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Biomedical subjects

S L Johnson

Publications and source records attributed to S L Johnson.

At least 37 records · Page 2Linked to original sources

Sequential interactions in the parent-child communications of depressed fathers and depressed mothers.

Parental depression predicts adjustment problems and depression in offspring, yet little is known about the factors that explain this intergenerational transmission. In the present study, the authors examined one model suggesting that families with a depressed member may respond differently to positive and negative communications than families without a depressed member, differences that have been theorized to adversely impact offspring development. The authors compared the sequential patterns of parent-child interaction among families with depressed mothers, depressed fathers, and nondepressed parents. Positivity suppression, defined as decreased rates of positivity following a positive communication from other family members, characterized the interactions of families with a depressed father, but not those with a depressed mother or no depressed parent. Father-child positivity suppression and low base rates of positivity were associated with child behavior problems, but not after accounting for paternal depression.

Adolescent↗

Mutational analysis of endothelin receptor b1 (rose) during neural crest and pigment pattern development in the zebrafish Danio rerio.

Pigment patterns of fishes are a tractable system for studying the genetic and cellular bases for postembryonic phenotypes. In the zebrafish Danio rerio, neural crest-derived pigment cells generate different pigment patterns during different phases of the life cycle. Whereas early larvae exhibit simple stripes of melanocytes and silver iridophores in a background of yellow xanthophores, this pigment pattern is transformed at metamorphosis into that of the adult, comprising a series of dark melanocyte and iridophore stripes, alternating with light stripes of iridophores and xanthophores. Although several genes have been identified in D. rerio that contribute to the development of both early larval and adult pigment patterns, comparatively little is known about genes that are essential for pattern formation during just one or the other life cycle phase. In this study, we identify the gene responsible for the rose mutant phenotype in D. rerio. rose mutants have wild-type early larval pigment patterns, but fail to develop normal numbers of melanocytes and iridophores during pigment pattern metamorphosis and exhibit a disrupted pattern of these cells. We show that rose corresponds to endothelin receptor b1 (ednrb1), an orthologue of amniote Ednrb genes that have long been studied for their roles in neural crest and pigment cell development. Furthermore, we demonstrate that D. rerio ednrb1 is expressed both during pigment pattern metamorphosis and during embryogenesis, and cells of melanocyte, iridophore, and xanthophore lineages all express this gene. These analyses suggest a phylogenetic conservation of roles for Ednrb signaling in the development of amniote and teleost pigment cell precursors. As murine Ednrb is essential for the development of all neural crest derived melanocytes, and D. rerio ednrb1 is required only by a subset of adult melanocytes and iridophores, these analyses also reveal variation among vertebrates in the cellular requirements for Ednrb signaling, and suggest alternative models for the cellular and genetic bases of pigment pattern metamorphosis in D. rerio.

Animals↗

Fibronectin and its fragments increase with degeneration in the human intervertebral disc.

STUDY DESIGN: This laboratory-based experiment correlates fibronectin content of intervertebral disc with a morphologic grade of degeneration. OBJECTIVES: To correlate the fibronectin content of the anulus fibrosus and nucleus pulposus with a gross morphologic grade of disc degeneration, and to determine the molecular size of the extractable fibronectin. SUMMARY OF BACKGROUND DATA: Intervertebral disc degeneration increases with age and can lead to low back pain. Fibronectin helps to organize the extracellular matrix and provides environmental cues by interaction with cell surface integrins. In other tissues, its synthesis is elevated in response to injury. Fibronectin fragments can stimulate cells to produce metalloproteases and cytokines and inhibit matrix synthesis. METHODS: In this study, 17 anuli fibrosis and 18 nuclei pulposus from 11 spines were graded by Thompson's gross morphologic scale. Fibronectin was sequentially extracted with 4 mol/L guanidine hydrochloride and trypsin, and then quantitated by enzyme-linked immunoassay. The size of extractable fibronectin was determined by Western blot analyses. RESULTS: The fibronectin content of the disc increased with grade and was significantly elevated between Grades 3 and 4. The percentage of extractable fibronectin varied widely, but it was more extractable from the nucleus. In both the nucleus and anulus, 30% to 40% of the extractable fibronectin existed as fragments. Many of the fragments contained functional heparin or collagen-binding sites. CONCLUSIONS: Fibronectin is elevated in degenerated discs and frequently present as fragments. Elevated levels of fibronectin suggest that disc cells are responding to the altered environment. Fibronectin fragments resulting from normal or enhanced proteolytic activity could be a mechanism that induces the cell to degrade the matrix further.

