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Functional differences between full and partial agonists: evidence for ligand-specific receptor conformations.

The interaction of an agonist-bound G-protein-coupled receptor (GPCR) with its cognate G-protein initiates a sequence of experimentally quantifiable changes in both the GPCR and G-protein. These include the release of GDP from G(alpha), the formation of a ternary complex between the nucleotide-free G-protein and the GPCR, which has a high affinity for agonist, followed by the binding of GTP to G(alpha), the dissociation of the GPCR/G-protein complex, and the hydrolysis of GTP. The efficacy of an agonist is a measure of its ability to activate this cascade. It has been proposed that efficacy reflects the ability of the agonist to stabilize the active state of the GPCR. We examined a series of beta(2)-adrenoceptor (beta(2)AR) agonists (weak partial agonists to full agonists) for their efficacy at promoting two different steps of the G-protein activation/deactivation cycle: stabilizing the ternary complex (high-affinity, GTP-sensitive agonist binding), and steady-state GTPase activity. We obtained results for the wild-type beta(2)AR and a constitutively active mutant of the beta(2)AR (beta(2)AR(CAM)) using fusion proteins between the GPCRs and G(salpha) to facilitate GPCR/G-protein interactions. There was no correlation between efficacy of ligands in activating GTPase and their ability to stabilize the ternary complex at beta(2)AR(CAM). Our results suggest that the GPCR state that optimally promotes the GDP release and GTP binding is different from the GPCR state that stabilizes the ternary complex. By strongly stabilizing the ternary complex, certain partial agonists may reduce the rate of G-protein turnover relative to a full agonist.

Adrenergic beta-2 Receptor Agonists↗

Regulation of resting and cycling human B lymphocytes via surface IgM and the accessory molecules interleukin-4, CD23 and CD40.

Experiments were designed in order to compare directly the ability of a new and potent monoclonal anti-mu chain antibody to initiate or maintain stimulation in resting and cycling B lymphocytes, respectively. Resting B cells could be stimulated by soluble anti-mu only in the presence of additional signals; these could be supplied by a high dose of phorbol ester or a combination of interleukin-4 (IL-4) and the CD40 antibody, G28-5. Immobilization of anti-mu not only increased the magnitude of the resting B-cell response but also diminished the co-factor requirements. The 'background' stimulation obtained when using a high concentration of immobilized anti-mu was unexpectedly reduced in the presence of IL-4 alone. The duration, but not the magnitude, of the IL-4 signal required for promoting optimal responses varied with the co-stimulation applied. Importantly, the threshold concentrations of soluble anti-mu needed to trigger the resting B cells were reduced upon the addition of each co-stimulant. With actively cycling B cells, both soluble and immobilized anti-mu were now capable of sustaining stimulation which could be prolonged on the addition of IL-4 and/or G28-5. In both resting and cycling populations, a strong correlation was noted between the magnitude of stimulation elicited when IL-4 was present and the release of the soluble CD23 molecule. Moreover, IL-4-promoted, but not other, stimulations could be augmented up to 10-fold by the inclusion of the CD23 antibody MHM6. Both the resting and cycling B-cell populations were found to secrete IgM in direct response to IL-4 and G28-5; this factor-driven production of IgM was differentially modulated by soluble and immobilized anti-mu in the two populations.

Antibodies, Monoclonal↗

Cloning and transcriptional analysis of the mouse receptor activity modifying protein-1 gene promoter.

BACKGROUND: Receptor activity modifying protein-1 (RAMP-1) is a single transmembrane-domain protein required for the functional expression of calcitonin gene-related peptide (CGRP) receptors. To date, little is known about the molecular mechanism(s) that activate/inhibit RAMP-1 gene expression. Such mechanism(s) are likely to play a major role in modulating the responsiveness of tissues to CGRP. RESULTS: To initiate studies on the transcriptional regulation of the mouse RAMP-1 gene, RAMP-1 transcriptional initiation sites were mapped in a variety of tissues. Analysis of RAMP-1 expression in C2C12 myoblasts demonstrated that RAMP-1 mRNA is expressed at greatest levels in confluent myoblasts verses non-confluent and fused myoblasts. Transfection of confluent C2C12 myoblasts and NIH 3T3 cells with RAMP-1 promoter/luciferase deletion constructs revealed that 4.7 kb of RAMP-1 5' flanking region demonstrated optimal promoter activity while 343 bp of 5' flanking region was defined as a minimal RAMP-1 promoter. In non-RAMP-1 expressing HEK293 cells, constructs containing 4.7 kb to 782 bp of RAMP-1 5' flanking region were transcriptionally inactive. However, deletion of sequences -782 to -343 activated RAMP-1 promoter activity. CONCLUSION: These findings suggest that tissue specificity of RAMP-1 gene expression is mediated by a negative acting transcription factor that represses RAMP-1 gene expression in non-RAMP-1 expressing tissues. This transcription factor is therefore likely to play an important role in modulating the responsiveness of tissues to CGRP.

