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Biomedical subjects

H Shapiro

Publications and source records attributed to H Shapiro.

At least 73 records · Page 4Linked to original sources

A new fluorescent dihydrofolate reductase probe for studies of methotrexate resistance.

A new fluorescent methotrexate analogue (PT430) was synthesized as a reported ligand for dihydrofolate reductase. The analogue was prepared by attachment of lysine in place of the glutamate side chain of methotrexate and conjugation to fluorescein isothiocyanate via the epsilon-amino group of lysine. Spectrophotometric enzyme inhibition assays showed PT430 to be about one-tenth as potent as methotrexate against either Lactobacillus casei or L1210 mouse leukemia enzyme; competitive radioligand binding assays using tritiated methotrexate gave similar results. In assays of L1210 cell proliferation in culture, on the other hand, PT430 was 100-fold less toxic than methotrexate. In dilute solution, the fluorescence intensity of PT430 was 5-fold lower than that of equimolar fluorescein and diminished with decreasing pH. On complexation with dihydrofolate reductase, however, fluorescence intensity was enhanced 3- to 5-fold depending on the pH. Measurement of fluorescence increase with added ligand provided data for the determination of the stoichiometric ratio, dissociation constant, and extent of fluorescence enhancement. Specificity of PT430 for methotrexate binding sites was indicated by the observation of decreased fluorescence uptake in PT430-treated L1210 cells in the presence of methotrexate. Fluorescence uptake occurred faster, and to a greater extent, in methotrexate-resistant dihydrofolate reductase overproducing L1210/R6 cells than in the methotrexate-sensitive parent line. Therefore, PT430 may be used as a flow cytometry probe to detect methotrexate resistance based on dihydrofolate reductase overproduction.

Animals↗

Management of recurrent and residual common duct stones.

When operating on patients with postcholecystectomy choledocholithiasis, a drainage procedure should be performed for the following indications: (1) multiple stones in the duct, (2) history of choledocholithotomy, (3) marked dilatation of the duct, (4) inability to remove all stones, and (5) presence of a ductal stricture. Patients with none of these are adequately treated by choledocholithotomy alone. Because endoscopic sphincterotomy has been shown to be safe and effective, however, it is currently our preferred method of treatment for the average patient with this condition.

Adult↗

Single dose piperazine therapy for Ascaris lumbricoides: an unsuccessful method of promoting growth.

One-hundred eighty-five Bangladeshi children age 1 1/2 to 8 yr with no Ascaris lumbricoides infection or with light, moderate, or heavy infection were randomly assigned to treatment of placebo groups, with treatment given in a double-blind fashion. The groups were comparable for nutritional and socioeconomic parameters. Treatment consisted of a single dose of piperazine citrate administered twice within a 2-wk period. The cure rates for the low, moderate, and heavy A. lumbricoides infected subgroups were 53, 31, and 36%, respectively. With more severe infections, worm eradication was more difficult and the rate of reinfection after treatment was more rapid. The rate of reinfection was significantly different for the low A. lumbricoides infected treatment and placebo subgroups for 5 months after treatment, for the moderate treatment and placebo subgroups for 3 months after treatment, and for the heavy A. lumbricoides infected treatment and placebo subgroups there was a difference, although not significant, for 1 month after treatment. Anthropometric measurements were obtained for a period of 11 months. Analysis of covariance revealed no significant difference for change of weight, change of height, weight-for age, weight-for-height, height-for-age, triceps skinfold, midarm circumference, and the abdominal girth to chest circumference ratio between the treatment and placebo groups after drug administration. The results of this study do not support single dose worm therapy as a means to enhance growth.

Anthelmintics↗

Methodology for intraventricular and subarachnoid continuous recording of intracranial pressure in clinical practice.

The methodology for continuous monitoring intracranial pressure (ICP) being presently employed in the Neurosurgery Service of the University of Pennsylvania is presented. The methods are intraventricular recording of ICP (IVP) and subarachnoid recording of ICP (SaP). The indications for employing either method are briefly presented. IVP is favored in those situations in which the lateral ventricles are enlarged and SaP is preferred in the cases of brain swelling or other situations in which there is a small ventricular system.

Cerebral Ventricles↗

Radiographic evaluation of pancreatico-jejunal shunts.

This paper describes opacification and identification of two surgically constructed pancreatico-jujunal shunts. A fibreoptic panendoscope was used with retrograde injection via the ampulla of Vater (ERCP). This procedure makes possible more accurate anatomical evaluation and so more precise clinical appraisal of both pre- and post-surgical states.

Adult↗

On the adaptation in potassium excretion associated with nephron reduction in the dog.

An effort to examine certain aspects of the adaptation in potassium excretion associated with nephron reduction was made in dogs with unilateral remnant kidneys. A constant intake of potassium was maintained by tube feeding and studies were performed before and after removal of the intact control kidney. The removal of the intact kidney created the need for the remaining nephrons of the remnant kidney to increase their rate of potassium excretion markedly. Sodium intake was held constant either at a normal or a low level. Mineralocorticoid hormone activity was maintained either at a high level by the administration of 0.2 mg 9-alpha-fluorohydrocortisone daily or at a low level by performing bilateral adrenalectomy and administering a minimal maintenance dose of deoxycorticosterone acetate (DOCA) and cortisol. Potassium excretion per nephron increased strikingly within 18 hr of contralateral nephrectomy and by 7 days, excretion rates were 600% of control values for the remnant kidney. More potassium was excreted in the first 5 hr after administration of a test dose of potassium by the remnant kidney alone in the postnephrectomy state than by both the remnant and intact kidneys in the prenephrectomy state. 24 hr excretion of potassium by the remnant kidney postnephrectomy averaged 92% of the administered load of potassium. The adaptation in potassium excretion was independent of the concurrent rate of sodium excretion and of mineralocorticoid hormone activity and persisted during constriction of the renal artery, a stimulus which presumably decreased distal delivery of sodium. The adaptation and the continued modulation of potassium excretion could not be explained adequately by an increase in impermeant anion excretion per nephron. Finally, known changes in hydrogen ion excretion per nephron associated with nephron reduction are in a direction opposite to those which would explain the acquired kaliuresis per nephron.

Adaptation, Physiological↗