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Biomedical subjects

L J Cooper

Publications and source records attributed to L J Cooper.

At least 19 recordsLinked to original sources

Choice-making treatment of young children's severe behavior problems.

The choice-making behavior of 5 young children with developmental disabilities who engaged in aberrant behavior was studied within a concurrent operants framework. Experimental analyses were conducted to identify reinforcers that maintained aberrant behavior, and functional communication training packages were implemented to teach the participants to gain reinforcement using mands. Next, a choice-making analysis, in which the participants chose one of two responses (either a mand or an alternative neutral response) to obtain different durations and qualities of reinforcement, was conducted. Finally, treatment packages involving choice making via manding were implemented to decrease inappropriate behavior and to increase mands. The results extended previous applications of choice making to severe behavior disorders and across behaviors maintained by positive and negative reinforcement.

Behavior Therapy

Brief experimental analysis of stimulus prompts for accurate responding on academic tasks in an outpatient clinic.

Brief multielement designs were used to examine the effects of specific instructional strategies on accuracy of academic performance during outpatient evaluations of 4 children with learning disorders. Instructional strategies that improved accuracy on academic tasks were identified for all participants. These results suggest that the application of experimental analysis methodologies to instructional variables may facilitate the identification of stimulus prompts that are associated with enhanced academic performance.

Ambulatory Care Facilities

The effects of meal schedule and quantity on problematic behavior.

We present 2 case examples that illustrate the effects of meal schedule and quantity on displays of problematic behavior. In the first example, self-injury displayed by a toddler with severe developmental delays was maintained by parent attention, but only when he was satiated for food. When he was food deprived, self-injury decreased but did not appear to be differentiated across low or high social conditions. In the second example, crying and self-injury displayed by an elementary-aged girl with severe disabilities were correlated: Both behaviors were associated with food quantity, and neither behavior was responsive to social stimuli. These results replicate and extend previous findings demonstrating that meal schedule or food quantity can affect problematic behavior. In the present studies, brief functional analyses of aberrant behavior provided useful information for interpreting distinct patterns of behavior displayed by each child. We discuss these results in terms of the concept of establishing operations.

Behavior Therapy

Complementarity, specificity and the nature of epitopes and paratopes in multivalent interactions.

Structural elements of an antibody (Ab) or antigen (Ag) distant from the actual sites mediating contact between Ab and Ag can exert substantial influence on binding to, and discrimination among, multivalent targets. Consequently, multivalent molecules that express the same number of identical binding sites, but that differ in other structural features, can exhibit differences in their ability to discriminate between multivalent ligands. Here, Neil Greenspan and Laurence Cooper review evidence for these effects, and explore implications of the conclusion that effective specificity in multivalent interactions is not completely determined by the degree of complementarity between epitopes and paratopes.

Antigen-Antibody Reactions

Use of component analyses to identify active variables in treatment packages for children with feeding disorders.

We evaluated the separate components in treatment packages for food refusal of 4 young children. First, treatment packages were implemented until food acceptance improved. Next, a component analysis was conducted within a multielement or reversal design to identify the active components that facilitated food acceptance. The results indicated that escape extinction was always identified as an active variable when assessed; however, other variables, including positive reinforcement and noncontingent play, were also identified as active variables for 2 of the children. The results suggest that the component analysis was useful for identifying variables that affected food acceptance.

Child, Preschool

Variable domain-identical antibodies exhibit IgG subclass-related differences in affinity and kinetic constants as determined by surface plasmon resonance.

We have analysed the binding of variable domain-identical mouse monoclonal antibodies (mAb) of the IgG3, IgG1 and IgG2b subclasses, as well as F(ab')2 fragments derived from the IgG3 and IgG1 mAb, to a multivalent glycoprotein target. Using a biosensor device (BIAcore, Pharmacia Biosensor) that measures the mass of the antibody (or other receptor molecule) deposited on a sensor chip displaying the relevant epitopes, we found that the IgG3 mAb binds more effectively than the other antibody species at a high but not a low epitope density. The greater functional affinity associated with the IgG3 mAb, at high epitope density, was correlated with both slower dissociation rate constants and faster association rate constants in comparison with the IgG1 and IgG2b mAb and the F(ab')2 fragments derived from the IgG3 and IgG1 mAb. Evidence for slower dissociation kinetics for the IgG3 mAb versus the IgG1 and IgG2b mAb was also obtained by ELISA and flow cytometry. These results demonstrate that: (1) differences in heavy chain constant (CH) domains can significantly influence apparent functional affinity for multivalent antigen, as determined without the use of covalently modified primary or secondary antibodies; (2) differences in CH domains can alter both association and dissociation rate constants for interactions between IgG antibodies and multivalent antigen; and (3) these effects of CH domains depend on epitope density. The effect of constant region differences on the apparent association rate constants suggests new approaches for achieving better binding or functional effectiveness through antibody engineering.