Adolescent↗

Social support and self-esteem predict changes in bipolar depression but not mania.

INTRODUCTION: Our own and other research has suggested that social support predicts course of bipolar disorder, with particularly strong effects on depressive symptoms. Within this paper, we examine which components of social support appear most powerful. METHODS: Thirty-one individuals with Bipolar I disorder were followed longitudinally for 9 months. Participants completed a standardized symptom severity interview monthly, and at a 2-month follow-up, they completed the Interpersonal Support Evaluation List. At a 6-month follow-up, they completed the Rosenberg Self-Esteem Inventory. RESULTS: Self-esteem support appeared to the most important predictor of change in depression across a 6-month follow-up, and multiple regression analyses suggested that social support effects were mediated through self-esteem. LIMITATIONS AND IMPLICATIONS: Although the small sample size suggests a need for replication, current results highlight the importance of psychosocial variables in the course of bipolar depression. Self-esteem may be a particularly important target for clinical interventions.

Adult↗

Coping and medication adherence in bipolar disorder.

BACKGROUND: Effective treatment of bipolar disorder depends on medication adherence, yet few correlates of adherence have been identified. The pleasure experienced during some manic episodes may render some individuals reluctant to adhere to medications that reduce these 'highs'. Clinical observers identify denial of the severity or existence of illness as common to both bipolar disorder and addiction. The Alcoholics Anonymous model promotes acceptance as a pathway to abstinence adherence. This report hypothesized that acceptance coping would correlate positively and denial coping would correlate inversely with adherence to mood-stabilizing medication among individuals with bipolar disorder. METHODS: Thirty-two participants diagnosed with bipolar I disorder were administered scales from the Brief COPE and an adherence self-report measure. RESULTS: Consistent with hypotheses, curvilinear relationships between acceptance and denial with adherence were detected, suggesting that low levels of acceptance and high levels of denial undermine medication adherence. LIMITATIONS: Given the cross-sectional, naturalistic design of the study, no causal inferences can be made. CONCLUSIONS: The results uncover links between coping styles and adherence in a psychiatric population. The link between acceptance-denial coping, and mature, self-supportive behavior may point the way towards more effective psychosocial interventions.

Adaptation, Psychological↗

Increases in manic symptoms after life events involving goal attainment.

Bipolar disorder has been conceptualized as an outcome of dysregulation in the behavioral activation system (BAS), a brain system that regulates goal-directed activity. On the basis of the BAS model, the authors hypothesized that life events involving goal attainment would promote manic symptoms in bipolar individuals. The authors followed 43 bipolar I individuals monthly with standardized symptom severity assessments (the Modified Hamilton Rating Scale for Depression and the Bech-Rafaelsen Mania Rating Scale). Life events were assessed using the Goal Attainment and Positivity scales of the Life Events and Difficulties Schedule. As hypothesized, manic symptoms increased in the 2 months following goal-attainment events, but depressed symptoms were not changed following goal-attainment events. These results are congruent with a series of recent polarity-specific findings.

Achievement↗

Sequential interactions in the marital communication of depressed men and women.

Despite studies showing patterns of sequential interaction between depressed wives and their husbands, no published research has contrasted sequential interactions of depressed husbands and their wives. This study compared problem-solving interactions of 49 couples with a depressed husband, 41 with a depressed wife, and 50 normal controls. Interactions were coded using the Marital Interaction Coding System. Although no clear patterns of sequential interaction distinguished couples with a depressed wife from normal control couples, results suggested a unique pattern of interaction between depressed husbands and their spouses, whereby positive communications from the husband resulted in decreased positivity and increased negativity from their wives. Given the importance of positivity for promoting effective problem solving, this pattern appears to have important implications for couples' long-term marital satisfaction and husbands' mood regulation.

Adult↗

Genetic analysis of isometric growth control mechanisms in the zebrafish caudal Fin.

The body and fins of the zebrafish grow rapidly as juveniles and slower as they reach maturation. Throughout their lives, the fins grow isometrically with respect to the body. Growth of individual fin rays is achieved by the distal addition of bony segments. We have investigated the genetic control of mechanisms that initiate new segments or control size of newly initiated segments. We find that both segment initiation and segment length are regulated during fin growth in wild-type fish. We examined the growth properties of lof and sof fin length mutants for effects on the number and length of fin ray segments. Fins of lof mutants continue to grow rapidly even after wild-type fin growth slows, resulting in positive allometric growth and additional fin ray segments. We suggest that lof mutants bypass mechanisms that limit segment initiation. Isometric growth is retained in sof mutants, resulting in shorter fins one-half the length of wild-type fins. The primary defect in sof mutants is that fin ray segments are shorter than wild-type segments, although segment number is also diminished. Double mutants for sof;lof reveal that segment length and segment number are controlled in different pathways. Our findings suggest that the lof gene product regulates segment initiation and the sof gene product regulates segment length.

