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Biomedical subjects

T C Smith

Publications and source records attributed to T C Smith.

At least 109 records · Page 6Linked to original sources
PubMed1981

The effect of the fluorescent probe, 3,3'-dipropylthiadicarbocyanine iodide, on the energy metabolism of Ehrlich ascites tumor cells.

The fluorescent dye, 3,3'-dipropylthiadicarbocyanine iodide, is frequently used to estimate the cell membrane potential of small cells. We have tested the effects of this dye on glycolytic rate, O2 consumption, and cellular ATP content in Ehrlich ascites tumor cells. Addition of the dye to steady state cells in the absence of glucose induces a rapid depletion (half-time approximately equal to 5 min) of cellular ATP, which is secondary to a 76% inhibition of O2 consumption. Aerobic glycolysis is stimulated by 76%. Valinomycin produces an additional stimulation of acid production. Our findings indicate that this fluorescent dye alters energy metabolism of Ehrlich ascites tumor cells. The response is consistent with primary inhibition of oxidative phosphorylation.

Adenosine Triphosphate↗
PubMed1981

Effect of H+ on the kinetics of Na+-dependent amino acid transport in Ehrlich ascites tumor cells: evidence for H+ as an alternative substrate.

The effects of H+ on the kinetics of alpha-aminoisobutyric acid (AIB) influx in Ehrlich ascites tumor cells have been investigated at different external Na+ concentrations. Elevation of [H+] in the presence of both high (154 mEq/l) and low (10 mEq/l) external Na+ leads to decreases in the maximum influx (Jmax) and increases in the apparent Michaelis-Menten constant (Km) for influx of AIB. In the virtual absence of external Na+ (0.96 +/- 0.04 mEq/l), alterations in [H+] are without measurable effect on AIB flux. Furthermore, addition of AIB (10 mM) to cell suspensions (pH 5.90) stimulates H+ uptake by the cells in either the presence or absence of Na+. The data are consistent with two kinetic models for Na+-dependent amino acid transport: an order bireactant (Na+-binding necessary before AIB binding) system or a random bireactant system. Both models require that H+ serve as an alternative substrate for Na+. The consistency of the models was tested by fit to data from the present study (not used to evaluate the kinetic parameters) and by prediction of the pH dependence of Na+-dependent amino acid transport compared to earlier studies.

Aminoisobutyric Acids↗
PubMed1981

The unsteady model. An alternative approach to nonlinear pharmacokinetics.

In this paper an alternative approach to nonlinear pharmacokinetics modelling has been developed from first principles. This "Unsteady Model" is able to describe the situation whereby one or more independent drugs and their metabolites compete for free attachment sites in liver, tissue, red blood cells etc. The Unsteady model collapses to well-known existing models viz: Michaelis-Menten, Langmuir tissue binding and the linear compartment models, under certain well-defined, limiting conditions. The Unsteady model and its collapse to existing models is derived mathematically and illustrated with simulations. For several reasons the Unsteady model would appear to have many advantages and wide application.

Kinetics↗
PubMed1980

Hazard of a ruptured exhalation mushroom diaphragm.

In most breathing circuits, ventilation of a patient requires some device to occlude the expiratory limb during inflation. Usually one or another modification of a mushroom exhalation valve is employed. Such valves are found in the Bourns Bear 1 ventilator, the Bennett MA-1 and MA-2 ventilators, and the Emerson postoperative ventilator, as well as in the Frumen valve for manual ventilation. Recently, the authors observed a defect that might cause permanent occlusion, raising the patient's airway pressure to the level of the limiting safety pop-off and effectively applying a prolonged Valsalva maneuver without ventilation. The defect responsible for this malfunction was a half-centimeter laceration in the mushroom valve. Although the defect occurred on a Bourns Bear 1 ventilator, the authors were able to reproduce it on other ventilators of different manufacturers.

Cough↗
PubMed1980

Quantification of tissue fluorescein delivery and prediction of flap viability with the fiberoptic dermofluorometer.

Quantitative fluorescence assessment with the fiberoptic dermofluorometer has been introduced to overcome the inadequacies of ultraviolet inspection following intravenous administration of fluorescein. Initial applications in the pedicle flap of the rat have indicated that this method can predict flap viability with reproducible precision and accuracy. This minimally invasive technique should be of considerable assistance to the evaluation of hypoperfused states in laboratory and clinical situations.

Animals↗
PubMed1980

Successful surgical excision of focal paroxysmal atrial tachycardia. Observations in vivo and in vitro.

A 41-year-old man had chronic, recurrent, drug-resistant paroxysmal right atrial tachycardia. Electrophysiologic studies revealed features suggesting atrial reentrance, including induction and termination of tachycardia with rapid atrial pacing and atrial extrastimuli. Endocardial catheter mapping localized the origin of tachycardia to the right atrial appendage. Intraoperative epicardial mapping refined the localization to the posterolateral rim of the appendage. The appendage was excised and the tachycardia was permanently cured. Microelectrode studies on the excised tissue revealed an inducible rhythm localized to a small area of the atrial endocardium, characterized by rapid pacing induction, rhythmicity generated from a suprathreshold afterdepolarization, low maximum diastolic potential, low overshoot potential and a smooth transition from phase 4 to phase 0, suggesting triggered automaticity. This is the first observation in man of probable triggerable atrial automaticity, which may be a direct counterpart of the clinical arrhythmia. The successful surgical outcome indicates that a focal atrial tachycardia can be excised in selected patients.

Adult↗
PubMed1979

Correlation of the effect of Ca+2 on Na+ and K+ permeability and membrane potential of Ehrlich ascites tumor cells.

