Biomedical subjects

W W Fisher

Publications and source records attributed to W W Fisher.

At least 19 recordsLinked to original sources

PubMed2000

Drosophila p53 is a structural and functional homolog of the tumor suppressor p53.

The importance of p53 in carcinogenesis stems from its central role in inducing cell cycle arrest or apoptosis in response to cellular stresses. We have identified a Drosophila homolog of p53 ("Dmp53"). Like mammalian p53, Dmp53 binds specifically to human p53 binding sites, and overexpression of Dmp53 induces apoptosis. Importantly, inhibition of Dmp53 function renders cells resistant to X ray-induced apoptosis, suggesting that Dmp53 is required for the apoptotic response to DNA damage. Unlike mammalian p53, Dmp53 appears unable to induce a G1 cell cycle block when overexpressed, and inhibition of Dmp53 activity does not affect X ray-induced cell cycle arrest. These data reveal an ancestral proapoptotic function for p53 and identify Drosophila as an ideal model system for elucidating the p53 apoptotic pathway(s) induced by DNA damage.

Amino Acid Sequence↗

PubMed2000

Facilitating tolerance of delayed reinforcement during functional communication training.

Few clinical investigations have addressed the problem of delayed reinforcement. In this investigation, three individuals whose destructive behavior was maintained by positive reinforcement were treated using functional communication training (FCT) with extinction (EXT). Next, procedures used in the basic literature on delayed reinforcement and self-control (reinforcer delay fading, punishment of impulsive responding, and provision of an alternative activity during reinforcer delay) were used to teach participants to tolerate delayed reinforcement. With the first case, reinforcer delay fading alone was effective at maintaining low rates of destructive behavior while introducing delayed reinforcement. In the second case, the addition of a punishment component reduced destructive behavior to near-zero levels and facilitated reinforcer delay fading. With the third case, reinforcer delay fading was associated with increases in masturbation and head rolling, but prompting and praising the individual for completing work during the delay interval reduced all problem behaviors and facilitated reinforcer delay fading.

Adult↗

PubMed2000

Functional analysis of aberrant behavior through measurement of separate response topographies.

Functional analysis results for multiple topographies of aberrant behavior were graphed in an aggregate fashion and then separately for 48 clients. The results indicated that multiple topographies of behavior may be maintained by different contingencies. These results indicate that graphing functional analysis data in an aggregate fashion and then separately may improve the accuracy of their interpretation.

Adolescent↗

PubMed2000

The effects of response cost in the treatment of aberrant behavior maintained by negative reinforcement.

Positive reinforcement contingencies can sometimes be used to decrease problem behavior maintained by negative reinforcement (e.g., escape). In the current study, we evaluated the extent to which response cost (i.e., contingent removal of a preferred stimulus) would compete with the negative reinforcer maintaining destructive behavior. The response cost contingency reduced destructive behavior by 87% from baseline levels even though the negative reinforcement contingency (i.e., escape) remained in place.

Adult↗

PubMed2000

Assessment of a response bias for aggression over functionally equivalent appropriate behavior.

We evaluated the effects of a dense (fixed-ratio 1) schedule of reinforcement for an 11-year-old boy's mands for toys while aggression produced the same toys on various schedules chosen on the basis of a progressive-ratio probe. Based on the probe session data, we accurately predicted that aggression would be more probable than mands when the schedules were equal or slightly discrepant, but that mands would be more probable when the schedule discrepancy was large.

Aggression↗

PubMed2000

The effects of noncontingent delivery of high- and low-preference stimuli on attention-maintained destructive behavior.

An adolescent with severe mental retardation and cerebral palsy who displayed attention-maintained destructive behavior was exposed to noncontingent reinforcer delivery (NCR) with either a high-preference or a low-preference stimulus while reinforcement for destructive behavior with attention remained in effect (i.e., NCR without extinction). NCR without extinction was effective only when the high-preference stimulus was available, suggesting that systematic assessment of stimulus quality may enhance the effectiveness of NCR with alternative stimuli.

Adolescent↗

PubMed1999

Joint action of two RNA degradation pathways controls the timing of maternal transcript elimination at the midblastula transition in Drosophila melanogaster.

Maternally synthesized RNAs program early embryonic development in many animals. These RNAs are degraded rapidly by the midblastula transition (MBT), allowing genetic control of development to pass to zygotically synthesized transcripts. Here we show that in the early embryo of Drosophila melanogaster, there are two independent RNA degradation pathways, either of which is sufficient for transcript elimination. However, only the concerted action of both pathways leads to elimination of transcripts with the correct timing, at the MBT. The first pathway is maternally encoded, is targeted to specific classes of mRNAs through cis-acting elements in the 3'-untranslated region and is conserved in Xenopus laevis. The second pathway is activated 2 h after fertilization and functions together with the maternal pathway to ensure that transcripts are degraded by the MBT.

