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Biomedical subjects

M Epstein

Publications and source records attributed to M Epstein.

At least 289 records · Page 16Linked to original sources

Structure-function studies of cholera toxin and its A and B protomers. Modification of tryptophan residues.

The tryptophan residues on cholera toxin and its A and B protomers have been modified by reaction with 2-nitrophenylsulfenyl chloride and 2,4-dinitrophenylsulfenyl chloride. Modification of the tryptophan residues of cholera toxin results in complete loss of toxicity measured in a skin permeability assay. Modification of cholera toxin and its B protomer results in the complete loss of binding activity toward membrane receptors, the ganglioside galactosyl-N-acetylgalactosaminyl-[N-acetylneuraminyl]-galactosylceramide (GM1), and the oligosaccharide moiety of the ganglioside GM1. Modification of cholera toxin and its A protomer results in a complete loss of the ADP-ribosylation activity exhibited by their native counterparts. Modification of the A protomer results in no apparent change in its physical properties by sedimentation velocity in the ultracentrifuge or by gel filtration chromatography. Modification of the B protomer, either directly or when it remains a component part of the holo toxin structure, results in a change in its sedimentation value and its elution from gel filtration columns. The changes are compatible with a conversion of the B protomer from a pentameric moiety in aqueous solvents to its existence as a monomer unit, i.e. to the individual polypeptide chains comprising the native B pentamer. Thiolysis of the 2,4-dinitrophenylsulfenyl chloride derivative of the B protomer reaggregates the individual-polypeptide chains but does not return its ability to interact with GM1.

Adenylyl Cyclases↗

Effects of vasopressin administration on diuresis of water immersion in normal humans.

Although previous studies have demonstrated that water immersion to the neck (NI) results in a significant diuresis, the mechanisms are incompletely delineated. Because recent studies in our laboratory have demonstrated that NI is associated with a suppression of antidiuretic hormone (ADH), it is possible that such a suppression mediates the encountered diuresis. The present study was undertaken to assess more directly the relative role of ADH suppression by determining the effects of vasopressin administration. Six hydrated normal subjects were studied on two occasions while undergoing 6 h of NI. During the second NI study, aqueous vasopressin (20 mU/h) was infused for the initial 4 h of study (NI + vasopressin). NI resulted in a significant increase in urinary flow rate beginning during hour 1 and persisting throughout NI. In contrast, during NI + vasopressin, the anticipated diuresis was abolished throughout the 4 h of vasopressin administration. Cessation of vasopressin administration during the final 2 h of NI + vasopressin resulted in a marked and prompt diuresis. The present observations are consistent with the formulation that ADH suppression participates importantly in mediating the diuresis of NI in hydrated normal subjects.

Adult↗

Functional adaptation to reduction in renal mass: renal handling of amino acids by isolated perfused remnant rat kidneys.

To date, the renal handling of amino acids by remnant kidneys remains undefined. We have determined the renal handling of eight amino acids using the isolated perfused rat kidney. 6 normal and 22 partially infarcted rat kidneys (16 stage III [contralateral kidney removed], and 6 stage II [contralateral kidney left intact] were evaluated at perfusate amino acid concentrations approximately ten times normal plasma levels. Despite the reduction in glomerular filtration rate, the urinary excretion of most amino acids in remnant kidneys tended to exceed that of controls. Fractional amino acid excretion by both stage II and III kidneys tended to be or was higher than that of controls. The findings indicate that the fractional reabsorption of amino acids by residual nephrons of remnant kidneys is decreased. Our observations suggest that the changes are unrelated to a functional adaptation to the uremic environment.

Adaptation, Physiological↗

Isoosmotic central blood volume expansion suppresses plasma arginine vasopressin in normal man.