5' Flanking Region↗

Diverse plasmid DNA vectors by directed molecular evolution of cytomegalovirus promoters.

Genetic vaccinations, gene therapy, and manufacturing of therapeutic proteins would benefit from promoter sequences that provide improved or prolonged expression levels. The cytomegalovirus (CMV) promoter is one of the most potent promoters known to date, and no previous examples of improved activity of this promoter by sequence mutagenesis have been reported. This study describes directed molecular evolution of CMV promoters derived from two human and two nonhuman primate strains of CMV by DNA shuffling and screening. Libraries of chimeric promoters were screened and analyzed for expression levels and immune responses, using plasmid DNA vectors encoding luciferase and beta-galactosidase. The results indicate that high functional diversity among CMV promoters can be generated, and the chimeric promoters selected after two rounds of DNA shuffling and particularly designed screening assays provided approximately 2-fold increased luciferase reporter gene expression and anti-beta-galactoside antibody response in vivo when compared with wild-type promoters. Sequence analysis of the shuffled promoters identified several mutations potentially contributing to the observed enhanced or reduced promoter activities and identified a 42-nucleotide region that appears obsolete for the functioning of the CMV promoter. Taken together, these data demonstrate the feasibility of generating diverse promoter sequences by DNA shuffling and screening methods, and provide novel structure- function information about CMV promoters. DNA shuffling and screening technologies provide a new approach to promoter optimization and development of optimal expression vectors for genetic vaccinations, gene therapy, and protein expression.

Animals↗

E2F and GATA-1 are required for the Sertoli cell-specific promoter activity of the follicle-stimulating hormone receptor gene.

The follicle-stimulating hormone receptor (FSHR) gene is expressed in Sertoli cells in males and in granulosa cells in females. Cis-acting sequences and associated binding factors responsible for the transcription of the TATA-less FSHR gene in Sertoli cells were analyzed with dimethylsulfate (DMS) footprinting assays and electrophoretic mobility shift assay (EMSA). In vivo footprints in the core promoter using nuclear proteins from Sertoli cells identified several protected sequences, including an inverted GATA (TATC, -88/-85), and an E2F (TTTCGCG, -45/-39) motif. EMSA showed the presence of one or more sequence-specific proteins interacting with these potential regulatory elements. Antibody-supershift assays as well as competition assays further revealed that testis-specific GATA-1 recognized the inverted GATA element. The functional role of the potential cis-acting elements was analyzed by transient transfection assays with and without mutations of the putative elements. The mutational analysis indicated that the GATA and E2F elements were each required for optimal promoter activity. The effects of each of the promoter elements was examined in transfections in which mutations were made in each of the known regulatory sites, including the E box, GATA, and E2F sites in various combinations. All of these sites contribute to the maximum promoter activity such that mutations of the E box, GATA, and E2F sites eliminated nearly all promoter activity.

Animals↗

Interaction of Sp1 with the growth- and cell cycle-regulated transcription factor E2F.

Within the region around 150 bp upstream of the initiation codon, which was previously shown to suffice for growth-regulated expression, the murine thymidine kinase gene carries a single binding site for transcription factor Sp1; about 10 bp downstream of this site, there is a binding motif for transcription factor E2F. The latter protein appears to be responsible for growth regulation of the promoter. Mutational inactivation of either the Sp1 or the E2F site almost completely abolishes promoter activity, suggesting that the two transcription factors interact directly in delivering an activation signal to the basic transcription machinery. This was verified by demonstrating with the use of glutathione S-transferase fusion proteins that E2F and Sp1 bind to each other in vitro. For this interaction, the C-terminal part of Sp1 and the N terminus of E2F1, a domain also present in E2F2 and E2F3 but absent in E2F4 and E2F5, were essential. Accordingly, E2F1 to E2F3 but not E2F4 and E2F5 were found to bind sp1 in vitro. Coimmunoprecipitation experiments showed that complexes exist in vivo, and it was estabilished that the distance between the binding sites for the two transcription factors was critical for optimal promoter activity. Finally, in vivo footprinting experiments indicated that both the sp1 and E2F binding sites are occupied throughout the cell cycle. Mutation of either binding motif abolished binding of both transcription factors in vivo, which may indicate cooperative binding of the two proteins to chromatin-organized DNA. Our data are in line with the hypothesis that E2F functions as a growth- and cell cycle regulated tethering factor between Sp1 and the basic transcription machinery.

