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Biomedical subjects

T Sandor

Publications and source records attributed to T Sandor.

At least 37 records · Page 2Linked to original sources

Compatibility of the two-site exchange model and 1H NMR relaxation rates.

We demonstrate a formalism for determining whether 1H longitudinal and transverse magnetic relaxation decay curves are compatible with a model of proton exchange between two sites with inherently different relaxation rates. We apply the method to published data in which both decay curves have been fit to normalized biexponential functions, a prediction of the simplest two-site exchange model. The analysis is applied to relaxation data of adsorbed water vapor on silica gel (J.R. Zimmerman and J.A. Lasater, J. Phys. Chem. 62, 1157 (1958] and to relaxation data reported in mycelia of Botrytis cinerea Persoon and pupae of the tobacco cutworm (M. Yoshida and K. Nose, Agric. Biol. Chem. 51, 3399 (1987]. Exchange parameters are calculated form these data sets and the compatibility of the two-site exchange model with the data is discussed for each case. The sensitivity of the calculated exchange parameters to errors in the bioexponential fitting parameters is treated in some detail.

Animals↗

CPMG imaging sequences for high field in vivo transverse relaxation studies.

Two-dimensional Fourier transform Carr-Purcell-Meiboom-Gill (CPMG) imaging sequences were implemented on 1.9-T and 1.5-T imaging systems in order to test their ability to characterize in vivo transverse decay curves (TDCs). Both hard- and soft-pulse CPMG imaging sequences, consisting of up to 128 echoes with echo spacings of approximately 10 ms were developed, implemented, and tested. These sequences provide one of the most detailed samplings of TDCs from image data sets reported to date. Good agreement between image-extracted T2 values and spectroscopically obtained T2 values of NiCl2-doped saline solutions was found with both hard- and soft-pulse sequences. In vivo TDCs were extracted from rabbit and human image data sets. For several tissues, biexponential TDC fits provided considerable improvement over monoexponential fits and the sensitivity of the fitting parameters to positive baseline offsets was examined. With the time coverage of the relaxation decay curves available from these sequences, the TDCs from white matter in humans appear largely monoexponential while those from cortical grey matter demonstrate biexponential behavior.

Adipose Tissue↗

Atherosclerosis, peripheral arterial disease and the vascular response to ketanserin.

Platelet activation releases thromboxane A2 and serotonin, which acts on blood vessels through a specific, 5-hydroxytryptamine (5-HT2) receptor. The development of ketanserin, the selective 5HT2 receptor blocker, has made it possible to explore the role of serotonin in patients with advanced atherosclerotic disease. Ketanserin in low doses (3 to 30 micrograms/kg) was administered intra-arterially to 23 patients with symptomatic peripheral occlusive vascular disease during peripheral angiography: an additional seven patients received a placebo. The angiographic response was evaluated by coded reading and by computer-assisted measurement of arterial segments in four anatomical regions (pelvis, thigh, knee, and lower leg). Hemodynamic changes were assessed by mercury strain gauge plethysmography and Doppler pressure measurement. Unequivocal vasodilatation was observed in zero of seven placebo-treated patients and in 13 of 23 (57%) treated patients primarily at the level of collateral vessels. Dilation of the geniculate arteries, a major source of collaterals to the calf, was associated with a significant increase in the blood flow delivery to the calf. There was a moderate drop of systemic blood pressure in patients who failed to respond with peripheral vasodilatation. Ketanserin induces hemodynamically significant vasodilatation in some patients with peripheral vascular disease, suggesting that serotonin may contribute to ischemia in some patients with advanced atherosclerosis.

Adult↗

Laser balloon angioplasty versus balloon angioplasty in normal rabbit iliac arteries.

