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Biomedical subjects

S MacLeod

Publications and source records attributed to S MacLeod.

12 recordsLinked to original sources

Effects of glucocorticoids on expression of the fos protooncogene in AtT-20 cells.

Glucocorticoid regulation of expression of the protooncogene fos has been examined in AtT-20 cells at both the RNA and protein levels. When cells were incubated continuously in the presence of dexamethasone, an early (30 min) rise in the expression of fos mRNA was observed, which declined by 1 h, but rose again after 2 h of hormone treatment. Six hours after hormone treatment, fos mRNA levels had returned to control levels in spite of the continued presence of dexamethasone. Serum treatment resulted in a sustained increase in fos mRNA levels; however, the glucocorticoid and serum effects were additive. Dexamethasone and/or serum both increased the steady state levels of fos protein. Glucocorticoid treatment of AtT-20 cells results in complex changes in fos expression, but does not affect their viability or growth rate; these results suggest that fos may play a role in mediation or modulation of glucocorticoid effects other than growth.

Animals

Interpretation of elevated postmortem serum concentrations of digoxin in infants and children.

The relationship between excessive postmortem digoxin concentrations (greater than 6.4 nmol/L) and administered dose, and antemortem levels and time of sampling after death were determined in 27 digitalized children who died in our hospital between March 24, 1981 and September 1, 1983. In all 27 cases, postmortem concentrations were higher than antemortem levels (9.5 +/- 2.5 nmol/L and 3.12 +/- 1.72 nmol/L, respectively). In none of these patients was there clinical or electrocardiographic evidence of digitalis toxicity. There was a significant correlation between antemortem and postmortem determinations, and between time of sampling after death and postmortem concentration. Positive correlation existed between antemortem or postmortem concentrations and dose per kilogram. The degree of elevation in digoxin levels was uniform in most cases, and the likelihood of elevation falling in the range 3.5 to 7.0 nmol/L was 66%. If the estimated concentration of digoxin at the time of death was taken as baseline, in 75% of cases the subsequent elevation was between 5.3 and 8.3 nmol/L (mean, 6.5 +/- 1.1 nmol/L). Digoxin concentrations measured in newborn infants not receiving digoxin were significantly higher after death (1.5 +/- 0.3 nmol/L) than in age-matched living infants not receiving digoxin (0.5 +/- 0.3 nmol/L). These data indicate that the size of antemortem dose, the time of sampling after death, and existence of endogenous digoxinlike factors affect postmortem readings of digoxin levels. Consequently, excessive postmortem determinations cannot be directly interpreted as proof of toxic antemortem levels.

Child, Preschool

Is pinworm a vanishing infection? Laboratory surveillance in a New York City medical center from 1971 to 1986.

Records of our parasitology laboratory were reviewed to determine trends in the frequency of specimens submitted for diagnosis of pinworm infection, the proportion of such specimens that were positive, and the proportion of such positive results for the pediatric age group from 1971 to 1986 in a major New York City medical center. These data demonstrate a markedly declining trend in the absolute number of sticky tape tests sent for pinworm diagnosis, from 248 in 1971 to 38 in 1986, an average of 8% decline per year. The number of specimens identifying Enterobius vermicularis among those submitted has similarly declined, from 57 in 1971 to none being positive in 1986, an average of 16% decline per year. The dramatic decline in pinworm identification and the fall in the number of specimens sent by practitioners at this medical center, and reported elsewhere in the United States by other investigators, may reflect a genuine decline in oxyuriasis occurring in the patient populations served.

Adolescent

The effects of maternal age and parity on birthweight: a population-based study in New York City.

New York City birth certificates for singletons born from September 1-December 31, 1981 (N = 36,056) were analyzed using multivariate regression techniques. The effects of maternal age and parity on birthweight were assessed. There was a significant progression of birthweight with advancing age. Birthweight similarly increased from parity 1 to parity 3, but dropped markedly in the higher parity groups. On stratification by gestational age, we found that age and parity influence birthweight by affecting fetal growth rather than the length of pregnancy.

Adolescent

Effects of quinidine on the renal tubular and biliary transport of digoxin: in vivo and in vitro studies in the dog.

