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Biomedical subjects

D McCall

Publications and source records attributed to D McCall.

At least 37 records · Page 2Linked to original sources
PubMed1986

Identification of a genetic locus, Rsm-1, controlling protective immunity against Schistosoma mansoni.

Mice of most inbred strains develop moderate to high levels of resistance to challenge infection on vaccination with radiation-attenuated cercariae of Schistosoma mansoni. P strain mice, however, fail to display significant protective immunity after exposure to the same vaccine. To examine the genetic basis of this polymorphism in host immunity, vaccine-induced resistance was examined in (C57/BL6J X P/N)F1, F2, and reciprocal backcross generations. The defective immunity which characterizes the P strain parent was found to be inherited in a fully recessive manner and to be controlled by a single genetic locus, which we have designated Rsm-1. Linkage analyses revealed that Rsm-1 is not genetically associated with the major histocompatibility complex (chromosome 17), the immunoglobulin heavy chain locus (chromosome 12), or a single locus influencing defective anti-schistosomulum IgM antibody responses in the P parental stock. These data provide the first example of single gene control of vaccine-induced immunity against a helminth infection. Because P mice are also defective in their capacity to develop tumoricidal macrophages and in their immunity to Leishmania major, genes encoded by the Rsm-1 locus may play a general role in resistance to infection and malignancy.

Animals↗
PubMed1986

Duplex pulsed Doppler echocardiography in mitral regurgitation.

The accuracy of duplex pulsed Doppler echocardiography (d-PDE) for detecting mitral regurgitation was evaluated in 35 patients undergoing d-PDE, cardiac auscultation, and left ventriculography. With three transducer positions, the overall d-PDE sensitivity was 95%, specificity was 100%, positive predictive value was 100%, negative predictive value was 94%, and diagnostic accuracy was 97% compared with ventriculography. This technique was superior to auscultation (sensitivity 74%, specificity 94%, positive predictive value 93%, negative predictive value 75%, diagnostic accuracy 83%). No false-positive d-PDE results occurred, but discordant false-negative results occurred frequently among the three transducer positions. If discordant negative results are considered to be false negative, then d-PDE is both sensitive and specific when mitral regurgitation is defined as systolic spectral broadening in any one transducer position.

Echocardiography↗
PubMed1986

Preventive dentistry in a health centre: effectiveness and cost.

The clinical and economic effects of a programme of preventive dentistry for children in an inner-city health centre are compared with those for traditional restorative care. Reductions in the rate of dental caries are estimated to be 70% for children aged 4-6 after 4 years in the programme (dmft) and 85% for children aged between 7 and 10 years after 4 years (DMFT). The cost-effectiveness analysis on which the economic appraisal is based identifies the issue of differences in the quality of output as critical to choices between the two treatment regimes. The preventive programme was primarily intended for pre-school children; for this younger group, assumptions about the quality of the preventive outcome would have to value it at between 0.8 and 1.2 times the quality of the restorative outcome in order to make up the difference in cost between the two regimes. For 7-10 year olds, the 4-year analysis showed the preventive programme to be more costly than restorative care largely because of low rates of incremental change at these ages. These rates were partly influenced by the design of the study and partly by the eruption status of the permanent dentition across this age-group. There is a need for further study of measures of dental outcome which combine aspects of both the quality and length of life of teeth.

Child↗
PubMed1986

The effects of histamine on contraction frequency, sodium influx, and cyclic AMP in cultured rat heart cells.

Histamine has been shown to have both positive inotropic and chronotropic effects. To evaluate the chronotropic effects, spontaneously contracting monolayers of cultured rat myocardial cells were treated with histamine, 10(-7) M-10(-4) M. This resulted in a dose-dependent increase in contraction frequency reaching a maximum in 10(-5) M histamine. Contraction frequency (mean +/- SEM) increased from a control of 121 +/- 5 contractions per minute to 153 +/- 4.5, 181 +/- 9, 212 +/- 4, and 216 +/- 1 in 10(-7) M, 10(-6) M, 10(-5) M, and 10(-4) M histamine, respectively (for each n = 10, p less than 0.001). The effect was time-dependent, taking 30 minutes to develop fully. Changes in contraction frequency were accompanied by parallel dose- and time-dependent increases in the verapamil-sensitive sodium influx. Verapamil-sensitive sodium influx (pmol/cm2/sec) increased from a control of 10.45 +/- 1.44 (mean +/- SEM) to 24.34 +/- 2.41 and 32.57 +/- 2.35 at 10- and 30-minute treatment with 10(-6) M histamine (n = 5, p less than 0.001). These data fit the previously described relation between verapamil-sensitive sodium influx and contraction frequency in these cells. Cimetidine (10(-4) M) but not diphenhydramine (10(-4) M) abolished both the contraction frequency and sodium influx response to histamine. Subsequent studies showed a dose- and time-dependent elevation of cyclic adenosine monophosphate (cAMP) with histamine treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenylyl Cyclase Inhibitors↗
PubMed1985