Reduction of vascular recoil is an important goal of laser balloon angioplasty (LBA), wherein Nd:YAG laser radiation is delivered radially during balloon inflation. To define the acute and chronic effects of LBA on the normal arterial lumen in comparison with those of balloon angioplasty (BA), 36 New Zealand White male rabbits (3-4 kg) were subjected to LBA of an external iliac artery and to BA of the contralateral artery with two 1-minute balloon inflations. During LBA, which was performed during the second balloon inflation, either 300 (n = 26) or 176 (n = 10) J were delivered to achieve high and moderate laser doses, respectively, in different LBA groups. Angiography was performed pre- and post-LBA/BA and subsequently at intervals of either 1, 2, 7, 28, 48, or 223 days. Automated analysis of digitized images was used to measure lumen diameter. No instance of perforation or thrombosis occurred. LBA-treated arteries acutely showed an increase in mean diameter over baseline (+ .5 mm, P less than .01) and that of BA-treated arteries (+ .4 mm, P less than .01). While arteries treated with the high laser dose showed a loss of the initial gain in lumen diameter by 1 month, caused by both extravascular fibrosis of the thinwalled (less than 0.1 mm) artery and mild neointimal proliferation which were not reduced by daily administration of aspirin in seven rabbits, arteries treated with the moderate laser dose retained the increment in mean diameter at 1 month over that of BA-treated arteries (+ .5 mm, P less than .05). Thus, unlike BA, LBA increases luminal diameter acutely and, at a moderate laser dose, chronically.

Angioplasty, Balloon↗

The effect of gadolinium DTPA on tissue water compartments in slow- and fast-twitch rabbit muscles.

Proton T2 relaxation and its biexponential components have been determined in rabbit skeletal muscle in the presence and absence of GdDTPA. The effect of GdDTPA, which distributes only in the extracellular space, was greatest in the longer-relaxing T2 component (T22). A 27% reduction in T22 was measured for slow-twitch (red) muscle and 17% for fast-twitch (white) muscle, consistent with the larger extracellular space of the former. Magnetic resonance images demonstrated apparent contrast between red and white rabbit muscles. This contrast was instantaneously enhanced by administration of GdDTPA and returned to near normal levels after approximately 30 min. These functional changes in tissue contrast are consistent with differences in blood perfusion and biological water compartmentation between fast- and slow-twitch skeletal muscles.

Animals↗

Steroid C-20 oxidoreductase activity of duck intestinal mucosa: the interrelations of the enzymatic activity with steroid binding.

The binding of corticosterone and aldosterone to domestic duck (Anas platyrhynchos)-dispersed colonic mucosal cells at 37 degrees was investigated. It was found that in contrast to experiments using cell-free intestinal preparations, corticosterone was extensively metabolized and it was the metabolite, not the native steroid that became receptor bound and all the bound ligand was in the nuclear fraction. The metabolite turned out to be identical with 4-pregnene-11 beta,20 beta, 21-triol-3-one (20 beta-dihydrocorticosterone, 20 beta-DHB). Binding experiments with [3H]corticosterone yielded the following kinetic parameters: Kd = 87.6 nM, Nmax = 337,900 sites/cell. When synthetic [3H]20 beta-DHB was used as the ligand a curvilinear-binding isotherm was obtained. This could be resolved into a high affinity-low capacity (HA) and a low affinity-high capacity (LA) component with the following binding parameters: Kd,HA = 91 nM, Nmax,HA = 130,800 sites/cell; Kd,LA = 5.4 x 10(-6) M, Nmax, LA = 3.7 x 10(6) sites/cell. Binding of the metabolite to cell-free preparations, at 0 degree, gave the following results: for cytosol, linear-binding isotherm, Kd = 14.0 nM, Nmax = 26.5 fmol/mg protein; and for crude nuclei, curvilinear-binding isotherm, Kd,HA = 45.0 nM, Nmax, HA = 5.33 pmol/mg DNA; Kd,LA = 2.2 x 10(-6) M, Nmax,LA = 286.6 pmol/mg DNA. [3H]Aldosterone was also bound by the dispersed whole cells and again, this binding was only nuclear (Kd = 9.3 nM, Nmax = 10,042 sites/cell). The bound ligand was unchanged aldosterone. Competition experiments have shown that aldosterone did not compete with 20 beta-DHB for binding sites and vice versa. The intracellular 20 beta-hydroxysteroid oxidoreductase responsible for the transformation of corticosterone was found mostly in the cytoplasm. Kinetic studies with the enzyme yielded classical Michaelis-Menten kinetics (Km = 15.7 microM, Vmax = 2.6 nmol/min/mg protein). The enzyme had an apparent Mr of 35 kDa and a Rs of 25.5 A. It is believed that our results might explain the binding of aldosterone to mineralocorticoid-binding sites in the presence of overwhelming concentrations of corticosterone and that experiments with cell-free tissue preparations, performed at 0 degree, do not reflect the true cellular-binding events.

