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T C Smith

Publications and source records attributed to T C Smith.

At least 91 records · Page 5Linked to original sources

Intracellular Na+, K+ and Cl- activities in Ehrlich ascites tumor cells.

Ehrlich ascites tumor cell membrane potential (Vm) and intracellular Na+, K+ and Cl- activities were measured under steady-state conditions in normal saline medium (Na+ = 154, K+ = 6, Cl- 150 mequiv./l). Membrane potential was estimated to be -23.3 +/- 0.8 mV using glass microelectrodes. Intracellular ion activities were estimated with similar glass electrodes rendered ion-selective by incorporation of ion-specific ionophores. Measurements of Vm and ion-activity differences were made in the same populations of cells. Under these conditions the intracellular Na+, K+ and Cl- activities are 4.6 +/- 0.5; 68.3 +/- 8.0; and 43.6 +/- 2.1 mequiv./l, respectively. The apparent activity coefficients for Na+ and K+ are 0.18 +/- 0.02 and 0.41 +/- 0.05 respectively. These are significantly lower than the activity coefficients expected for the ions in physiological salt solutions (0.71 and 0.73, respectively). The activity coefficient for intracellular Cl- (0.67 +/- 0.03), however, is close to that of the medium (0.73), and the transmembrane electrochemical potential difference for Cl- is not different from zero. The results establish that the energy available from the Na+ electrochemical gradient is much greater than previously estimated from chemical measurements.

Animals↗

The use of HgCl2 to evaluate the cosubstrate: amino acid transport stoichiometry in Ehrlich ascites tumor cells.

Recent investigations have indicated that cellular rheogenic properties may interfere with the correct estimation of Na+ and amino transport stoichiometry. We have reevaluated the stoichiometry of Na+ and alpha-aminoisobutyric acid (alpha-AIB) cotransport in Ehrlich ascites tumor cells depleted of Na+ and ATP by incubation in Na+-free HEPES-buffered medium (pH 7.2) containing 160 mM K+ and 2.5 microM valinomycin. Transfer of the cells to a medium with 10 mM 22Na+, 10 mM 3H-AIB, and 150 mM K+ resulted in an enhancement of Na+ flux above basal levels, which represents 0.6 of the AIB uptake. Under these conditions the membrane potential, -7.0 +/- 0.1 mV (SEM), does not change with the addition of AIB, -7.3 +/- 0.6 mV (SEM). HgCl2 (10 microM) added to the medium inhibited AIB flux and AIB-stimulated Na+ flux by 45-50% but did not change the coupling ratio. HgCl2 (10 microM) does not inhibit the basal Na+ flux nor does it affect cellular Na+ or K+ content. In physiological medium cotransport is electrogenic. The membrane potential of Ehrlich cells in physiological medium is -22.3 +/- 0.8 mV (SEM) and depolarizes to -16.7 +/- 0.7 mV (SEM) upon addition of AIB. Under these conditions the coupling ratio was highly variable but the ratio of codepression is 0.90 +/- 0.02 (SEM) in the presence of HgCl2 (10 microM). These results are consistent with a model (Smith and Robinson, 1981) in which the stoichiometry is one cosubstrate molecule per molecule of alpha-AIB. We suggest that H+ provides the alternative cosubstrate in this low Na+ environment and that in high Na+ medium the Na+:AIB stoichiometry approaches 1:1.

Amino Acids↗

Time course of ventilatory depression after thiopental and midazolam in normal subjects and in patients with chronic obstructive pulmonary disease.

Using a dual isohypercapnic technique, the authors compared the effect on ventilatory control of midazolam (0.2 mg/kg) and thiopental (3.5 mg/kg) in normal volunteers and in subjects with chronic obstructive pulmonary disease (COPD). In normal volunteers the slope of the CO2 response curve decreased from 1.77 +/- 0.16 l . min-1 . mmHg-1 (mean +/- SEM) to a minimum of 1.14 +/- 0.17 l . min-1 . mmHg-1 3.5 min after midazolam, returning to 1.32 +/- 0.21 l . min-1 . mmHg-1 15 min after injection. In the same subjects, the slope of the CO2 response curve fell from 1.89 +/- 0.18 l . min-1 . mmHg-1 to a minimum of 1.37 +/- 0.29 l . min-1 . mmHg-1 one minute after injection of thiopental, returning to 1.69 +/- 0.22 l . min-1 . mmHg-1 15 min after injection. These changes were not statistically significant. In subjects with clinical COPD, the slope of the CO2 response curve decreased from 1.89 +/- 0.63 l . min-1 . mmHg-1 to a minimum of 0.39 +/- 0.19 l . min-1 . mmHg-1 two minutes after injection of midazolam (P less than 0.05 compared with control), while 15 min after injection, the slope recovered to only 0.62 +/- 0.40 l . min-1 . mmHg-1 (P less than 0.05 compared with control). In the same subjects, the slope of the CO2 response curve decreased from 1.53 +/- 0.17 to a minimum of 0.69 +/- 0.25 l . min-1 . mmHg-1 0.5 min after injection of thiopental, recovering to 1.47 +/- 0.28 l . min-1 . mmHg-1 15 min after injection. This was significantly greater than the corresponding slope after midazolam (P less than 0.05). The authors conclude that while the time course of ventilatory depression after thiopental is similar in normal volunteers and in patients with COPD, the ventilatory depression 15 minutes after midazolam is more profound in patients with COPD than in normal subjects.

