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P M Weiss

Publications and source records attributed to P M Weiss.

At least 19 recordsLinked to original sources
PubMed1992

13C and 15N isotope effects as a probe of the chemical mechanism of Escherichia coli aspartate transcarbamylase.

13C and 15N isotope effects have been measured for the aspartate transcarbamylase (ATCase) reaction in an effort to elucidate the chemical mechanism of this highly regulated enzyme. The observed 15(V/K(asp))H2O value for the ATCase holoenzyme at saturing carbamyl phosphate and 12 mM L-aspartate is 1.0045 at pH 7.5, and this value remains unchanged in the presence of 5 mM ATP (activator) or 5 mM CTP (inhibitor). The fact that the isotope effect is not changed by the allosteric modifiers supports the conclusion that the kinetic properties of the active form of ATCase are not influenced by ATP or CTP. The observed 15(V/K(asp)) values for the catalytic subunit of ATCase are also the same as those determined for the holoenzyme, suggesting that the chemical mechanisms of both enzyme species are the same. Quantitative analysis of 13C and 15N isotope effects in both H2O and D2O has led to the proposal of a chemical model for the ATCase reaction which involves a precatalytic conformational change to form an activated complex that facilitates deprotonation of L-aspartate by an enzyme functional group. Nucleophilic attack on the carbonyl carbon of carbamyl phosphate by the alpha-amino group of L-aspartate results in the formation of a tetrahedral intermediate. An intramolecular proton transfer leads to formation of products N-carbamyl-L-aspartate and inorganic phosphate.

Aspartate Carbamoyltransferase↗
PubMed1991

Transition-state structures for enzymatic and alkaline phosphotriester hydrolysis.

The primary and secondary 18O isotope effects for the alkaline (KOH) and enzymatic (phosphotriesterase) hydrolysis of two phosphotriesters, O,O-diethyl p-nitrophenyl phosphate (I) and O,O-diethyl O-(4-carbamoylphenyl) phosphate (II), are consistent with an associative mechanism with significant changes in bond order to both the phosphoryl and phenolic leaving group oxygens in the transition state. The synthesis of [15N, phosphoryl-18O]-, [15N, phenolic-18O]-, and [15N]-O,O-diethyl p-nitrophenyl phosphate and O,O-diethyl O-(4-carbamoylphenyl)phosphate is described. The primary and secondary 18O isotope effects for the alkaline hydrolysis of compound I are 1.0060 and 1.0063 +/- 0.0001, whereas for compound II they are 1.027 +/- 0.002 and 1.025 +/- 0.002, respectively. These isotope effects are consistent with the rate-limiting addition of hydroxide and provide evidence for a SN2-like transition state with the absence of a stable phosphorane intermediate. For the enzymatic hydrolysis of compound I, the primary and secondary 18O isotope effects are very small, 1.0020 and 1.0021 +/- 0.0004, respectively, and indicate that the chemical step in the enzymatic mechanism is not rate-limiting. The 18O isotope effects for the enzymatic hydrolysis of compound II are 1.036 +/- 0.001 and 1.0181 +/- 0.0007, respectively, and are comparable in magnitude to the isotope effects for alkaline hydrolysis, suggesting that the chemical step is rate-limiting. The relative magnitude of the primary 18O isotope effects for the alkaline and enzymatic hydrolysis of compound II reflect a transition state that is more progressed for the enzymatic reaction.

Aryldialkylphosphatase↗
PubMed1991

Multiple isotope effects with alternative dinucleotide substrates as a probe of the malic enzyme reaction.