20-Hydroxysteroid Dehydrogenases↗

Two-site exchange revisited: a new method for extracting exchange parameters in biological systems.

A new analysis is presented which links real volume fractions, relaxation rates, and intracompartmental exchange rates directly with apparent volume fractions and relaxation rates obtained from biexponential fits of transverse magnetization decay curves. The analysis differs from previous methods in that measurements from two paramagnetic doping levels are used to close the two-site exchange equations. Both the new method and one previously described by Herbst and Goldstein (HG) have been applied to paramagnetically doped whole-blood data sets. Significant differences in the calculated exchange parameters are found between the two methods. A small dependence of the intracellular relaxation rate on extracellular paramagnetic agent concentration, assumed nonexistent with the HG method, is inferred from the new analysis. The analysis was also applied to published data on perfused rat hearts, and we obtained a limited assessment of two-site exchange in this system.

Body Fluids↗

Renal vasomotion in essential hypertension: influence of vasodilators.

To assess factors responsible for phasic behavior of renal blood flow in essential hypertension, we applied an analytic method based on the estimation of power spectral density to xenon transit through the kidney and examined the renal vasodilator response to a range of agents in 53 normal subjects and 53 patients with essential hypertension. The renal vasodilator response to the calcium channel blocking agent diltiazem, but not the response to alpha-adrenergic blockade (phentolamine) or angiotensin converting enzyme inhibition (teprotide or captopril), was associated with a significant reduction in the amplitude of renal vasomotion. Acetylcholine, a vasodilator that acts through the release of a vasorelaxant factor or factors from endothelium, induced an unanticipated increase in renal vasomotion. These observations further dissociate factors responsible for basal renal vascular tone and periodic changes in renal vascular tone and raise the possibility that abnormalities in the flux of calcium into renal arterioles contribute to increased renal vasomotion in essential hypertension.

Angiotensin II↗

Age-related differences in computed tomographic scan measurements.

Seventy-nine healthy men ranging in age from 31 to 87 years underwent a computed tomographic (CT) scan and were administered a neuropsychologic test battery. Midventricular, high ventricular, and supraventricular CT slices were analyzed for each individual. Computerized techniques calculated the percent of fluid volume and the mean CT density for each slice. The mean CT density of a standard tissue sample was also evaluated. The results suggest that fluid volume at the level of the ventricles is fairly stable until individuals are in their 60s, when a dramatic increase occurs. The percent of fluid volume above the level of the ventricles appears to increase slightly the ventricles appears to increase slightly in the 50s and then level off. Whole slice mean CT density numbers decreased in a linear fashion with increasing age, but the mean CT density of a standard tissue sample did not. A discriminant function derived from the CT measures was significantly correlated with a discriminant function derived from the neuropsychologic test battery. Findings based on subjects whose health status has been less carefully screened may differ from those in the present study.

Adult↗

Computerized axial tomographic reconstruction of coronary tree cross sections from a small number of cineradiographic views.

