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Biomedical subjects

J L Powers

Publications and source records attributed to J L Powers.

14 recordsLinked to original sources
PubMed1998

Control of voltage-independent zinc inhibition of NMDA receptors by the NR1 subunit.

Zinc inhibits NMDA receptor function through both voltage-dependent and voltage-independent mechanisms. In this report we have investigated the role that the NR1 subunit plays in voltage-independent Zn2+ inhibition. Our data show that inclusion of exon 5 into the NR1 subunit increases the IC50 for voltage-independent Zn2+ inhibition from 3-fold to 10-fold when full length exon 22 is also spliced into the mature NR1 transcript and the NMDA receptor complex contains the NR2A or NR2B subunits; exon 5 has little effect on Zn2+ inhibition of receptors that contain NR2C and NR2D. Mutagenesis within exon 5 indicates that the same residues that control proton inhibition, including Lys211, also control the effects of exon 5 on Zn2+ inhibition. Amino acid exchanges within the NR1 subunit but outside exon 5 (E181Q, E339Q, E342Q, N616R, N616Q, D669N, D669E, C744A, and C798A) that are known to decrease the pH sensitivity also decrease the Zn2+ sensitivity, and concentrations of spermine that relieve tonic proton inhibition also relieve Zn2+ inhibition. In summary, our results define the subunit composition of Zn2+-sensitive NMDA receptors and provide evidence for structural convergence of three allosteric regulators of receptor function: protons, polyamines, and Zn2+.

Animals↗
PubMed1996

Mechanism-based inactivation of dopamine beta-monooxygenase in adrenal chromaffin cells.

Dopamine beta-monoxygenase (DBM, E.C. 1.14.17.1) is an attractive target point for possible modulation of adrenergic activity, and a variety of DBM-targeted pseudosubstrates and inhibitors have been developed in this laboratory and other laboratories. We now demonstrate the efficacy of a DBM-targeted mechanism-based inactivator, as well as enzymatic processing of two alternate DBM substrates, within functional adrenal chromaffin cells. When cultured adrenal medullary chromaffin cells were incubated with the mechanism-based inactivator 1-(4'-hydroxyphenyl)-1-(aminomethyl)-ethene (HOPAME), vesicular DBM activity was markedly decreased. Similarly, the alternate substrates 4'-hydroxyphenyl-2-aminoethyl sulfide and 4'-hydroxyphenyl-2-aminopropyl selenide each undergo uptake and DBM-catalyzed oxygenation within these cells. The simultaneous action of both the mechanism-based inactivator and an alternate substrate within functional chromaffin cells was also demonstrated. These results provide support for a direct mechanistic link between the enzymological properties of DBM-targeted adrenergic agents and their in-vivo pharmacological activities.

Adrenal Medulla↗
PubMed1996

Properties of azithromycin that enhance the potential for compliance in children with upper respiratory tract infections.

BACKGROUND: Azithromycin, the prototypical azalide antibiotic, has a wide spectrum of activity that is characterized by resistance to beta-lactamase-producing microbes and efficacy against Gram-positive and Gram-negative pathogens, including Haemophilus influenzae. Tissue-directed pharmacokinetics include tissue concentrations up to 100-fold higher than those in plasma and a tissue half-life of up to 4 days. Pharmacokinetics of azithromycin permits a reduction in dosage frequency and duration while maintaining efficacy comparable to that of conventional 7- to 10-day three or four times daily regimens. Dosage interval, duration of treatment, side effects and palatability can affect compliance and thus clinical outcome. Compliance among children is important in light of the high incidence of community-acquired infections such as otitis media and streptococcal pharyngitis. OBJECTIVE: To compare the flavor, taste acceptability and color preference of oral antibiotic suspensions given to children. METHODS: The taste and acceptability of the oral suspension form of azithromycin vs. cefixime, cefpodoxime proxetil, cefprozil, clarithromycin or loracarbef were rated by children during blinded taste tests and with acceptability/ preference questionnaires. RESULTS: Analysis of the mean acceptability/ preference rating from 769 children demonstrated that the flavor of azithromycin was rated significantly higher than that of cefpodoxime (4.3 vs. 2.8), cefprozil (4.0 vs. 3.4) and clarithromycin (4.3 vs. 2.7) and was comparable to that of cefixime (4.0 vs. 4.2) and loracarbef (4.4 vs. 4.5). A greater percentage of children preferred the taste of azithromycin to that of cefpodoxime (90.0% vs. 5.2%), cefprozil (63.0% vs. 33.1%) and clarithromycin (89.0% vs. 11.0%). The taste of azithromycin was not preferred to that of cefixime (39.0% vs. 53.9%) or loracarbef (36% vs. 58.5%). CONCLUSIONS: The efficacy and safety of azithromycin in otitis media and streptococcal pharyngitis, the simple dosing regimen and a highly palatable oral suspension formulation should increase compliance among pediatric patients and thereby improve clinical outcomes.