3T3 Cells↗

Cloning of human preprotachykinin-I promoter and the role of cyclic adenosine 5'-monophosphate response elements in its expression by IL-1 and stem cell factor.

Preprotachykinin-I gene (PPT-I) encodes several peptides with organ-specific functions that link the neuroendocrine-immune-hemopoietic axis. We cloned upstream of the initiation site of human PPT-I promoter and identified consensus sequences for two cAMP response elements (CRE). PPT-I is induced by cytokines including those that signal through the cAMP pathway. Therefore, we studied the role of the two CRE in IL-1alpha and stem cell factor (SCF) stimulation of bone marrow stroma because both cytokines induce endogenous PPT-I in these cells and activate the cAMP pathway. Furthermore, bone marrow stroma expresses the transcription factors regulated by the cAMP pathways such as the repressor (ICERIIgamma) and activator (CREMtau). Mutagenesis of the two CRE and/or cotransfection with vectors that express ICERIIgamma or CREMtau indicated that the two CRE have major roles in PPT-I expression. The two CRE are also required for optimal promoter activity by SCF and IL-1alpha. A particular cytokine could concomitantly induce PPT-I and the high affinity G protein-coupled receptor for PPT-I peptides, NK-1R. We showed that SCF, a representative cytokine, induced PPT-I and NK-1R leading to autocrine and/or paracrine cell activation. Because NK-1R activates cAMP through the G protein, the results suggest that the presence of CRE sequences within PPT-I promoter could be important in the regulation of PPT-I expression by cytokines, irrespective of their ability to signal through cAMP. As PPT-I is implicated in hemopoietic regulation, immune responses, breast cancer, and other neural functions, these studies add to the basic biology of these processes and could provide targets for drug development.

5' Untranslated Regions↗

Clinical risk: discharging patients with no-one at home.

This article reports a study designed to assure if guidelines for discharge planning actually promoted optimal patient safety following endoscopic procedures. A flow chart was drafted to include discharge planning at the time of referral, immediately preprocedure, and postprocedure. A telephone survey was carried out postprocedure to see if patients were deemed to be safe at home, document pain and discomfort levels, and note if they thought they could have managed without their caregiver. Further education of endoscopists and nurses in the outpatient department was necessary to emphasize to patients preprocedure the need for a responsible adult to stay overnight following the procedure and to identify patients who may not be able to meet this requirement. The telephone survey showed a significant number of patients experienced a postprocedure issue. Planning and reviewing guidelines for patient discharge postendoscopically has significantly reduced potential problems and promoted safe practice for patients postprocedure.

Activities of Daily Living↗

Selective application of fundoplication during laparoscopic heller myotomy ensures favorable outcomes.

We propose that selective fundoplication during laparoscopic Heller myotomy achieves optimal outcomes. Fundoplication was applied selectively in 21 of 100 patients undergoing laparoscopic Heller myotomy with hiatus hernia, patulous esophageal hiatus, or intraoperative perforation. Dysphagia and heartburn incidence and severity in patients undergoing myotomy with or without fundoplication were compared before and after myotomy. Median follow-up was 19 months and was similar for both groups. Preoperative symptoms were similar for both groups of patients and showed significant improvement following myotomy with or without fundoplication. As well, there were no significant differences in postoperative dysphagia (26% vs. 14%), dysphagia score (1.1 +/- 1.4 vs. 0.8 +/- 1.3), heartburn (21% vs. 27%), or heartburn score (0.9 +/- 1.5 vs. 1.4 +/- 1.6). Overall improvement was seen in 86% of patients undergoing myotomy with fundoplication and in 97% without fundoplication (P = 0.06). Selective application of fundoplication during laparoscopic Heller myotomy promotes optimal outcomes.

Adolescent↗

Drosophila Pkd2 is haploid-insufficient for mediating optimal smooth muscle contractility.