Acetylglucosamine

Brief hierarchical assessment of potential treatment components with children in an outpatient clinic.

Seven patients conducted assessments in an outpatient clinic using a prescribed hierarchy of antecedent and consequence treatment components for their children's problem behavior. Brief assessment of potential treatment components was conducted to identify variables that controlled the children's appropriate behavior. Experimental control via a brief reversal was achieved for 6 of the 7 children, (1 child continued to behave appropriately following initial improvement in behavior). For these 6 children, improved behavior occurred with changes in treatment components. Our results extend previous studies of direct assessment procedures conducted in outpatient clinic settings.

Ambulatory Care

The impact of functional analysis methodology on outpatient clinic services.

The impact of the article by Iwata, Dorsey, Slifer, Bauman, and Richman (1982) on research in severe behavior disorders has been impressive. Equally impressive, however, but not as fully recognized, has been the impact of this methodology on the routine professional activities of those who employ functional analysis methods in their daily work. As one example of this impact, we describe the evolution of assessment procedures based on "brief functional analysis" methodology in our outpatient clinics. Less apparent have been the collateral effects that occur from using these procedures. Interactions with clients and colleagues have changed in ways that result in increased positive reinforcement. In this article, we briefly discuss the positive impact functional analysis has had on one specific work behavior--outpatient clinic assessment--and describe some of the generalized effects we have experienced in related aspects of our daily professional activities.

Ambulatory Care Facilities

Role of heavy chain constant domains in antibody-antigen interaction. Apparent specificity differences among streptococcal IgG antibodies expressing identical variable domains.

In this report, we examine the influence of CH domains on antibody specificity, in the context of variable epitope density on bacteria and synthetic glycoconjugates. Hybridomas secreting IgG1 and IgG2b mAb, specific for the N-acetyl-glucosamine (GlcNAc) residues of streptococcal group A carbohydrate, were previously generated from a hybridoma secreting a mouse IgG3 mAb. We show that these three mAb have identical H and L chain V domains, as determined by 1) cDNA sequencing, 2) binding to soluble Ag, and 3) binding to nine monoclonal anti-idiotopes. Nevertheless, the IgG3 mAb binds more effectively than the V region-identical IgG1 or IgG2b mAb to each of three strains of group A streptococci that display different amounts of terminal GlcNAc residues on their cell walls. The magnitude of the subclass-associated differential in binding varies with the target strain, and, whereas the IgG3 mAb binds best to the strain expressing an intermediate amount of GlcNAc, the IgG1 and IgG2b mAb and IgG3-derived F(ab')2 fragments bind best to the strain expressing the highest amount of GlcNAc. The IgG3 mAb also binds better than the IgG1 and IgG2b mAb to solid-phase GlcNAc50-BSA, but the IgG2b mAb binds best to otherwise identical conjugates with lower ratios of GlcNAc to BSA (20:1, 10:1, 5:1, and 1:1). These results suggest that epitope density can significantly influence the magnitude of IgG subclass-associated binding differences, and that structural differences in the CH regions, particularly the CH2 and CH3 domains, can influence the apparent specificities of IgG molecules for multivalent Ag.

Acetylglucosamine

Variable region-identical monoclonal antibodies of different IgG subclass directed to Pseudomonas aeruginosa lipopolysaccharide O-specific side chain function differently.

Antibodies directed to polysaccharide (PS) antigens of bacteria are crucial to host immunity to infection. The isotypes of antibodies made to PS, however, are restricted primarily to IgM and IgG1 and IgG2 in man and to IgM and IgG3 in mice. Using sequential sublining and sib selection, an IgG1 murine monoclonal antibody that has variable regions identical to those of a parent IgG3 monoclonal antibody directed to the high-molecular-weight component of the O-specific side chain of Pseudomonas aeruginosa immunotype 1 lipopolysaccharide was derived. These antibodies differed markedly in their antigen binding and effector functions. IgG3 was superior in binding to multivalent PS both in purified and whole bacterial form, fixation of the third component of complement to the bacterial surface, and opsonization of P. aeruginosa for uptake by both murine and human phagocytes. These data suggest that the IgG subclass of these murine anti-LPS antibodies is an important determinant of both avidity for multivalent antigen and biologic function.

Animals

A brief component analysis of potential treatment packages in an outpatient clinic setting with young children.

The purpose of this study was to develop outpatient clinic assessments that allowed us to assess multiple treatment variables, produce relatively quick effects, and isolate active treatment components. Assessment began by evaluating a treatment package consisting of antecedent and consequence variables followed by a component analysis to determine the separate effects of the treatment variables. Three examples of the findings are presented.

Ambulatory Care

Intermolecular cooperativity: a clue to why mice have IgG3?

Mouse IgG3 subclass antibodies predominate in humoral responses to bacterial polysaccharide antigens. The reasons for this isotype restriction are not fully understood. Here, Neil Greenspan and Laurence Cooper propose that intermolecular cooperativity, a novel mechanism of antibody binding, may help to explain the preferential expression of IgG3 antibodies in these responses.

