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Biomedical subjects

S W Graves

Publications and source records attributed to S W Graves.

62 records · Page 4Linked to original sources
PubMed1984

An endogenous ouabain-like factor associated with hypertensive pregnant women.

Levels of a ouabain-like factor (OLF) were measured in amniotic fluid from 49 undigitalized third trimester pregnant women by means of its cross-reactivity in a digoxin RIA and its inhibition of ouabain-sensitive [Na,K]ATPase. The results from these 2 assays were significantly correlated (P less than 0.05). Of the women included in this study, 25 had blood pressures considered normal for their gestational age, while 24 had developed during their current pregnancy blood pressures judged to be elevated. When levels of OLF in the amniotic fluids from the normotensive and hypertensive pregnant women were compared, significantly higher levels were present in the hypertensive group for both assays (P less than 0.002). Further, there was a significant correlation between the diastolic blood pressures of these women at the time of amniocentesis and the amniotic fluid OLF levels determined by either assay (P less than 0.002). These results are consistent with OLF having a role in hypertensive complications of pregnancy.

Adolescent↗
PubMed1983

Endogenous substance in newborn infants causing false positive digoxin measurements.

We report the detection of a digoxin-like immunoequivalent substance in the plasma of neonates and infants and in amniotic fluid. Time-course studies in individual infants indicate that the substance probably is produced endogenously and is not exclusively retained by the infants from external sources. Digoxin recovery studies demonstrated that the presence of this material caused falsely elevated digoxin values. Our results cast considerable doubt on the reliability and clinical utility of digoxin radioimmunoassay measurements on the serum or plasma of neonatal and infant patients.

Amniotic Fluid↗
PubMed1983

An endogenous digoxin-like substance in patients with renal impairment.

Digoxin concentrations were measured in serum samples from 102 patients with renal impairment who were receiving digoxin therapy. Many patients had values that differed widely on several currently available immunoassays, with differences as great as 2.9 ng/mL. In contrast, patients with normal renal function who were receiving digoxin had few discrepant results, with the largest difference being 0.5 ng/mL. We also assayed serum samples from 54 patients with renal impairment not on digoxin therapy and found that more than 60% of these digoxin-free patients had false-positive digoxin values on most assays. Our data suggest that a substance with digoxin-like immunoactivity is present in many patients with renal insufficiency. This substance may seriously compromise the accuracy and interpretation of digoxin concentration measurements.

Creatinine↗
PubMed1982

Interaction of N-substituted ethanolamine analogs with ethanolamine ammonia-lyase, an adenosylcobalamin-requiring enzyme.

A number of N-substituted ethanolamine derivatives have been found to interact productively with ethanolamine ammonia-lyase, an adenosylcobalamin (AdoCbl) requiring enzyme that catalyzes the conversion of vicinal amino alcohols to oxo compounds. Inhibition, inactivation, cleavage of AdoCbl, and exchange of tritium out of [5'-3H]AdoCbl were all observed, the effects varying from analog to analog. The most striking effects were seen with azetidin-2-ol and pyrrolidin-3-ol, two aliphatic heterocycles composed of ethanolamine in which the nitrogen is tied back to the carbinol carbon by methylene bridges containing one and two carbon atoms, respectively. Incubation of azetidinol with the enzyme.AdoCbl complex resulted in extensive inactivation of the enzyme accompanied by cleavage of the cofactor; exchange of 3H from [5'-3H]AdoCbl into a nonbasic compound was also seen. Pyrrolidinol interacted with the enzyme.AdoCbl complex in a substrate-like way, causing exchange of 3H from labeled cofactor into a basic compound (perhaps the pyrrolidinol itself) together with a slight amount of C-Co bond cleavage. The interaction of the enzyme.AdoCbl complex with pyrrolidinol suggests that productively bound substrate is associated with the active site in such a way that the dihedral angle between the nitrogen and the oxygen is about 120 degrees, a configuration which maximizes bond-bond repulsions between the substituents on the adjacent carbon atoms.

Ammonia-Lyases↗
PubMed1980

The mechanism of action of ethanolamine ammonia-lyase, an adenosylcobalamin-dependent enzyme. Studies with isopropanolamine, a true substrate.

Ethanolamine ammonia-lyase catalyzes the adenosylcobalamin (AdoCbl)-dependent deamination of 1-amino-3-propanol (isopropanolamine) to acetone and NH3. During the course of the reaction a hydrogen is transferred from the carbinol carbon of the substrate to one of the methyl carbons of the product, the cofactor serving as intermediate hydrogen carrier. This result, together with previous results obtained with this and other AdoCbl-requiring enzymes, suggests that an initial step in the catalytic mechanism is the abstraction of a hydrogen atom from the substrate to produce the 1-amino-2-hydroxyprop-2-yl radical. This is a bulky species which for steric reasons is unlikely to alkylate cob(II)alamin. Thus, an organocobalamin formed by a reaction between the substrate radical and cob(II)alanin is probably not involved in the mechanism of deamination of isopropanolamine by ethanolamine ammonia-lyase.

Ammonia-Lyases↗
PubMed1980

Deamination of 2-aminopropanol by ethanolamine ammonia-lyase, an AdoCbl-requiring enzyme. Kinetics and isotope effects for the R and S enantiomers of the substrate.

Both (R)-2-aminopropanol and (S)-2-aminopropanol are substrates for ethanolamine ammonia-lyase, reacting to yield propionaldehyde and ammonia via a common enzyme-bound intermediate. (S)-Propanolamine shows a lower Km and a higher Vmax than the R enantiomer, indicating that the former is a substantially better substrate than the latter. From the isotope effects and other considerations, it appears that the rate-limiting step for (S)-propanolamine is the same as that for ethanolamine, namely, the transfer of hydrogen from the cofactor to the product. In contrast, isotope effects seen with (R)-propanolamine indicate that there are two rate-limiting steps, both located in the segment of the reaction mechanism which is unique to the R enantiomer. One of these is the transfer of hydrogen from the substrate to the cofactor. The other is a subsequent step whose rate is similar to that of the first hydrogen transfer step but which does not involve the rupture of a carbon-hydrogen bond. It is speculated that this second rate-limiting step may have to do with the migration of the amino group.

Ammonia-Lyases↗
PubMedDate not supplied

A labile sodium pump inhibitor from the peritoneal dialysate of hypertensive renal failure patients: estimates of potency.

Estimations of concentration of the labile sodium pump inhibitor isolated from human peritoneal dialysate were made using supercritical fluid chromatography coupled to flame ionization detection to determine the quantity of this factor in half of a purified preparation of the factor compared to the bioactivity of the other half in different assays. Ouabain was used for comparison. The labile factor appeared to be 30 times more effective than ouabain against canine renal [Na,K]ATPase. Moreover, this same factor appeared to be approximately 1,000 times more potent than ouabain in causing vascular smooth muscle contraction. The differences between this labile sodium pump inhibitor and ouabain most likely reflect their respective binding affinities. The assay differences in half maximal response to the labile sodium pump inhibitor may be due to differences in sodium pump alpha isoform sensitivity.

Animals↗