The effect of Ca+2 on the transport and intracellular distribution of Na+ and K+ in Ehrlich ascites tumor cells was investigated in an effort to establish the mechanism of Ca+2-induced hyperpolarization of the cell membrane. Inclusion of Ca+2 (2 mM) in the incubation medium leads to reduced cytoplasmic concentrations of Na+, K+ and Cl- in steady cells. In cells inhibited by ouabain, Ca+2 causes a 41% decrease in the rate of net K+ loss, but is without effect on the rate of net Na+ accumulation. Net K+ flux is reduced by 50%, while net Na+ flux is unchanged in the transport-inhibited cells. The membrane potential of cells in Ca+2-free medium (-13.9 +/- 0.8 mV) is unaffected by the addition of ouabain. However, the potential of cells in Ca+2-containing medium (-23.3 +/- 1.2 mV) declines in one hour after the addition of ouabain to values comparable to those of control cells (-15.2 +/- 0.7 mV). The results of these experiments are consistent with the postulation that Ca+2 exerts two effects on Na+ and K+ transport. First, Ca+2 reduces the membrane permeability to K+ by 25%. Second, Ca+2 alters the coupling of the Na/K active transport mechanism leading to an electrogenic hyperpolarization of the membrane.

Animals↗
PubMed1979

Ehrlich ascites tumor cell surface labeling and kinetics of glycocalyx release.

Ehrlich ascites tumor cells spontaneously release cell surface material (glycocalyx) into isotonic saline medium. Exposure of these cells to tritium-labeled 4,4'-diisothiocyano-1,2-diphenylethane-2,2'-disulfonic acid (3H2DIDS) at 4 degrees C leads to preferential labeling of the cell surface coat. We have combined studies of the kinetics of 3H2DIDS-label release, the effects of enzymatic treatment, and cell electrophoretic mobility to characterize the 3H2DIDS-labeled components of the cell surface. Approximately 73% of the cell-associated radioactivity is spontaneously released from the cells after 5 h at 23 degrees C. The kinetics of release is consistent with the first-order loss of two fractions; a slow (tau 1/2 = 360 min) component representing 33% of the radioactivity and a fast (tau 1/2 = 20 min) component representing 26%. The remaining 14% of the labile binding may reflect mechanically induced surface release. Trypsin (1 microgram/ml) also removes approximately 73% of the labeled material within 30 min and converts the kinetics of release to that of a single component (tau 1/2 = 5.5 min). The specific activity (SA) of material released by trypsin immediately after labeling is 83% of the SA of the material spontaneously lost in 1 h. However, trypsinization following a 2-h period of spontaneous release yields material of reduced (43%) SA. Neither 3H2DIDS labeling nor the initial spontaneous loss of labeled material alters cell electrophoretic mobility. However, extended spontaneous release is accompanied by a significant decrease in surface charge density. Trypsinization immediately following labeling or after spontaneous release (2 h) reduces mobility by 32%. We have tentatively identified the slowly released compartment as contributing to cell surface negativity.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗
PubMed1978

Bioavailability of norethindrone in human subjects.

A competitive protein binding assay for norethindrone was developed to measure plasma levels in human subjects. The plasma levels were considerably higher in women than in men, especially at low dose levels. The plasma levels were directly related to the dose in men; but greater variations in the plasma levels were observed in women. The plasma half-life was about 5 h in both sexes with single oral doses of 5 to 20 mg. A comparative bioavailability study with norethindrone from 2 different manufacturers, formulated in the same manner, showed no significant differences in absorption characteristics and provided sufficient data for pharmacokinetic analysis.

Adult↗
PubMed1978

Calcium transport by the normal rat colon in vivo and in vitro.

We studied calcium transport in vivo and in vitro in large bowel of normally fed young male rats. Solutions containing zero, 1.7, 3.4 and 5.0 mM calcium and isotopic 45Ca as tracer were perfused in vivo through the lumen of cecum and descending colon. In vitro flux studies were also carried out in cecum with 2.0 and 0.2 mM calcium solutions utilizing the technique of Ussing and Zerahn whereby both chemical and electrical gradients across planar sheets of cecal tissues were nulled. The combined findings demonstrated that (i) cecum was more permeable to calcium than descending colon indicating a proximal to distal absorption gradient in large bowel; (ii) the transport of calcium in both segments increased with increasing luminal calcium concentration, and (iii) calcium transport in both cecum and descending colon was passive only. Thus the large bowel appears to play only a minor role in calcium homeostasis in the normally fed rat.

Animals↗
PubMed1977

Intracellular compartmentation of Na+, K+ and Cl- in the Ehrlich ascites tumor cell: correlation with the membrane potential.

The intracellular distribution of Na+, K+, Cl- and water has been studied in the Ehrlich ascites tumor cell. Comparison of the ion and water contents of whole cells with those of cells exposed to La3+ and mechanical stress indicated that La3+ treatment results in selective damage to the cell membrane and permits evaluation of cytoplasmic and nuclear ion concentrations. The results show that Na+ is sequestered within the nucleus, while K+ and Cl- are more highly concentrated in the cell cytoplasm. Reduction of the [Na+] of the incubation medium by replacement with K+ results in reduced cytoplasmic [Na+], increased [Cl-] and no change in [K+]. Nuclear concentrations of these ions are virtually insensitive to the cation composition of the medium. Concomitant measurements of the membrane potential were made. The potential in control cells was -13.7 mV. Reduction of [Na+] in the medium caused significant depolarization. The measured potential is describable by the Cl- equilibrium potential and can be accounted for in terms of cation distributions and permeabilities. The energetic implications of the intracellular compartmentation of ions are discussed.

Animals↗