Administration, Oral↗
PubMed1995

Structural requirements for cocaine-sensitive and -insensitive uptake of phenethylamines into the adrenal chromaffin cell.

The adrenal medullary chromaffin cell is a commonly used model for the adrenergic neuron. Although much work has been done to study the transport system in the adrenal chromaffin vesicles, relatively little is known about cellular transport, especially with regard to structural features of phenethylamines required for intracellular accumulation. We have now investigated the structural requirements of phenethylamine-related compounds for their accumulation into cultured adrenal chromaffin cells. We find that two types of cellular uptake, previously described only for dopamine, norepinephrine, and epinephrine, are also present for [3H]tyramine. Although two types of accumulation occur, tyramine accumulation occurs mainly via a cocaine-insensitive process, whereas dopamine accumulation occurs predominantly via a cocaine-sensitive process. The accumulation of [14C]-phenethylamine and p-methoxyphenethylamine is not affected by cocaine, suggesting that a ring hydroxyl substituent is necessary for cocaine-sensitive accumulation. The compounds p-hydroxyphenylpropylamine and p-hydroxyphenyl-2-aminoethyl sulfide accumulate in the cell only via a cocaine-insensitive process, indicating that lengthening of the aminoalkyl side chain prevents cocaine-sensitive accumulation. We have performed conformational analyses of this series of compounds to determine whether the conformation of these compounds can be related to the kinetic data. For dopamine, tyramine, phenethylamine, and p-methoxyphenethylamine, two groups of energy-minimized conformers were found. We find that there is an approximately linear relationship between the Km values for these phenethylamines and the differences in minimized energies between the low- and highest energy conformer groups of each compound. A similar correlation was found for p-hydroxyphenyl-2-aminoethyl sulfide. These results are consistent with the hypothesis that these compounds undergo a conformational change from the low-energy conformer to the highest energy conformer before their cocaine-insensitive accumulation.

Adrenal Glands↗
PubMed1993

The epidemiology of child abuse: findings from the Second National Incidence and Prevalence Study of Child Abuse and Neglect.

The epidemiology of child abuse was investigated with data from the Second National Incidence and Prevalence Study of Child Abuse and Neglect. A statistical comparison of incidence rates suggested that age, family income, and ethnicity were risk factors for both sexual abuse and physical abuse, but county metrostatus was not. Gender was a risk factor for sexual abuse but not for physical abuse. A logistic regression analysis showed that ethnicity, county metrostatus, and a gender-by-income interaction distinguished sexual abuse from physical abuse.

Adolescent↗
PubMed1993

Accepting and refusing assignments.

Guidelines define the professional, ethical and legal responsibilities involved when challenging or delegating patient assignments. Maintaining safe nursing practice levels is possible through such alternatives as enabling practice environments and cross-training. These significant factors identify options available to nurse managers and their staff without compromising patient safety.

Humans↗
PubMed1990

Maltreatment among runaway and homeless youth.

A sample of 223 adolescents who sought services from runaway and homeless youth programs in New York State during 1986-1987 was identified as having a history of maltreatment. A demographic profile is presented and the nature of their maltreatment described. The majority of these youth were female and between 15-16 years of age. Less than 25% came from intact families and one-third were born to single mothers. Of the sample, 60% had allegedly experienced physical abuse, 42% emotional abuse, 48% neglect, and 21% sexual abuse. Over one-third were "pushed out" of their homes by their families. Biological mothers were the most frequently cited perpetrators of maltreatment (63%), followed by biological fathers (45%). The sample of maltreated runaways is compared to both statewide and national samples of runaway and homeless youth with regard to their demographic characteristics and the problems they present to staff at intake (e.g., depression, substance abuse, etc.). Youth in the maltreated sample were more likely to be female and were more likely to have engaged in suicidal behavior. Otherwise, the maltreated runaways were not readily distinguished from the runaway and homeless youth population at large.

Adolescent↗
PubMed1988

The maltreatment of adolescents.

