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Biomedical subjects

V Chang

Publications and source records attributed to V Chang.

At least 37 records · Page 2Linked to original sources

Coexistence and localization of beta 1- and beta 2-adrenoceptors in the human heart.

Quantitative autoradiography was used to determine the location and density of beta 1- and beta 2-adrenoceptors in the right atrium (RA), left ventricular free wall (LVFW), right ventricular free wall (RVFW), interventricular septum (IVS), right atrium from an area near the atrioventricular node (RAAV) and cardiac nerves (N) taken from a patient with end-stage cardiac failure. The densities of beta-adrenoceptors detected by the non-selective beta-adrenoceptor antagonist radioligand (-)-[125I] cyanopindolol (50pM) were 4.93 (N), 10.6 (RVFW), 12.2 (RA), 12.4 (IVS), 15.8 (LVFW) and 18.7 fmol (mg protein)-1 (RAAV). The proportion of beta 2-adrenoceptors ranged from 19.5% (RAAV) to 95% (N). RA taken from patients with ischaemic heart disease had a higher density of beta-adrenoceptors (29.3 fmol (mg protein)-1). The results suggest that both beta 1- and beta 2-adrenoceptors are down-regulated in patients with end-stage cardiac failure. Positive inotropic responses were established to (-)-isoprenaline, RO363 (beta 1-selective), procaterol (beta 2-selective) and dopexamine in the absence or presence of the antagonist CGP 20712A (beta 1-selective) or ICI 118,551 (beta 2-selective) in electrically driven human right atrial appendage strips. RO363 and procaterol were nearly full agonists in this preparation and produced their responses through activation of beta 1- or beta 2-adrenoceptors, while dopexamine was a partial agonist which produced its inotropic responses through activation of both receptor subtypes. These studies demonstrate the presence and location of beta 1- and beta 2-adrenoceptors in the human heart.

Animals↗

Mechanisms of the development and resolution of paradoxical interventricular septal motion after uncomplicated cardiac surgery.

Of 16 patients with normal preoperative left ventricular (LV) function studied by simultaneous two-dimensional and M-mode echocardiography before and after uncomplicated cardiac surgery, M-mode interventricular septal motion remained normal in seven (group I) and was paradoxical in nine (group II) 7 to 13 days postoperatively, but was normal in all 12 patients (7 group II) studied 3 to 18 months later. An abnormal systolic increase in normalized septal curvature, the essential feature of truly paradoxical septal motion, was not observed in either group during any study period (mean = 0.92 +/- 0.08), nor were significant differences found in septal thickening, LV fractional shortening, or fractional area change. In contrast, systolic anterior motion of the LV center increased from -0.1 +/- 1.6 mm preoperatively to 4.8 +/- 2.5 mm postoperatively in group II (p less than 0.001), and the LV posterior wall motion:thickening ratio increased from 1.10 +/- 0.33 to 2.16 +/- 0.45 (p less than 0.01), but both parameters had returned to preoperative levels at the follow-up study. Both parameters remained stable in group I during all study periods. In addition, direct intraoperative M-mode recordings (n = 14) demonstrated normal septal motion in both groups before chest closure, but esophageal echocardiograms (n = 10) demonstrated exaggerated anterior systolic LV motion within 2 hours of surgery in those from group II. Thus, early after uncomplicated cardiac surgery, apparently paradoxical septal motion relative to a fixed reference point is an artifact due to exaggerated cardiac mobility that resolves with the progressive restraining effect of postoperative adhesions.

Adult↗

Flow analysis for optimal configuration of hemoperfusion device.