Kinetics of thallium exchange in cultured rat myocardial cells.

The kinetics of thallium exchange in cultured rat myocardial cells were studied and compared to those of potassium in the same tissue. Studies were carried out using low concentrations (10 nM to 5 microM) of thallium-204, approximating those likely to be encountered during clinical myocardial scintigraphy. Both thallium uptake and release could be described by a single exponential with a half-time of exchange which was approximately half that of potassium and which was largely independent of extracellular thallium concentration. Some 60% of thallium uptake occurred via an "active" or ouabain-inhibitable mechanism which, in the absence of extracellular potassium, could be activated by low concentrations (10 nM to 5 microM) of thallium. The apparent Km for thallium on this active transport mechanism was 2-7 microM. Increasing extracellular potassium from 0-10 mM caused significant, concentration-dependent decreases in both the total and the active component of the thallium influx. Similarly nonradioactive thallium (0.10 microM to 0.10 mM) caused a concentration-dependent decrease in active potassium influx. Analysis of these results by both Lineweaver-Burk plots and Dixon plots confirmed competitive inhibition, potassium on thallium influx and vice versa, for the active component of the fluxes, and noncompetitive in the remainder. These findings indicate that active transport accounts for the greater portion of the influx of thallium and potassium, and that this active transport occurs via a common mechanism.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1984

Single coronary artery with the right coronary artery arising from the first septal perforator.

A 50-year-old woman with chest pain and an exercise thallium-201 scintigram positive for focal ischemia was found on coronary arteriography to have a heretofore unreported variant of single left coronary artery with the right coronary artery originating as a branch from the first septal perforator. Proximally, the aberrant vessel coursed through the ventricular septum at the level of the right ventricular outflow tract. A conus artery was absent and this is a possible basis for the focal basal ventricular ischemia and the patient's symptoms.

Coronary Vessel Anomalies↗
PubMed1979

Cation exchange and glycoside binding in cultured rat heart cells.

The Na/K-exchange characteristics, ouabain-binding kinetics, and Na pump turnover rates of synchronously contracting monolayers of neonatal rat myocardial cells were studied. The cells exchange Na rapidly (T1/2 = 35 s) with a mean Na flux of approximately 25 (pmol/cm2)/s. The half time (T1/2) of K exchange is much longer (12 min); the mean K flux is 13 (pmol/cm2)/s. Active Na/K transport, as measured by K influx, is relatively ouabain sensitive, and 10(-6) M ouabain produces half-maximal inhibition. Ouabain (10(-2)M) inhibits 60% of the Na efflux and 75% of the K influx. The cells bind [3H]ouabain rapidly (T1/2 = 8 min), but release it very slowly (T1/2 = 11 h), and both the amount bound and the rate of binding were inversely proportional to extracellular K. Specific [3H]ouabain binding demonstrates saturation reaching a maximum of 1.6 x 10(6) molecules per cell at 2 x 10(-7) M [3H]ouabain. From cell surface area and ouabain-sensitive flux measurements, the Na pump density was calculated at 720/micrometer2 with an individual pump turnover rate of 50/s. Thus the studies indicate that despite their neonatal origin, the behavior of the Na pump in these cells is very similar to that in other mammalian tissues.

Animals↗
PubMed1978

Responses of cultured heart cells to procainamide and lignocaine.