Official reports of maltreatment involving adolescent victims were compared to those involving younger children in a representative sample of protective services' reports drawn from New York State in 1985. Specific case characteristics, including age, gender, ethnicity of the victim, and source of report, are described and their relation to case substantiation is examined. Analyses revealed that adolescents represent a substantial proportion of all victims of official child maltreatment reports. The impact of age on substantiation varied as a function of the type of maltreatment, where for adolescents sexual abuse reports were more likely to be substantiated, while neglect and physical abuse reports were less likely to be substantiated. Reports involving adolescents were significantly more likely to involve a female victim. Significant gender differences in substantiation rate were found only for sexual abuse reports involving adolescents. White children were also found to be under-represented in this sample, while blacks were over-represented relative to their numbers in the population. The impact of minority status on substantiation was significant for neglect and physical abuse reports involving children. The majority of adolescent reports came from mandated sources, which had a significantly higher substantiation rate than reports from non-mandated sources.

Adolescent↗
PubMed1979

Spironolactone-associated digoxin radioimmunoassay interference.

Apparent digoxin was measured in the serum of 21 patients receiving spironolactone and in 21 controls, by use of a sequential-saturation 3H-radioimmunoassay (RIA) and an equilibrium 125I-RIA. No patient had been given digoxin for at least four weeks. "Digoxin" values in the former group were significantly (p less than 0.05) higher than in the control group, and often were in or near the "therapeutic" range by the equilibrium 125I-RIA, but not by the sequential-saturation 3H-RIA. Canrenone (a major active metabolite of spironolactone) in the serum of the former group was measured by a newly developed liquid-chromatographic technique and correlated (r = 0.73) with "digoxin" concentrations by the 125I-RIA. However, external addition of canrenone to control serum in comparable concentrations did not cause appreciable "digoxin" values by the 125I-RIA. These findings suggest that other metabolites of spironolactone are responsible for the assay interference, the degree of which appears to depend on antibody specificity. Therefore, assay specificity should be established in clinical laboratories by using digoxin-free serum from patients ingesting spironolactone, and not by using spironolactone- or canrenone-fortified digoxin-free serum.

Digoxin↗
PubMed1978

Determination of quinidine by high-performance liquid chromatography.

Quinidine in serum was measured at 330 nm, after protein precipitation, with an alkyl phenyl reversed-phase chromatographic column by peak-height determination (external standards.) Sensitivity was 0.3 mg/liter, with linear response to at least 10 mg/liter serum. Interassay precision, measured on 20 consecutive days, gave a CV of 8.2% at 2 mg/liter of serum and 5.1% at 5 mg/liter. Quinine and primaquine are not separable from quinidine under the assay conditions, and dihydroquinidine and chloridazepoxide are only partly resolved. No assay interference was encountered with a series of control serum samples obtained from patients with various diseases, who were being treated with various drugs other than quinidine, except in one serum sample with a high bilirubin concentration (300 mg/liter). If such an assay interference is present, an alkaline extraction of quinidine before analysis has to be used. Results by our assay and those by a single-extraction fluorescence method correlated poorly (r=0.87), and the fluorescence assay gave 50% +/- 7% (SEM) higher values than our method, due to chromatographic separation of a major fluorescent non-phenolic metabolite of quinidine, which can also be measured by our assay.

Chromatography, High Pressure Liquid↗
PubMed1977

Measurement of procainamide and N-acetylprocainamide in serum by high-performance liquid chromatography.

We measured procainamide (I) and its metabolite, N-acetylprocainamide (II), in human serum samples by solvent extraction, high-performance liquid chromatography on a reverse phase column, and detection at 280 nm, with use of external standards. The method requires 0.2 ml of serum and is sensitive to 0.3 mg of I and 0.6 mg of II per liter of serum, with intra-assay standard deviations of 0.22 and 0.24 mg/liter, respectively, at 5 mg/liter (N=10) and inter-assay standard deviations of 0.63 and 0.81 mg/liter, respectively, at 7.5 mg/liter (CV 8.4 and 10.5%, respectively, n = 20). Concentrations measured by high-performance liquid chromatography and by an established fluorescence technique correlated well (r = 0.98 for I and 0.97 for II). No interfering substances were found in 20 randomly selected sera from patients receiving a large number of other drugs. Of the pure drug substances tested only sulfathiazole interfered with the assay of II. The method is therefore suitable for routinely monitoring these compounds in serum in a clinical laboratory. The high concentrations of the metabolite in a significant number of patients demonstrate the need to consider it as well as the parent drug as guides in optimizing dosage regiments for I.

Chromatography, High Pressure Liquid↗