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Biomedical subjects

D L Fry

Publications and source records attributed to D L Fry.

At least 19 recordsLinked to original sources
PubMed1993

Arterial permeability dynamics and vascular disease.

There is a growing consensus that regional susceptibility to atherosclerosis correlates topographically with an increased endothelial permeability to macromolecules such as low-density lipoprotein. Earlier research suggested that increases in arterial macromolecular permeability accompany the adaptation of the endothelial lining to changes in fluid dynamic shear stress, and that permeability might therefore be chronically increased where the endothelium is exposed to a shear stress environment that changes throughout the day. Thus the temporal variability of hemodynamic stresses at the vessel wall, with time constants of many minutes or a few hours, may affect local susceptibility to disease. Changes in the hemodynamic stresses on the endothelial surface ('local' stress) result from the normal variations in more 'global' hemodynamic variables such as blood flow rate, heart rate, and flow partition at branches, that occur throughout the day in response to changes in peripheral metabolic demand. Thus, at any given time, the permeability at a site is determined by: (1) the steady-state relationship between the local permeability and local shear stress; (2) the dynamics of the permeability change induced by changes in local shear; and (3) the extent to which the shear stress at the site is affected by changes in the global variables. Regional variations in any or all of these three factors can lead to corresponding variations in endothelial permeability, macromolecular uptake and, apparently, atherosclerotic risk. Among the three factors, the first may be relatively unimportant if most transport takes place while the endothelium is responding to hemodynamic changes.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Local intimal-medial uptakes of 125I-albumin, 125I-LDL, and parenteral Evans blue dye protein complex along the aortas of normocholesterolemic minipigs as predictors of subsequent hypercholesterolemic atherogenesis.

This report describes the normalized intimal-medial uptakes [uptake (M, mg.cm-2) divided serum concentration (c0, mg.cm-3)] of 125I-albumin, 125I-low-density lipoprotein (LDL), and in vivo Evans blue dye (EBD)-albumin complex as functions of pressure (P), time (t), molecular species (i), and location (z) along a ventral longitudinal z axis of the normal, intact, aortic endothelial surface in adult normocholesterolemic Sinclair Research Farm (SRF) minipigs and compares these uptake (M/c0) measurements with atherogenesis in hypercholesterolemic cohorts. Uptakes of porcine serum 125I-albumin (n = 21) and 125I-LDL (n = 10) were measured in freshly excised, metabolically supported aortas using a recently developed organ-support system. In vivo intimal-medial EBD uptake vs z data were measured photometrically on opened descending aortas from another group (n = 6) of normocholesterolemic, adult, SRF minipigs 18 hours after the intravenous administration of EBD. For comparison purposes, the corresponding incidence of atherosclerotic lesions along the aortic z axis was calculated using topographic data from hypercholesterolemic minipig cohorts (n = 39). The results showed that uptakes varied greatly with t, z, and macromolecule (i) but not with P. More specifically, the value of M/c0 at any location (z) rose with t, was insensitive to P, decreased with macromolecular (i) size, and varied with z in a pattern that "peaked" in the upstream region, decreased to a nadir in the downstream region, and then rose again as it approached the abdominal celiac orifice. The spatially z-averaged uptake rates for the three different labeled serum proteins were 0.31 x 10(-3) cm.h-1 for 125I-albumin, 0.42 x 10(-3) cm.h-1 for EBD-albumin, and 0.04 x 10(-3) cm.h-1 for 125I-LDL. Nondimensionalized analysis of the individual sets of uptake data indicated that the overall uptake relationship [M(t,P,z,i)/c(io), cm] could be characterized empirically by the simple product of two separate functions: one, a "scaling function" [m(z,i)], that described the uptake magnitude for a given i and z and appeared to be independent of t or P; the other, a "shape function" [s(t,P)], that described the shapes of the uptake vs t and P relationships and appeared to be independent of z or i. The "scaling function" [m(z,i)] vs z contour appeared to correlate well with the corresponding atherosclerotic lesion incidence vs z contour from the group of hypercholesterolemic minipig cohorts. Assuming passive transport, it was shown ("Appendix") that m(z,i) can be interpreted physically in terms of an endothelial diffusive permeability coefficient (P,cm.s-1).(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1992

Effect of endothelial integrity, transmural pressure, and time on the intimal-medial uptake of serum 125I-albumin and 125I-LDL in an in vitro porcine arterial organ-support system.

