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R A Caldwell

Publications and source records attributed to R A Caldwell.

At least 19 recordsLinked to original sources
PubMed1998

Flanking proline residues identify the L-type Ca2+ channel binding site of calciseptine and FS2.

Calciseptine and FS2 are 60-amino acid polypeptides, isolated from venom of the black mamba (Dendroaspis polylepis polylepis), that block voltage-dependent L-type Ca2+ channels. We predicted that these polypeptides contain an identical functional site between residues 43 and 46 by searching for proline residues that mark the flanks of protein-protein interaction sites [Kini, R. M., and Evans, H. J. (1966) FEBS Lett. 385, 81-86]. The predicted Ca2+ channel binding site also occurs in closely related toxins, C10S2C2 and S4C8. Therefore, it is likely that these toxins also will block L-type Ca2+ channels. To test the proposed binding site on calciseptine and FS2, an eight-residue peptide, named L-calchin (L-type calcium channel inhibitor), was synthesized and examined for biological activity. As expected for an L-type Ca2+ channel blocker, L-calchin reduced peak systolic and developed pressure in isolated rat heart Langendorff preparations without affecting diastolic pressure or heart rate. Furthermore, L-calchin caused a voltage-independent block of L-type Ca2+ channel currents in whole-cell patch-clamped rabbit ventricular myocytes. Thus the synthetic peptide exhibits the L-type Ca2+ channel blocking properties of the parent molecules, calciseptine and FS2, but with a lower potency. These results strongly support the identification of a site in calciseptine and FS2 that is important for binding to L-type Ca2+ channels and reinforce the importance of proline brackets flanking protein-protein interaction sites.

Amino Acid Sequence↗
PubMed1996

Production of congenic mouse strains carrying genomic intervals containing SLE-susceptibility genes derived from the SLE-prone NZM2410 strain.

Systemic lupus erythematosus is inherited as a complex polygenic trait. Four genomic intervals containing major SLE-susceptibility loci were previously identified by interval mapping in the NZM2410 mouse model. In this paper, we utilized a marker-assisted selection protocol to produce four congenic mouse strains, each carrying an NZM2410-derived SLE-susceptibility interval on a C57BL/6-resistant background. Each strain carries only one susceptibility allele derived from this polygenic model and consequently can be used to characterize the specific component phenotypes contributed by individual SLE-susceptibility genes. We illustrate the efficacy of this approach with phenotypic data for one of our congenic strains, B6.NZMH2(z). Our results indicate that this single genomic interval from Chromosome (Chr) 17 of NZM2410 can mediate increased levels of IgG autoantibodies specific for chromatin and that, similar to results obtained in our original genetic cross, B6.NZMH2(z/b) heterozygotes are more prone than B6.NZMH2(z) homozygotes to the development of humoral autoimmunity to nuclear antigens. These results illustrate the feasibility of using congenic strains to dissect the complex pathogenic mechanisms that mediate polygenic SLE. These congenic strains will be valuable tools in the genetic analysis of SLE susceptibility. In future studies, these congenic strains will be interbred to produce bi- and tri-congenic strains in order to assess the role of genetic interactions in the expression of specific components of SLE pathogenesis. They will also be instrumental to the positional cloning and identification of the genes responsible for SLE susceptibility, via the production of congenic recombinants.

Animals↗
PubMed1991

Mediational screening: is the benefit worth the cost?

Argued that Pillow et al. (1991) may have overestimated the benefits of mediational screening and underestimated the costs involved in the procedure. The three benefits they suggest: increased statistical power to detect prevention effects, increased cost-effectiveness, and decreased iatrogenic effects are shown to be modest at best. Costs associated with misclassifying people as either false positives or false negatives are considered in the total cost/benefit analysis of mediational screening. Because we cannot accurately predict who will react to the occurrence of life stress by developing the conditions we are interested in preventing, universal interventions are advocated.

Adaptation, Psychological↗
PubMed1991

Nanosecond kinetic absorption and calorimetric studies of cyclopentenone: the triplet, self-quenching, and the predimerization biradicals.

The photolysis of 2-cyclopentenone has been studied by a combination of kinetic absorption spectrophotometry and time-resolved photoacoustic calorimetry. The lifetime of the cyclopentenone triplet is strongly concentration dependent and corresponds to a value of 380 +/- 75 ns at infinite dilution in acetonitrile. The biradical intermediate (or pair of isomeric biradicals) immediately preceding formation of photodimer forms with very high efficiency upon quenching of triplet cyclopentenone by a second ground state cyclopentenone molecule and has an energy of 47 kcal/mol relative to two molecules of reactant. Quenching of the cyclopentenone triplet by conjugated dienes is much slower than expected, which is the reason that early estimates of the triplet lifetime were much too short.

Calorimetry↗
PubMed1990

Determination of triplet excitation energies of cyclic enones by time-resolved photoacoustic calorimetry.

