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Biomedical subjects

S Chien

Publications and source records attributed to S Chien.

At least 181 records · Page 10Linked to original sources
PubMed1987

Regional cerebral metabolic activity in the rat following experimental subarachnoid hemorrhage.

A new experimental model was employed to investigate alterations of cerebral metabolic activity in rats subjected to extensive subarachnoid hemorrhage (SAH). The hemorrhages were produced in anesthetized animals by inserting 0.37 ml fresh autologous arterial blood into the subarachnoid space. Rats that underwent sham operations received subarachnoid injections of mock CSF to study the effects of sudden raised intracranial pressure (ICP). Forty-eight hours after subarachnoid injection, the unanesthetized rats were given intravenous injections of [14C]2-deoxyglucose. Experiments were terminated 45 min later by decapitation, and the brains were removed and frozen. Regional brain metabolic activity was studied employing quantitative autoradiography. In comparison with control animals, cerebral metabolic activity was diffusely decreased following SAH. Statistically significant decreases in metabolic activity of less than 34% were observed in 17 of 30 brain regions studied. The largest percentage reductions were in regions displaying the highest basal metabolic rates. Subarachnoid injections of mock CSF also produced depression of cerebral metabolic activity, but quantitatively these changes were not as pronounced as in the hemorrhage group. These studies demonstrate regional changes in brain function following SAH. The data relate these changes to both the presence of blood in the subarachnoid space and sudden raised ICP.

Animals↗
PubMed1987

Molecular biology in physiology.

The aim of this symposium on molecular biology in physiology was to introduce molecular biology to physiologists who had relatively little exposure to the new developments in this field, so that they can become conversant on this topic and contribute to the advancement of physiology by incorporating molecular biological approaches as a part of their research arsenal. After the discussion of the basic concepts, terminology, and methodology used in molecular biology, it was shown how these basic principles have been applied to the study of the genes encoding two membrane proteins that have important transport functions (band 3 and ATPase). The second half of the symposium consisted of papers on the state-of-the-art developments in the application of molecular biology to the studies of the atrial natriuretic factor and renin genes, adenylate cyclase-coupled adrenergic receptors, acetylcholine receptors and sodium channel, and long-term and short-term memories. The ultimate goal is that these examples will provide an impetus for the opening of new frontiers of research in physiology by taking advantage of the tools developed from recent advances in molecular biology.

Anion Exchange Protein 1, Erythrocyte↗
PubMed1987

The effect of nimodipine on post-ischemic cerebral glucose utilization and blood flow in the rat.

The authors hypothesized that pretreatment with the calcium entry blocker nimodipine would preserve cerebral glucose utilization and maintain favorable brain blood flow after cerebral ischemia. Three groups of pentobarbital anesthetized rats were studied: control (group 1), ischemia (group 2), and ischemia plus nimodipine pretreatment, 1 mg X kg-1 ip, 1 h prior to ischemia (group 3). Forebrain ischemia was induced with bilateral carotid clamping, administration of trimethaphan, and blood withdrawal to obtain a mean arterial pressure of 50 mmHg. The carotid clamps were released and blood re-infusion was begun 9 min after the onset of an isoelectric EEG signal. Ten minutes later, determination of regional cerebral glucose utilization (rCGU) was begun by injecting 3H-2-deoxyglucose in saline. After 60 min of reperfusion, regional cerebral blood flow (rCBF) was determined by the indicator fractionation method, using 14C-iodoantipyrine. The brain was divided into hemisphere, diencephalon, cerebellum, and brainstem. Tissue radioactivities were determined by standard techniques. Compared to group 1, hemispheric rCGU (mean +/- SEM, mumoles X 100 g-1) was significantly (P less than 0.05) reduced in groups 2 and 3 (40 +/- 3 vs. 27 +/- 2 and 22 +/- 2). Hemispheric rCGU was not significantly different in groups 2 and 3. Group 2 exhibited significantly (P less than 0.05) reduced rCBF (mean +/- SEM, ml X 100 g-1 X min-1) in the hemispheres compared to control (85 +/- 6 vs. 135 +/- 17). However, nimodipine pretreatment prevented this post-ischemic hypoperfusion in group 3 (133 +/- 18).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1987

Rheology of leukocytes.

