Homologous recombination and the repair of double-strand breaks during cotransformation of Dictyostelium discoideum.

We examined the ability of unlinked nonreplicating plasmid molecules to undergo homologous recombination during cotransformation of Dictyostelium amoebae. The transformation vector B10S confers resistance to the antibiotic G418 and was always presented to amoebae as a closed circle. Cotransforming DNA, containing a slime mold cDNA and sequences homologous to the primary vector, was presented either as a closed circle or as a linear molecule after digestion with restriction endonucleases which cut within one of three distinct regions of the plasmid. Remarkably, homologous recombination occurred in every clone examined. Moreover, the products of recombination were identical in all instances, irrespective of the presence or position of linearized ends. The ends of the linear templates were not recombinogenic. Repair of the introduced double-strand break occurred frequently during recombination. The repair could occur intermolecularly or, more likely, intramolecularly, i.e., by recircularization. Many of the recombination events were of a nonreciprocal nature. Despite the startlingly frequent level of homologous recombination, the use of cotransforming DNA which contains no homology to the selected vector established that such recombination was not required for cotransformation.

Hyperactive children and peer interaction: knowledge and performance of social skills.

This study investigated hyperactive children's peer relations using the framework of social skills theory. Subjects' (15 hyperactive and 15 control boys aged 7 through 11) knowledge of socially appropriate behavior was assessed using the Social Knowledge Interview (Geraci & Asher, 1980). Additionally, performance of social skills with peers was rated by independent judges during free play, a cooperative puzzle task, and a persuasion task. Peers also rated subjects' desirability as partners for work, play, and friendship. Analyses showed that hyperactive subjects had deficits in knowledge of how to maintain relationships and handle interpersonal conflict, and demonstrated more negative behavior in the cooperative puzzle task than did controls. Hyperactive subjects also were rated by judges as less likely to achieve academic success than controls and were rated by peers as less desirable potential work partners in school. Significant correlations between social knowledge and performance with peers were found. It was concluded that hyperactive boys exhibit deficits both in their social knowledge and in their performance of socially skilled behavior.

A case management agency and bank create a service innovation.

Connecticut Community Care, Inc. (CCCI), a statewide, nonprofit case management agency, in collaboration with Connecticut National Bank (CNB), developed a unique model of delivering case management services to bank trust clients. No reports of such a collaborative model have been found in the published literature in the United States. The article presents a historical overview of this innovative initiative; the identification of the target population; the delivery of the assessment, coordination, and monitoring services; and the marketing techniques. Utilization statistics, a synopsis of the model outcomes as viewed by the trust officers, and suggestions for replication are also presented.

Childhood chronic illness as a family stressor.

Investigated the impact of childhood chronic illness within a family context. We interviewed 30 mothers of 6- to 14-year-old children with asthma or diabetes and 30 mothers of healthy children of the same age and sex. Family functioning, extrafamilial social support available to mothers, and child life stress events were examined in relation to the children's psychological adjustment and illness events. The mothers of asthmatic children reported a greater number of internalizing behavior problems in their children, perceived their own social support as less adequate, and reported a greater number of stressful events. Regression analyses demonstrated that family functioning, maternal social support, and chronic illness were significantly related to the psychological adjustment of the child. The importance of family functioning and resources available to the family, such as social support, are discussed as protective influences in coping with childhood chronic illness.

Developmental outcome of preterm infants with intraventricular hemorrhage at one and two years of age.

Around 1980, many perinatal centers began prospective cranial screening of preterm infants using portable ultrasonography at the bedside. This study examined developmental outcome at 1 and 2 years in relation to the presence and severity of neonatal intraventricular hemorrhage (IVH). It varies from earlier reports in the size of the sample, restriction to infants without periventricular leukomalacia (PVL), and an attempt to formulate a predictive model by examining development longitudinally. Parametric and nonparametric analyses demonstrated that IVH related to Bayley mental and motor scores and neurologic ratings at 1 year but not at 2 years. Developmental delay and/or neurologic abnormality were more prevalent in infants with severe IVH but were far from universal. Regression analyses on prediction from neonatal and 1-year performance to 2-year scores revealed significant associations between the 1- and 2-year measures but not the neonatal and outcome measures. A direct insult to the CNS such as IVH thus constitutes only a limited model of risk status.

NCBI's LocusLink and RefSeq.

The NCBI has introduced two new web resources-LocusLink and RefSeq-that facilitate retrieval of gene-based information and provide reference sequence standards. These resources are designed to provide a non-redundant view of current knowledge about human genes, transcripts and proteins. Additional information about these resources is available on the LocusLink web site at http://www.ncbi.nlm.nih.gov/LocusLink/

Positive selection of CD4+ T cells by TCR ligation without aggregation even in the absence of MHC.

The developmental fate of immature thymocytes is determined by the specificity of their T-cell antigen receptors (TCRs). Immature CD4+8+ thymocytes are positively selected to differentiate into mature T cells by recognition of peptides associated with major histocompatibility complex (MHC) encoded molecules on thymic epithelial cells. But neither the identity of molecules transducing positive selection signals nor the nature of the signals themselves is fully known. Here we report that direct ligation of TCR molecules by monoclonal antibodies specific for either clonotypic or CD3 chains can signal immature thymocytes to differentiate into mature CD4+8- T cells, even in the absence of MHC expression and MHC-dependent CD4 co-receptor signalling. Moreover, we show that TCR engagement induces positive selection signals only in the absence of TCR aggregation and that TCR aggregation is inhibitory for positive selection. Thus, low valency of TCR crosslinking is a critical parameter, distinguishing positive selection from other TCR-mediated signalling events.

