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Biomedical subjects

S Hyun

Publications and source records attributed to S Hyun.

12 recordsLinked to original sources
PubMed2001

Computational particle-hemodynamics analysis and geometric reconstruction after carotid endarterectomy.

Transient three-dimensional laminar incompressible dilute suspension flow in rigid in-plane carotid artery bifurcations has been solved with a user-enhanced finite-volume program. Instantaneous velocity vector and wall shear stress vector fields illustrate strong "disturbed flow" patterns. Implications of elevated surface contours of hemodynamic wall parameters, indicating such disturbed flows, and particle deposition sites are discussed and a relative comparison in terms of indicator functions between the endarterectomized carotid artery bifurcation and two design improvements is shown. Although the combined perioperative mortality and non-fatal stroke rate for carotid endarterectomy ranges only from 2% to 7%, the final geometric design recommendation presented merits consideration because it may significantly lower the chances of post-operative complications such as stroke, ischemic attack, or even death. The new carotid artery bifurcation design is based on the overall reduction of "disturbed flow" indicator functions, including the time-averaged wall shear stress angle deviation and a wall deposition parameter for critical blood particles, such as monocytes.

Carotid Stenosis↗
PubMed2001

Hemodynamic parameters and early intimal thickening in branching blood vessels.

Intimal thickening due to atherosclerotic lesions or intimal hyperplasia in medium to large blood vessels is a major contributor to heart disease, the leading cause of death in the Western World. Balloon angioplasty with stenting, bypass surgery, and endarterectomy (with or without patch reconstruction) are some of the techniques currently applied to occluded blood vessels. On the basis of the preponderance of clinical evidence that disturbed flow patterns play a key role in the onset and progression of atherosclerosis and intimal hyperplasia, it is of interest to analyze suitable hemodynamic wall parameters that indicate susceptible sites of intimal thickening and/or favorable conditions for thrombi formation. These parameters, based on the wall shear stress, wall pressure, or particle deposition, are applied to interpret experimental/clinical observations of intimal thickening. Utilizing the parameters as "indicator" functions, internal branching blood vessel geometries are analyzed and possibly altered for different purposes: early detection of possibly highly stenosed vessel segments, prediction of future disease progression, and vessel redesign to potentially improve long-term patency rates. At the present time, the focus is on the identification of susceptible sites in branching blood vessels and their subsequent redesign, employing hemodynamic wall parameters. Specifically, the time-averaged wall shear stress (WSS), its spatial gradient (WSSG), the oscillatory shear index (OSI), and the wall shear stress angle gradient (WSSAG) are compared with experimental data for an aortoceliac junction. Then, the OSI, wall particle density (WPD), and WSSAG are segmentally averaged for different carotid artery bifurcations and compared with clinical data of intimal thickening. The third branching blood vessel under consideration is the graft-to-vein anastomosis of a vascular access graft. Suggested redesigns reduce several hemodynamic parameters (i.e., the WSSG, WSSAG, and normal pressure gradient [NPG]), thereby reducing the likelihood of restenosis, especially near the critical toe region.

Animals↗
PubMed2000

Fringe forms a complex with Notch.

The Fringe protein of Drosophila and its vertebrate homologues function in boundary determination during pattern formation. Fringe has been proposed to inhibit Serrate-Notch signalling but to potentiate Delta-Notch signalling. Here we show that Fringe and Notch form a complex through both the Lin-Notch repeats and the epidermal growth factor repeats 22-36 (EGF22-36) of Notch when they are co-expressed. The Abruptex59b (Ax59b) and AxM1 mutations, which are caused by missense mutations in EGF repeats 24 and 25, respectively, abolish the Fringe-Notch interaction through EGF22-36, whereas the l(1)N(B) mutation in the third Lin-Notch repeat of Notch abolishes the interaction through Lin-Notch repeats. Ax mutations also greatly affect the Notch response to ectopic Fringe in vivo. Results from in vitro protein mixing experiments and subcellular colocalization experiments indicate that the Fringe-Notch complex may form before their secretion. These findings explain how Fringe acts cell-autonomously to modulate the ligand preference of Notch and why the Fringe-Notch relationship is conserved between phyla and in the development of very diverse structures.

Animals↗
PubMed2000

Hemodynamics analyses of arterial expansions with implications to thrombosis and restenosis.

It is assumed that critical hemodynamic factors play an important role in the onset, localization and degree of post-operative complications, for example, thrombosis and restenosis. Of special interest are sudden expansion flows, which may occur in straight artery segments such as the common carotid after endarterectomy or end-to-end anastomoses. Sudden expansion geometries are possible origins of early post-operative emboli and significant myointimal hyperplasia resulting in early or late complications. Transient laminar axisymmetric and fully three-dimensional blood flows were simulated employing a validated finite volume code in conjunction with a Runge-Kutta particle tracking technique. Disturbed flow indicators, which may predict the onset of thrombosis and/or restenosis, were identified and employed to evaluate 90 degrees -step and smooth expansion geometries. Smooth expansion geometries have weaker disturbed flow features than step expansion geometries. Specifically, the regions near the expansion wall and the reattachment point are susceptible to both atherosclerotic lesion and thrombi formations as indicated by non-uniform hemodynamic indicators such as near-zero wall shear stress and elevated wall shear stress gradients as well as blood particle accumulation and deposition. A new parameter, the wall shear stress angle deviation (WSSAD) has been introduced, which indicates areas of abnormal endothelial cell morphology and particle wall deposition. In turn, regions of low wall shear stress and high wall shear stress gradients are recognized as susceptible sites for arterial diseases. Thus, it is interesting to note that high WSSAD surface areas cover low wall shear stress, high wall shear stress gradient locations as well as high wall particle deposition.A gradual change in step expansion geometry provides better results in terms of WSSAD values and hence potentially reducing atherosclerosis as well as thrombi formation.