This report describes a new in vitro, metabolically supported, Sinclair Research Farm minipig aortic preparation in which the intimal-medial uptakes (M, mg.cm-2 of intimal surface) of porcine 125I-albumin and normocholesterolemic (nonoxidized) porcine 125I-low density lipoprotein (LDL) from a stirred, autogenous serum (containing a 125I-protein concentration of c0, mg.cm-3 at 37 degrees C and pH 7.4) were studied as functions of transmural pressure (0 < or = P < or = 150 mm Hg), time (30 < or = t < or = 120 minutes), and endothelial integrity. The following new observations were made: 1) The normalized transendothelial uptakes (M/c0, cm) of both albumin and LDL across normal intact aortic endothelial surfaces were insensitive to P. This indicated that these macromolecular solutes were not readily convected across the normal aortic endothelial surface despite increasing P. 2) However, the associated transendothelial M/c0 versus t relations for the normal intact surfaces were shown to increase monotonically with t in a manner consistent with a simple diffusive transport across a large surface barrier into the subjacent media, either with (Cases 2A and 2B) or without (Case 1) an associated transmural water convection. 3) The shapes of these temporal M/c0 curves of albumin and LDL were virtually the same; however, the magnitude of the albumin M/c0 curve was about sevenfold greater than that of LDL. 4) The M/c0 across the injured endothelial surface (Case 2C) not only increased monotonically with t but also increased significantly with P, indicating that in the absence of a normal endothelial surface, a very large convective component was added to the transport processes across the exposed aortic endothelial basement membrane and internal elastica. We conclude that: 1) the normal porcine aortic endothelial surface can provide a virtually complete barrier to the transendothelial convective transport of both albumin and LDL, 2) the diffusive barrier of the normal endothelial surface to LDL was sevenfold greater than that to albumin, 3) loss of the endothelial cell layer was associated with a threefold increase in the (P = 0) diffusive intimal-medial uptake of serum albumin in contrast to an eightfold increase in the pressurized (P = 150 mm Hg) combined diffusive-convective intimal-medial albumin uptake in the same vessel.

Animals↗
PubMed1992

Effect of various blood-derived and semisynthetic nutrient media on in vitro uptake of 125I-albumin across the intact porcine aortic endothelial surface in an organ-support system.

The effects on porcine arterial structure and permeability of a 4-hour in vitro incubation at 37 degrees C in eight different blood-derived and synthetic nutrient media were examined. Changes in arterial permeability were inferred from the normalized, 1-hour, pressurized, transendothelial uptake (M/c0 cm) of porcine 125I-albumin in 60 porcine aortic tissue preparations using an organ-support system. The organ-support system provided experimental control of ambient gas composition, temperature, transmural pressure, flow (stirring), and nutrient media at a number of sites along the vessel. Light and electron microscopic (scanning and transmission) structural correlations with the observed permeability changes were examined. The M/c0 from the autogenous serum (AS) medium was used as the "control" measurement in each vessel preparation. (Grand mean M/c0 for AS from all studies was 0.312 +/- 0.011 [x10(-3)] [mean +/- SEM] cm, n = 60.) For brevity, M/c0 values from the other media are expressed below as a percentage of the corresponding paired M/c0 from the AS. Uptake from heparinized autogenous blood was 113 +/- 9% of that from AS (p = 0.119); from heparinized autogenous plasma was 135 +/- 10% (p = 0.048); from AS+heparin was 97 +/- 5% (p = 0.498); from pooled porcine serum was 113 +/- 9% (p = 0.037); from a synthetic medium was 131 +/- 8% (p = 0.004); and from a physiological hetastarch solution was 532 +/- 8% (p = 0.0002). Associated light microscopic structural changes and ultrastructural changes were not found. We conclude that 1) incubation with AS and heparinized blood (both of which are autogenous blood substances containing platelet products or platelets) provided the best support for the endothelial barrier function, whereas heparin plasma, pooled serum, a synthetic medium, and particularly hetastarch provided poorer support; 2) arterial permeability can increase significantly without discernible endothelial ultrastructural changes; and 3) AS and to a lesser extent heparin blood should provide a suitable nutrient medium for short-term (less than 4-hour) metabolic support of the endothelial surface and subjacent tissues.

Animals↗
PubMed1985

Mathematical models of arterial transmural transport.

