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Biomedical subjects

C H Kennedy

Publications and source records attributed to C H Kennedy.

At least 37 records · Page 2Linked to original sources
PubMed1994

Nodality effects during equivalence class formation: An extension to sight-word reading and concept development.

Three students with moderate disabilities were taught to read and match-to-sample sight words comprising stimulus sets based upon the four food groups. We taught students conditional discriminations within four four-member sets using a single-sample/four-comparison procedure. Students were taught A-B, B-C, and C-D conditional discriminations for each of the four potential stimulus classes. Subsequent probes tested for relations based upon symmetry and one-node and two-node transitivity. The performances for all students indicated that symmetric relations emerged before one-node transitive relations, and that one-node transitive relations emerged before two-node transitive relations. These results are consistent with a pattern of responding, referred to as a "nodality effect," in which relations with fewer nodes are demonstrated prior to the demonstration of relations with a greater number of nodes. These results extend this area of research to sight-word reading for students with moderate disabilities.

Journal Article↗
PubMed1993

Effect of dose on the disposition of 2-ethoxyethanol after inhalation by F344/N rats.

Glycol ethers such as 2-ethoxyethanol (EE) are widely used as solvents because they are miscible in aqueous and organic solutions. Toxic effects of EE in rodents include teratogenicity, fetotoxicity, hematotoxicity, and testicular atrophy. The purpose of this study was to determine the effect of dose on the absorption, metabolism, and excretion of 2-ethoxy [U-14C]ethanol by F344/N rats after inhalation exposure. Rats were exposed to either 5 ppm EE for 5 hr 40 min or 46 ppm EE for 6 hr. The uptake and metabolism of EE were linear in the concentration range studied. Significant percentages of the retained doses were exhaled during (22%) and after exposure (16%) as 14CO2. Forty-six percent of the retained dose was excreted in the urine. Approximately 10% of the retained dose was detected in the carcass 66 hr after exposure. The major urinary metabolite was ethoxyacetic acid (EAA), the toxic metabolite of EE. The amount of EAA excreted was linearly related to exposure concentration. Ethylene glycol and N-ethoxyacetyl glycinate were identified as minor metabolites excreted in the urine. The results of this study suggest that the toxicity of inhaled EE should be directly proportional to the exposure concentration up to 46 ppm if the toxicity of EE is due to EAA.

Administration, Inhalation↗
PubMed1993

Effect of dose on the metabolism of 1,1,2,2-tetrabromoethane in F344/N rats after gavage administration.

1,1,2,2-Tetrabromo[U-14C]ethane ([14C]TBE) was used to study the metabolism of TBE in rats. Three graded doses of TBE (1.17, 13.6, and 123 mg/kg; 1 microCi 14C/rat at each dose) were administered by gavage to three groups of four rats each. Excreta samples were collected at various time intervals up to 96 hr. Following euthanization, 14C activity was measured in the excreta, tissues, and carcass. The fraction of the dose exhaled as volatile metabolites of TBE, excluding 14CO2, was approximately 9-10% higher in rats given the high dose of TBE compared to that in rats given either the low or the medium dose. The fraction excreted in the urine decreased with increasing TBE dosage. 1,2-Dibromoethylene and tribromoethylene were identified as exhaled metabolites at the high dose. Three major urinary metabolites were identified: dibromoacetic acid, glyoxylic acid, and oxalic acid. The results of this study indicate that the metabolism of TBE was linear up to a dose of 13.6 mg/kg, but the contribution of various TBE metabolic pathways was different at a dose of 123 mg/kg.

Acetates↗
PubMed1993

Effects of setting events on the problem behavior of students with severe disabilities.

Two studies analyzed the effects of preceding setting events on the problem behavior of students with severe disabilities. Using ABAB withdrawal designs, the occurrence versus nonoccurrence of preceding setting events was analyzed in relation to the frequency of problem behavior. Data were collected throughout a student's school day, with interventions focusing upon the elimination of setting events that occurred before school. The results indicate that (a) the occurrence of preceding setting events was related to higher frequencies of problem behavior and (b) interventions designed to eliminate preceding setting events were consistently associated with low frequencies of problem behavior.

Activities of Daily Living↗
PubMed1993

Teaching choice making during social interactions to students with profound multiple disabilities.

