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Biomedical subjects

L V McIntire

Publications and source records attributed to L V McIntire.

139 records · Page 8Linked to original sources
PubMed1977

Rheological evaluation of hemoglobin S and hemoglobin C hemoglobinopathies.

The concept of optimum hematocrit was used to compare the rheology of bloods from patients with various hemoglobin S and hemoglobin C hemoglobinopathies. The technique involved the utilization of cone and plate viscometric data to predict average flow rates under representative physiological-fluid mechanical conditions. The shape of the curve relating optimum hematocrit to oxygen tension, rather than the absolute magnitude of the optimum hematocrit at fixed oxygen tension, is shown to give an indication of clinical severity of the disease.

Adolescent↗
PubMed1977

Mechanical trauma in leukocytes.

Mechanical and surface traumas in cardiopulmonary bypass circuits alter the function and morphology of human leukocytes. The effect of controlled in vitro shear stess (0 to 2,000 dynes/cm2, 2 to 10 min, 37 degrees C) on electronic cell count, morphology, adhesiveness, and phosphatase cytochemical staining was studied on whole blood from normal donors. Electronic cell counts droppped significantly after shear stress exposure (25% at 600 dynes/cm2 for 10 min). The frequency of disrupted leukocytes in blood smears increased with shear stress above 150 dynes/cm2, and aggregates of the disrupted cells appeared after exposure to higher shear stresses (450 dynes/cm2, 10 min). Cytochemical staining of the alkaline phosphatase in the granules of intact neutrophils was significantly reduced by the application of shear stress (150 dynes/cm2 for 10 min, or greater), but staining of acid phosphatase-containing granules was almost unaffected. Increased cell retention in columns of nylon fibers suggests that increased leukocyte adhesiveness results from exposure to shear stress. Thus exposure to shear stress may alter or disrupt leukocyte morphology and function at values somewhat lower than the 1,500 dynes/cm2 for 2 min which is required to hemolyze erythrocytes.

Cell Adhesion↗
PubMed1975

Rheological properties of fibrin clots. Effects of fibrinogen concentration, Factor XIII deficiency, and Factor XIII inhibition.

The effect of fibrinogen concentration, Factor XIII deficiency, and Factor XIII inhibition, utilizing hydroxylamine, on the formation of clot structure in vitro was studied in human platelet-free plasma systems. Rheological and biochemical techniques were employed to relate changes in clot elasticity and viscosity to clot structure formation following recalcification of citrate anticoagulated samples. Classical theories of linear viscoelasticity for swollen crosslinked materials were shown to give an excellent estimate of the number of covalent crosslinks per fibrin monomer, which is directly attainable from rheological data. SDS gel electrophoresis was utilized to show qualitatively that decreases in maximum clot elasticity, at constant fibrinogen concentration, are directly related to a decrease in Factor XIII-mediated intermolecular crosslinking. The use of the technique to investigate both kinetic and equilibrium crosslinking (or structure formation) abnormalities in plasma systems is discussed.

Blood Coagulation↗
PubMedDate not supplied

1992 ALZA Distinguished Lecture: bioengineering and vascular biology.

The vascular system is naturally dynamic; fluid mechanics and mass transfer are closely integrated with blood and vascular cell function. We are beginning to understand how local wall shear stress and strain modulate endothelial cell metabolism at the gene level. This knowledge may help explain the focal nature of many vascular pathologies, including atherosclerosis. Understanding mechanical control of gene regulation at the level of specific promoter elements and transcription factors involved will lead to development of novel constructs for localized delivery of specific gene products in regions of high or low shear stress or strain in the vascular system. In addition, recent research has shown how local fluid mechanics can alter receptor specificity in cell-to-cell and cell-to-matrix protein adhesion and aggregation. Knowledge of the specific molecular sequences involved in cell-to-cell recognition will allow development of targeted therapeutics, with applications in thrombosis, inflammation, cancer metastasis, and sickle-cell anemia. Bioengineers are uniquely qualified to be leaders in this field, because advances require a synthesis of cell and molecular biology with systems analysis, transport phenomena, and quantitative modeling. Rapid progress in tissue engineering applications will require this new kind of biomedical engineer, which represents both a challenge and an opportunity for our profession.

Biomedical Engineering↗
PubMedDate not supplied

Shear stress-mediated changes in the expression of leukocyte adhesion receptors on human umbilical vein endothelial cells in vitro.

