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Biomedical subjects

N Davids

Publications and source records attributed to N Davids.

18 recordsLinked to original sources

The association reaction between hemoglobin and carbon monoxide as studied by the isolation of the intermediates. Implications on the mechanism of cooperativity.

The concentrations of the intermediates in the association reaction between human hemoglobin and CO at 20 degrees C, pH 7, under conditions of negligible dissociation of the ligand, were measured by cryogenic techniques. The monoligated species were predominant at all values of overall ligand bound studied. The analysis of the experimental data assuming a scheme of four consecutive reactions indicated that the binding rates increased in a continuous fashion. A significant acceleration after the binding of the second molecule of ligand occurred in the presence of 0.1 M KCl, but not with the addition of an excess of inositol hexaphosphate, indicating that major functional, and possibly structural, transitions occur at the diligated state. Differences in the concentrations of the intermediates in the same state of ligation were observed under all conditions. The analyses of the data on the basis of schemes of multiple pathways of reaction indicated that the beta subunits reacted about 1.5 times faster than the alpha subunits in the first ligation reaction. After the addition of inositol hexaphosphate, the alpha subunits reacted about 1.5 times faster than the beta subunits in the first ligation step, but the overall rate of the first CO binding step was unchanged.

Adult

Hemodynamic evaluation of arterial stenoses by computer simulation.

A new method to assess the hemodynamic severity of arterial stenoses was proposed and evaluated. It is based on a previously developed finite element computer simulation model for laminar-separated flow in arteries of axially varying cross-section; the present modification allows use of angiographic stenosis shapes acquired by automatic edge-detection algorithms. The method was validated by comparing its results with published experimental and theoretic results for ideal stenosis shapes. At moderate flowrates (Reynolds number = 500), poststenosis flow separation was predicted for moderately severe (75% area reduction) but not for mild (25%) stenoses. For high flowrates (Reynolds number = 900) in a severe stenosis (89%), stagnation and reversed flow were predicted and the experimental nondimensional pressure drop of 48.5 was correctly determined. Bernoulli's Equation, which neglects viscosity, predicted a drop of only 40. For a severe stenosis (89%), even at low Reynolds numbers (50), reversed flow agreeing with other theoretic solutions was predicted. Predictions are especially useful at low flow rates, where experiments are difficult to conduct. The height of the curve on the graph of nondimensional pressure gradient vs. Reynolds number reflects the hemodynamic severity of a particular stenosis; these curves were predicted for moderate and severe ideal stenoses and agree with experiments. A similar analysis is applied to an actual human coronary artery stenosis, and the results are demonstrated to have use in assessing interventions during angiography.

Arterial Occlusive Diseases

An automated differential thermal and potentiometric titration apparatus for binding studies.

A differential pH-thermal titration apparatus is described which can detect pH differences with a sensitivity of +/- 0.0001 pH units and a thermal sensitivity of +/- 0.00002 degree C at a time constant of 0.1 s. With a reaction which yields 1 kcal mol-1, the current system can detect concentrations as low as 4 X 10(-6) M or, in a 2 ml volume, a total amount of 40 nmol. With a time constant of 0.1 s, the sensitivity is 20 +/- 4 micro degrees C. The experimental protocol is specified by a microprocessor and three modes of operation are possible: titration at constant rate of reagent addition, titration at variable rates of addition so that the contents of both cells are at either constant pH or at a constant temperature and variable rate when a rate of change is specified. Experimental data are collected in files, corrected for heat loss, initial baseline drift, and changes in volume. The final corrected data from the standardized run of 0.01338 M HCl in 0.2 M KCl at 25 degrees C calibrate the pH scale and yield the calorimetric conversion constants and pKw which are calculated and stored for subsequent corrections for the titration of an unknown acid or the measurement of binding constants and heats.

Calorimetry

Application of the finite element simulation method to the adiabatic and potentiometric corrections of calorimetric titration data.

A general numerical analysis procedure is described which has been applied to an automated differential pH-thermal titration apparatus operated isoperibolically to obtain thermal corrections for heat loss. It is based on the Direct Byte (D-B) finite element computer simulation technique (FEST) applied to the heat conduction behavior of the instrument with time. Thermal constants of the numerical model are determined, and the results of the correction for titration data obtained from acid-base runs show that a constant upper baseline is achieved using this technique for both fast and slow reactions to an accuracy of 2%. The method is equally valid for endothermic and exothermic reactions.

Calorimetry

Computer simulation for deconvolution of a heat conduction batch microcalorimeter by the D-B Finite Element Technique.

The method described here is a general numerical analysis procedure which has been applied to a heat conduction Batch calorimeter for the deconvolution of its thermograms, and is based on a computer simulation of the heat conduction behavior of the instrument with time. We show by means of test signals that the method can deconvolute the signal with a resolving time that is about two orders of magnitude smaller than the time constant of the calorimeter itself. The method can be applied to time signals generally, provided that the instrument producing them can be simulated.

Calorimetry

Finite element methods of studying mechanical factors in blood flow.

This paper reviews some biomechanical analyses of blood flow in large arteries based on a general computer modeling using the finite element method. We study the following question: What is the role played by the interrelated factors of mechanical stress, flow irregularities, and diffusion through the endothelium on the etiology of atherosclerosis or the aggravation of vascular injury. It presents the computational features of the method and stresses the physiological significance of the results, such as the effect of geometric complexities, material nonlinearities, and non-Newtonian rheology of the blood. The specific mechanical and fluid dynamic factors analyzed are wall shear stress, flow profiles, and pressure variations. After simulating tubes of circular cross section, we apply the analysis to a number of physiological situations of significance, including blood flow in the entrance region, at bifurcations, in the annular region between an inserted catheter of varying diameter and the vessel. A model study of pulsatile flow in a 60 degree bifurcated channel of velocity profiles provided corroborative measurements of these processes with special emphasis on reversed or distributed flow conditions. The corresponding analysis was extended to the situation in which flow separates and reverses in the neighborhood of stagnation points. This required developing the nonlinear expression for the convective velocity change in the medium. A computer algorithm was developed to handle simultaneous effects of pressure and viscous forces on velocity change across the element and applied to the canine prebranch arterial segment. For mean physiological flow conditions, low shear stresses (0-10 dynes/cm2) are predicted near the wall in the diverging plane, higher values (50 dynes/cm2) along the converging sides of the wall. Backflow is predicted along the outer wall, pressure recovery prior to and into the branches, and a peak shear at the divider lip.

Arteriosclerosis