The effects of procainamide and lignocaine, in concentrations from 10(-6) to 10(-2) mol.litre(-1), on the Na influx and contraction frequency of cultured heart cells were studied. Both drugs produced a prompt, dose-dependent reduction in Na influx which was significant (P less than 0.01) for all concentrations tested. Lignocaine affected only that portion of the Na influx which was also verapamil-sensitive, whereas procainamide suppressed in addition, the verapamil-insensitive influx. In addition both drugs produced a concomitant decrease in the spontaneous contraction frequency of the cells. A close linear correlation (r = 0.99) between verapamil-sensitive Na influx and contraction frequency, in the presence of both procainamide and lignocaine was found. From this, and previous studies indicating a dependency of contraction frequency on the inward verapamil-sensitive Na influx, it is suggested that the drugs modify the automaticity of this preparation by a primary influence on membrane Na exchange.

Animals↗
PubMed1976

Electrocardiographic changes and cardiac arrhythmias in patients receiving psychotropic drugs.

Eight patients had cardiac manifestations that were life-threatening in five while taking psychotropic drugs, either phenothiazines or tricyclic antidepressants. Although most patients were receiving several drugs, Mellaril (thioridazine) appeared to be responsible for five cases of ventricular tachycardia, one of which was fatal in a 35 year old woman. Supraventricular tachycardia developed in one patient receiving Thorazine (chlorpromazine). Aventyl (nortriptyline) and Elavil (amitriptyline) each produced left bundle branch block in a 73 year old woman. Electrocardiographic T and U wave abnormalities were present in most patients. The ventricular arrhythmias responded to intravenous administration of lidocaine and to direct current electric shock; ventricular pacing was required in some instances and intravenous administration of propranolol combined with ventricular pacing in one. The tachyarrhythmias generally subsided within 48 hours after administration of the drugs was stopped. Five of the eight patients were 50 years of age or younger; only one clearly had antecedent heart disease. Major cardiac arrhythmias are a potential hazard in patients without heart disease who are receiving customary therapeutic doses of psychotropic drugs. A prospective clinical trial is suggested to quantify the risk of cardiac complications to patients receiving phenothiazines or tricyclic antidepressant drugs.

Adrenergic Agonists↗
PubMed1976

Effect of verapamil and of extracellular Ca and Na on contraction frequency of cultured heart cells.

Monolayer cultures of myocardial cells were prepared by trypsin dispersion of neonatal rat ventricles. The cells were cultured for 4-5 days by which time a synchronously contracting monolayer of some 1.0 x 10(6) cells per 6-cm diam petri dish had formed. The contraction frequency and Na influx of the cells were unaffected by tetrodotoxin (2 x 10(-5) mg/ml) but both were markedly reduced by the addition of verapamil (10(-9) M to 10(-5) M). The effect of verapamil on both parameters occurred very rapidly. Although unresponsive to change in [Ca]0 between 0.3 mM and 3.0 mM, the contraction frequency of the cells declined rapidly as the [Ca]0 was reduced below 0.3 mM. On the other hand the beating rate of the cells was linearly related to [Na]0 below 40 mM the cells ceased to contract. It is therefore apparent that both [Ca]0 and [Na]0 contribute to the maintenance of the contraction frequency of cultured myocardial cells, but the latter is by far the more important. There also appeared to be, under all conditions, a close relationship between verapamilsensitive Na influx and contraction frequency. For the greater part this relationship was linear although at higher Na influx values it appeared to show evidence of saturation.

Animals↗
PubMed1976

Influence of procainamide on sodium and potassium exchange and permeabilities in cultured human cells.

The effect of procainamide on membrane cation exchange was investigated using monolayer cultures of Girardi heart cells. The initial effect of procainamide (10(-6) to 10(-3) mol/litre) was to produce a prompt reduction of the passive Na influx, dose-dependent along a sigmoid log dose-response curve. This effect was complete within 3 min and thereafter showed no further time-dependent increase. Mean passive Na influx (pmol-cm-2/s) decreased from 19.1 to 17.7 (P less than 0.05) and 10.4 (P less than 0.001) in 10(-5) and 10(-3) mol/litre procainamide, respectively. No effect on active Na extrusion was noted before 3 min following exposure to the drug, after which time it progressively declined reaching a minimum value for each concentration by 6 min and remaining at this level throughout a further 60 min exposure. For each concetnration this minimum value was similar to the Na influx measured under identical conditions. Na-coupled active K influx showed a parallel pattern of inhibition. K efflux was not decreased until approximately 20 min following exposure to the drug, but once present the reduction was similar in magnitude to that in the correspondingly measured K influx. Kinetic flux analysis revealed a decrease in both PNa and PK but indicated a greater effect on PNa. The results suggest that all of the above effects could be explained on the basis of one direct action of the drug, namely, the prompt initial decrease in PNa and Na influx. All other effects noted, both active and passive, could then be secondary to this phenomenon.