The rheological properties of human leukocytes (WBCs) have been studied by micropipette aspiration and filtration tests. A small aspiration pressure applied via a micropipette (diameter approximately equal to 3 micron) causes the WBC to undergo a rapid elastic deformation followed by a slow creep. The data can be analyzed with a viscoelastic model: an elastic element K1 in parallel with a Maxwell element (elastic element K2 in series with viscous element mu). Neutrophils and B lymphocytes are similar in K1, K2, and mu, but these values are higher for T lymphocytes. Treatment of neutrophils with colchicine decreases K2 and mu without changing K1, whereas cytochalasin B decreases all three coefficients; these results indicate the importance of cytoskeletal microtubules and microfilaments in WBC rheology. In the presence of Ca2+, WBCs form protopods which have increased viscoelastic coefficients. Inhibition of protopod formation with pentoxifylline is associated with an increase in WBC deformability. The ruffled surface of the apparently round WBC provides an area about twice that needed to enclose a smooth sphere of the same volume; this geometric feature plays an important role in whole WBC deformability tested through 4-5 micron filter pores or micropipettes. Because of its larger volume and higher cellular viscosity, each WBC is equivalent to approximately 700 erythrocytes in its tendency to block 5-micron channels. The rheology of WBCs has significant implications in their functional behavior, including flow through the microcirculation and interaction with endothelial cells.

Capillaries↗
PubMed1987

Influence of reduced red cell deformability on regional blood flow.

The effects of a reduction in red blood cell (RBC) deformability on regional blood flow and RBC distribution were studied in rats anesthetized with pentobarbital sodium. RBCs were subjected to minimum hardening by incubation in a very diluted solution of glutaraldehyde (0.025%). Normal and partially hardened RBCs, labeled with 51Cr or 111In, were injected into the femoral vein, while an equal volume of blood was simultaneously withdrawn from the femoral artery. Approximately 70% of the labeled, partially hardened RBCs disappeared from the circulating blood within 25 min after injection, compared with less than 2% of the labeled normal RBCs. The relative distribution of RBCs with reduced deformability to normal RBCs in tissues was determined from radioactivity counting; this ratio (mean +/- SD) was 7.95 +/- 0.85 in the spleen, 7.44 +/- 0.43 in the sternum, 7.10 +/- 1.09 in the lung, 4.54 +/- 0.31 in the liver, and 3.50 +/- 0.61 in the femur bone. The results indicate a significant degree of trapping of RBCs with reduced deformability in these regions. This ratio of relative distribution of RBCs with reduced deformability as compared with normal RBCs was 1.06 +/- 0.13 in the heart, indicating the absence of preferential trapping of RBCs with reduced deformability in this organ. Regional blood flows were determined with 15-microns microspheres in the control period and after infusion of RBCs with reduced deformability (experimental).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1987

Significance of vessel size and type in vascular heat transfer.

This study was undertaken to gain a better understanding of the fundamental mechanisms of micro- and macrovascular heat transfer by experimentally identifying those vessels most important in the process. Tissue temperature fields around thermally nonequilibrated vessels were determined using a small temperature sensor that was guided through the rabbit thigh to generate a detailed temperature map. The measurements revealed that the lower limit of vessel size for thermal nonequilibration was 100 microns for arteries and 400 microns for veins. Local temperature fields were found around four of the five (80%) arteries that were greater than 300 microns in diameter but in only 3 of the 12 (25%) veins greater than 400 microns. These experimental results are in good agreement with previously published theoretical studies (5) in which it was concluded that thermal equilibration in the branching countercurrent vascular network of the rabbit limb occurs in vessels an order of magnitude larger than the capillaries. In those studies the smallest vessels capable of carrying heat were predicted to be 50 microns ID with the major blood tissue heat exchange occurring in vessels greater than 100 micron ID. These findings contrast with the view that most heat transfer occurs in the capillaries and suggest that vascular heat transfer analysis must take into account the vascular architecture of the 50- to 1,000-micron vessels where most heat transfer occurs.

Animals↗
PubMed1987

Increased rigidity of red blood cell membrane in young spontaneously hypertensive rats.

The micropipette test was used to study the effects of age on the elasticity of red blood cell (RBC) membrane in spontaneously hypertensive rats (SHR) and age-matched normotensive Wistar-Kyoto rats (WKY), ranging from 3 to 23 weeks of age. The development of hypertension in the SHR started at 3 weeks and was fully established at 7 to 8 weeks. In the developmental phase of hypertension (3-5 weeks), the SHR showed a significant increase in RBC membrane elastic modulus (i.e., a decrease in RBC membrane deformability) when compared with the age-matched normotensive control rats (WKY). After the establishment of hypertension (7-8 weeks), however, the deformability of the RBC membrane of SHR improved and became comparable to that of the WKY. These results indicate that abnormal erythrocyte membrane elasticity is an early event in SHR and that adaptive recovery occurs when hypertension is fully developed.