Energies and lifetimes of triplet states of a series of 2-cyclohexenones have been measured in solution under ambient conditions by time-resolved photoacoustic calorimetry (PAC). The PAC triplet lifetimes are in excellent agreement with lifetimes measured by kinetic absorption spectrophotometry (KAS) using nanosecond flash techniques, indicating that the present data indeed pertain to the enone triplets previously studied using KAS. The data demonstrate that, as previously proposed, the pi pi triplet energies in these systems are indeed correlated with triplet lifetimes, and vary sensibly with the anticipated extent of conformational flexibility of the C = C bond. No evidence supporting formation of metastable trans-cyclohexenones was obtained. The data also demonstrate greater precision and, for lifetimes, greater accuracy than has hitherto been claimed for the PAC technique for study of transients with lifetimes in the 25 ns range.

Calorimetry↗
PubMed1988

The assessment of child abuse potential and the prevention of child abuse and neglect: a policy analysis.

A frequently advocated strategy for increasing the efficiency of child abuse prevention programs is to deliver prevention services to "high-risk" populations. This article critically reviews procedures for the reliable and valid assessment of child abuse potential within an ecological perspective. Factors that limit the usefulness of child abuse risk assessment are discussed. These factors include the uncertain criteria of child abuse and neglect, the low base rate of the phenomenon, and the financial and social costs of such procedures. Finally, the prevention implications of the current and future state of the art in child abuse risk assessment are considered and preventive interventions that do not depend on individual case risk screening are advocated.

Child↗
PubMed1988

Surgical spectrum of aortic stenosis in children: a thirty-year experience with 257 children.

Aortic stenosis accounts for 5 to 6% of infants and children seen for surgical repair of congenital heart disease. The clinical presentation and reported results of operation for aortic stenosis are highly variable. This retrospective review was undertaken to assess our operative mortality and the degree of gradient reduction afforded by each of several surgical techniques used to treat aortic stenosis in children over a 30-year period. Two hundred fifty-seven patients ranging in age from 1 day to 19 years were operated on between 1957 and 1986. The indication for operation included asymptomatic patients with gradients greater than 50 mm Hg to patients in profound cardiogenic shock. The operative mortality for children older than 6 months was 4%, whereas neonates seen with critical aortic stenosis had a 60% mortality. The late mortality was 2%. Eighty percent of surviving patients to date have undergone cardiac catheterization after repair. This shows an overall reduction of 57 mm Hg in the left ventricular-aortic gradient. Patients with supravalvular aortic stenosis and discrete subvalvular aortic stenosis as well as patients undergoing aortic valve replacement showed a reduction in or elimination of associated aortic insufficiency, whereas patients undergoing aortic valvotomy or neonates having valvotomy had a significant increase in demonstrable aortic insufficiency. The incidence of third-degree heart block or cerebral emboli following operation for aortic stenosis was less than 1%. However, the incidence of late bacterial endocarditis following repair was nearly 5%; six of eleven cases occurred in the group with discrete subvalvular aortic stenosis. Twenty-nine (13%) of the 223 long-term survivors have undergone a subsequent procedure for relief of residual or recurrent obstruction; 12 have had insertion of an aortic valve prosthesis, 12 have had insertion of an apicoaortic conduit, and 6 have required repeat aortic valvotomy. These data demonstrate the low operative mortality and excellent hemodynamic benefit of surgical relief of single-level aortic stenosis in children older than neonates. Conduits placed for complex obstructions or operative procedures in neonates have acceptable hemodynamic benefits, but operative mortality remains high.

Adolescent↗
PubMed1982

A preventive program for the newly separated: initial evaluation.

A 6-month long preventive intervention program for newly separated persons was designed on the basis of an analysis of the literature that identified the major stressful elements in the separation experience. Following the implementation of the program, its impact was assessed by contrasting persons who were assigned to the program (n = 100) with newly separated persons who were randomly selected to serve as a no-treatment control group (n = 50). Of the nine dependent measures of adjustment used in this evaluation, five significant posttreatment differences were found, in each case favoring the intervention group. The nature of these significant differences is particularly encouraging in light of the preventively oriented objectives of the intervention program. Detailed analysis of program characteristics resulted in the identification of desirable program modifications that could be implemented when the program is reinstituted.

Adaptation, Psychological↗
PubMed1982

Social support: its structure and impact on marital disruption.

Availability of social support has been hypothesized to play a role in influencing adjustment to marital disruption either directly or by moderating the debilitating effects of stress. Yet previous research has not adequately conceptualized or measured the nature and availability of social support. In an effort to learn more about the structure and impact of social support as it relates to marital disruption, 50 newly separated men and women were interviewed at 2 months and again at 8 months after their separations. The structure of social support was found to include (a) several important sources of support, including family, friends, and the larger community; (b) an index of social activity; and (c) a sense of satisfaction with present marital status. Although the stress associated with separation was positively related to poorer adjustment, certain aspects of social support were found to moderate this relationship.

Adaptation, Psychological↗
PubMed1975

Normative and parametric analyses of school maladjustment.

Format and instructional revisions were made in the TRF, a previously reported school adjustment measure, to extend its diagnostic, prescriptive, and empirical utility. Factor analyses of school adjustment ratings on the revised CARS with a normative sample of "healthy" primary graders demonstrated that while the revisions maintained the scale's original three-factor structure, they increased specific item factor loadings and accounted scale variance. To extend the screening utility of the proposed measure, normative and parametric comparisons are reported describing adjustment ratings for sex, age, and city/country subgroups. Comparisons of children who are or are not referred to a secondary prevention program provide evidence of the CARS discriminative validity and screening potential.

Age Factors↗