Humans heterozygous for PKD1 or PKD2 develop autosomal dominant polycystic kidney disease, a common genetic disorder characterized by renal cyst formation and extrarenal complications such as hypertension and vascular aneurysms. Cyst formation requires the somatic inactivation of the wild type allele. However, it is unknown whether this recessive mechanism applies to life-threatening vascular aneurysms, which could involve weakening of the endothelial lining or surrounding vascular smooth muscle cells (SMCs). Drosophila Pkd2 at 33E3 (Pkd2) encodes a PKD2 family of Ca(2+)-activated Ca(2+)-permeable cation channels. We show here that loss-of-function Pkd2 mutations severely reduced the contractility of the visceral SMCs, which was restored by expressing wild type Pkd2 cDNA via a muscle-specific Gal4 driver. The effect of Pkd2 mutations alone on the skeletal muscle was minimal but was exacerbated by ryanodine-induced perturbation of intracellular Ca(2+) stores. Consistent with this, Pkd2 interacted strongly with a ryanodine receptor mutation, causing a synergistic reduction of larval body wall contraction rate that is normally regulated through Ca(2+) oscillation during excitation-contraction coupling in the skeletal muscle. These results suggest that PKD2 cooperates with the ryanodine receptor to promote optimal muscle contractility through intracellular Ca(2+) homeostasis. Further genetic analysis indicated that Pkd2 is strongly haploinsufficient for normal SMC contractility. Since Ca(2+) homeostasis is a conserved mechanism for optimal muscle performance, our results raise the possibility that inactivation of just one PKD2 copy is sufficient to compromise vascular SMC contractility and function in PKD2 heterozygous patients, thus explaining their increased susceptibility to hypertension and vascular aneurysms.

Animals↗

Synergistic cooperation between Sp1 and Smad3/Smad4 mediates transforming growth factor beta1 stimulation of alpha 2(I)-collagen (COL1A2) transcription.

Transforming growth factor-beta1 (TGFbeta) is a strong activator of extracellular matrix accumulation. TGFbeta stimulates the gene coding for human alpha2(I)-collagen (COL1A2) by inducing binding of an Sp1-containing complex to an upstream promoter element (TGFbeta responsive element or TbRE) that contains a CAGA box. Here we report that the CAGA box of the TbRE is the binding site of the Smad3/Smad4 complex, and that the binding of the complex is required for TGFbeta-induced COL1A2 up-regulation. Recombinant Smad3 and Smad4 bind in vitro to the CAGA box of COL1A2; TGFbeta treatment of cultured fibroblasts induces Smad3/Smad4 binding to the TbRE; transient overexpression of Smad3 and Smad4 in fibroblasts transactivates TbRE-driven transcription; and COL1A2 gene up-regulation by TGFbeta is abolished in cells stably transfected with plasmids that express dominant negative forms of Smad3 or Smad4. In Sp1-deficient Drosophila Schneider cells, there was cooperative synergy between Smad3/Smad4 and Sp1 at the TbRE site. The analysis also emphasized the requirement of both Sp1- and Smad-binding sites for optimal promoter transactivation. In cells stably transfected with a plasmid expressing a dominant negative form of Sp1, the synergy was shown to be promoter-specific and dependent on the binding of Sp1 to the TbRE. Interestingly, overexpression of dominant negative Sp1 was found to block the antagonistic signal of tumor necrosis factor-alpha on COL1A2 transcription, as well. These results provide the first linkage between the Smad3 and Smad4 proteins and TGFbeta stimulation of type I collagen biosynthesis.

3T3 Cells↗

Direct gene transfer to mouse melanoma by intratumor injection of free DNA.

Long-term expression of a reporter gene has previously been reported in skeletal and cardiac muscles after direct injection of naked plasmid DNA. In this study, we have shown that the direct injection of free plasmid DNA into mouse melanoma BL6 solid tumor can also result in a high level of transfection. THe average amount of chloramphenicol acetyltransferase (CAT) expressed by injecting 30 micrograms plasmid DNA containing a CAT gene into a single BL6 tumor was 1.9 +/- 1.0 ng, which is comparable to that reported in the skeletal muscle. Cationic liposomes, Lipofectamine and DC-chol/DOPE, inhibited gene expression in a dose-dependent manner. Transgene expression by free DNA persisted for at least 10 days. The size of tumor did not seem to affect the gene expression, but proper choice of a diluent solution for DNA was an important factor. Genes driven by the CMV promoter were expressed much more efficiently than genes driven by the SV40 or T7 promoter. Optimal dosage of injected DNA was from 30 to 70 micrograms per tumor. Other mouse melanomas, human melanomas and cervical carcinomas are also able to express directly injected plasmid DNA, but the transfection efficiency is lower than the BL6 tumor. Direct injection of free plasmid DNA is a simple and effective approach and might be a potential method for cancer gene therapy.