A finite-element model (FEM) and corresponding five-parameter analytical model (AM) were derived to study the one-dimensional transport of chemically reactive macro-molecules across (x) arterial tissue. Derivations emphasize chemical activity [a(x)], its gradient, and water flux as driving forces for chemical reactions and transport. The AM was fitted to 28 measured 125I-albumin transmural concentration [c(x)] curves giving parameter estimates of diffusivity (DA), convective velocity (nu A), and so on as functions of pressure (P), location (z) along the vessel, etc. The FEM was used to study 1) intimal-medial a(x) associated with molecular sieving and medial edema, 2) reversible binding, and 3) errors of AM in analysis of c(x). Results are as follows. Average relative error for the 28 AM fits was 5.3%. Only estimates of DA and nu A had acceptable coefficients of variation. DA (approximately 0.10 X 10(-7) cm2 X s-1) decreased with P, increased with z to a maximum, and then decreased; nu A was approximately proportional to P (approximately 0.12 X 10(-7) cm X s-1 X mmHg-1) and decreased slightly with z; distribution coefficient (epsilon F) decreased with z and was smaller for serum than for simple albumin reagent. Assumed boundary conditions for AM were associated with approximately 1.4% error in AM c(x). Parameter estimates were sensitive to wall inhomogeneity, e.g., approximately 15% error. In conclusion, the AM and FEM simulated measured c(x) well; the FEM is useful for study of mechanisms, experimental designs, and AM errors; trends of AM parameter estimates suggest dependence on P, z, and composition of reagent for further FEM and experimental study.

Arteries↗
PubMed1984

Histochemical detection and differentiation of free and esterified cholesterol in swine atherosclerosis using filipin.

The fluorescent probe, filipin, and the lipid-soluble dye, oil red O, have been used to simultaneously detect and differentiate free and esterified cholesterol, respectively, in tissue sections prepared from spontaneous atherosclerotic lesions of swine. This was possible because filipin stains free cholesterol but does not stain cholesteryl ester and because oil red O stains cholesteryl ester but does not stain free cholesterol. Oil red O-stained lipid accumulated intra- and extracellularly but separate from filipin-stained lipid. Spherical filipin-stained particles and elongated filipin-stained crystals accumulated in the extracellular space. Interestingly, some cells appeared to accumulate these filipin-stained particles exclusively. The spherical filipin-stained particles have not been previously recognized because they are not stained by oil red O. This and the fact that extensive compartmentalization of filipin and oil red O-stained lipid occurs in atherosclerotic lesions are new observations to be considered in the pathogenesis of vascular cholesterol accumulation.

Animals↗
PubMed1983

Mechanical characterization of membranelike biological tissue.

Experimental and analytical methods are presented which enable one to examine the local rheological properties of biological tissues which can be captured as flat sheets between matching pressure manifolds and deformed under experimentally prescribed hydrostatic loading conditions. In spite of the fact that most biological tissues, including arteries, are nonlinearly elastic when considered over wide ranges of strain, it was found that the deformation of swine and canine arterial wall specimens in the physiological range of wall strain can be approximated by an isotropic, linearily elastic membrane model. In view of this, the elastic behavior was characterized approximately by an incremental modulus over the range of 0.45 to 0.65 strain. The incremental modulus in both species was shown to increase by a factor of three along the descending thoracic aorta from the ductus scar to the celiac orifice.

Animals↗
PubMed1983

Effect of pressure and stirring on in vitro aortic transmural 125I-albumin transport.

The in vitro transport of 125I-albumin across the endothelial-injured canine aortic preparation was studied as a function of pressure (P) at various locations (z) along the vessel from stirred and quiescent reagents [serum (S) and a comparable albumin (A) reagent] to study mechanisms of vascular protein accumulation. Uptake (M, nmol X cm-2) was calculated from tissue radioactivity and strain-corrected vessel specimen surface area. Corresponding transmural concentration distributions [c(x)] were measured by quantitative microautoradiography. The results showed that 1) M and c(x) increased with P, decreased with z, and were lower from S than from A; 2) changes in M with stirring failed to demonstrate significant concentration gradients in the liquid at the vessel interface even with large uptake rates; 3) the c(x) contours were consistent with simple diffusion and convection in a homogeneous slab; 4) c(x) in the media near the intima increased with P above the assumed equilibrium concentration, suggesting interstitial solute rejection or edema formation with P; and 5) lower c(x) with S than A was consistent with a decreased reagent albumin activity, tissue binding, or tissue hydration.

