteasome in the antigen-processing pathway for MHC class I molecules.

Amino Acid Chloromethyl Ketones↗
PubMed2000

Economic investigation of the use of three-compartment total parenteral nutrition bag: prospective randomized unblinded controlled study.

Optimal strategy for total parenteral nutrition (TPN) administration is essential both in terms of clinical effectiveness and economic efficiency. The aim of the present economic analysis was to provide a systematic and comprehensive cost comparison of the application of three currently available TPN systems: Separate Bottles (SB), Hospital-Compounded Bags (HCB) and Three-Compartment Bags (TCB). Sixty patients, admitted to the Geneva University Hospital and requiring TPN, were randomly assigned to one of the three systems. Three standard TPN formulas were prescribed to meet the patients' protein energy needs. TPN-related activities of medical, nursing and pharmacy staff were timed for the 24 hours of TPN administration. Manpower, nutrient solutions and medical supplies costs were calculated on the basis of mean Swiss salaries and hospital prices. TCB was the least expensive TPN system. SB and HCB systems' application costs were 120 and 150% of TCB cost, respectively. All intersystems cost comparisons were statistically significant (ANOVA p < or = 0.01). SB system required more items and manipulations, resulting in higher nurses manpower cost. Pharmacy overhead cost due to compounding was responsible for the higher cost of HCB system. Detailed manpower data presented in this study allow for an estimation of TPN application costs in other hospitals, using local salaries, specific product prices and compounding costs.

Cost-Benefit Analysis↗
PubMed2000

The influence of positioning on spectroscopic measurements of brain oxygenation.

This study was designed to evaluate the influence of body position during neurosurgical and cerebrovascular operations on regional cerebral oxygen saturation (rSO2). Awake volunteers (group I; n = 14), anesthetized patients (group II; n = 48) undergoing lumbar discectomy, and 12 patients undergoing carotid endarterectomy (group III) with internal carotid artery (ICA) stenosis were studied. Anesthesia in the patient groups was performed with sevoflurane (1.1 Vol% insp.) in N2O2/O2 mixture (FiO2 0.4) rSO2 was monitored with a INVOS 4100 cerebral oxymeter (Somanetics Corporation, Troy, MI). Measurements were done in all groups in supine position with head turned to the right and left side. Furthermore, in groups I and II, rSO2 was measured in right lateral, left lateral, prone, or sitting position. In each position the parameters were registered at three times (1, 3, and 5 min after taking up the position). In the healthy volunteers, the mean rSO2 values of both hemispheres were 71.3 +/- 5.0%. No significant changes of rSO2 were found interhemispherical and upon turning the head to both sides or positioning to the prone and both lateral positions. After assuming the sitting position, the decrease of rSO2 was not significant. In group II, rSO2 decreased significantly in the sitting position. In group III, baseline readings for rSO2 obtained from the side of ICA stenosis were significantly lower, compared to the contralateral side. After turning the head to the ipsilateral side, this difference diminished. In contrast, turning the head toward the contralateral side, the rSO2 difference remained nearly constant, both values decreasing constantly throughout the observation period. In conclusion, after different positioning maneuvers awake and under anesthesia, alterations of rSO2 can be registrated by near-infrared spectroscopy (NIRS).

Adult↗