Aging↗
PubMed1987

Left ventricular hypertrophy in hypertension. Prevalence and relationship to pathophysiologic variables.

In less than a decade since development of echocardiographic measurement of left ventricular muscle mass, studies using this technique have provided considerable information about the prevalence and pathophysiology of left ventricular hypertrophy in human hypertension. Increased left ventricular mass has been found in a significant minority of patients with systemic hypertension, with the exact prevalence dependent both on how a population is selected and on the sex, race, and possibly age composition of its members. All published studies have reported that left ventricular hypertrophy is more closely related to blood pressure recorded in the patient's natural setting during normal activity or exercise-whether measured by portable recorder or home manometer-than to blood pressure measured by the physician. In addition, studies indicate that the classic hypertensive abnormalities of concentric left ventricular hypertrophy and increased peripheral resistance are interrelated, while left ventricular hypertrophy is absent in a subgroup of patients with mild essential hypertension who exhibit high cardiac output and evidence of supernormal myocardial contractility. Conversely, the left ventricular functional response to exercise is inversely related to the degree of hypertrophy. High levels of blood viscosity, which would tend to blunt the reduction in peripheral resistance expected during sleep or exercise, have also been associated with left ventricular hypertrophy in patients with essential hypertension. Echocardiographic studies have provided evidence both for and against the hypothesis that activity of the sympathetic or reninangiotensin systems plays a direct role in causing hypertensive cardiac hypertrophy. These findings demonstrate the useful role that echocardiographic assessment of left ventricular structure and function may play in hypertension research.

Age Factors↗
PubMed1987

Theory of filtration of mixed blood suspensions.

A theory is developed for the flow of suspensions of blood cells through filters in which the properties of the cells are defined by statistical distributions. It is shown that conditions are generally transient, and computational procedures are developed to compute the pressure drop and the fraction of the pores of the filter containing cells of various types as a function of time. The computations show a large influence of very small concentrations of stiff cells which gradually collect in the filter and effectively plug the filter during the time of a typical test. It is also shown that the mean value of the resistance offered by a cell population with a limited distribution of resistances is more important than dispersion of resistances about the mean in determining the observable pressure curve. Experimental data are presented demonstrating that the drug pentoxifylline reduces the stiffness of leukocytes.

Blood Flow Velocity↗
PubMed1987

Molecular biology in biorheology.

This presentation is aimed at giving some background information on molecular biology, thus serving as an introduction to the Symposium on Molecular Biorheology held during the Sixth International Congress of Biorheology in Vancouver. The papers presented at this Symposium indicate that the use of molecular biological techniques allows the understanding of normal and abnormal rheological properties of cells and organs at the molecular level. It is hoped that these examples will provide an impetus for us to open new frontiers of research in biorheology by taking advantage of the powerful tools developed from recent advances in molecular biology.

DNA↗
PubMed1987

Rheology of sickle cells and its role in microcirculatory dynamics.

The alterations in the viscoelastic properties of the hemoglobin S solution following deoxygenation can be correlated, on the one hand, with the gelation of the HbS molecules and, on the other hand, with changes in the rheological behavior of the deoxygenated SS erythrocytes. The abnormal rheology of SS erythrocytes forms the basis of their altered flow behavior through filter pores in vitro and microcirculation in vivo. The results support the notion that the rheological behavior of sickle cells is an important link between the molecular events in hemoglobin S following deoxygenation and the behavior of the cell in the microcirculation. Although recent advances have shed considerable lights on the rheology of sickle cells in a variety of conditions, further studies are needed in order to elucidate the pathophysiological role of cell rheology in this disease, especially in terms of the influence of individual SS cells in the heterogeneous populations and the correlation between in vitro and in vivo behavior of SS cells.

Anemia, Sickle Cell↗
PubMed1987

Evaluation of a filter aspiration technique to determine membrane deformability.

A filter aspiration technique for the measurement of red cell membrane deformability described by Brailsford et al. (Blood Cells 1977;3:25) was evaluated. Pore diameters of 0.6 and 1.0 micron were used. Portions of red cells were aspirated with various hydrostatic pressures between 1 and 9 mm H2O. After fixation the filter was removed and the length and radius of the pressure-induced tongues measured by scanning electron microscopy. One to several tongues per cell were observed. The number of tongues had no influence on the measurements at pressures less than or equal to 7 mm H2O. The elastic modulus of the red cell membrane was calculated; it yielded 2.9 (+/- 0.4) X 10(-3) dynes/cm. Data obtained with filter aspiration were compared with the results obtained concurrently with the micropipette technique. A good correlation was found for normal red cells (r = 0.74, P less than 0.001). Stomatocytes produced by chlorpromazine in vitro had an increased elastic modulus with both methods. For echinocytes produced by salicylate or adenosine triphosphate depletion, the elastic modulus as determined by filter aspiration was normal, but the modulus as measured by micropipette aspiration was increased. Possible reasons for the difference are discussed. We conclude that the filter aspiration is a valid technique to measure elastic properties of red cell membranes, except when there are surface irregularities, such as those in the echinocytes.