Deuterium isotope effects and 13C isotope effects with deuterium- and protium-labeled malate have been obtained for both NAD- and NADP-malic enzymes by using a variety of alternative dinucleotide substrates. With nicotinamide-containing dinucleotides as the oxidizing substrate, the 13C effect decreases when deuterated malate is the substrate compared to the value obtained with protium-labeled malate. These data are consistent with a stepwise chemical mechanism in which hydride transfer precedes decarboxylation of the oxalacetate intermediate as previously proposed [Hermes, J. D., Roeske, C. A., O'Leary, M. H., & Cleland, W. W. (1982) Biochemistry 21, 5106]. When dinucleotide substrates such as thio-NAD, 3-acetylpyridine adenine dinucleotide, and 3-pyridinealdehyde adenine dinucleotide that contain modified nicotinamide rings are used, the 13C effect increases when deuterated malate is the substrate compared to the value obtained with protium-labeled malate. These data, at face value, are consistent with a change in mechanism from stepwise to concerted for the oxidative decarboxylation portion of the mechanism. However, the increase in the deuterium isotope effect from 1.5 to 3 with a concomitant decrease in the 13C isotope effect from 1.034 to 1.003 as the dinucleotide substrate is changed suggests that the reaction may still be stepwise with the non-nicotinamide dinucleotides. A more likely explanation is that a beta-secondary 13C isotope effect accompanies hydride transfer as a result of hyperconjugation of the beta-carboxyl of malate as the transition state for the hydride transfer step is approached.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Modification of a thiol at the active site of the Ascaris suum NAD-malic enzyme results in changes in the rate-determining steps for oxidative decarboxylation of L-malate.

A thiol group at the malate-binding site of the NAD-malic enzyme from Ascaris suum has been modified to thiocyanate. The modified enzyme generally exhibits slight increases in KNAD and Ki metal and decreases in Vmax as the metal size increases from Mg2+ to Mn2+ to Cd2+, indicative of crowding in the site. The Kmalate value increases 10- to 30-fold, suggesting that malate does not bind optimally to the modified enzyme. Deuterium isotope effects on V and V/Kmalate increase with all three metal ions compared to the native enzyme concomitant with a decrease in the 13C isotope effect, suggesting a switch in the rate limitation of the hydride transfer and decarboxylation steps with hydride transfer becoming more rate limiting. The 13C effect decreases only slightly when obtained with deuterated malate, suggestive of the presence of a secondary 13C effect in the hydride transfer step, similar to data obtained with non-nicotinamide-containing dinucleotide substrates for the native enzyme (see the preceding paper in this issue). The native enzyme is inactivated in a time-dependent manner by Cd2+. This inactivation occurs whether the enzyme alone is present or whether the enzyme is turning over with Cd2+ as the divalent metal activator. Upon inactivation, only Cd2+ ions are bound at high stoichiometry to the enzyme, which eventually becomes denatured. Conversion of the active-site thiol to thiocyanate makes it more difficult to inactivate the enzyme by treatment with Cd2+.

Animals↗
PubMed1991

Secondary 18O isotope effects for hexokinase-catalyzed phosphoryl transfer from ATP.

Secondary 18O isotope effects in the gamma-position of ATP have been measured on phosphoryl transfer catalyzed by yeast hexokinase in an effort to deduce the structure of the transition state. The isotope effects were measured by the remote-label method with the exocyclic amino group of adenine as the remote label. With glucose as substrate, the secondary 18O isotope effect per 18O was 0.9987 at pH 8.2 and 0.9965 at pH 5.3, which is below the pK of 6.15 seen in the V/K profile for MgATP. With the slow substrate 1,5-anhydro-D-glucitol, the value was 0.9976 at pH 8.2. While part of the inverse nature of the isotope effect may result from an isotope effect on binding, the more inverse values when catalysis is made more rate limiting by decreasing the pH or switching to a slower substrate suggest a dissociative transition state for phosphoryl transfer, in agreement with predictions from model chemistry. The 18O equilibrium isotope effect for deprotonation of HATP3- is 1.0156, while Mg2+ coordination to ATP4- does not appear to be accompanied by an 18O isotope effect larger than 1.001.

Adenosine Triphosphate↗
PubMed1990

Single and multiple worm infections of Echinostoma caproni (Trematoda) in the golden hamster.

Six of 10 hamsters fed a single metacercarial cyst of Echinostoma caproni (single-worm infections) and 13 of 19 hamsters fed either 2 or 5 cysts (multiple-worm infections) were infected with adult echinostomes at necropsy 22 days post-infection. Considerable histopathological changes to the small intestine occurred in hamsters carrying single-worm infections. There were no differences in either mean length, width or wet weight of echinostomes in single- versus multiple-worm infections. The mean number of eggs/worm from single-worm infections (525) was significantly greater than that from multiple-worm infections (288). The average percentage of fully developed miracidia/worm from single worms (94%) was similar to that from worms in multiple infections (92-95%). Single worms of E. caproni were capable of self-fertilization and production of viable eggs. Miracidia derived from single worms were as capable of infecting laboratory-reared Biomphalaria glabrata and producing patent rediae as were those from multiple infections.