Quinidine is known to inhibit the renal clearance of digoxin without affecting glomerular filtration rate. The renal interaction between these drugs was investigated by a combination of in vivo and in vitro methods. The uptake of digoxin by brush border membrane vesicles was not affected by quinidine. Similarly, digoxin did not inhibit the uptake of the cation N-methylnicotinamide by these vesicles and did not alter the binding kinetics of digoxin to the Na+, K+-adenosine triphosphatase by the antiluminal membrane vesicles. By using the in vivo multiple indicator dilution technique transtubular transport of digoxin was documented; renal-artery infusion of quinidine did not affect the recovery of digoxin in the renal vein or urine. Clearance studies documented that the decrease in the renal clearance of digoxin is paralleled by a significant fall in renal blood flow evidenced by a decrease in p-aminohippuric acid clearance. It is concluded that quinidine inhibits the renal excretion of digoxin not by competition at the tubular cell membrane level, but rather by decreasing renal blood flow. A parallel decrease in biliary clearance of digoxin is documented and may suggest a similar mechanism.

Animals

Cellular mechanisms of digoxin transport and toxic interactions in the kidney.

Renal tubular secretion of digoxin appears to be one of the main ports of elimination of the glycoside from the body. Because of its narrow therapeutic window and severe toxicity, the mechanisms of tubular handling of digoxin are important. Moreover, several drugs which are commonly administered with digoxin, including quinidine, spironolactone, verapamil and amiodarone have been shown to decrease renal clearance of digoxin without affecting GFR. We studied the handling of digoxin using in vitro and in vivo approaches. The handling of the glycoside by the brush border suggests passive reabsorption which is not enhanced by commonly coadministered drugs. Digoxin binding to the antiluminal (basal) membrane suggests that the secretion of the glycoside may not involve the pharmacologic receptor, the Na+, K+, ATPase. Using the multiple indicator dilution technique, we could directly show the two steps of secretion of digoxin: Its sequestration from the postglomerular circulation, and its appearance in the urine after transtubular transport. Digoxin transport is not inhibited by a cationic or anionic molecule (PAH and tolazoline). It is possible that digoxin is secreted by a yet unidentified transport mechanism.

Animals

Performance on a reciprocal tapping task with variations in intertapping interval.

Fitts' law was investigated in a study of the effect of the index of difficulty (ID) and intertapping interval upon reaction time (RT) and movement time (MT) for a reciprocal tapping task. ID showed its well-established relationship with MT as described by Fitts' law: MT = aID + b. Improvement in the linearity of this relationship was, however, demonstrated by expressing MT in logarithmic units. While ID had an unsubstantial (though significant) effect on RT, increases in intertapping interval from zero to any level of discrete tapping led to significant increases in RT of about 135 msec. The results are interpreted as lending support to Fitts' thesis that RT and MT reflect independent phases of information processing.

Humans

Ethanol and spinal presynaptic inhibition in man.

Ethanol, 0.65 gm per kilogram of body weight, was administered orally to 6 normal subjects. The mean blood ethanol levels ranged from 0.74 to 0.99 gm per liter over a subsequent 40-minute testing period. The proportion of the soleus motoneuron pool activated by the Achilles tendon reflex was reduced. Vibratory inhibition of the monosynaptic reflex was used as an estimate of spinal presynaptic inhibition. It was unaffected by ethanol.

Adult

Diazepam effect on reflex activity in patients with complete spinal lesions and in those with other causes of spasticity.

The effects of diazepam on reflex pathways in patients having complete spinal lesions and in patients having incomplete lesions of the spinal cord or multiple sclerosis are compared to determine whether diazepam has an action at spinal level. The drug produced no significant alteration in the excitability of the monosynaptic arc in the patients with complete spinal lesions. In contrast, in the group with incomplete spinal lesions or multiple sclerosis, diazepam reduced the excitability of the monosynaptic arc. This action did not appear to result from a reduction in fusimotor drive. Diazepam also reduced the tonic vibration reflex in this group. It is postulated that these effects may be due to a supraspinal action of the drug.

Achilles Tendon

The effect of diazepam on presynaptic inhibition in patients with complete and incomplete spinal cord lesions.

The effect of diazepam on presynaptic inhibition in man has been examined in 5 patients with complete spinal transections and 7 patients with incomplete lesions. The inhibition of the H reflex by vibration applied to the tendo Achilles was used to assess presynaptic inhibition of the Ia monosynaptic pathway. Diazepam increased this inhibition in the patients with incomplete lesions, but had no significant effect on the inhibition in the patients with complete spinal transections. Evidently diazepam can enhance presynaptic inhibition in man. The effect, however, cannot be demonstrated in patients with longstanding complete spinal lesions possibly because of some alteration in the segmental presynaptic inhibitory mechanism in this group.

Adult