Three-dimensional reconstruction of the coronary tree from a conventional cineangiographic study is limited, in part, by the small number of available cineangiographic views. The potential utility of a maximum entropy iterative algorithm (MENT) for reconstruction of myocardial planes perpendicular to the axis of cineangiographic rotation from a small number (n = 6-18) of cineangiographic views was tested in vitro. The coronary arteries of postmortem human, canine, and calf hearts were filled with a silicone/thorium oxide mold to simulate in vivo angiographic contrast. Thirty-five-millimeter cineradiographs of each heart were obtained at 10 degrees intervals over 180 degrees about a myocardial central axis of rotation under exposure conditions which simulated the clinical setting. Projection data were derived from cinedensitometric scans across the entire myocardial shadow, perpendicular to the axis of rotation in each view, after 512 X 512 digitization with a vidicon camera/digitizer interfaced to a VAX computer. Comparison of MENT-reconstructed images with corresponding anatomic myocardial cross sections indicate that as few as 6 to 12 views can be used to reconstruct the cross sections of the multiple coronary branches (n = 6-11) within a plane of reconstruction.

Algorithms↗

Application of the maximum likelihood principle to separate exponential terms in T2 relaxation of nuclear magnetic resonance.

The method of maximum likelihood has been implemented for the estimation of multiple exponential components of T2 decay curves in spin echo NMR measurements on biologic tissues. Each Each component contributes an exponential term described by two parameters (initial amplitude and T2) to the T2 decay curve. The maximum likelihood method estimates the parameters and their standard errors for all terms simultaneously, avoiding the subjectivity inherent in methods such as graphical peeling. In the model used, it was assumed that water protons are compartmentalized and that the measured spin echo signals from the protons undergoing relaxation obey the Poisson distribution. A system of non-linear equations was derived and solved iteratively for the values of the exponential parameters which maximize the likelihood of obtaining the observed data under these assumptions. The approach was implemented for bi- and tri-exponential models on a MicroVAX II computer (Digital Equipment Corporation, Maynard, MA). Simulations of bi- and tri-exponential data, with and without system noise, were analyzed to assess the accuracy and reproducibility of the method. A subset of the simulations was repeated with non-linear least squares techniques and was compared to the results obtained with maximum likelihood. Rabbit muscle and gerbil brain samples were measured and analyzed with the maximum likelihood method. The simulations showed that within specific limits on relative sizes and relaxation rates of components, these parameters can be estimated with errors less than 5%. The comparison to non-linear least squares analysis showed that the maximum likelihood method is generally superior in estimating the parameters in difficult cases. The results from tissue measurements demonstrate that the method is effective even in cases where graphical peeling would clearly not yield reliable results.

Algorithms↗

Endothelial injury provokes collateral arterial vasoconstriction: response to a serotonin 2 antagonist, thromboxane antagonist or synthetase inhibition.

To assess the influence on collateral arteries of vasoactive factors released from activated platelets we used angiography and blood flow measurement to study the limb blood supply in 29 rabbits, 2 weeks after superficial femoral artery ligation. Minutes after balloon catheter injury to the lower aorta, striking spasm of the collateral arteries was routinely evident on the arteriograms, and limb blood flow fell. Spasm was partly reversed either by blockade of thromboxane synthesis (UK-38,485) or its vascular action (SQ 29,548) or by ketanserin, the serotonin receptor antagonist when used alone. Ketanserin combined with either UK-38,485 or SQ 29,548 reversed the spasm completely. We conclude that a combined action of serotonin and thromboxane induces collateral artery spasm when platelets are activated.

Animals↗

Differential effects of reperfusion on incidence of ventricular arrhythmias and recovery of ventricular function at 4 days following coronary occlusion.