Animals↗
PubMed1989

Enzymatic synthesis and inhibitory characteristics of tartronate semialdehyde phosphate.

The immediate product of the pyruvate kinase catalyzed phosphorylation of beta-hydroxypyruvate is the enol of tartronate semialdehyde phosphate (TSP). The reaction has the same pH profile as that for the phosphorylation of pyruvate with pK's of 8.2 and 9.7 observed in H2O. This enol tautomerizes in solution to the aldehyde, which in turn becomes hydrated. 31P NMR spectra indicate that the enol resonates approximately 1 ppm upfield from the hydrated aldehyde. By following the tautomerization spectrophotometrically at 240 nm, we have found it to be independent of pH (0.2 min-1 below pH 6 in water), except that it is 2-fold slower above the pK of the phosphate group (6.3 in H2O and 6.7 in D2O). It is 3.6-fold slower in D2O. When this TSP is reduced with NaBH4, approximately 50% of the product is D-2-phosphoglyceric acid (substrate for enolase). Thus, while the immediate product of the phosphorylation rection is the enol of TSP, the eventual product is D,L-TSP. Both the enol and the aldehyde forms of TSP were found to be potent inhibitors of yeast enolase with apparent Ki values of 100 nM and 5 microM, respectively. However, since the aldehyde form is 95-99% hydrated [Stubbe, J., & Abeles, R. (1980) Biochemistry 19, 5505], the true Ki for the aldehyde species is 50-250 nM. The enol of TSP shows slow binding behavior, as expected for an intermediate analogue, with a t1/2 for this process of approximately 15 s (k = 0.046 s-1) and an initial Ki of approximately 200 nM.

Cadmium↗
PubMed1988

Use of primary deuterium and 15N isotope effects to deduce the relative rates of steps in the mechanisms of alanine and glutamate dehydrogenases.

We have used deuterium and 15N isotope effects to study the relative rates of the steps in the mechanisms of alanine and glutamate dehydrogenases. The proposed chemical mechanisms for these enzymes involve carbinolamine formation, imine formation, and reduction of the imine to the amino acid [Grimshaw, C.E., Cook, P.F., & Cleland, W.W. (1981) Biochemistry 20, 5655; Rife, J.E., & Cleland, W.W. (1980) Biochemistry 19, 2328]. These steps are almost equally rate limiting for V/Kammonia with alanine dehydrogenase, while with glutamate dehydrogenase carbinolamine formation, imine formation, and release of glutamate after hydride transfer provide most of the rate limitation of V/Kammonia. Release of oxidized nucleotide is largely rate limiting for Vmax for both enzymes. When beta-hydroxypyruvate replaces pyruvate, or 3-acetylpyridine NADH (Acpyr-NADH) or thio-NADH replaces NADH with alanine dehydrogenase, nucleotide release no longer limits Vmax, and hydride transfer becomes more rate limiting. With glutamate dehydrogenase, replacement of alpha-ketoglutarate by alpha-ketovalerate makes hydride transfer more rate limiting. Use of Acpyr-NADPH has a minimal effect with alpha-ketoglutarate but causes an 8-fold decrease in Vmax with alpha-ketovalerate, with hydride transfer the major rate-limiting step. In contrast, thio-NADPH with either alpha-keto acid causes carbinolamide formation to become almost completely rate limiting. These studies show the power of multiple isotope effects in deducing details of the chemistry and changes in rate-limiting step(s) in complicated reaction mechanisms such as those of alanine and glutamate dehydrogenases.

Alanine Dehydrogenase↗
PubMed1988

Kinetics and mechanism of benzoylformate decarboxylase using 13C and solvent deuterium isotope effects on benzoylformate and benzoylformate analogues.