Extensive monocyte recruitment is an early phenomenon associated with the development of atherosclerotic lesions, suggesting an active role for the involvement of adhesion receptors expressed by endothelial cells. In this study we describe the contribution of hemodynamic shear forces in regulating the expression of a few of the monocyte adhesion receptors, including intercellular adhesion molecule (ICAM-1), vascular cell adhesion molecule (VCAM-1), and E-selectin on endothelial cells. A parallel plate flow chamber and recirculating flow loop device was used to expose human umbilical vein endothelial cells (HUVECs) to different levels of shear (2-25 dyn/cm2). Subsequently the cells were analyzed either for shear induced changes in the mRNA levels of adhesion receptors by Northern blot analyses or for changes in the surface expression of ICAM-1 using flow cytometry. Results from the fluorescence analysis showed a transient increase in the surface expression of ICAM-1, 12 hr after exposure to 25 dyn/cm2 shear, returning to basal levels within 24 hr. This was quite different from the time dependent response of ICAM-1 to lipopolysaccharide (LPS), where ICAM-1 expression was maximally induced 18-24 hr post-stimulus. ICAM-1 mRNA level appeared slightly elevated after exposure to shear for 1 hr, compared to basal values, but dropped below basal levels within 6 hr. This biphasic response was seen irrespective of the magnitude of applied shear stress. VCAM-1 mRNA expression, in contrast, decreased below the baseline expression within an hour after onset of flow, and appeared to be considerably down-regulated within 6 hr. After exposure to shear for 24 hr, no increase in mRNA levels could be detected for either molecule, at any shear magnitude. E-selectin mRNA was less responsive to shear stress, especially at the lower magnitudes of shear. After an hour of exposure to flow E-selectin mRNA level appeared slightly reduced compared with control levels, but it remained at this level even after 6 hr of flow. These results indicate that the expression of adhesion receptors is sensitive to local shear stresses in a manner that is molecule specific in the short term even though prolonged exposure to flow results in similar down-regulation for both ICAM-1 and VCAM-1.

Cell Adhesion Molecules↗
PubMedDate not supplied

Shear sensitivity of hybridoma cells in batch, fed-batch, and continuous cultures.

Previously, we observed that CRL-8018 hybridoma cells were more sensitive to well-defined viscometric shear during the lag and stationary phases than during the exponential phase of batch cultures. Some potential hypotheses for explaining the increase in shear sensitivity are (1) nutrient limitations that result in a decrease in production of specific cellular components responsible for the mechanical strength of the cell, (2) nutrient limitations that lead to synchronization of the culture in a cell cycle phase that is more sensitive to shear, or (3) a link between cell growth and shear sensitivity, such that slowly growing cells are more sensitive to shear. Here, the duration of the exponential phase was increased with use of fed-batch, and the effect on shear sensitivity of the cultures was measured with a viscometric technique. Extension of exponential growth resulted in an increased period during which the cells were insensitive to shear. Additionally, the shear sensitivity of the cells was constant over a wide range of growth rates and metabolic yields in chemostat cultures. These observations suggest that as long as the cells are actively (exponentially) growing, their shear sensitivity does not depend on the growth rate or metabolic state of the cell as expressed by metabolic yields. Thus, hypothesis 3 above can be dismissed.

Cell Division↗
PubMedDate not supplied

Rapid flow-induced responses in endothelial cells.

Endothelial cells alter their morphology, growth rate, and metabolism in response to fluid shear stress. To study rapid flow-induced responses in the 3D endothelial cell morphology and calcium distribution, coupled fluorescence microscopy with optical sectioning, digital imaging, and numerical deconvolution techniques have been utilized. Results demonstrate that within the first minutes of flow application nuclear calcium is increasing. In the same time frame whole cell height and nuclear height are reduced by about 1 microm. Whole cell height changes may facilitate reduction of shear stress gradients on the luminal surface, whereas nuclear structural changes may be important for modulating endothelial growth rate and metabolism. To study the role of the cytoskeleton in these responses, endothelial cells have been treated with specific disrupters (acrylamide, cytochalasin D, and colchicine) of each of the cytoskeleton elements (intermediate filaments, microfilaments, and microtubules, respectively). None of these compounds had any effect on the shear-induced calcium response. Cytochalasin D and acrylamide did not affect the shear-induced nuclear morphology changes. Colchicine, however, completely abrogated the response, indicating that microtubules may be implicated in force transmission from the plasma membrane to the nucleus. A pedagogical model based on tensegrity theory principles is presented that is consistent with the results on the 3D endothelial morphology.

Acrylamide↗
PubMedDate not supplied

Characterization of endothelial cell locomotion using a Markov chain model.

A Markov chain model was developed to characterize the two-dimensional locomotion of bovine pulmonary artery endothelial (BPAE) cells cultured with or without basic fibroblast growth factor (bFGF). This model provides a detailed description of the migration process by computing the following locomotory parameters: (i) the speed of cell locomotion; (ii) the expected duration of cell movement in any given direction; (iii) the probability distribution of turn angles that will decide the next direction of cell movement; (iv) the frequency of cell stops; and (v) the duration of cell stops. Eight directional states and a stationary state were used in our Markov analysis. From cell trajectory data, the transition probabilities among the various states and the waiting times for the directional and the stationary states were computed. The steady-state probabilities were also calculated to obtain the ultimate direction of cell motion and, thus, determine whether cell motion was random. Our results showed how the addition of bFGF enhanced the locomotory capability of BPAE cells. Cells cultured with 30 ng/mL bFGF had lower probability of moving to the stationary state than those cultured without bFGF. In addition, cells cultured with 30 ng/mL bFGF remained in the stationary state for shorter periods of time than cells cultured without bFGF. In both these cases, however, the transition probabilities from the stationary state to any directional state were uniformly distributed and were not affected by the presence of bFGF.

Algorithms↗