Animals↗
PubMed1982

Yucatan miniature swine as a model for diet-induced atherosclerosis.

Nine female Yucatan miniature swine, a breed not previously evaluated for their potential usefulness as a model for experimental atherosclerosis studies, were fed a high-fat, high-cholesterol diet for 10-12 months. These swine and 4 control (low-fat, low-cholesterol-fed) swine underwent a complete necropsy at the end of this period to characterize the atherosclerosis both by gross and microscopic examination. Cholesterol feeding led to elevated serum cholesterol levels and the development of accelerated atherosclerosis. Control animals on a low-cholesterol diet had little gross or microscopic atherosclerosis. All of the cholesterol-fed swine had more extensive atherosclerosis than any of the controls by gross inspection of the Sudan-stained arterial tissue. There was individual variation suggesting the interaction of factors in addition to the plasma cholesterol which determine the extent and severity of atherosclerosis. However, it was possible to show a positive correlation between hypercholesterolemia and (1) intimal thickening in the terminal abdominal aorta and mesenteric artery, and (2) increased fat deposition in the mesenteric artery. The cholesterol-induced atherosclerosis was characterized by the deposition of lipid in and around cells. Complicated atherosclerotic lesions similar to human atherosclerosis were characterized by marked animal proliferation, necrosis, cholesterol crystal deposition, and calcification. It is concluded that the Yucatan miniature swine represent an important additional animal model in which to study certain aspects of atherosclerosis.

Animals↗
PubMed1982

Effect of serum and stirring on diffusive 125I-albumin and Evans blue dye uptake.

The diffusive in vitro uptake of homologous 125I-albumin (MA, nmol.cm-2) and Evans blue dye (EBD) (ME, nmol.cm-2) by the deendothelialized canine aorta from serum and from a simple albumin solution with and without EBD and with and without vigorous stirring was measured in 18 preparations. The results show that 1) MA and ME were significantly smaller from serum than from a simple albumin solution, 2) vigorous stirring of the liquid phase caused a slight decrease (approximately 5%) in MA and increase (approximately 9%) in ME, 3) MA was not influenced by the presence of EBD, and 4) at least 90% of the radioactivity in the tissue was free 125I-albumin with an electrophoretic mobility identical to its nonlabeled cohort molecules and albumin in the original reagent. These observations confirm the identity of the tissue radioactivity with the labeled protein in the reagent, show that less than 10% of the labeled protein is irreversibly bound in the tissue, indicate that significant concentration gradients do not occur in the reagent phase, and indicate that albumin appears to interact with other plasma components in the reagent phase.

Animals↗
PubMed1981

Aortic transmural serum protein transport: effect of concentration, time, and location.

The diffusive transport of certain 125I-labeled purified serum proteins, canine (C), human (H), and porcine (P) serum albumin (A), as well as human high-density lipoprotein (HDL), into the isolated deendothelialized intimal-medial thoracic aortic preparation was measured as a function of protein concentration (c0), intimal surface exposure time (T), and location (z) along the vessel at 21 degrees C. Selected proteins were studied in each of 11 canine preparations and 1 porcine preparation. The resulting uptake (M, nmol/cm2) was measured by direct gamma counting of specially excised fixed tissue specimens, and the transmural concentration distributions [c(xi), nmol/cm3] were calculated from electron probe X-ray microanalysis of the silver distributions across specially prepared microautoradiographs. The results showed 1) that the processes associated with the diffusive transport of CA, HA, PA, and HDL into the intimal-medial system are independent of c0, i.e., uptake is proportional to c0, 2) that the uptake of CA for short times appeared to be linear with T 1/2, 3) that the apparent wall-plasma partition coefficient for albumin rangers between 0.1 and 0.2, 4) that the apparent tissue albumin diffusion coefficient is approximately 2.7 X 10(-8) cm2/s, 5) that the transport processes for HA and CA are indistinguishable, 6) that the processes for the transport of HDL are two times slower than those for HA or CA, and 7) that the transport rate for albumin tends to decrease with z.

Animals↗
PubMed1981

Effect of arterial stretch on transmural albumin and Evan's blue dye transport.