3' Untranslated Regions↗

PubMed1999

Different 3' untranslated regions target alternatively processed hu-li tai shao (hts) transcripts to distinct cytoplasmic locations during Drosophila oogenesis.

Cytoplasmic mRNA localization is one method by which protein production is restricted to a particular intracellular site. We report here a novel mechanism for localization of transcripts encoding distinct protein isoforms to different destinations. Alternative processing of transcripts produced in the Drosophila ovary by the hu-li tai shao (hts) locus introduces distinct 3' untranslated regions (3'UTRs) that differentially localize the mRNAs. Three classes of hts mRNA (R2, N32 and N4) are synthesized in the germ line nurse cells and encode proteins with adducin-homologous amino-terminal regions but divergent carboxy-terminal domains. The R2 and N32 classes of mRNA remain in the nurse cells and are not transported into the oocyte. In contrast, the N4 class of transcripts is transported from the nurse cells into the oocyte starting at stage 1, is subsequently localized to the oocyte cortex at stage 8 and then to the anterior pole from stage 9 on. All aspects of N4 transcript transport and localization are directed by the 345-nucleotide(nt)-long 3' untranslated region (3'UTR). The organization of localization elements in the N4 3'UTR is modular: a 150 nt core is sufficient to direct transport and localization throughout oogenesis. Additional 3'UTR elements function additively together with this core region at later stages of oogenesis to maintain or enhance anterior transcript anchoring. The swallow locus is required to maintain hts transcripts at the anterior pole of the oocyte and functions through the N4 3'UTR. In addition to the three classes of germ line-expressed hts transcripts, a fourth class (R1) is expressed in the somatic follicle cells that surround the germ line cells. This transcript class encodes the Drosophila orthologue of mammalian adducin.

3' Untranslated Regions↗

PubMed1999

Decreasing signs of negative affect and correlated self-injury in an individual with mental retardation and mood disturbances.

We evaluated the effects of an enriched environment, based on a paired-choice preference assessment, on both rates of self-injurious behavior (SIB) and percentage of session intervals during which signs of negative affect were displayed by a woman with mental retardation and a mood disorder. Results suggested that SIB and signs of negative affect were highly correlated and that the enriched environment effectively reduced both.

Adult↗

PubMed1999

Clarifying an ambiguous functional analysis with matched and mismatched extinction procedures.

Results of functional analysis were ambiguous in suggesting that self-injurious behavior (SIB) was maintained by escape, sensory reinforcement, or both. To help clarify these results, we compared escape extinction, sensory extinction, and the combined treatments. Sensory extinction proved to be a necessary and sufficient treatment, whereas escape extinction failed to decrease SIB. These analyses helped to clarify the function of SIB and to identify an effective and efficient treatment.

Adult↗

PubMed1998

The effects of noncontingent and contingent attention for self-injury, manding, and collateral responses.

To date, most functional analysis studies have focused on the effects of treatment contingencies on specific targeted aberrant and alternative responses. In the current investigation, the main and collateral effects of the assessment and treatment of attention-maintained self-injury were assessed. Specifically, we evaluated the effects of noncontingent and contingent social attention on four categories of behavior: self-injury, a novel mand, preexisting prosocial responses (e.g., babbling and reaching out), and other aberrant responses (i.e., aggression and destruction). Results suggested that self-injury, prosocial responses, and other aberrant behaviors were within the same functional response class. Possible impact of these results when selecting mands for functional communication training is discussed.

Attention↗

PubMed1998

Using chronotherapy to treat severe sleep problems: a case study.

Chronotherapy was used to treat severe sleep problems (irregular sleep onset times, frequent night and early wakings, and short total sleep times) in a girl with mental retardation. Chronotherapy involved systematically delaying the child's bedtime each night while maintaining a regular schedule during waking hours until an age-appropriate bedtime was achieved. Immediate improvements in the child's sleep pattern were observed with the introduction of treatment, and an age-appropriate bedtime was achieved in 11 days. Four months of follow-up data indicated that improvements maintained in the home. Although chronotherapy was developed specifically for adults with delayed sleep phase insomnia, the current results suggest that the treatment may be useful for other populations and problems.

Child↗

PubMed1998

The evaluation and treatment of aggression maintained by attention and automatic reinforcement.

In the current investigation, we used direct and indirect methods to assess and treat several topographies of aggression that were hypothesized to have separate operant functions in a young boy with severe mental ratardation and pervasive developmental disorder. First, a functional analysis of aggression, using the methods described by Iwata, Dorsey, Slifer, Bauman, and Richman (1982/1994), was conducted and produced inconclusive results. Next, indirect methods were used to develop a second functional analysis, which showed that chin grinding (firmly pressing and grinding his chin against the skin and bones of others) persisted independent of social contingencies and that the other topographies of aggression (e.g., hitting, kicking) were maintained by social positive reinforcement (attention). A treatment designed to decrease aggression maintained by attention--functional communication training with extinction--reduced all forms of aggression except chin grinding. This latter topography of aggression, which we hypothesized was maintained by automatic reinforcement, was reduced when the response--reinforcer relation was interrupted through response blocking and the child was provided with an alternative form of chin stimulation.

