A Statement on Abortion by 170 Obstetricians/Gynecologists after the Reversal of Roe v Wade.

In a recent American Journal of Obstetrics and Gynecology, 900 professors submitted a Special Report calling for reinstating federal protection for abortion. Here, we provide an alternative consensus statement. Induced abortion is not a constitutional right.

A bioluminescent assay for measuring glucose uptake.

Identifying activators and inhibitors of glucose uptake is critical for both diabetes management and anticancer therapy. To facilitate such studies, easy-to-use nonradioactive assays are desired. Here we describe a bioluminescent glucose uptake assay for measuring glucose transport in cells.

A bioluminescence assay for aldehyde dehydrogenase activity.

The aldehyde dehydrogenase (ALDH) family of enzymes is critical for cell survival and adaptation to cellular and environmental stress. These enzymes are of interest as therapeutic targets and as biomarkers of stem cells. This article describes a novel, homogeneous bioluminescence assay to study the activity of the ALDH enzymes.

Engineered luciferase reporter from a deep sea shrimp utilizing a novel imidazopyrazinone substrate.

Bioluminescence methodologies have been extraordinarily useful due to their high sensitivity, broad dynamic range, and operational simplicity. These capabilities have been realized largely through incremental adaptations of native enzymes and substrates, originating from luminous organisms of diverse evolutionary lineages. We engineered both an enzyme and substrate in combination to create a novel bioluminescence system capable of more efficient light emission with superior biochemical and physical characteristics.

Characterization of active site residues of nitroalkane oxidase.

The flavoenzyme nitroalkane oxidase catalyzes the oxidation of primary and secondary nitroalkanes to the corresponding aldehydes and ketones plus nitrite. The structure of the enzyme shows that Ser171 forms a hydrogen bond to the flavin N5, suggesting that it plays a role in catalysis. Cys397 and Tyr398 were previously identified by chemical modification as potential active site residues.

Differential quantum tunneling contributions in nitroalkane oxidase catalyzed and the uncatalyzed proton transfer reaction.

The proton transfer reaction between the substrate nitroethane and Asp-402 catalyzed by nitroalkane oxidase and the uncatalyzed process in water have been investigated using a path-integral free-energy perturbation method. Although the dominating effect in rate acceleration by the enzyme is the lowering of the quasiclassical free energy barrier, nuclear quantum effects also contribute to catalysis in nitroalkane oxidase. In particular, the overall nuclear quantum effects have greater contributions to lowering the classical barrier in the enzyme, and there is a larger difference in quantum effects between proton and deuteron transfer for the enzymatic reaction than that in water.

Crystal structures of intermediates in the nitroalkane oxidase reaction.

The flavoenzyme nitroalkane oxidase is a member of the acyl-CoA dehydrogenase superfamily. Nitroalkane oxidase catalyzes the oxidation of neutral nitroalkanes to nitrite and the corresponding aldehydes or ketones. Crystal structures to 2.

Bioluminescent assays for ADMET.

Bioluminescent assays couple a limiting component of a luciferase-catalyzed photon-emitting reaction to a variable parameter of interest, while holding the other components constant or non-limiting. In this way light output varies with the parameter of interest. This review describes three bioluminescent assay types that use firefly luciferase to measure properties of drugs and other xenobiotics which affect their absorption, distribution, metabolism, elimination and toxicity.

Mechanistic and structural analyses of the roles of Arg409 and Asp402 in the reaction of the flavoprotein nitroalkane oxidase.

The flavoprotein nitroalkane oxidase (NAO) catalyzes the oxidation of primary and secondary nitroalkanes to the corresponding aldehydes and ketones. The enzyme is a homologue of acyl-CoA dehydrogenase. Asp402 in NAO has been proposed to be the active site base responsible for removing the substrate proton in the first catalytic step; structurally it corresponds to the glutamate which acts as the base in medium chain acyl-CoA dehydrogenase.

A bioluminescent assay for monoamine oxidase activity.

This article describes a novel two-step homogeneous bioluminescent assay for monoamine oxidase (MAO) that is simple, sensitive, and amenable to high-throughput screening. In the first step, MAO reacts with an aminopropylether analog of methyl ester luciferin. In the second step, a luciferin detection reagent inactivates MAO and converts the product of the first step into a luminescent signal.

New bioluminogenic substrates for monoamine oxidase assays.

Novel bioluminogenic substrates were designed for probing monoamine oxidase (MAO) activity based on a simple and effective beta-elimination strategy. By modifying the amino group and the central core of luciferin derivatives, we have developed a series of substrates useful for assays of MAO A or B, or both. One of these substrates, exhibiting low Km values and high signal-to-background ratios with both isozymes, was shown to accurately measure the Ki values of known MAO inhibitors.

Crystal structures of nitroalkane oxidase: insights into the reaction mechanism from a covalent complex of the flavoenzyme trapped during turnover.

Nitroalkane oxidase (NAO) from Fusarium oxysporum catalyzes the oxidation of neutral nitroalkanes to the corresponding aldehydes or ketones with the production of H(2)O(2) and nitrite. The flavoenzyme is a new member of the acyl-CoA dehydrogenase (ACAD) family, but it does not react with acyl-CoA substrates. We present the 2.

Prevalence of severe pelvic organ prolapse in relation to job description and socioeconomic status: a multicenter cross-sectional study.

The aim of this study was to determine if certain occupations or socioeconomic levels are associated with pelvic organ prolapse. Investigators at six American sites performed pelvic organ prolapse quantification examinations on women presenting for routine gynecologic care. Between September 1999 and March 2002, 1,004 patients were examined.