Benzoylformate decarboxylase (benzoylformate carboxy-lyase, BFD; EC 4.1.1.7) from Pseudomonas putida is a thiamine pyrophosphate (TPP) dependent enzyme which converts benzoylformate to benzaldehyde and carbon dioxide. The kinetics and mechanism of the benzoylformate decarboxylase reaction were studied by solvent deuterium and 13C kinetic isotope effects with benzoylformate and a series of substituted benzoylformates (pCH3O, pCH3, pCl, and mF). The reaction was found to have two partially rate-determining steps: initial tetrahedral adduct formation (D2O sensitive) and decarboxylation (13C sensitive). Solvent deuterium and 13C isotope effects indicate that electron-withdrawing substituents (pCl and mF) reduce the rate dependence upon decarboxylation such that decreased 13(V/K) effects are observed. Conversely, electron-donating substituents increase the rate dependence upon decarboxylation such that a larger 13(V/K) is seen while the D2O effects on V and V/K are not dramatically different from those for benzoylformate. All of the data are consistent with substituent stabilization or destabilization of the carbanionic intermediate (or carbanion-like transition state) formed during decarboxylation. Additional information regarding the mechanism of the enzymic reaction was obtained from pH studies on the reaction of benzoylformate and the binding of competitive inhibitors. These studies suggest that two enzymic bases are required to be in the correct protonation state (one protonated and one unprotonated) for optimal binding of substrate (or inhibitors).

Benzoates↗
PubMed1987

Evidence from nitrogen-15 and solvent deuterium isotope effects on the chemical mechanism of adenosine deaminase.

We have determined 15N isotope effects and solvent deuterium isotope effects for adenosine deaminase using both adenosine and the slow alternate substrate 7,8-dihydro-8-oxoadenosine. With adenosine, 15N isotope effects were 1.0040 in H2O and 1.0023 in D2O, and the solvent deuterium isotope effect was 0.77. With 7,8-dihydro-8-oxoadenosine, 15N isotope effects were 1.015 in H2O and 1.0131 in D2O, and the solvent deuterium isotope effect was 0.45. The inverse solvent deuterium isotope effect shows that the fractionation factor of a proton, which is originally less than 0.6, increases to near unity during formation of the tetrahedral intermediate from which ammonia is released. Proton inventories for 1/V and 1/(V/K) vs percent D2O are linear, indicating that a single proton has its fractionation factor altered during the reaction. We conclude that a sulfhydryl group on the enzyme donates its proton to oxygen or nitrogen during this step. pH profiles with 7,8-dihydro-8-oxoadenosine suggest that the pK of this sulfhydryl group is 8.45. The inhibition of adenosine deaminase by cadmium also shows a pK of approximately 9 from the pKi profile. Quantitative analysis of the isotope effects suggests an intrinsic 15N isotope effect for the release of ammonia from the tetrahedral intermediate of approximately 1.03 for both substrates; however, the partition ratio of this intermediate for release of ammonia as opposed to back-reaction is 14 times greater for adenosine (1.4) than for 7,8-dihydro-8-oxoadenosine (0.1).(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Deaminase↗
PubMed1987

Effect of the presence of a reversible inhibitor on the time course of slow-binding inhibition.

The half-time for the initial burst seen when a slow-binding inhibitor is present in an enzyme assay decreases from 0.693/k4 to 0.693/(k3 + k4) as the concentration of the slow-binding inhibitor is increased from zero to infinity (k3 and k4 are forward and reverse rate constants for the isomerization causing the slow-binding behavior). If the inhibitor solution contains a classical reversible inhibitor in addition to the slow-binding one, the half-time decreases from the same limit at zero inhibitor to a level which is higher at infinite inhibitor concentration (k3 is divided by (1 + xKi/Kj), where x is the ratio of classical and slow-binding inhibitor concentrations, and Ki and Kj are their initial inhibition constants before the slow-binding phase). Thus if one is using a racemic inhibitor, both enantiomers of which inhibit initially but only one of which shows slow-binding behavior, one will not obtain the correct parameters for the pure slow-binding inhibitor. A similar situation would apply if one were using a mixture of inhibitors such as antibiotics, several of which inhibit initially, but only one of which is a slow-binding inhibitor. This theory is illustrated by determining the half-times for the slow-binding inhibition of yeast hexokinase by various levels of TmATP in the presence and absence of HoATP, which shows little slow-binding behavior.

Adenosine Triphosphate↗
PubMed1985

Use of nitrogen-15 and deuterium isotope effects to determine the chemical mechanism of phenylalanine ammonia-lyase.