Animals↗

Position of the American Dietetic Association: food fortification and dietary supplements.

Wise food choices provide the necessary foundation for optimal nutrition. Science has not fully identified the specific chemical components that account for the benefits of healthy eating patterns. Selection of a variety of foods, using tools such as the USDA/HHS Dietary Guidelines for Americans and the USDA Food Guide Pyramid, is the best way to provide a desirable balance, without excessive intakes of macronutrients, micronutrients and other beneficial components of foods. Nevertheless, for certain nutrients and some individuals, fortification, supplementation, or both may also be desirable. Nutrient intakes from all these sources should be considered in dietary assessments, planning and recommendations. The recommendations of the National Academy of Sciences' Food and Nutrition Board provide a sound scientific basis for vitamin and mineral intakes. Intakes exceeding those recommendations have no demonstrated benefit for the normal, healthy population. Dietetics professionals should base recommendations for use of fortified foods or supplements on individualized assessment and sound scientific evidence of efficacy and safety. It is the position of the American Dietetic Association that the best nutritional strategy for promoting optimal health and reducing the risk of chronic disease is to wisely choose a wide variety of foods. Additional vitamins and minerals from fortified foods and/or supplements can help some people meet their nutritional needs as specified by science-based nutrition standards such as the Dietary Reference Intakes (DRI).

Controlled Clinical Trials as Topic↗

Herpesvirus-mediated gene delivery into the rat brain: specificity and efficiency of the neuron-specific enolase promoter.

1. Herpesvirus infection with genetically engineered vectors is a way to deliver foreign gene products to various cell populations in culture and in vivo. Selective neuronal gene expression can be achieved using the neuron-specific enolase (NSE) promoter regulating expression of a transgene placed in and delivered by a herpesvirus vector. 2. We sought to determine the anatomical specificity and efficiency of herpesvirus-mediated gene transfer into the rat brain following placement of virus particles carrying a transgene (lacZ) under control of the NSE promoter. The virus utilized was thymidine kinase (TK) deficient and therefore replication deficient in the brain. 3. Infusion of 10(6) plaque-forming units of virus into the striatum caused a limited number of striatal neurons to express the lacZ transgene mRNA and protein product 7 days postinfection. In addition, small numbers of neurons expressing the transgene mRNA and protein were found ipsilateral to the viral injection in the frontal cortex, substantia nigra pars compacta, and thalamus. Neurons at these anatomic loci project directly to the striatal injection site. No other cells within the brains of injected animals expressed the lacZ gene. 4. While this herpesvirus NSE vector was capable of introducing novel functional genetic information into postmitotic neurons within defined neuroanatomic constraints, the numbers of neurons expressing detectable levels of beta-galactosidase was minimal. The calculated efficiency of delivery and transgene expression at 7 days postinfection was 1 transgenic neuron per 10(4) virus particles infused. 5. We conclude that NSE probably is not an optimal promoter for use in gene delivery to CNS neurons in herpesvirus vectors and that the efficacy of gene delivery using other neuron-specific promoters placed at various sites in the herpes viral genome needs to be explored.

Animals↗

Physical activity in aging: changes in patterns and their relationship to health and function.

Sedentary behavior is an important risk factor for chronic disease morbidity and mortality in aging. However, there is a limited amount of information on the type and amount of activity needed to promote optimal health and function in older people. The purpose of this review is to describe the change in patterns of habitual physical activity in aging and the relationship of these changes to physical function and selected chronic diseases. We undertook a literature review of large population-based studies of physical activity in older people, and there is encouraging evidence that moderate levels of physical activity may provide protection from certain chronic diseases. Additionally, substantial health effects can be accrued independent of the fitness effects achieved through sustained vigorous activity. Thus, regular participation (i.e., 30 minutes/day on most days of the week) in activities of moderate intensity (such as walking, climbing stairs, biking, or yardwork/gardening), which increase accumulated daily energy expenditure and maintain muscular strength, but may not be of sufficient intensity for improving fitness, should be encouraged in older adults. Public policy should focus on ways of increasing volitional and lifestyle activity in older people, as well as on increasing the availability and accessibility of senior and community center programs for promoting physical activity throughout the life span.