Roles of the equatorial tyrosyl iron ligand of protocatechuate 3,4-dioxygenase in catalysis.

The active site Fe(III) of protocatechuate 3,4-dioxygenase (3,4-PCD) from Pseudomonas putida is ligated axially by Tyr447 and His462 and equatorially by Tyr408, His460, and OH(-). Tyr447 and OH(-) are displaced as protocatechuate (3,4-dihydroxybenzoate, PCA) chelates the iron and appear to serve as in situ bases to promote this process. The role(s) of Tyr408 is (are) explored here using mutant enzymes that exhibit less than 0.

The effect of pregnancy and mode of delivery on the prevalence of urinary and fecal incontinence.

Objective: The purpose of this study was to determine the relative effects of pregnancy and mode of delivery on the prevalence of urinary and fecal incontinence.

Study Design: This was a prospective, observational multicenter study of women presenting to 6 gynecology clinics. Demographic data collected included: height, weight, gravidity, parity, and number of vaginal deliveries.

Pelvic Organ Support Study (POSST) and bowel symptoms: straining at stool is associated with perineal and anterior vaginal descent in a general gynecologic population.

Objective: The purpose of this study was to evaluate the association of constipation symptoms and anal incontinence with vaginal wall and pelvic organ descent in a general gynecologic population.

Study Design: In this multicenter, cross-sectional study, 1004 women attending routine gynecologic healthcare underwent pelvic organ prolapse quantification (POPQ) measurements, and were surveyed regarding anal incontinence, digitation, < 2 bowel movements (BMs)/week, and > 25% frequency of: straining, hard/lumpy stools, and incomplete emptying. Constipation scores reflected the sum of positive responses.

Pelvic Organ Support Study (POSST): the distribution, clinical definition, and epidemiologic condition of pelvic organ support defects.

Objective: The purpose of this study was to describe the distribution of pelvic organ support in a gynecologic clinic population to define the clinical disease state of pelvic organ prolapse and to analyze its epidemiologic condition.

Study Design: This was a multicenter observational study. Subjects who were seen at outpatient gynecology clinics who required an annual gynecologic examination underwent a pelvic organ prolapse quantification examination and completed a prolapse symptom questionnaire.

Establishing the kinetic competency of the cationic imine intermediate in nitroalkane oxidase.

The flavoprotein nitroalkane oxidase catalyzes the oxidation of neutral nitroalkanes to the corresponding aldehydes and ketones. Cyanide inactivates the enzyme during turnover in a concentration-dependent fashion. Mass spectrometry of the flavin from enzyme inactivated by cyanide in the presence of nitroethane or nitrohexane shows that a flavin cyanoethyl or cyanohexyl intermediate has formed.

Nitroalkane oxidase, a carbanion-forming flavoprotein homologous to acyl-CoA dehydrogenase.

While several flavoproteins will oxidize nitroalkanes in addition to their physiological substrates, nitroalkane oxidase (NAO) is the only one which does not require the anionic nitroalkane. This, in addition to the induction of NAO by nitroethane seen in Fusarium oxysporum, suggests that oxidation of a nitroaliphatic species is the physiological role of the enzyme. Mechanistic studies of the reaction with nitroethane as substrate have established many of the details of the enzymatic reaction.

Crystallization and preliminary analysis of active nitroalkane oxidase in three crystal forms.

Nitroalkane oxidase (NAO), a flavoprotein cloned and purified from Fusarium oxysporum, catalyzes the oxidation of neutral nitroalkanes to the corresponding aldehydes or ketones, with the production of H2O2 and nitrite. In this paper, the crystallization and preliminary X-ray data analysis of three crystal forms of active nitroalkane oxidase are described. The first crystal form belongs to a trigonal space group (either P3(1)21 or P3(2)21, with unit-cell parameters a = b = 103.

Comparison of enzymatic and non-enzymatic nitroethane anion formation: thermodynamics and contribution of tunneling.

In the reaction of nitroalkane oxidase (NAO), the oxidation of nitroalkanes to the corresponding aldehydes or ketones is initiated by the deprotonation of the neutral nitroalkane. The energetics of nitroethane ionization for both the enzymatic and non-enzymatic reactions have been determined by measuring rate constants as a function of temperature. At 25 degrees C, the rate constant for the acetate-catalyzed reaction is a billionfold smaller than the kcat/Km value for NAO.

Treatment of overactive bladder with botulinum toxin type B: a pilot study.

The purpose of this study was to determine the efficacy and safety of botulinum toxin type B (BTX-B/Myobloc) in the treatment of patients with overactive bladder. This open-label dose-escalation study enrolled 15 female patients with urinary frequency with or without incontinence. The BTX-B doses used in this study were 2500, 3750, 5000, 10 000 and 15 000 units.

Inactivation of nitroalkane oxidase upon mutation of the active site base and rescue with a deprotonated substrate.

Mutation of Asp402 in nitroalkane oxidase to Asn or Ala inactivates the enzyme with neutral nitroethane as substrate, but the activity can be rescued with the nitroethane anion. The V/K values of the D402N and D402A enzymes with the nitroethane anion are independent of pH, whereas the V/K values of the wild-type and D402E enzymes are pH dependent with both the protonated and the deprotonated forms of nitroethane. Moreover, although the V/K value of the D402E enzyme with neutral nitroethane is 20-fold less than that of the wild-type enzyme, there is only a 2-fold difference in the V/K values with the nitroethane anion.