Arteries↗
PubMed2000

Aerosol transport and deposition in sequentially bifurcating airways.

Deposition patterns and efficiencies of a dilute suspension of inhaled particles in three-dimensional double bifurcating airway models for both in-plane and 90 deg out-of-plane configurations have been numerically simulated assuming steady, laminar, constant-property air flow with symmetry about the first bifurcation. Particle diameters of 3, 5, and 7 microns were used in the simulation, while the inlet Stokes and Reynolds numbers varied from 0.037 to 0.23 and 500 to 2000, respectively. Comparisons between these results and experimental data based on the same geometric configuration showed good agreement. The overall trend of the particle deposition efficiency, i.e., an exponential increase with Stokes number, was somewhat similar for all bifurcations. However, the deposition efficiency of the first bifurcation was always larger than that of the second bifurcation, while in general the particle efficiency of the out-of-plane configuration was larger than that of the in-plane configuration. The local deposition patterns consistently showed that the majority of the deposition occurred in the carinal region. The distribution pattern in the first bifurcation for both configurations were symmetric about the carina, which was a direct result of the uniaxial flow at the inlet. The deposition patterns about the second carina showed increased asymmetry due to highly nonuniform flow generated by the first bifurcation and were extremely sensitive to bifurcation orientation. Based on the deposition variations between bifurcation levels and orientations, the use of single bifurcation models was determined to be inadequate to resolve the complex fluid-particle interactions that occur in multigenerational airways.

Aerosols↗
PubMed2000

Computer simulation and geometric design of endarterectomized carotid artery bifurcations.

The main goal of this computational study is to establish surgical guidelines for optimal geometries of carotid endarterectomy reconstructions that may measurably reduce postoperative complications, that is, thrombosis, stroke, and/or restenosis. The underlying hypotheses are that nonuniform hemodynamics, or "disturbed flows," are linked to arterial diseases and consequently that minimization of "disturbed flow" indicators leads to geometric bifurcation designs that lower postoperative complication rates. Considering transient 3-D laminar blood flow in partially occluded, in-plane, rigid-wall carotid artery bifurcations, the results presented include time-averaged indicators of "disturbed flow", such as the wall shear stress, spatial wall shear stress gradient, and wall shear stress angle deviation. In addition, trajectories and deposition patterns of critical blood particles (i.e., monocytes) are shown and evaluated. Within given physiological constraints, the vessel geometry was then changed in order to reduce the magnitudes of key indicators associated with thrombosis (i.e., blood clot formation) or restenosis (e.g., renewed atherosclerosis and/or hyperplasia). The quantitative results and knowledge base generated will be crucial for future clinical trials.

Blood Flow Velocity↗
PubMed1998

Establishment and characterization of cell lines constitutively expressing hepatitis B virus X-protein.

We prepared human hepatoma cell lines, which expressed the human hepatitis B virus-X gene product. The plasmid pMAMneo-X, containing an HBV-X gene promoter, an enhancer and a structural gene was constructed. Transfected HBV-X gene integration and expression were detected by Southern and Northern blotting, as well as by chloramphenicol acetylase transferase (CAT) assay using various kinds of promoter-CAT reporter systems. HBV-X protein expression in stable transfectants was confirmed by immunofluorescence microscopy. Transfected cell lines showed permanent expression of HBV-X proteins. The HBV-X transfectant activated its target promoters in promoter-CAT constructs as reporters. The HBV-X transfectant enhanced AP-1 transcription factor binding to its target DNA. Therefore, X-transfectants are not only stable, but also have specific biological functions. Cell cycle analysis by flow cytometry showed that the majority of the transfectant cells are arrested in the G1 or G2 phase of the cell cycle. These cell lines may be useful in analyzing the biological functions of HBV-X and its functional role in the formation of hepatocellular carcinomas.

Carcinoma, Hepatocellular↗
PubMed1994

Elevated in vivo and in vitro secretion of CD8-alpha molecules in patients with systemic lupus erythematosus.

Endogenously activated CD8+ cells contribute to the aberrant immune regulation that characterizes SLE. Because stimulation of CD8+ cells with lectin/Ag triggers release of CD8-alpha molecules (sCD8), we measured, in patients with SLE, serum sCD8 content, its correlation with disease activity, and the in vitro release of sCD8 by SLE PBMCs. sCD8 levels, measured by ELISA in sera of 50 SLE patients, were higher than normal in 16 out of 21 mildly active and 15 out of 15 active SLE patients. sCD8 correlated positively with the clinical index for disease activity (r = 0.57, p = 0.001) and with sIL-2R levels (r = 0.52, p < 0.0001), and negatively with serum C3 levels (r = -0.5, p < 0.04). Freshly isolated SLE PBMCs had higher than normal CD8-alpha mRNA levels and secreted high levels of sCD8 in vitro (p < 0.05 vs control PBMC). sCD8 in vitro release by SLE PBMCs may be modulated by non-CD8+ cells. Thus, anti-CD2 mAb inhibited sCD8 release, whereas anti-HLA mAb increased it in unseparated PBMCs, but not in CD8+ enriched cultures. Moreover, sCD8 release increased significantly in PBMC cultures enriched for CD8+ DR+ cells by negative selection. Added-back monocytes decreased sCD8 to original levels, but not after glutaraldehyde fixation, nor in the presence of anti-HLA mAb. Further, lectin-induced IgG production and proliferation were reduced in the presence of sCD8, suggesting that the soluble CD8 molecules may be immunoregulatory. Because the high sCD8 levels in sera of active SLE likely reflect pathogenic cell activation, serum CD8 content may be an additional serologic activity marker, and its study could provide insights into mechanisms of disease.

CD8 Antigens↗