Erythrocyte Deformability↗
PubMed1987

Increased resistance to membrane deformation of shape-transformed human red blood cells.

The study of shape-transformed human erythrocytes is of hematological interest since several clinical conditions are associated with erythrocyte shape changes. Using the micropipette technique, we examined the rheological behaviors of echinocytes induced by sodium salicylate or ATP depletion and of stomatocytes induced by chlorpromazine. Both the discocyte-echinocyte and discocyte-stomatocyte transformations resulted in an increased resistance to extension. Sodium salicylate-treated erythrocytes could be returned to normal morphology and normal membrane rheology by addition of chlorpromazine. We conclude that these morphological changes are associated with detrimental effects on the intrinsic membrane deformability of the human erythrocyte.

Adenosine Triphosphate↗
PubMed1986

Determination of junction avidity of cytolytic T cell and target cell.

A direct measurement of the avidity of the junction between a cytotoxic T lymphocyte and its target cell was achieved by using a biophysical approach. A micromanipulation technique was used to determine the force required to separate a cytotoxic T cell (human clone F1, with specificity for HLA-DRw6) from its specific target cell (JY: HLA-A2, -B7, -DR4, w6) prior to delivery of the lethal hit. The force required to separate the F1-JY pair is 1.5 X 10(4) dynes per square centimeter. This junction avidity for F1-JY pairs is 6 to 13 times greater than that for F1-F1 and JY-JY pairs; the F1-JY conjugate requires a stronger separating force and is more easily rejoined than the homologous cell pairs. This study provides an estimate of the avidity of cytotoxic T cells for their target cells and insights into the biophysical correlates of the molecular complexes formed in the interaction of cytotoxic T cells and their targets during the cytotoxic process.

Cell Communication↗
PubMed1986

Membrane protein phosphorylation during stomatocyte-echinocyte transformation of human erythrocytes.

The normal, discoid shape of red blood cells represents an equilibrium between two opposing factors, i.e., stomatocytic and echinocytic transformations. Most stomatocytic agents were found to be inhibitors of calmodulin, a regulator of the phosphorylation of membrane proteins. We determined whether red cell shape transformations could be caused by changes in phosphorylation of membrane proteins, specifically the cAMP-dependent phosphorylation of ankyrin and band 4.1. Red blood cells were incubated with 32P and 100 microM chlorpromazine (stomatocytic transformation) or 30 mM sodium salicylate (echinocytic transformation) for various time intervals. Ghost membrane proteins were examined by polyacrylamide gel electrophoresis and autoradiography. Spectrin (beta-chain), ankyrin, band 3, band 4.1 and 4.9 were phosphorylated. No change was found in the degree and pattern of phosphorylation after stomatocytic transformation. Salicylate caused a reversible inhibition of transmembranous phosphate transport in both directions. The results indicate that the stomatocytic transformation induced by chlorpromazine and the echinocytic transformation induced by salicylate do not involve a change in phosphorylation, but that the echinocytic transformation induced by salicylate is associated with an inhibition of transmembranous transport of phosphate. Studies with salicylate suggest that the phosphorylation sites of band 3 are found mainly on the endofacial side of the membrane.

Aspirin↗
PubMed1986

Fibers, crystals, and other forms of HbS polymers in deoxygenated sickle erythrocytes.

We have examined by electron microscopy the formation of fibers and crystals from sickle hemoglobin within sickle erythrocytes following deoxygenation during capillary storage from 1 to 132 days. Intracellular fibers were found on the first day and throughout the period of study. The fibers exhibited a diameter (mean +/- SD) of 17.4 +/- 0.62 nm and were aligned in the cell with a fiber-to-fiber spacing of 18.6 nm (x-axis) by 22.7 nm (y-axis). Between 65 and 132 days, extracellular hemoglobin crystals developed, with a lattice periodicity of 9.63 +/- 0.6 nm. Fibers and crystals coexist as separate structures. These results suggest that crystal formation upon storage of packed deoxygenated sickle erythrocytes may proceed via a phase of fiber dissolution followed by hemoglobin reassembly into extracellular crystals, rather than by a progressive alignment and direct fusion of existing fibers.

Anemia, Sickle Cell↗