We taught 4 students with profound multiple disabilities to use a microswitch communication system to request a change in recreational stimuli during social interactions with nondisabled peers. In Study 1, we conducted a preference assessment across a range of stimuli for each student. The most and least preferred stimuli were incorporated into microswitch communication system training in Study 2. During the second study, 3 of the 4 students (a) learned to use the microswitch communication system to control stimulus presentation, (b) more clearly differentiated their time among stimuli, and (c) increased their level of general alertness. Study 3 extended the use of the microswitch communication system to social interactions with nondisabled peers. Two students were more engaged in interactions when they chose when to change stimuli; 1 student was more alert when a peer chose when to change activities; a 4th student showed an undifferentiated pattern. The outcomes of the investigation are discussed in terms of the effects of controlling stimulus presentation on the behavior of students with profound multiple disabilities and the stability of preference hierarchies over time.

Adolescent↗
PubMed1992

Application of the EPR spin-trapping technique to the detection of radicals produced in vivo during inhalation exposure of rats to ozone.

Ozone is known to induce lipid peroxidation of lung tissue, although no direct evidence of free radical formation has been reported. We have used the electron paramagnetic resonance (EPR) spin-trapping technique to search for free radicals produced in vivo by ozone exposure. The spin trap alpha-(4-pyridyl-1-oxide)-N-tert-butylnitrone (4-POBN) was administered ip to male Sprague-Dawley rats. The rats were then exposed for 2 hr to either 0, 0.5, 1.0, 1.5, or 2.0 ppm ozone with 8% CO2 to increase their respiratory rate. A six-line 4-POBN/radical spin adduct signal (aN = 15.02 G and a beta H = 3.27 G) was detected by EPR spectroscopy in lipid extracts from lungs of rats treated with 4-POBN and then exposed to ozone. Only a weak signal was observed in the corresponding solution from rats exposed to 0 ppm ozone (air with CO2 only). The concentration of the radical adduct increased as a function of ozone concentration. After administration of 4-POBN, rats were exposed for either 0.5, 1.0, 2.0, or 4.0 hr to either 0 or 2.0 ppm ozone (with CO2). The radical adduct concentration of the ozone-exposed groups at exposure times of 2.0 and 4.0 hr was significantly different from that of the corresponding air control groups. A correlation was observed between the radical adduct concentration and the lung weight/body weight ratio. These results demonstrate that ozone induces the production of free radicals in rat lungs during inhalation exposure and that radical production may be involved in the induction of pulmonary toxicity by ozone. This is the first direct evidence for ozone-induced free radical production in vivo.

Administration, Inhalation↗
PubMed1992

tert-Butyl hydroperoxide-induced radical production in rat liver mitochondria.

When rat liver mitochondria are treated with tert-butyl hydroperoxide (TBHP) in the presence of the spin trap 5,5-dimethyl-1-pyrroline N-oxide (DMPO), electron paramagnetic resonance (EPR) signals are detected attributable to spin adducts resulting from the trapping of methyl, tert-butoxyl, and tert-butylperoxyl radicals. The addition of respiratory substrate results in a 3- to 7.5-fold increase in the signal intensity of the DMPO/methyl adduct, no change in the signal intensity of the DMPO/tert-butoxyl adduct, and complete loss of the DMPO/tert-butylperoxyl adduct signal. The magnitude of increase of methyl radical production in the presence of respiratory substrate is related to the respiratory control ratio (RCR) of the mitochondrial preparation. In the presence of antimycin A, which blocks electron flow between cytochromes b and c1, no stimulation of methyl radical production is detected with respiratory substrate. Stimulation of methyl radical production by the addition of respiratory substrate is detected in cytochrome c-depleted mitochondria. A similar increase in methyl radical production is detected when ferrous cytochrome c is treated with TBHP in the presence of DMPO (as compared to when ferricytochrome c is used). These results indicate that TBHP is reduced directly by either cytochrome c1, cytochrome c, or by both of these electron transport chain components in mitochondria undergoing state 4 respiration.

3-Hydroxybutyric Acid↗
PubMed1991

Trace transition metal-catalyzed reactions in the microsomal metabolism of alkyl hydrazines to carbon-centered free radicals.