The objective of this experiment was to determine the flow characteristics of a hemoperfusion device. The standard device consists of a cylindrical container which is tapered towards the outlet end. Flow enters the column through a small inlet tube into the wide frontal area of the column. Having passed through the column containing collodian coated activated charcoal spheres, it leaves by the tapered outlet. In order to achieve our aim, we designed and built a two-dimensional plexiglass model consisting of a vertical cross section of the actual hemoperfusion device. Glass beads were used to simulate the artificial carbon cells and a colored solution was used to enable us to visualize the flow. In the normal configuration, it was determined that stagnation and channelling were present. The model was then analysed in the inverse configuration. This way, flow inlet is through the tapered end and flow outlet is towards the wider cylindrical end. This inverse flow configuration improved the flow characteristics and eliminated most of the channelling and stagnation.

Biomedical Engineering↗

A mutant that affects the function of autonomously replicating sequences in yeast.

We previously reported the isolation of a series of mcm mutants that are defective in the maintenance of minichromosomes in yeast. These minichromosomes are circular plasmids, each containing an autonomously replicating sequence (ARS) and a centromere. One of the mcm mutants, mcm2, has the following phenotype: at room temperature it affects the stability of only some minichromosomes depending on the ARS present, while at high temperature it affects all minichromosomes tested irrespective of the ARS present. Here we show that the mcm defect as well as its temperature-dependent specificity for ARSs can be demonstrated with circular as well as linear plasmids that do not contain centromeric sequences. Larger chromosomes containing multiple ARSs are also unstable in this mutant. Further analyses indicate that the mcm2 mutation causes the loss, rather than the aberrant segregation, of the circular minichromosomes. In addition, this mutation appears to stimulate mitotic recombination frequencies. These properties of the mcm2 mutant are consistent with the idea that the mcm2 mutation results in a defect in the initiation of DNA replication at ARSs, the putative chromosomal replication origins in yeast.

Centromere↗

Rationale for simultaneous carotid endarterectomy and aortocoronary bypass.

Seventy-eight patients were treated for coexistent carotid and coronary stenosis by simultaneous reconstructions. Five patients died (6.4%), one from a stroke contralateral to the carotid reconstruction. Four others suffered a perioperative stroke (total stroke incidence 6.4%). Three myocardial infarctions occurred (3.8%) including one fatal infarct. Analysis of the most recent 36 combined reconstructions indicates that the extramorbidity in this group increased the stroke or death rate for all carotid endarterectomies carried out in the same period by only 1%. Alternatively if these patients had been operated upon by aortocoronary grafting alone the mortality would have increased by 0.1% assuming no neurologic complications. Since these 36 patients had severe carotid stenosis and would have been refused carotid endarterectomy as an isolated procedure the results seem better than would have been achieved by staged operations.

Adult↗

A closed loop microprocessor controller for treatment of hypertension after cardiac surgery.

Hypertension after cardiac surgery is common and requires accurate control by carefully regulated infusions of drugs such as sodium nitroprusside. A microprocessor-based controller has been designed to close the loop between the blood pressure response and the infusion rate of a hypotensive drug. This system has been refined by computer simulation of the blood pressure response to sodium nitroprusside and by experience gained in using the controller in eleven patients in the early recovery period after cardiac surgery. The controller was able automatically to maintain blood pressure within 10% of a specified value. Provision of sophisticated safety features in automatic drug infusion controllers is essential for patient protection.

Cardiac Surgical Procedures↗

Combined carotid coronary reconstructions--synchronous or sequential?

Analysis of 16 synchronous with 26 sequential combined carotid coronary reconstructions showed no statistical advantage of either approach. Sequential operations are more convenient but increase the total operating time by an hour or so. Synchronous operations can be carried out without carotid shunting despite hypotension provided hypothermia is established. In other circumstances the internal carotid back pressure is used to indicate the need for carotid shunting. In the 42 patients there were three strokes (7%) including one fatal stroke (2%) and two myocardial infarctions, both fatal (5%).

Cardiopulmonary Bypass↗

An analytical method for the selective retrieval of iminobiotin-derivatized plasma membrane proteins.