Phenylalanine ammonia-lyase has been shown to catalyze the elimination of ammonia from the slow alternate substrate 3-(1,4-cyclohexadienyl)alanine by an E1 cb mechanism with a carbanion intermediate. This conclusion resulted from comparison of 15N isotope effects with deuterated (0.9921) and unlabeled substrates (1.0047), and a deuterium isotope effect of 2.0 from dideuteration at C-3, with the equations for concerted, carbanion, and carbonium ion mechanisms. The 15N equilibrium isotope effect on the addition of the substrate to the dehydroalanine prosthetic group on the enzyme is 0.979, while the kinetic 15N isotope effect on the reverse of this step is 1.03-1.04 and the intrinsic deuterium isotope effect on proton removal is in the range 4-6. Isotope effects with phenylalanine itself are small (15N ones of 1.0021 and 1.0010 when unlabeled or 3-dideuterated and a deuterium isotope effect of 1.15) but are consistent with the same mechanism with drastically increased commitments, including a sizable external one (i.e., phenylalanine is sticky). pH profiles show that the amino group of the substrate must be unprotonated to react but that a group on the enzyme with a pK of 9 must be protonated, possibly to catalyze addition of the substrate to dehydroalanine. Incorrectly protonated enzyme-substrate complexes do not form. Equilibrium 15N isotope effects are 1.016 for the deprotonation of phenylalanine or its cyclohexadienyl analogue, 1.0192 for deprotonation of NH4+, 1.0163 for the conversion of the monoanion of phenylalanine to NH3, and 1.0138 for the conversion of the monoanion of aspartate to NH4+.(ABSTRACT TRUNCATED AT 250 WORDS)

Ammonia-Lyases↗
PubMed1984

Kinetic mechanism and location of rate-determining steps for aspartase from Hafnia alvei.

Coupled spectrophotometric assays that monitor the formation of fumarate and ammonia in the direction of aspartate deamination and aspartate in the direction of fumarate amination were used to collect initial velocity data for the aspartase reaction. Data are consistent with rapid equilibrium ordered addition of Mg2+ prior to aspartate but completely random release of Mg2+, NH4+, or fumarate. In addition to Mg2+, Mn2+ can also be used as a divalent metal with Vmax 80% and a Kaspartate 3.5-fold lower than when Mg2+ is used. Monovalent cations such as Li+, K+, Cs+, and Rb+ are competitive vs. either aspartate or NH4+ but noncompetitive vs. fumarate. A primary deuterium isotope effect of about 1 on both V and V/Kaspartate is obtained with (3R)-L-aspartate-3-d, while a primary 15N isotope effect on V/Kaspartate of 1.0239 +/- 0.0014 is obtained in the direction of aspartate deamination. A secondary isotope effect on V of 1.13 +/- 0.04 is obtained with L-aspartate-2-d. In addition, a secondary isotope effect of 0.81 +/- 0.05 on V is obtained with fumarate-d2, while a value of 1.18 +/- 0.05 on V is obtained by using (2S,3S)-L-aspartate-2,3-d2. These data are interpreted in terms of a two-step mechanism with an intermediate carbanion in which C-N bond cleavage limits the overall rate and the rate-limiting transition state is intermediate between the carbanion and fumarate.

Ammonia↗
PubMed1984

N-hydroxycarbamate is the substrate for the pyruvate kinase catalyzed phosphorylation of hydroxylamine.

The true substrate for the pyruvate kinase catalyzed phosphorylation of hydroxylamine at high pH which is activated by bicarbonate is shown to be N-hydroxycarbamate, since a lag is seen when the reaction is started by the addition of bicarbonate or hydroxylamine but a burst appears when it is started with a mixture of the two. The lag can be diminished by addition of carbonic anhydrase but not eliminated, showing that CO2 is an intermediate in the formation of the carbamate and that both the formation of CO2 and the subsequent reaction of CO2 with hydroxylamine limit the rate of carbamate formation. The equilibrium constant for the reaction bicarbonate + hydroxylamine reversed N-hydroxycarbamate is 1.33 M-1. The product of the phosphorylation decomposes by loss of CO2 to O-phosphorylhydroxylamine, which is stable at 25 degrees C between pH 3 and 11 and has pK2 = 5.63 for the phosphate and pK3 = 10.26 for the amino group.

Bicarbonates↗
PubMed1984

Reaction intermediate analogues for enolase.