Cell Membrane Permeability↗
PubMed1976

Effect of quinidine and temperature on sodium uptake and contraction frequency of cultured rat myocardial cells.

The effects of quinidine and temperature on Na influx and contraction frequency of synchronously contracting rat myocardial cells in monolayer cultures were studied. Quinidine (10(-6) M to 10(-1) M) produced a prompt reduction in Na influx, maximum after 30 seconds of exposure, and dose-dependent along a sigmoid log dose-response curve. At 37 degrees C, Na influx (mumol/10(11) cells per sec) decreased from 30.19 to 24.70 (P less than 0.001) and 10.49 (P less than 0.001) on exposure to quinidine, 10(-6) and 10(-2) M, respectively. Simultaneously the contraction frequency decreased from a control of 120/min to 105/min and 48/min with 10(-6) M and 5 X 10(-4) M quinidine. At higher concentrations spontaneous contractions ceased. The effects on Na influx and contraction were reversible by washing the cells free of the drug (30 seconds). A temperature-dependent decrease in the Na influx between 37 degrees C and 22 degrees C also induced a decrease in contraction frequency. Between 25 degrees C and 35 degrees C the Q10 values for Na influx and contraction frequency were 2.41 and 2.44 respectively. Under all conditions tested there was a constant linear relationship (r = 0.98) between Na influx and contraction frequency for all values of Na influx greater than 11.82 mumol/10(11) cells per sec. Na influx and contraction frequency were insensitive to tetrodotoxin (10(-5) g/ml) but very sensitive to verapamil and to changes in extracellular Na. Quinidine affected only the verapamil-sensitive Na influx. The results indicate a close relationship between verapamil-sensitive inward Na movement and automaticity in these cells and demonstrate that the quinidine-induced changes in automaticity are closely linked to the effect on Na influx.

Action Potentials↗
PubMed1976

Effect of quinidine on cation exchange in cultured cells.

The effects of quinidine on membrane ion exchange were examined using monolayer cultures of mammalian cells. Quinidine, in concentrations from 10(-6) to 10(-3) M, produced a prompt inhibition of the passive Na influx, dose-dependent along a sigmoid log dose-response curve. This effect was at a maximum for each concentration of the drug within 30 seconds of application. Passive Na influx (pmol/cm2/sec) decreased from 18.8 to 17.6 (P less than .05) and 10.5 (P less than .001) in the presence of 10(-6) and 10(-3) M quinidine, respectively. In the continued presence of quinidine, there was no further time-dependent effect on the Na influx, nor was there any tendency for the influx to recover. Washing the cells free of quinidine, however, resulted in a return of Na influx to control levels within 1 to 3 minutes. After 1 to 2 minute of quinidine treatment, coupled active Na efflux/K influx rapidly declined, reaching minimum values for each concentration between 2 to 4 minutes of drug treatment. Beyond that time, active Na/K fluxes again increased, but to values which remained significantly less than control, for up to 4 hours. Ten minutes of exposure to quinidine were required before any demonstrable effect on the passive K efflux could be recorded. In the presence of quinidine, there was reduced membrane turnover of both Na and K, but such that after a brief initial period (10 minutes or less) both ions were in flux equilibrium, explaining the absence of change in [Nai] and [Ki] in the presence of quinidine. Calculations of Ec1 indicated that, when present for 4 hours, quinidine did not change the Em in these cells although significant (P less than .001) reductions in apparent PNa and Pk values were recorded. The effect on PNa was much greater than that on Pk. The quinidine-induced flux changes occurred in a definite temporal sequence suggesting that they could all be explained on the basis of one direct initial action. This initial direct action, namely the prompt reduction in Na influx, by modifying Na pump activity, could lead to a decreased K efflux, secondary to the depressed Na-coupled active K influx via the Na pump.

Biological Transport, Active↗