[The influencing of driving performance by an intermediate tranquilizer. Objectifying studies].
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Biomedical subjects
Publications and source records attributed to U Seydel.
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The structural polymorphisms of rough mutant lipopolysaccharides (LPS) Rd, Rc, Rb, and Ra from Salmonella minnesota (strains R4, R7, Rz, R5, R345, and R60, respectively) were investigated as a function of temperature, water content, and Mg2+ concentration. The gel to liquid crystalline (beta<==>alpha) phase transition temperature (Tc) and the state of order within each phase were measured by Fourier transform infrared spectroscopy. The amount of bound water was determined by differential scanning calorimetry and the three-dimensional structures in each phase state were characterized by synchrotron radiation X-ray diffraction. The results indicate an extremely complex dependence of the structural behavior of LPS on ambient conditions. The beta<==>alpha acyl chain melting temperatures at high water contents (95-97%), Tc = 31 to 32 degrees C for LPS Rd, 33 to 35 degrees C for LPS Rc to Rb, and 36 degrees C for LPS Ra, increase with decreasing water content and in the presence of Mg2+ cations with a concomitant broadening of the transition range. Below 30 to 50% water content, no distinct phase transitions can be observed. These effects are most pronounced for LPS with the shortest sugar chains. Below 50% water content, only lamellar structures can be observed in the temperature range 5 to 80 degrees C, independent of the Mg2+ concentration. Above 50% water concentration, for large [LPS]:[Mg2+] molar ratios the predominant structure above Tc is nonlamellar; for smaller [LPS]:[Mg2+] molar ratios a superposition of lamellar and nonlamellar structures is found. For all LPS Rd to Rb at low Mg2+ concentrations, the phase transition is connected with a change in the three-dimensional structure from lamellar or mixed lamellar/nonlamellar to a pure nonlamellar, probably cubic structure. The tendency to form non-lamellar structures decreases with the length of the core oligosaccharide. At an equimolar ratio of [LPS] and [Mg2+] a multibilayered organization is observed. Some of the nonlamellar structures are cubic phases with periodicities between 12 and 16 nm. The molecular dimensions of the single endotoxin molecules in the absence and the presence of external water are estimated from the different lamellar periodicities, including those of free lipid A and deep rough mutant LPS Re. These observations are discussed with respect to the biological importance of LPS as a potent inducer of biological effects in mammals.
We have reported here on the structural polymorphism of lipid A, the "endotoxic principle" of bacterial lipopolysaccharide. For lipid A of rough mutant lipopolysaccharide from Salmonella minnesota and Escherichia coli, the three-dimensional supramolecular structures were determined with x-ray diffraction utilizing synchrotron radiation. The investigations were performed in the water concentration range 10 to 95% by weight, at [lipid A]:[Mg2+] molar ratios from 1:0 to 0.1:1, and in the temperature range from 20 to 70 degrees C. These data were correlated with measurements of the beta----alpha phase behaviour which was monitored with differential scanning calorimetry and Fourier-transform infrared spectroscopy. We found that the transition temperature of the acyl chains ranges--in the absence of Mg2(+)-from 45 degrees C at high to 56 degrees C at low water content, and-at an equimolar content of Mg2(+)-from 52 degrees C at high to 59 degrees C at low water concentrations. In the gel phase-in which the lipid A acyl chains are more disordered than those from saturated phospholipids-cubic phases are adopted at high water content (greater than 60%) and at high [lipid A]:[Mg2+] molar ratios. At low water contents, lamellar states are assumed exclusively. In the liquid crystalline state of lipid A, the hexagonal HII state is adopted under all conditions. The structural variability of lipid A is highest at high water concentrations, and structural changes may be induced by only slight changes in temperature, water content, and Mg2+ concentration. Under physiological conditions, however, the lipid A assemblies exhibit a strong preference to cubic structures.