A number of compounds that appear to be analogues of the aci form of the normal carbanion intermediate are good inhibitors of yeast enolase. These include (3-hydroxy-2-nitropropyl)phosphonate (I), the ionized (pK = 8.1) nitronate form of which in the presence of 5 mM Mg2+ has a Ki of 6 nM, (nitroethyl)phosphonate (III) (pK = 8.5; Ki of the nitronate in the presence of 5 mM Mg2+ = 1 microM), phosphonoacetohydroxamate (IV) (pK = 10.2; Ki with saturating Mg2+ for the ionized form = 15 pM), and (phosphonoethyl)nitrolate (VII) (Ki at 1 mM Mg2+ = 14 nM). The oxime of phosphonopyruvate (VI) has a pH-independent Ki of 75 microM. I, IV, VI, and VII are slow binding inhibitors. All of these compounds are trigonal at the position analogous to C-2 of 2-phosphonoglycerate and contain a phosphono group, but a negatively charged metal ligand at the position isosteric with the hydroxyl attached to C-3 of 2-phosphoglycerate (as in IV) appears to contribute more to binding than a nitro group isosteric with the carboxyl of 2-phosphoglycerate (I and III). These data support the carbanion mechanism for enolase and suggest that the 3-hydroxyl of 2-phosphoglycerate is directly coordinated to Mg2+ prior to being eliminated to give phosphoenolpyruvate.

Indicators and Reagents↗
PubMed1983

Multifunctionality of lipoamide dehydrogenase promotion of electron transferase reaction.

Various approaches to promote the one-electron transfer reaction of lipoamide dehydrogenase have been investigated. An addition of riboflavin facilitates the electron transfer between NADH and Fe(CN) 3-/6. Aminocarboxymethylation and cadmium derivatization of the catalytic disulfide moderately activate the electron transfer reaction. An enhancement in the electron transferase activity of the Co(II)-enzyme complex is associated with decreased Michaelis and inhibition constants. Phosphopyridoxamidation identifies the suppressive effect on the electron transferase activity of carboxyl groups proximal to the catalytic histidine residue of lipoamide dehydrogenase. Amidation of these carboxyl groups with diamine greatly promote the one-electron transfer reaction. The increased electron transferase activity of the amidated enzyme is related to the charge nature of the amidated nucleophile and associated with the increased catalytic efficiency which undergoes a shift in the pH profile. The introduction of cationic aminoethyl groups presumably encourages the formation of an anionic flavosemiquinone which promotes the one-electron transfer reaction.

Animals↗
PubMedDate not supplied

Does centralized monitoring affect perinatal outcome?

A retrospective study was performed comparing centralized monitoring to noncentralized monitoring in regard to perinatal outcome. The study was conducted at Lehigh Valley Hospital (Allentown, PA) between August 1994 and February 1995. All deliveries during a 28-week-period were studied retrospectively. The study was designed such that for 14 weeks all patients were centrally monitored (Group A). During the following 14 weeks, no patients were centrally monitored (Group B). Patients not requiring monitoring, such as elective cesarean sections, were excluded from the study. The variables that were studied were the 5-minute Apgar, cord blood pH, perinatal mortality, admissions to the neonatal intensive care unit (NICU), spontaneous vaginal deliveries, cesarean sections, and operative vaginal deliveries. A total of 1,622 deliveries occurred during the 28 weeks of antenatal care. Group A consisted of 805 centralized monitored patients and Group B had 817 noncentralized monitored patients. There was no statistical difference in the 5-minute Apgar, umbilical artery pH, perinatal mortality, or the NICU admissions between the two groups. However, there was a significant statistical difference in the percent of cesarean sections performed for nonreassuring fetal heart rate tracings (Group A, 17.89% vs. Group B, 12.16%; P = 0.02). The overall cesarean section rate was increased in the centrally monitored group (Group A, 23.6% vs. Group B, 18.1%; P = 0.01). There were also statistically significant differences in operative vaginal deliveries (forceps and vacuum) for fetal heart rate abnormalities between Group A, 0.52% vs. Group B, .39% (P = 0.05). Centralized monitoring may be associated with an increase in the overall cesarean section rate. In addition, the rate of operative vaginal and abdominal deliveries appears to be increased for the indication of nonreassuring fetal heart rate tracings with the use of centralized monitoring.

Apgar Score↗