The influence of arterial wall circumferential stretch (lambda) on the 32-min diffusive mural uptake of 125I-albumin and of Evan's blue dye (EBD) across the injured endothelial surface was studied in the intimal-medial preparation of the canine descending thoracic aorta (DTA). Albumin uptake (MA nmol/cm2) was measured by standard gamma counting techniques and the corresponding EBD uptake (ME) by the reflectance method. MA and ME were measured at a physiological stretch (lambda = 1.4) and at a hypertensive stretch (lambda = 1.8) at four equispaced locations (z) along the DTA. When lambda was changed from 1.4 to 1.8, the average percentage change of MA was -2% and of ME was -4%. These decreases were not significant (P greater than 0.10), and we conclude that arterial wall stretch exerts only minor influence on the parameters governing albumin and EBD-albumin accumulation in the intimal surface of the deendothelialized arterial intimal-medial tissue system.

Absorption↗
PubMed1980

Disseminated mucocutaneous herpes simplex type 2 infection in a renal transplant recipient: response to adenine arabinoside (Vidarabine).

A 27-year-old woman with a well-functioning cadaveric renal transplant presented with recurrent mucocutaneous herpes simples type two infection associated with a severe systemic illness. Two courses of treatment with adenine arabinoside (Vidarabine) were associated with rapid healing of the herpetic lesions and an improvement in her general condition. Treatment was associated with nausea but no toxic effect were noted.

Adult↗
PubMed1980

Methods to quantify silver in autoradiographs.

The developed silver in specially prepared photographic films (PF) and autoradiographs (AR) of radiolabeled arterial tissue was quantified by direct grain counting (GC), microdensitometry (OD), and by electron probe X-ray microanalysis (EPA). The EPA data was proportional to the OD data with a very small variance. The GC data increased with the EPA data, but showed a large variance. The EPA signal was shown 1) to be reproducible even after multiple traverses across the specimen, 2) to be directly proportional to the electron beam current and emulsion silver concentration, and 3) to be insensitive to a) beam size, b) current density, c) energy above 17 keV, or d) nonuniformities in the thickness of the conductive coating on the specimen.

Autoradiography↗
PubMed1980

Quantitative microautoradiography of arteries: comparison of radioactivity to silver.

The local concentration of silver in developed aortic transmural microautoradiographs was compared to the corresponding 125I-labeled albumin radioactivity concentration [ci(x)] in the subjacent tissue. Silver [s(x)] was measured by electron probe X-ray microanalysis (EPA) and the corresponding ci(x) by direct gamma-ray counting. The results show 1) that the relationship between volume-averaged values of radioactivity (ci) and EPA signal (s) is adequately described by ci = Ks, where K is a proportionality constant, and 2) that ci(x) measured by EPA [i.e., Ks(x)] agrees closely with ci(s) measured direcly from en face microtomy slices of corresponding unfixed tissue specimens.

Animals↗
PubMed1980

Atherosclerosis in the Erythrocebus patas, an old world monkey.

Fifty monkeys of the species Erythrocebus patas were fed a control monkey chow, a semi-synthetic diet containing 25% lard, or a semisynthetic diet containing 25% lard and 0.5% cholesterol for 2 years. The patas monkeys had naturally occurring atherosclerosis that was greatly accelerated by feeding a diet containing cholesterol. The atherosclerosis involved the aorta, predominantly the abdominal portion, the coronary arteries, and various peripheral vessels. Histologically, the atherosclerosis was characterized by intimal proliferative lesions associated with intra- and extracellular lipid deposition. Complicated lesions that developed after 2 years on the cholesterol-containing diet were associated with lipid crystals, necrosis, mineralization, and encroachment upon the media. Adventitial reactions characterized by increased vascularity and the presence of inflammatory cells were seen. All of these observations have been described as components of the human atherosclerotic disease process. The similarity of the patas monkey atherosclerosis to human atherosclerosis, the relatively large size and easy handling of the animals, and the fact that previous studies have shown the lipoproteins of both control and cholesterol-fed monkeys to resemble human lipoproteins all contribute to making the patas monkey a useful model for the study of experimental atherosclerosis.

Animals↗
PubMed1980

A renal lesion in a woman with Reiter's disease.

A 17 year old girl with Reiter's disease had extensive involvement of the entire urinary tract in addition to arthritis, vaginitis, and ocular involvement. In addition to a severe urethritis, cystitis and ureteritis there was evidence of glomerular and tubular dysfunction and abnormalities were seen on renal biopsy. The patient was treated with a five week course of doxycycline and made a slow but complete recovery.

Adolescent↗