Anesthetics↗

Bioavailability of calcium valproate in normal men compared with the free acid and sodium salt.

Calcium valproate has been formulated into tablets containing the equivalent of 250 mg valproic acid (VPA). The bioequivalence of this preparation (Valontin, Parke-Davis) has been studied in 12 normal adult males in parallel with other products containing the free acid (Depakene capsules, Abbott) and the sodium salt (Depakene syrup, Abbott). Each subject received a single 500-mg oral dose of each product at 2-week intervals in a randomized three-way crossover study. Assays were carried out for VPA in blood and urine specimens which were collected over extended time periods. Peak plasma levels were attained on the average within 30 min with the syrup, 1.13 h with the capsules, and 1.38 h with the tablets. There were no significant differences in the peak plasma levels attained with the three products, or in the plasma half-lives of VPA and areas under the time-concentration curves. The plasma level curves appeared to be biexponential, with terminal half-lives that averaged 16.6 h. One subject showed a remarkably long half-life (28-38 h) after each of the three doses, indicating the possibility of genetic differences between individuals in the disposition of VPA. The urinary excretion of VPA in most subjects ran parallel to the plasma levels and could not be detected 96 h after dosing; however, the subject with the long plasma half-life continued to excrete VPA in his urine for at least 2 additional days. The mean recovery of VPA in 6-day urine represented 12-14% of the dose and ranged from 5.5 to 27.9% in different individuals. There were no significant differences between the three formulations in the pattern of urinary excretion.

Adult↗

Hematologic, serum chemistry and serologic values of Dall's sheep (Ovis dalli dalli) in Alaska.

In June 1979, 73 Dall's sheep were captured near Tok, Alaska to determine selected hematologic and serum metabolite parameters and to determine the presence of antibodies to selected pathogens. Hematology and serum metabolite values were compared with values for domestic sheep and bighorn sheep (Ovis canadensis). Antibodies were detected against Brucella sp. (4%), Campylobacter feti (30%), contagious ecthyma virus (23%) and bovine parainfluenza type 3 virus (1%). Antibodies were not detected against Anaplasma sp., Leptospira sp., bovine virus diarrhea virus, bluetongue virus, infectious bovine rhinotracheitis virus, ovine progressive pneumonia, and Toxoplasma sp.

Alaska↗

The use of fluorescent dyes to measure membrane potentials: a response.

The use of fluorescent cyanine dyes to estimate membrane potential in cell suspensions has been considered. Several problems related tot he application of the dyes have been reviewed. These problems include: 1) alteration of the membrane potential (Em) and factors involved in establishing Em by the dyes themselves, 2) the effects of altered energy metabolism on the fluorescent response of the dyes and on Em, and 3) calibration of dye fluorescence. Recent reports that advocate the use of the fluorescent dyes are misleading.

Adenosine Triphosphate↗

Time course of ventilatory response to carbon dioxide after intravenous diazepam.

Dual isohypercapnic studies on the time course of depression following intravenous diazepam permit detailed analysis of changes in the ventilatory response to carbon dioxide. The mean slope of the CO2 response curves of eight healthy volunteers dropped from 2.38 to 1.21 1 . min-1 . mmHg-1 ( P less than 0.05) within three minutes after injection of diazepam 0.4 mg/kg. Twenty-five minutes after injection, the slope was only 1.49 1 . min-1 . mmHg-1, still significantly lower than control (P less than 0.05). At 30 min, the slope has increased to 1.73 1 . min-1 . mmHg-1 and was no longer different from control at the 0.05 level of significance. There was also a significant correlation between the slope of the CO2 response curve and level of consciousness (r = 0. 81). There was little or no displacement of the response curve at any selected ventilation except as accounted for by the slope change. The authors conclude that ventilatory depression resulting from intravenous diazepam begins within one minute and lasts at least 25 min after injection.

Adult↗

Phenytoin metabolism in subjects with long and short plasma half-lives.

Normal adult men with long and short phenytoin plasma half-lives were given 300-mg oral doses of phenytoin once daily for 15 days. Plasma levels of phenytoin (DPH) and its major metabolite (p-HPPH) were measured during the period of drug administration and for 5 days thereafter. Average steady-state plasma levels of DPH rose to 13.4 micrograms/ml in the long half-life group, compared with 3.6 micrograms/ml in the short half-life group. HPPH levels in the long half-life group were about one half of those observed in the short half-life group. The DPH/HPPH ratios in plasma specimens showed excellent correlation with the plasma half-lives of DPH and average steady-state levels, suggesting that this ratio could provide guidance in the selection of optimum dosage regimens for problem patients.

Adult↗

Haematology.

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Anemia, Pernicious↗

Colon and rectum.

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Adolescent↗