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Biomedical subjects

L J Cooper

Publications and source records attributed to L J Cooper.

33 records · Page 2Linked to original sources
PubMed1993

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↗
PubMed1993

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↗
PubMed1993

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↗
PubMed1992

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↗
PubMed1992

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↗
PubMed1992

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↗
PubMed1991

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↗
PubMed1990

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↗
PubMed1989

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↗
PubMed1989

The use of behavioral assessment to prescribe and evaluate treatments for severely handicapped children.

Behavioral assessment procedures were used to prescribe and evaluate treatments of maladaptive behavior for 2 children with severe multiple handicaps. In Experiment 1, the results of an assessment of reinforcer preference were used in conjunction with a functional analysis of the conditions maintaining self-injurious behavior to prescribe a treatment for a child with severe disabilities. The treatment procedure involved the use of a pressure-sensitive microswitch to activate reinforcing stimuli during two solitary conditions, during which self-injurious behavior had occurred at high rates. The results were evaluated with a multiple baseline across settings design and indicated that self-injury decreased with concomitant increases in microswitch activation. Results were maintained at 6 weeks, 8 weeks, and 6 months. In Experiment 2, the results of behavioral assessments of reinforcer preference and self-injurious behavior were combined to develop a treatment for a second severely handicapped child, who exhibited high rates of self-injury in demand situations. This treatment was evaluated with a multiple baseline across tasks design and resulted in the elimination of self-injury for up to 15 months.

Behavior Therapy↗
PubMed1988

Fc region-dependence of IgG3 anti-streptococcal group A carbohydrate antibody functional affinity. I. The effect of temperature.

Previous studies have demonstrated that IgG3 anti-streptococcal group A carbohydrate (GAC) mAb bind to the surfaces of heat-killed, pepsin-digested group A streptococcal cells in an Fc region-dependent cooperative manner. This form of positive cooperative binding of antibody to Ag was hypothesized to result from noncovalent association of Fc regions of antibodies bound close to one another on the Ag surface. Because IgG3 Fc regions are self-aggregating and IgG3 molecules are frequently cryoprecipitable, we have now investigated the effect of temperature on the binding, and cooperative binding, of IgG3 anti-GAC mAb to solid-phase (sp) Ag. The Ag used was a covalent conjugate of N-acetyl-D-glucosamine (GlcNAc; the epitopes on GAC) and BSA. The main findings were: 1) IgG3 anti-GAC mAb bind to sp GlcNAc-BSA to greater extents at lower temperatures, 2) IgM anti-GAC mAb and Fab and F(ab')2 fragments, derived from an IgG3 anti-GAC mAb, bind to sp GlcNAc-BSA to comparable extents at different temperatures, 3) idiotope-expressing IgG3 anti-GAC mAb bind to sp anti-idiotope to comparable extents at different temperatures, and 4) unlabeled IgG3 anti-GAC mAb enhance the binding of radiolabeled IgG3 anti-GAC mAb to sp GlcNAc-BSA, and the degree of this enhancement is greater at lower temperature. These, and additional results, support the conclusion that for some sp Ag the functional affinities of IgG3 antibodies, are influenced by the Fc region in a temperature-dependent manner.

Acetylglucosamine↗
PubMed1985

Circulating immunoreactive parathyroid hormone levels in premature infants and the response to calcium therapy.

Serum immunoreactive parathyroid hormone (iPTH), calcium, magnesium, and phosphorus levels were measured in 13 premature infants during the first 96 hours of life. Hypocalcemia at 12-24 hours of age was associated with a markedly elevated mean serum iPTH level. Six of the hypocalcemic infants received a continuous infusion of calcium while seven were not treated. In the untreated infants, the mean serum calcium remained in the hypocalcemic range while the serum iPTH progressively increased. By contrast, the mean serum calcium in the treated infants increased to 2.35 mmol/l at 96 hours of age and was accompanied by a decline in serum iPTH. At 72 and 96 hours, the mean serum iPTH was twofold greater in the untreated than in the treated infants. The results indicate that the parathyroid glands of premature infants respond to calcium signals and that a factor(s), other than parathyroid insufficiency, plays an etiologic role in the hypocalcemia of prematurity.

Calcium↗