Biomedical subjects
Publications and source records attributed to P Laszlo.
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What really happened? To recount a pivotal 20th century chemical discovery, the assignment of its structure to ferrocene, ain't easy! One might have thought that telling the story would be straightforward, from published papers and correspondence with some of their authors. Not so. One emerges with a good bit of sympathy for historians of science-who did just what and why is pretty hard to determine, even when less than fifty years have elapsed.
Limited information seems to be available about the role of reduced endothelial production of endotheliumderived relaxing factor (EDRF)-nitrate/nitrite (NO) in the pathogenesis of diabetic angiopathy in insulindependent diabetes. A report of urinary and serum nitrate/nitrite, glucometabolic parameters, endothelial and in vivo platelet activation markers of 22 insulin dependent diabetics (IDDM) patients are given. Urinary and serum nitrate/nitrite concentrations were reduced in IDDM. This was independent of disease duration, presence of angiopathy and the glucometabolic parameters. A significant and inverse correlation of nitrate/nitrite excretion with endothelial markers (von Willebrand factor, soluble thrombomodulin) was documented. Moreover, reduced nitrate/nitrite excretion was strongly associated with elevated plasmatic beta -thromboglobulin levels. EDRF-NO production is reduced in IDDM and this reduction correlates with endothelial damage. Decreased nitrate/nitrite excretion may also influence in vivo platelet function, which results in increased in vivo platelet activation and suggests that the reduced intravascular production of EDRF-NO might play a role in the pathogenesis of angiopathy in IDDM.
The role of reduced endothelial production of EDRF-NO in the pathogenesis of diabetic angiopathy has received much attention, however, most of the rather conflicting data were gained from animal experiments. Limited human experience seems to be available in insulin dependent diabetes, calling attention to decreased EDRF-NO production. Hereby the clinical, as well as laboratory investigation (urinary and serum nitrate/nitrite, lipid peroxidation, glucometabolic parameters, endothelial and in vivo platelet activation markers, etc.) of 35 non-insulin dependent (NIDDM) and 15 insulin dependent diabetics (IDDM) patients are given. Urinary and serum nitrate/nitrite concentrations were proven to be reduced in both patients groups. This change was independent of diabetes duration, presence of macroangiopathy, coronary heart disease and the glucometabolic parameters, however, correlation was registered with lipid peroxidation (total antioxidant status). An inverse correlation of nitrate/nitrite excretion with endothelial markers (von Willebrand factor, soluble thrombomodulin) was documented in NIDDM, this correlation was much stronger in IDDM. Moreover, in IDDM patients reduced nitrate/nitrite excretion was strongly associated with elevated plasmatic beta-thromboglobulin levels. The data presented here support to the hypothesis, that EDRF-NO production is reduced in diabetes and this reduction seems to correlate with endothelial damage. In IDDM the decreased nitrate/nitrite excretion may also lead to increased in vivo platelet activation, which suggests that the reduced amount of EDRF-NO might play a role in the pathogenesis of angiopathy in IDDM.
The structure and dynamics at the interface of swelling clays (smectites) are crucial to such diverse applications as drilling for oil, cosmetics, paints, water treatment, or chemical reactions. From our previous NMR studies on clay suspensions, we have shown how the orientation of interfacial molecules is affected by the clay structure1, by the nature of counterions 2, or by the composition of the liquid phase3. These results have been mainly obtained from the analysis of residual quadrupolar splittings of nuclei from interfacial species. In this work, we report our studies on a clay montmorillonite suspended in aqueous solutions of non ionic polymers. The polymer perturbs the structure within the interfacial region as deduced from the variations of the splittings of water quadrupolar nuclei and of sodium-23 relaxation parameters in terms of the polymer concentration. Proton self-diffusion coefficients and carbon-13 relaxation times are measured to describe the influence of the clay on the polymer mobility. The dependence of the polymer nature on these parameters is also investigated.
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Properties of interfacial water have been studied in saponite, hectorite and montmorillonite suspensions. These data, together with our previous results are explained by the presence of two water interfacial sites or by a fast exchange between them.
Use of a fluorescent probe for the intravesicular pH shows that synergisms previously observed in Pr3+ transport across phosphatidylcholine vesicles are explained by an increase in the proton counter-transport.