Despite numerous studies which have characterized the regulation of antidiuretic hormone (ADH), the role of volume in governing ADH release remains incompletely defined. Most studies have examined the quantitative effects of hypovolemia on arginine vasopressin (AVP). In contrast, few have assessed the role of hypervolemia on AVP regulation. Furthermore, there are no data to date on the effect of acute isoosmotic volume expansion on plasma AVP in man. The successful characterization of the water immersion model (NI) and the demonstration that it induces an acute central volume expansion without changes in plasma composition commended its utilization in the present study. Twelve normal subjects were studied after 14 h of dehydration on two occasions: control and during 4 h of NI. Blood was obtained every 30 min for AVP. AVP was unaltered during the control period. In contrast, there was a prompt and sustained suppression of AVP throughout NI (P < 0.05 vs. control). There were no concomitant changes in plasma osmolality. Since the changes in AVP occurred consequent to central volume expansion but in the absence of concomitant changes in plasma composition, the current data support the concept that acute isoosmotic central volume expansion in man results in a suppression of plasma AVP.

Adult↗

Infarction of the spinal cord as a complication of pneumococcal meningitis. Case report.

Spinal cord infarction in association with pneumococcal meningitis has not been previously recognized. The case is reported of a 5 1/2-year-old boy who had Streptococcus pneumoniae meningitis complicated by the sudden onset of flaccid paraplegia and loss of all sensory modalities below the level of T-2. At operation, the spinal cord was pale and enveloped by dense adhesions, suggesting compromise of the arterial vasculature with concomitant infarction.

Child, Preschool↗

Calorimetric studies of ligand-induced modulation of calcium adenosine 5'-triphosphatase from sarcoplasmic reticulum.

The enthalpy change (delta H degrees ') associated with the binding of Mg2+ to the sarcoplasmic reticulum calcium adenosine 5'-triphosphatase [(Ca2+)ATPase] is -76 kcal/mol. The affinity constant for Mg2+ obtained from calorimetric measurements agrees with the Km value for Mg2+ in the phosphorylation of the enzyme by inorganic phosphate (Pi). The delta H degrees ' of binding of Pi to the enzyme is -23.5 kcal/mol, and the affinity constant for Pi obtained from the calorimetry also agrees with the Km value for Pi in the phosphorylation reaction. delta H degrees ' of Mg2+ binding is reduced to -35 kcal/mol in the presence of either 20 mM Pi or 1.2 mM Ca2+ without a significant change in the affinity of the enzyme for Mg2+. delta H degrees ' of Pi binding to the enzyme drops to -8.5 kcal/mol in the presence of 10 mM Mg2+ without a significant change in the affinity of the enzyme for Pi. On the other hand, the presence of Ca2+ does not affect the delta H degrees ' for the binding of the substrate analogue 5'-adenylyl beta,gamma-imidodiphosphate [App(NH)p], and the presence of this analogue does not affect the delta H degrees ' for Ca2+ binding. The results suggest a model in which a conformational change, largely controlled by Mg2+ binding to the enzyme, leads to the formation of the covalent phosphoprotein intermediate.

Animals↗

Endoscopy: developments in optical instrumentation.

Optical fibers transmit high-intensity illumination for viewing internal organs and tissue. Remote viewing is obtained by relays of lenses or graded-index-of-refraction rods in rigid endoscopes and by precisely aligned fiber-optic bundles in flexible fiberscopes. Endoscopy is considered for routine examinations, such as in colonoscopy. Lasers are used as surgical tools through endoscopes for cutting and coagulation. They may also be used to provide illumination for the efficient transmission of light through thin optical fibers.

Colonoscopes↗

Dissociation of renin--aldosterone and renal prostaglandin E during volume expansion induced by immersion in normal man.