To determine the influence of coronary reperfusion on ventricular arrhythmias and ventricular function at 4 days post occlusion, anesthetized dogs randomly received no occlusion (sham), permanent occlusion, or 1-, 2-, 3-, 4-, or 6-hour occlusions of the left anterior descending coronary artery, followed by reperfusion. An ambulatory ECG was recorded between 78 and 96 hours. The total runs of ventricular tachycardia were 1 +/- 0 (sham), 155 +/- 101 (1 hour), 66 +/- 32 (2 hours), 56 +/- 35 (3 hours), 167 +/- 68 (4 hours), 942 +/- 618 (6 hours), and 1422 +/- 486 (permanent occlusion); the runs of ventricular tachycardia were significantly less in the combined 1- to 4-hour groups (93 +/- 24) compared to the 6-hour and permanent occlusion groups (1282 +/- 384; p less than 0.006). Similar results were obtained for the number of hours in which ventricular tachycardia or frequent ventricular premature beats occurred. At 96 hours, improvement in percent systolic wall thickening of the ischemic myocardium assessed by two-dimensional echocardiography was seen in the group reperfused at 1 hour (p less than 0.01). Similar results were obtained for the reduction in degrees of wall circumference showing systolic thinning. In summary, at 4 days post occlusion in a dog model, spontaneous ventricular arrhythmias are reduced by reperfusion within 4 hours, while return of ventricular function is only improved by reperfusion within approximately 1 hour of coronary occlusion.

Animals↗

Characterization of steroid receptors in the gut and kidney of the frog (Rana catesbeiana) and in the gut of the turtle (Chrysemys picta).

Paraglucocorticoid- and paramineralocorticoid-binding cytosolic receptors (pGR, pMR) were demonstrated in the intestine and kidney of the frog, Rana catesbeiana and in the intestine of the turtle, Chrysemys picta, in the presence of sodium molybdate. These receptors were of high affinity and low capacity with the following binding parameters: pGR:Kd:frog intestine (FI), triamcinolone acetonide (TA): 3.3 nM, corticosterone (B): 3.4 nM; frog kidney (FK), TA:4.3 nM, B: 9.3 nM; turtle intestine (TI), TA: 4.8 nM; Nmax: FI, TA: 357, B: 371; FK, TA: 301, B: 157; TI, TA: 350 fmol/mg protein. pMR:Kd: FI, aldosterone: 0.9 and 90 nM (biphasic curves); FK, aldosterone: 0.6 and 36 nM (biphasic curves); Nmax: FI, 13 and 147 fmol/mg protein; FK, 78 and 109 fmol/mg protein. The receptor had the following ligand affinities: pGR: FI and FK: triamcinolone acetonide greater than DOC greater than 11 beta-hydroxyprogesterone greater than progesterone greater than corticosterone greater than cortisol greater than aldosterone greater than 11-dehydrocorticosterone greater than 17 alpha-hydroxyprogesterone greater than cortisone; TI: triamcinolone acetonide greater than corticosterone greater than progesterone greater than DOC greater than cortisol greater than aldosterone; pMR: FI and FK: corticosterone greater than 11 beta-hydroxyprogesterone greater than aldosterone greater than triamcinoline acetonide = cortisol greater than DOC greater than 11-dehydrocorticosterone greater than progesterone greater than 17 alpha-hydroxyprogesterone greater than cortisone. Androgens, estrogens or 18-hydroxycorticosterone did not compete for binding in either tissue. The heat activated frog receptors did not bind to naked DNA, though the turtle receptor did. It was possible to show that cytosol receptor-ligand complexes from all tissues were bound by nuclear acceptor sites. On linear sucrose gradients, the FI TA-receptor complex sediments with a single peak (7.5S), the FK TA-receptor complex gave two peaks (8.0 and 4.4S) and the TI TA-receptor complex showed a single peak (9.0S). The hydrodynamic parameters of the pGR's were determined by gel exclusion on Sephacel S-300. The following results were obtained: Mr: FI, 265, 80, 40 kDa (multiple proteins); FK, 280, 60, 20 kDa (multiple proteins); TI, 366 kDa; Rs: FI, 6.9, 3.9 nm; FK, 6.9, 2.9 nm; TI, 7.6 nm; f/f0: FI, 1.6; FK, 1.6; TI, 1.6. It is suggested on the basis of the binding and hydrodynamic parameters that non-mammalian epithelia corticosterone receptors have undergone biochemical evolution from one class of vertebrates to another.