Aged↗

Role of the HIV/AIDS case manager: analysis of a case management adherence training and coordination program in North Carolina.

Highly active antiretroviral therapy (HAART) adherence rates of 90%-95% or more are required to be effective at treating the virus and preventing drug resistance. From both a medical and public health perspective, it is essential that HIV-positive clients strictly adhere to antiretroviral treatment regimens. One promising approach to promoting optimal adherence rates among HIV-positive individuals is training and reimbursing case managers to provide adherence coordination services to HIV-positive clients. In this study, a sample of 16 HIV/ AIDS case managers from agencies across North Carolina participated in a Case Management Adherence Training and Coordination Program for a 3-month period. After case manager training, case managers enrolled 1-4 of their existing clients, who met eligibility criteria, to receive the adherence coordination program. Data were analyzed from focus group interviews and individual interviews conducted with case manager participants; their respective client care plans were also analyzed to identify primary barriers and strategies reported by case managers. Although case managers perceived themselves to be well positioned to provide adherence coordination services for their HIV-positive clients, they also identified barriers that they face in providing these services, including lack of reimbursement for their time, inadequate training, and insufficient knowledge of HIV/AIDS and medications. The findings of this study suggest that, with appropriate training and reimbursement, HIV/AIDS case managers can play a pivotal role in promoting and improving client adherence to antiretroviral medications.

Antiretroviral Therapy, Highly Active↗

Unsaturated fatty acids.

There is good scientific evidence that dietary fatty acid composition is involved in the aetiology of many diseases. Increasing the supply of n-3 polyunsaturated fatty acids (PUFA) may reduce the risk of CHD. Several scientific organizations (for example, see Department of Health, 1991, 1994; British Nutrition Foundation, 1992; Scientific Committee for Food, 1993; Food and Agriculture Organization/World Health Organization, 1998) have made recommendations for n-3 PUFA; however, there is a high degree of variation both in terms of the type and amount of n-3 PUFA (up to 7-fold). This variation reflects the different scientific axioms which underlie the different recommendations. Optimal nutrition may be defined in terms of the level of a nutrient required to avoid deficiency, or the amount required to have an effect on biomarkers and functional indicators of nutrient intake, or the level of a nutrient which prevents disease. Functional biomarkers of n-3 PUFA include plasma, platelet and erythrocyte phospholipid-n-3 PUFA levels. Plasma triacylglycerol concentrations represent a functional indicator of n-3 PUFA because n-3 PUFA exert a consistent hypotriacylglycerolaemic effect which is dose-dependent and persistent. In terms of disease status, epidemiological studies have demonstrated that the incidence of CHD is inversely associated with consumption of n-3 PUFA. Despite the health benefits of n-3 PUFA, the mean daily intake falls far short of most of the recommendations. Increasing fish intake is the most obvious way to increase n-3 PUFA intake. However, a large percentage (up to 65) of the population do not eat fish. Thus, there is a need for alternative sources of n-3 PUFA, such as functional foods, whose unique fatty acid composition could fortify staple foods thereby promoting optimal levels of n-3 PUFA intake.

Coronary Disease↗

Mastery motivation and temperament of 7-month-old infants.

PURPOSE: To examine relationships among infant mastery motivation, temperament, and cognition with the goal of highlighting infant behaviors to which nurses should be alert in the clinical environment to promote optimal infant development. SAMPLE: Subjects were 26 healthy, full-term infants, age 7 months, recruited from a well baby clinic. METHOD: A descriptive correlational design was used. Tools included the Bayley Scales of Infant Development, Fagan Test of Infant Intelligence, the Dimensions of Mastery Questionnaire, and the Revised Infant Temperament Questionnaire. RESULTS: Cognition was not related to either mastery motivation or temperament. Several relations between mastery motivation and temperament emerged. Infants with high mastery pleasure were rated as more cooperative and less difficult, and tended to be rated as more active and less irritable. Independent mastery, on the other hand, showed no correlation with temperament scores. Infants who were rated as high in persistence on the mastery motivation questionnaire were rated as more cooperative, more rhythmical, and less difficult on the temperament questionnaire, and they tended to be rated as more approachable and less irritable. Infants who were rated as high in competence tended to be rated as less difficult. CONCLUSIONS: While temperament and mastery motivation are related, information on mastery motivation provides additional information to the nurse that may be helpful both in planning interventions to promote infant development and in providing anticipatory guidance for parents.

Child Development↗