It is now well accepted that clays could have concentrated prebiotic organic molecules, protected them from UV radiation and served as templates and catalysts in their prebiotic evolution. A complementary question is: How did prebiotic organics in the oceans, in ground water, or in hydrothermal solutions affect the formation and inorganic evolution of oxides, hydroxides, and clay minerals? In this study predominantly amorphous Al oxyhydroxides (Al gels) and crystalline Mg hydroxyoxides were synthesized, and then crystallized and recrystallized respectively, to Al and Mg hydroxides via wet and dry (w/d) cycling using both water and organic solutions. The products that resulted were examined using IR spectroscopy and X-ray diffraction (XRD). XRD scans of the products formed by w/d cycling of the Al gels with either water or 0.1 M aqueous solutions of methanol or formaldehyde showed that bayerite (alpha Al2O3) was the major phase formed. The acetonitrile treated sample exhibited the most defined XRD peaks, and no crystalline phase could be observed by XRD of the 0.1 M formamide solution treated sample. Cycling the Mg hydroxyoxide with water, or 0.1 M solutions of methanol, formamide, formaldehyde, or acetonitrile resulted in the formation of brucite (Mg(OH)2) (in varying amounts) and of three unidentified phases. One unidentified phase, 'phase II', was observed in the formaldehyde cycled sample (and tentatively identified in the methanol and formamide cycled samples), 'phase III' in the formamide and formaldehyde cycled sample, and 'phase IV' in only the formaldehyde. XRD peaks with a spacing of approximately 11.5 Angstrom (assigned to phase III) suggest intercalation of formamide and formaldehyde into the interlayer spaces of the brucite. Phosphate treatment, prior to w/d cycling with water, and also with the above mentioned organics, while totally preventing subsequent formation of any crystalline Al hydroxide, enhanced the formation of Mg phases, shown by XRD data. Formation of brucite was impeded only by w/d cycling using concentrated methanol solution, but even these effects were reversible. The XRD scans of the products resulting from the aqueous and organic solution cycling treatments of the Mg starting materials showed peaks due to brucite and three unidentified phases. Only the brucite is evident in oriented sample XRD scans of the Mg starting material when treated with methanol, formamide, and acetonitrile. In random powder sample XRD scans of the Mg starting material treated with: 1) methanol--the unidentified phase 11 is evident, 2) formamide--phase II and III are seen, and 3) formaldehyde--phases II, III, and IV are evident.
Na+ and K+ fluxes mediated by lasalocid A across erythrocyte membranes have been determined from 23Na-NMR peak areas and chemical shifts, respectively. In similar experiments, Cl- transport has been monitored by NMR signal intensities. Taking into account the external pH variations, the results are readily explainable in terms of charge-balance conservation. The effect of disodium 4,4'-diisothiocyanostilbene-2,2'-disulfonate, an anion-exchange inhibitor, has also been studied.
23Na-NMR probes the ionic composition in the immediate vicinity of the DNA molecule, in the presence of a series of quaternary ammonium bromides, of varying hydrocarbon chain length. The 23Na-NMR line shows two Lorentzian components, in accordance with quadrupolar relaxation theory for S = 3/2 nuclei under slow modulation. Deconvolution of the observed lineshape provides, in a reliable manner, the relative fraction of sodium counterions neutralizing the phosphate sites on DNA. This quantity (p B chi 2) serves as an index of the relative affinities of various surfactant ions toward DNA, Na+ being the reference cation. The results are consistent with site binding of detergent ions to the nucleic acid, an interaction dominated by hydrophobic forces.
Using computer simulations, with realistic values for the intrinsic thermodynamic binding constants and kinetic on and off rate constants at the four metal-binding sites, the calmodulin molecule is shown to have been optimally adjusted by evolution for biological function. Despite a very large number of potential molecular states, depending upon occupation by potassium, calcium, or magnesium ions, the system restricts itself to a small number of physiologically-significant equilibrium species. It appears to possess built-in triggers for biological processes, with rapid (approximately 20 ms time-scale), step-function shaped, changes of the populations of the CMKK, CMMK, CKKK, CMMM (and CCKK) states. The time-response of calmodulin to periodic changes in ionic levels (2 and 5 s-1) makes it quite adequate for repeated stimulations. In short, calmodulin appears as a very selective information transmitter at the molecular level.
Transport of Pr3+ across phosphatidyl choline vesicles, as monitored by 31P nmr, is second-order in the crown ether carboxylic acid 2, as it is with respect to lasalocid (X-537 A). When the synthetic (2) and the natural (lasalocid) ionophores are incorporated together in approximately 3:1 ratio into the lipidic phase, the transport velocity is markedly enhanced.
A modified Poisson-Boltzmann treatment is applied to aqueous solutions of sodium heparinate, in the presence of added salts (NaCl, LiCl, KCl, CaCl2). The results show that 23Na-NMR line widths for the counterions are determined nearly exclusively by Na+ in the immediate vicinity of the linear polyelectrolyte. Hence, two-state treatments, despite their crude character, can reproduce such experimental data rather well.
Decalcified bovine Gla protein binds sodium cations on the three gamma-carboxylglutamic (Gla) residues. Sodium-23 nuclear magnetic resonance serves to determine the correlation time tau c of bound sodium ions. Its value (tau c = 2.5 ns) matches the reorientational correlation time of the protein (tau R = 2.6 ns).
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Explore the source record for details and available documents.