The structural polymorphism of deep rough mutant lipopolysaccharide--in many biological systems the most active endotoxin--from Salmonella minnesota strain R595 was investigated as function of temperature, water content, and Mg2+ concentration. Differential scanning calorimetry was used to determine the amount of bound water and the enthalpy change at the beta<==>alpha gel to liquid crystalline acyl chain melting. The onset, midtemperature Tc, and completion of the beta<==>alpha phase transition were studied with Fourier-transform infrared spectroscopy. Synchrotron radiation X-ray diffraction was used to characterize the supramolecular three-dimensional structures in each phase state. The results indicate an extremely complex dependence of the structural behavior of LPS on ambient conditions. The beta<==>alpha acyl chain melting temperature Tc lying at 30 degrees C at high water content (95%) increases with decreasing water content reaching a value of 50 degrees C at 30% water content. Concomitantly, a broadening of the transition range takes place. At still lower water content, no distinct phase transition can be observed. This behavior is even more clearly expressed in the presence of Mg2+. In the lower water concentration range (< 50%) at temperatures below 70 degrees C, only lamellar structures can be observed independent of the Mg2+ concentration. This correlates with the absence of free water. Above 50% water concentration, the supramolecular structure below 70 degrees C strongly depends on the [LPS]:[Mg2+] ratio. For large [LPS]:[Mg2+] ratios, the predominant structure is nonlamellar, for smaller [LPS]:[Mg2+] ratios there is a superposition of lamellar and nonlamellar structures. At an equimolar ratio of LPS and Mg2+ a multibilayered organization is observed. The nonlamellar structures can be assigned in various cases to structures with cubic symmetry with periodicities between 12 and 16 nm. Under all investigated conditions, a transition into the hexagonal II structure takes place between 70 and 80 degrees C. These observations are discussed in relation to the biological importance of LPS as constituent of the outer membrane of gram-negative bacteria and as potent inducer of biological effects in mammals.
Aseptic loosening of joint prostheses is a quantitatively increasing problem. For evaluation of the pathogenesis of prosthesis loosening joint capsules and tissue membranes taken from the femoral and acetabular bone-cement-interface of 23 hips revised for aseptic loosening were examined. In all cases we found an excessive inflammatory histiocytic reaction with intracytoplasmatic incorporation of a small granular foreign material. This could be identified to be zirconium oxide by LAMMA-analysis. Zirconium oxide and polymethylmethacrylate (PMMA) wear particles could be shown in the cytoplasm of histiocytes by transmission electron microscopy. By quantitative grading of the histiocytic reaction and the intracellular granular wear particles we found that both were evenly distributed around the loosened prosthesis. Chronic inflammation due to bone cement abrasion is regarded as a leading cause of aseptic prosthesis loosening.
Lipopolysaccharides (LPS) are major integral components of the outer membrane of Gram-negative bacteria being exclusively located in its outer leaflet facing the bacterial environment. Chemically they consist in different bacterial strains of a highly variable O-specific chain, a less variable core oligosaccharide, and a lipid component, termed lipid A, with low structural variability. LPS participate in the physiological membrane functions and are, therefore, essential for bacterial growth and viability. They contribute to the low membrane permeability and increase the resistance towards hydrophobic agents. They are also the primary target for the attack of antibacterial drugs and proteins such as components of the host's immune response. When set free LPS elicit, in higher organisms, a broad spectrum of biological activities. They play an important role in the manifestation of Gram-negative infection and are therefore termed endotoxins. Physico-chemical parameters such as the molecular conformation and the charges of the lipid A portion, which is responsible for endotoxin-typical biological activities and is therefore termed the 'endotoxic principle' of LPS, are correlated with the biological activity of chemically different LPS.
Using the carrier-ion complex valinomycin-K+, current/voltage (I/U) characteristics were registered for planar asymmetric lipid bilayers composed on one side of a phospholipid mixture and on the other side of rough mutant lipopolysaccharide. This system resembles the lipid matrix of the outer membrane of Gram-negative bacteria. The evaluation of the current/voltage curves yielded a highly asymmetric electrical potential barrier. The total potential difference between the phospholipid and the lipopolysaccharide was -85 mV, a result which cannot be explained by contributions of Gouy-Chapman potentials alone. The possible contribution of dipole potentials and influences of headgroup effects are discussed. It is shown that the asymmetry of the I/U-characteristic results from the differences of the surface charge densities of the two monolayers but not from those of the states of order of their hydrocarbon chains.
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