Developing a shared language: interdisciplinary communication among diverse health care professionals.

Multidisciplinary teams of nurses, physicians, and other professionals may have difficulty communicating because of inconsistent theoretical underpinnings. A theoretical base that spans both clinical outcomes and professional boundaries is needed. The web of causation is a theoretical framework that provides a platform of communication connecting issues related to infant mortality among various health-related professions. It includes professional, community, and institutional issues relevant to pregnant women and new mothers as infant caregivers. The article discusses how the web was used for interdisciplinary health care professional interaction and how it was used to develop a series of research protocols that will affect the care of mothers and infants in the District of Columbia.

Retention of low income mothers in a parenting intervention study.

Women with inadequate prenatal care were recruited to a multi-component parenting intervention study. Because it was anticipated that this high-risk population might present challenges to retention, a variety of strategies were employed to maintain their participation in the study. This report reviews the results of these retention efforts and compares the population that completed the study versus those that terminated prior to study completion. Two hundred and eighty-six women were randomized to an intervention or control group. Careful tracking of the mothers, offering incentives for completing various study activities and providing a culturally competent staff were among the strategies employed to maintain participation. Comparison was made of those mothers terminating before study completion versus those retained, and of those terminating early in the study period versus later. Despite retention efforts, attrition at a level of 41% occurred. A few characteristics of mothers terminating early from the study were significant including older maternal age, a larger number of children, and incidence of no prenatal care. Despite comprehensive tracking procedures, some mothers were lost to follow up after change of residence. Other reasons for attrition included child outplacement and refusal of services or data collection procedures.

Early response to light therapy partially predicts long-term antidepressant effects in patients with seasonal affective disorder.

OBJECTIVE: To determine if the antidepressant effect of 1 hour of light therapy is predictive of the response after 1 and 2 weeks of treatment in patients with seasonal affective disorder (SAD). PATIENTS: Twelve patients with SAD. SETTING: National Institutes of Health Clinical Center, Bethesda, Md. INTERVENTIONS: Light therapy for 2 weeks. OUTCOME MEASURES: Scores on the Seasonal Affective Disorder Version of the Hamilton Depression Rating Scale (SIGH-SAD) on 4 occasions (before and after 1 hour of light therapy and after 1 and 2 weeks of therapy) in the winter when the patients were depressed. Change on typical and atypical depressive scores at these time points were compared. RESULTS: Improvement of atypical depressive symptoms after 1 hour of light therapy positively correlated with improvement after 2 weeks of therapy. CONCLUSION: In patients with SAD, the early response to light therapy may predict some aspects of long-term response to light therapy, but these results should be treated with caution until replicated.

Effect of cerebral lesions on continuous performance test responses of school age children born prematurely.

Examined attention skills, as measured by the Continuous Performance Test (CPT), in a group of 64 children born premature and 40 full-term children, ages 6 to 8 years. Premature children were classified by neonatal cerebral lesions into no lesion, mild lesion, and severe lesion groups. It was predicted that severity of lesion would be associated with CPT performance. While mean differences among the groups of prematures did not reach significance, children with severe lesions made significantly more errors of omission and commission than the full-term comparison group. Children with mild lesions were poorer than full terms in errors of commission. Children with no lesions also made more errors of omission and commission than full terms, suggesting attention deficits secondary to prematurity even in the absence of identified brain lesion. With increasing severity of lesion, increasing percentages of each group were found to perform more than 2 SD below the mean in errors of commission. Results suggest that premature children, with and without identified lesions, are at risk for attention deficits.

Skewed X inactivation in a female MZ twin results in Duchenne muscular dystrophy.

One of female MZ twins presented with muscular dystrophy. Physical examination, creatine phosphokinase levels, and muscle biopsy were consistent with Duchenne muscular dystrophy (DMD). However, because of her sex she was diagnosed as having limb-girdle muscular dystrophy. With cDNA probes to the DMD gene, a gene deletion was detected in the twins and their mother. The de novo mutation which arose in the mother was shown by novel junction fragments generated by HindIII, PstI, or TaqI when probed with cDNA8. Additional evidence of a large gene deletion was given by novel SfiI junction fragments detected by probes p20, J-Bir, and J-66 on pulsed-field gel electrophoresis (PFGE). Immunoblot analysis of muscle from the affected twin showed dystrophin of normal size but of reduced amount. Immunofluorescent visualization of dystrophin revealed foci of dystrophin-positive fibers adjacent to foci of dystrophin-negative fibers. These data indicate that the affected twin is a manifesting carrier of an abnormal DMD gene, her myopathy being a direct result of underexpression of dystrophin. Cytogenetic analysis revealed normal karyotypes, eliminating the possibility of a translocation affecting DMD gene function. Both linkage analysis and DNA fingerprint analysis revealed that each twin has two different X chromosomes, eliminating the possibility of uniparental disomy as a mechanism for DMD expression. On the basis of methylation differences of the paternal and maternal X chromosomes in these MZ twins, we propose uneven lyonization (X chromosome inactivation) as the underlying mechanism for disease expression in the affected female.