Animals

Use of descriptive and experimental analyses to identify the functional properties of aberrant behavior in school settings.

We conducted descriptive and experimental analyses of aberrant behavior in school settings with 2 children with autism, using teachers as assessors. Experimental functional analyses carried out by the investigators were followed by training teachers to conduct a descriptive analysis and a classroom experimental analysis. A comparison of the assessment procedures showed that each procedure identified negative reinforcement as a maintaining variable for aberrant behavior. The teacher implemented an intervention based on the assessment with mixed results. We then replicated the initial results by having the first teacher train a second teacher to carry out the two assessment procedures. The results of these analyses were also in agreement, again identifying negative reinforcement as a variable maintaining aberrant behavior. An intervention based on negative reinforcement was then successfully implemented. These results suggest the applicability and utility of functional analyses carried out in school settings.

Adolescent

Analysis of the effects of task preferences, task demands, and adult attention on child behavior in outpatient and classroom settings.

Two studies were conducted with children who displayed behavior problems to evaluate the effects of task preference, task demands, and adult attention on child behavior. In Study 1, we conducted brief functional analyses in an outpatient clinic to identify variables that facilitated appropriate behavior. For 8 of 10 children, distinct patterns of performance occurred; 3 children displayed improved behavior with changes in task demands, 1 child displayed improved behavior with a preferred task, and 4 children displayed improved behavior with changes in adult attention. In most cases, the children's parents carried out the assessments with adequate procedural integrity. In Study 2, we applied similar assessment methods to a classroom setting over an extended period of time. We identified independent variables controlling appropriate, on-task, and academic behavior for 2 children on two tasks, with slightly different treatment procedures across tasks for both children. In addition, the results of brief functional analyses for both children corresponded to the extended classroom assessments.

Adjustment Disorders

H chain C domains influence the strength of binding of IgG for streptococcal group A carbohydrate.

We have produced a panel of murine anti-streptococcal mAbs, expressing identical V domains and different H chain C domains, corresponding to the IgG3, IgG1, and IgG2b subclasses. We have used these mAb to evaluate the role of IgG subclass-specific C region determinants in modulating the interaction between antibody and the bacterial surface. We report, for the first time, that V region-identical murine IgG of different subclasses exhibit substantial differences in binding to specific Ag; IgG3 mAb binds more strongly to streptococci than the IgG1 and IgG2b mAb or IgG3-derived F(ab')2 fragments. Furthermore, the IgG3 mAB binds cooperatively to the bacteria, whereas the IgG1, IgG2b, and IgG3-derived F(ab')2 fragments do not exhibit significant cooperativity, which suggests that differences in Fc region structure can affect antibody binding to multivalent Ag by modulating the potential for cooperative binding. These results suggest a plausible mechanism by which murine IgG3 could be more effective, than other antibodies bearing identical V domains, but of different gamma-subclass, in mediating bacterial immunity.

Animals

Using parents as therapists to evaluate appropriate behavior of their children: application to a tertiary diagnostic clinic.

We conducted a preliminary analysis of maintaining variables for children with conduct disorders in an outpatient clinic. Eight children of normal intelligence between the ages of 4 and 9 years were evaluated during 90-min sessions. The children's parents conducted the assessments by varying task demands (easy and difficult) and parental attention (attention and no attention) within a multielement design. The assessment focused on appropriate child behavior and was conducted to formulate hypotheses regarding maintaining contingencies. Results demonstrated that the children's appropriate behavior varied across assessment conditions and, for 7 of the 8 children, occurred at a higher rate during one condition than during other conditions. In addition, treatment integrity data demonstrated that parents were able to implement the procedures as intended. The recommended treatments were rated as being both effective and acceptable to parents for up to 6 months following the evaluation. Our results extend previous studies of functional analytic procedures conducted by trained experimenters with severely handicapped children in more controlled settings.

Attention

Cooperative binding of two antibodies to independent antigens by an Fc-dependent mechanism.

Binding of a murine N-acetylglucosamine (GlcNAc)-specific IgG3 monoclonal antibody to a solid phase expressing GlcNAc determinants and phosphocholine (PC) determinants is enhanced by IgG3, but not IgG2b, PC-specific monoclonal antibody. The cooperative binding requires an intact Fc region on the GlcNAc-specific monoclonal antibody and is hypothesized to result from Fc-Fc association. Although the in vivo relevance of this phenomenon requires further study, intermolecular cooperativity in binding of antibody to multivalent antigens, such as bacterial cell wall antigens, could represent an adaptive mechanism for antibodies expressing low intrinsic affinities for highly repeated epitopes. Furthermore, the ability of antibodies of distinct specificity to participate in cooperative binding offers, at least in principle, new approaches to optimizing antibody targeting.

Acetylglucosamine