An analytical method for the selective retrieval of surface plasma membrane proteins which have been covalently "tagged" with the low-molecular-weight ligand 2-iminobiotin has been developed. Retrieval is based upon the specific interaction between the 2-iminobiotin molecule, avidin, antiavidin antibody, and insoluble protein A from Staphylococcus aureus. Conditions for the reaction include moderately basic pH (8.0-9.0) and moderately high ionic strength (300 mM NaCl). The retrieval reaction is insensitive to 4% (w/v) Triton X-100, NP-40, and Lubrols PX and WX and is inhibited by octyl-beta-D-glucopyranoside and Ammonyx-LO. Large numbers of samples can be processed quickly and simultaneously. Immunoprecipitated proteins can be readily released into solution by incubation in the presence of either low pH, biotin, or sodium dodecyl sulfate.

Antibodies↗

Membrane-associated purine metabolizing enzyme activities of human peripheral blood cells.

Sealed and unsealed plasma membrane vesicles were prepared from human erythrocytes and lymphocytes. Phosphoribosylpyrophosphate synthetase (PRibPP synthetase), hypoxanthine phosphoribosyltransferase (HPRTase), and adenine phosphoribosyltransferase (APRTase) activities are detectable on both inside-out and right-side-out sealed vesicles. Ghost preparations were about 0.2%, 1%, and 1.2% of the total erythrocyte and 0.5%, 5.3%, and 9.7% of the lymphocyte APRTase, HPRTase, and PRibPP synthetase activities. The rapid decrease in these enzyme activities, upon further purification of the membranes, seemed to suggest that they might be loosely bound extrinsic proteins. Evidence confirming the localization of these enzymes on the cell surface was obtained by measuring production of [14C]AMP by intact cells in medium containing [14C]adenine, ribose 5-phosphate, and Mg2+ATP. The formation of AMP was linear with time and number of cells present. Magnesium and phosphate exerted different effects on the production of extracellular AMP than on intracellular, which involves transport as well as phosphoribosylation. Cytosoluble and membrane-bound APRTase and PRibPP synthetase exhibited different catalytic properties and sensitivities to effectors. Membranes of erythrocytes of HPRTase-deficient patients contain little or no HPRTase activity when assayed in the absence of Triton. Reisolation of these membranes from admixture with normal hemolysates did not result in any bound activity; thus, the membrane-bound activity is not an artifact of the isolation procedure. Lysis with Triton released activity equal to about half that of control membranes. This is further evidence that the enzyme is firmly bound to the membrane.

Adenine Phosphoribosyltransferase↗

Preventing hyperphagia normalizes 3-hydroxy-3-methylglutaryl-CoA reductase activity in small intestine and liver of diabetic rats.

Rats with streptozotocin-induced diabetes stop growing, develop high cholesterol and triacylglycerol levels in plasma, and have decreased activity of the rate-limiting enzyme in cholesterol synthesis, 3-hydroxy-3-methylglutaryl CoA reductase (EC 1.1.1.34), in liver and increased activity in small intestine. They also eat more than normal. To determine the contribution of hyperphagia to these changes in lipid metabolism, we restricted intake of chow to the amount eaten ad lib by normal rats. Rats were meal-fed for 8 or 22 days from the time diabetes was induced. This regimen normalized reductase activity in both liver and intestine at mid-dark and mid-light, and all but eliminated high plasma cholesterol and triacylglycerol levels, although plasma insulin remained low and glucose remained high. Activation of hepatic reductase by endogenous phosphatase in vitro was reduced in hyperphagic diabetic rats but was normal in diabetic rats eating a normal amount of food. We conclude that hyperphagia, rather than direct effects of insulin deficiency as is usually assumed, is responsible for perturbations of lipid metabolism in chronically diabetic rats. These results support the proposal that hyperphagia increases the input of dietary and newly synthesized cholesterol from the small intestine, and that this increased input raises plasma cholesterol level and inhibits reductase activity in liver.

Animals↗