Radical production from alkyl hydrazines (i.e. phenelzine and benzylhydrazine) in rat liver microsomes has been proposed to occur via cytochrome P-450-catalyzed one-electron oxidation followed by beta-scission of an alkyl radical. In microsomes treated with phenelzine (2-phenylethylhydrazine), NADPH, and the spin trap alpha-(4-pyridyl 1-oxide)-N-tert-butylnitrone (4-POBN), the 4-POBN/2-phenylethyl radical adduct was detected by electron paramagnetic resonance spectroscopy. The addition of catalase and superoxide dismutase resulted in a 28.5 and 24% decrease in radical production, respectively. The concentration of the 4-POBN/2-phenylethyl radical adduct decreased significantly in the presence of metal chelators, i.e. EDTA, diethylenetriaminepentaacetic acid (DTPA), or deferoxamine mesylate. When phenelzine was incubated with deferoxamine mesylate-washed microsomes and NADPH in Chelex-treated incubation buffer, no significant radical adduct formation was detected. Addition of iron-chelator complexes (either Fe(3+)-DTPA or Fe(3+)-EDTA) greatly stimulated production of the 4-POBN/2-phenylethyl radical adduct in this system. These results show that the 2-phenylethyl radical produced from phenelzine in a microsomal system arises via a trace transition metal-catalyzed reaction. This reaction may occur through oxidation of phenelzine by the hydroxyl radical, which has also been spin-trapped with 4-POBN in this system.

Animals↗
PubMed1990

A reexamination of the cytochrome P-450-catalyzed free radical production from a dihydropyridine. Evidence of trace transition metal catalysis.

Radical production from 3,5-bis(ethoxycarbonyl)-4-ethyl-2,6-dimethyl-1,4- dihydropyridine (DDEP) in rat liver microsomes has been attributed to one-electron oxidation via cytochrome P-450 followed by extrusion of an ethyl radical. In the presence of the spin trap alpha-(4-pyridyl 1-oxide)-N-tert-butylnitrone (4-POBN), this radical was detected as the 4-POBN/ethyl radical adduct by electron paramagnetic resonance spectroscopy. The addition of catalase resulted in over a 50% decrease in radical production. The concentration of the 4-POBN/ethyl radical adduct increased about 9-fold in the presence of EDTA and approximately 2-fold in the presence of either diethylenetriaminepentaacetic acid (DTPA) or deferoxamine mesylate. When DDEP was incubated with deferoxamine mesylate-washed microsomes and NADPH in Chelex-treated incubation buffer, much less 4-POBN/ethyl radical formation occurred. Addition of either DTPA, EDTA, or the ferric complexes of these chelators greatly stimulated production of the 4-POBN/ethyl radical adduct in this system. These results suggest that the ethyl radicals produced from DDEP in a microsomal system arise via trace transition metal-catalyzed reactions.

Animals↗
PubMed1990

In vivo thiyl free radical formation from hemoglobin following administration of hydroperoxides.

Although free radical formation due to the reaction between red blood cells and organic hydroperoxides in vitro has been well documented, the analogous in vivo ESR spectroscopic evidence for free radical formation has yet to be reported. We successfully employed ESR to detect the formation of the 5,5-dimethyl-1-pyrroline-N-oxide (DMPO)/hemoglobin thiyl free radical adduct in the blood of rats dosed with DMPO and tert-butyl hydroperoxide, cumene hydroperoxide, ethyl hydrogen peroxide, 2-butanone hydroperoxide, 15(S)-hydroperoxy-5,8,11,13-eicosatetraenoic acid, or hydrogen peroxide. We found that pretreating the rats with either buthionine sulfoximine or diethylmaleate prior to dosing with tert-butyl hydroperoxide decreased the concentration of nonprotein thiols within the red blood cells and significantly enhanced the DMPO/hemoglobin thiyl radical adduct concentration. Finally, we found that pretreating rats with the glutathione reductase inhibitor 1,3-bis(2-chloroethyl)-1-nitrosourea prior to dosing with tert-butyl hydroperoxide enhanced the DMPO/hemoglobin thiyl radical adduct concentration and induced the greatest decrease in nonprotein thiol concentration within the red blood cells.

Animals↗
PubMed1990

Contextual control of problem behavior in students with severe disabilities.

We investigated the impact of contextual variation on the effectiveness of two interventions. The problem behavior of 2 students with severe disabilities was analyzed across two contexts (task and leisure). Effects of differential reinforcement of other behavior (DRO) and time-out procedures were examined in the two contexts. Results indicated that in the task context the DRO procedure effectively reduced the problem behavior and increased task performance, whereas the time-out procedure was ineffective. In addition, rate of correct task performance increased during DRO relative to baseline and time-out. In contrast, in the leisure context, the time-out procedure effectively reduced the same problem behavior and the DRO procedure was ineffective. The results are discussed in terms of contextual control of problem behavior and alternative strategies for the design of DRO procedures.