The relationship of the renin--angiotensin--aldosterone axis with renal prostaglandin E is complex. Although studies have suggested that these two hormonal systems respond to experimental manipulations in a parallel manner, their interdependence has not been assessed fully during volume expansion. Since studies have demonstrated that in normal man the central hypervolaemia induced by water immersion to the neck produces a prompt and profound suppression of plasma renin activity and plasma aldosterone concentration without concomitant alteration of plasma composition, immersion afforded a unique opportunity to assess simultaneously the effects of central hypervolaemia on plasma renin activity, plasma aldosterone concentration and prostaglandin E excretion. 2. Seven normal subjects were studied twice while in balance on a diet containing 10 mmol of sodium/day, 100 mmol of potassium/day: with indomethacin administration (50 mg given every 6 h for five doses) and without indomethacin. Urinary prostaglandin E excretion was measured hourly and plasma renin activity and plasma aldosterone concentration at 30 min intervals. 3. Immersion was associated with a marked suppression of plasma renin activity (59 +/- 7%) and plasma aldosterone concentration (55 +/- 3%) with a return to pre-study values during the recovery hour. Concomitantly, urinary prostaglandin E excretion increased from 4.7 to a peak of 10.9 ng/min. Although administration of indomethacin lowered the basal rate of urinary prostaglandin E excretion and plasma renin activity, it did not prevent the subsequent augmentation of urinary prostaglandin E or the suppression of plasma renin activity and plasma aldosterone during the subsequent 4 h of immersion. 4. These results demonstrate a dissociation of renin--aldosterone and prostaglandin E during hypervolaemia and suggest that whereas prostaglandin E may constitute one of the major determinants of renin release clinically and experimentally, these two hormonal systems can be dissociated from each other in response to central volume expansion in man.

Adult↗

Uptake and release of amino acids by normal and remnant kidneys: studies in the isolated perfused rat kidney.

In order to evaluate the capacity of normal and remnant kidneys to take up and release amino acids when plasma concentrations are increased above normal levels, we have determined the simultaneous net uptake or release of eight representative amino acids using the isolated perfused rat kidney model. Eight normal and five partially infarcted kidneys from Sprague-Dawley rats were perfused with Krebs-Ringer's bicarbonate buffer containing glucose 8 g/100 ml albumin and amino acids at concentrations approximately 10 times above normal plasma levels. Urine was collected every 15 min for 75 min, and perfusate samples were obtained at the midpoint of each urine collection. Amino acids were measured by gas-liquid chromatography. During perfusion, there was substantial net utilization of asparate, proline, alanine, and glycine by normal kidneys. In remnant kidneys the net uptake of amino acids tended to be lower than that of the normal kidneys. The fractional excretion of most amino acids by remnant kidneys was significantly higher than that of controls. These studies demonstrate the substantial capacity of the kidney to take up or release amino acids when presented with an increased load. The findings suggest that the fractional reabsorption of amino acids by residual nephrons of remnant kidneys is decreased.

Amino Acids↗

Embolization of multiple pulmonary artery fistulas.

Therapeutic embolization of pulmonary arteriovenous fistulas is described as an alternate method of treatment for patients with diffuse pulmonary involvement in whom resection is not feasible.

Arteriovenous Malformations↗

Characterization of renal response to prolonged immersion in normal man.

During the initial phase of spaceflight, there is a translocation of fluid from the lower parts of the body to the central vascular compartment with a resultant natriuresis, diuresis, and weight loss. Whether this natriuresis and diuresis result in the attainment of a new steady state or whether the circulatory adjustment is incomplete is the subject of continuing controversy. Because water immersion is regarded as an appropriate model for studying the redistribution of fluid that occurs in weightlessness, we carried out an immersion study of relatively prolonged duration in order to characterize the temporal profile of the renal adaptation to central hypervolemia. Twelve normal male subjects underwent an immersion study of 8-h duration in the sodium-replete state. Immersion resulted in marked natriuresis and diuresis which were sustained throughout the immersion period. The failure of that natriuresis and diuresis of immersion to abate or cease despite marked extrcellular fluid volume contraction as evidenced by a mean weight loss of -2.2 +/- 0.3 kg suggests that central blood volume was not restored to normal and that some degree of central hypervolemia probably persisted.

Adolescent↗