Aggression↗

PubMed1998

Treatment of pica through multiple analyses of its reinforcing functions.

We conducted functional analyses of the pica of 3 participants. The pica of 1 participant appeared to be maintained by automatic reinforcement; that of the other 2 participants appeared to be multiply controlled by social and automatic reinforcement. Subsequent preference and treatment analyses were used to identify stimuli that would complete with the automatic function of pica for the 3 participants. These analyses also identified the specific aspect of oral stimulation that served as automatic reinforcement for 2 of the participants. In addition, functional analysis-based treatments were used to address the socially motivated components of 2 of the participants' pica. Results are discussed in terms of (a) the importance of using the results of functional analyses to develop treatments for pica and (b) the advantages of developing indirect analyses to identify specific sources of reinforcement for automatically reinforced behavior.

Adolescent↗

PubMed1998

Effectiveness of functional communication training with and without extinction and punishment: a summary of 21 inpatient cases.

Functional communication training (FCT) is a frequently used treatment for reducing problem behavior exhibited by individuals with developmental disabilities. Once the operant function of problem behavior is identified by a functional analysis, the client is taught to emit an appropriate communicative response to obtain the reinforcer that is responsible for behavioral maintenance. Studies on FCT have typically used small numbers of participants, have reported primarily on clients for whom FCT was successful, and have varied with respect to their use of other treatment components. The main purposes of the present study were to evaluate the efficacy of FCT for treating severe problem behavior in a relatively large sample of individuals with mental retardation (N = 21) and to determine the contribution of extinction and punishment components to FCT treatment packages. FCT with extinction was effective in reducing problem behavior for the majority of clients and resulted in at least a 90% reduction in problem behavior in nearly half the applications. However, when demand or delay-to-reinforcement fading was added to FCT with extinction, treatment efficacy was reduced in about one half of the applications. FCT with punishment (both with and without fading) resulted in at least a 90% reduction in problem behavior for every case in which it was applied.

Adolescent↗

PubMed1998

Functional analysis and treatment of destructive behavior maintained by termination of "don't" (and symmetrical "do") requests.

We used descriptive assessment information to generate hypotheses regarding the function of destructive behavior for 2 individuals who displayed near-zero rates of problem behavior during an experimental functional analysis using methods similar to Iwata, Dorsey, Slifer, Bauman, and Richman (1982/1994). The descriptive data suggested that destructive behavior occurred primarily when caregivers issued requests to the participants that interfered with ongoing high-probability (and presumably highly preferred) behaviors (i.e., a "don't" or a symmetrical "do" request). Subsequent experimental analyses showed that destructive behavior was maintained by contingent termination of "don't" and symmetrical "do" requests but not by termination of topographically similar "do" requests. These results suggested that destructive behavior may have been maintained by positive reinforcement (i.e., termination of the "don't" request allowed the individual to return to a highly preferred activity). Finally, a treatment (functional communication training plus extinction) developed on the basis of these analyses reduced destructive behavior to near-zero levels.

Adolescent↗

PubMed1998

Reductions in self-injury produced by transcutaneous electrical nerve stimulation.

Transcutaneous electrical nerve stimulation is used to reduce pain but also may be useful for self-injurious behavior (SIB). In the current investigation, a microcurrent electromedical device, classified as a transcutaneous electrical nerve stimulator (TENS), was applied with a man with Down syndrome who displayed SIB that persisted in the absence of social contingencies. Although clinically significant results were not maintained, a clear difference in the rates of SIB during active and inactive TENS was observed.

Adult↗

PubMed1998

Assessment and treatment of destructive behavior maintained by stereotypic object manipulation.

In the current investigation, 2 participants with mental retardation displayed property destruction and stereotypy, and both responses involved the same materials (e.g., breaking and tapping plastic objects). Three experiments were conducted (a) to indirectly assess the functions of these two responses, (b) to determine their relation to one another, and (c) to develop a treatment to reduce the more serious behavior, property destruction. In Experiment 1, previously destroyed materials were either present or absent, and their presence reduced property destruction but not stereotypy. In Experiment 2, matched toys (ones that produced sensory stimulation similar to stereotypy) were either present or absent, or were replaced by unmatched toys (for 1 participant). Matched toys produced large reductions and unmatched toys produced small reductions in property destruction and stereotypy. In Experiment 3, attempts to pick up undestroyed objects were either blocked or not blocked while matched toys were continuously available. Response blocking reduced property destruction (and attempts), prevented stereotypy, and increased manipulation of matched toys. These results suggest that the two aberrant responses formed a chain (e.g., breaking and then tapping the object), which was maintained by the sensory consequences (e.g., auditory stimulation) of the terminal response, and that previously destroyed material or matched toys made the initial response (property destruction) unnecessary.

Adolescent↗