Adolescent↗
PubMed1989

Radical production in liver mitochondria by peroxidic tumor promoters.

Eleven peroxides have been tested to determine if there is a correlation between tumor-promoting activity and the ability to stimulate radical production in mitochondria. When non-respiring rat liver mitochondria are treated with these peroxidic compounds in the presence of DMPO, ESR signals are observed from the spin trapping of carbon- and oxygen-centered radicals in the case of 4 of the 7 peroxides that are known to be tumor promoters. Enhancement of carbon-centered radical production is observed in the presence of respiratory substrate. Thus there does not appear to be a correlation between tumor-promoting activity of peroxidic compounds and radical production in mitochondria. Oxidants can act as promoters either by 1- or 2-electron oxidation pathways; both types of mechanisms may be inhibited by antioxidants, which can scavenge either radicals or electrophiles.

Animals↗
PubMed1989

Benzoyl peroxide interaction with mitochondria: inhibition of respiration and induction of rapid, large-amplitude swelling.

When micromolar concentrations of benzoyl peroxide (BPO) are added to rat liver mitochondria, inhibition of mitochondrial NADH-oxidase and succinoxidase is observed. The addition of 2,4-dinitrophenol, an uncoupler of oxidative phosphorylation, results in only partial release of this inhibition, suggesting that BPO inhibits both electron and energy transfer in mitochondria. Release of inhibition is also observed when an electron donor, N,N,N',N'-tetramethyl-p-phenylenediamine, is added, suggesting that inhibition occurs on the substrate side of cytochrome c. When BPO is added to respiring submitochondrial particles, only reduced cytochrome b is observed to accumulate in the difference spectrum (reduced minus oxidized) in a manner analogous to that observed in the presence of antimycin A. These results indicate that BPO interacts at coupling site II between cytochromes b and c1. When respiring SMP are treated with BPO in the presence of the spin trap 5,5-dimethyl-1-pyrroline-N-oxide, electron spin resonance signals attributable to the hydroxyl and superoxide adducts are observed. Catalase and superoxide dismutase inhibit the formation of these adducts, suggesting the involvement of both hydrogen peroxide and superoxide radicals in this process. BPO also induces rapid, large-amplitude swelling of mitochondria; the swelling is dependent on the presence of monovalent cations but is independent of the presence of calcium, oxygen, and respiratory substrate. BPO-induced swelling appears to be disassociated from radical production and lipid peroxidation.

Animals↗
PubMed1988

Units of analysis in task-analytic research.

We develop and discuss four criteria for evaluating the appropriateness of units of analysis for task-analytic research and suggest potential alternatives to the units of analysis currently used. Of the six solutions discussed, the most commonly used unit of analysis in current behavior analytic work, percentage correct, meets only one of the four criteria. Five alternative units of analysis are presented and evaluated: (a) percentage of opportunities to perform meeting criterion, (b) trials to criteria, (c) cumulative competent performances, (d) percentage correct with competent performance coded, and (e) percentage correct with competent performance coded and a grid showing performance on individual steps of the task analysis. Of the solutions evaluated, only one--percentage correct with competent performance coded and a task analysis grid--met all four criteria.

Adolescent↗
PubMed1987

Teaching generalization of purchasing skills across community settings to autistic youth using videotape modeling.

Three young autistic adults were trained to purchase items. Training was conducted in one setting with concurrent generalization probes taken in three community stores. Training in one setting failed to produce generalization to the three probe settings. Generalization training, which consisted of viewing videotapes of models who purchased items in the probe settings and answering questions about the models' responses, was then introduced. Training with the videotapes resulted in generalization to the three community stores. Results of the use of videotapes as a cost-effective means to program generalization in community training programs are discussed.

Activities of Daily Living↗
PubMed1986

Hydroperoxide-induced radical production in liver mitochondria.

When isolated rat liver mitochondria are treated with tert-butyl hydroperoxide in the presence of the spin trap 5,5-dimethyl-1-pyrroline-N-oxide, a six-line ESR signal is observed with parameters characteristic of a carbon-centered radical. The radical is shown to be CH3. using 2-methyl-2-nitrosopropane as the spin trap. Inhibition of radical production by EDTA and N-ethylmaleimide provides evidence for participation by metals and reduced sulfhydryl groups in the radical-generating reaction. It is proposed that radicals are formed through the reaction between a reducing agent, a metal and the hydroperoxide.

Animals↗