Aldosterone↗

Influence of norepinephrine and angiotensin II on vasomotion of renal blood supply in humans.

Oscillatory behavior of smooth muscle, including arterial smooth muscle, has been identified in many preparations. In this study we have extended observations on vasomotion of the renal blood supply in humans by assessing the response to norepinephrine or angiotensin II infused directly into the renal artery in doses sufficient to reduce renal blood flow by 25-33% but not influence blood pressure. In placebo-treated patients, renal blood flow and the indexes of vasomotion determined by an estimation of power spectral density of xenon transit through the human kidney did not change. Norepinephrine induced a striking increase in the amplitude but not the cycle length of oscillatory activity, whereas angiotensin (despite a somewhat larger reduction in renal blood flow) induced only a modest change in amplitude. The phasic response to norepinephrine infused continuously makes it unnecessary to invoke phasic norepinephrine release in the response to maneuvers that increase sympathetic nervous system activity. Moreover, oscillatory activity reflects phenomena that may be related to but are not dependent on changes in mean renal blood flow. The results of this study may provide insight into the pathogenesis of the increase in vasomotion evident in the renal blood supply of some patients with essential hypertension.

Angiotensin II↗

Automated morphologic evaluation of pulmonary arteries in primary pulmonary hypertension.

Pulmonary wedge angiograms have been shown to reflect the severity of pulmonary vascular disease in congenital heart disease. Thirteen pulmonary wedge angiograms with a balloon occlusion catheter were performed in 11 adult patients (five normals and six with primary pulmonary hypertension [PPH]) and their features related to the resting pulmonary artery pressure (PAP). Individual cine frames from each study were selected and digitized with a computer-assisted operator-interactive program. By fitting densitometric profiles from the vessel segments, serial arterial cross-sectional diameters were calculated from mathematically derived points. There was a strong correlation between arterial taper (T, change in vessel caliber per unit axial length) and a power function of mean PAP with T = 0.304 X PAP-0.59, R = .91, P less than .001. These results demonstrate a correlation between an angiographically derived morphologic characteristic of the pulmonary vasculature (taper) and a hemodynamic parameter (PAP) in PPH. This offers a method to follow the course of the disease and the effects of drug therapy by assessing anatomic changes in the vessels.

Humans↗

Relation between the transmural extent of acute myocardial infarction and associated myocardial contractility two weeks after infarction.

To characterize the relation between the transmural extent of acute myocardial infarction (AMI) and associated regional contractility after recovery from ischemia, 11 mongrel dogs underwent occlusion of the proximal left anterior descending coronary artery and were evaluated 2 weeks after infarction. Occlusion was permanent in 5 dogs, and reperfusion was allowed after 2 hours of occlusion in 6 dogs. All dogs had computer-assisted quantitative wall-thickening analysis by 2-dimensional echocardiography and infarct localization by the triphenyl-tetrazolium chloride technique. Percent systolic wall thickening was correlated with the transmural extent of AMI in 40 regions of interest, each measuring approximately 60 arc degrees in circumference. In 11 non-infarct-containing regions, the mean wall thickening was 59 +/- 16% (+/- standard deviation). In 29 infarct-containing segments (with transmural extent of infarction 11 to 100%) systolic wall thickening ranged from -4% to 47%. Wall thickening and transmural extent of AMI were inversely related. Least-squares regression analysis found the relation to be best described by the logarithmic function, percent wall thickening = 61 - 26 log (percent transmural extent of infarction +1), r = -0.87. The nature of this relation between structure and function suggests that salvage of small amounts of myocardium (transmural extent less than 30 to 40%) by coronary reperfusion or other means may have little effect on systolic myocardial function when compared with the function of transmural infarcts. Alternatively, salvage of more than 40% of the jeopardized myocardium should be expected to appreciably augment myocardial function.

Animals↗