Aging↗

Genetic linkage mapping of zebrafish genes and ESTs.

Genetic screens in zebrafish (Danio rerio) have isolated mutations in hundreds of genes essential for vertebrate development, physiology, and behavior. We have constructed a genetic linkage map that will facilitate the identification of candidate genes for these mutations and allow comparisons among the genomes of zebrafish and other vertebrates. On this map, we have localized 771 zebrafish genes and expressed sequence tags (ESTs) by scoring single-stranded conformational polymorphisms (SSCPs) in a meiotic mapping panel. Of these sequences, 642 represent previously unmapped genes and ESTs. The mapping panel was comprised of 42 homozygous diploid individuals produced by heat shock treatment of haploid embryos at the one-cell stage (HS diploids). This "doubled haploid" strategy combines the advantages of mapping in haploid and standard diploid systems, because heat shock diploid individuals have only one allele at each locus and can survive to adulthood, enabling a relatively large quantity of genomic DNA to be prepared from each individual in the mapping panel. To integrate this map with others, we also scored 593 previously mapped simple-sequence length polymorphisms (SSLPs) in the mapping panel. This map will accelerate the molecular analysis of zebrafish mutations and facilitate comparative analysis of vertebrate genomes.

Animals↗

The syntenic relationship of the zebrafish and human genomes.

The zebrafish is an important vertebrate model for the mutational analysis of genes effecting developmental processes. Understanding the relationship between zebrafish genes and mutations with those of humans will require understanding the syntenic correspondence between the zebrafish and human genomes. High throughput gene and EST mapping projects in zebrafish are now facilitating this goal. Map positions for 523 zebrafish genes and ESTs with predicted human orthologs reveal extensive contiguous blocks of synteny between the zebrafish and human genomes. Eighty percent of genes and ESTs analyzed belong to conserved synteny groups (two or more genes linked in both zebrafish and human) and 56% of all genes analyzed fall in 118 homology segments (uninterrupted segments containing two or more contiguous genes or ESTs with conserved map order between the zebrafish and human genomes). This work now provides a syntenic relationship to the human genome for the majority of the zebrafish genome.

Animals↗

Calcium phosphate nanoparticle adjuvant.

Vaccination to protect against human infectious diseases may be enhanced by using adjuvants that can selectively stimulate immunoregulatory responses. In a murine model, a novel nanoparticulate adjuvant composed of calcium phosphate (CAP) was compared with the commonly used aluminum (alum) adjuvants for its ability to induce immunity to herpes simplex virus type 2 (HSV-2) and Epstein-Barr virus (EBV) infections. Results indicated that CAP was more potent as an adjuvant than alum, elicited little or no inflammation at the site of administration, induced high titers of immunoglobulin G2a (IgG2a) antibody and neutralizing antibody, and facilitated a high percentage of protection against HSV-2 infection. Additional benefits of CAP include (i) an insignificant IgE response, which is an important advantage over injection of alum compounds, and (ii) the fact that CAP is a natural constituent of the human body. Thus, CAP is very well tolerated and absorbed. These studies were performed with animal models. By virtue of the potency of this CAP adjuvant and the relative absence of side effects, we believe that this new CAP formulation has great potential for use as an adjuvant in humans.

Adjuvants, Immunologic↗

An orthologue of the kit-related gene fms is required for development of neural crest-derived xanthophores and a subpopulation of adult melanocytes in the zebrafish, Danio rerio.

Developmental mechanisms underlying traits expressed in larval and adult vertebrates remain largely unknown. Pigment patterns of fishes provide an opportunity to identify genes and cell behaviors required for postembryonic morphogenesis and differentiation. In the zebrafish, Danio rerio, pigment patterns reflect the spatial arrangements of three classes of neural crest-derived pigment cells: black melanocytes, yellow xanthophores and silver iridophores. We show that the D. rerio pigment pattern mutant panther ablates xanthophores in embryos and adults and has defects in the development of the adult pattern of melanocyte stripes. We find that panther corresponds to an orthologue of the c-fms gene, which encodes a type III receptor tyrosine kinase and is the closest known homologue of the previously identified pigment pattern gene, kit. In mouse, fms is essential for the development of macrophage and osteoclast lineages and has not been implicated in neural crest or pigment cell development. In contrast, our analyses demonstrate that fms is expressed and required by D. rerio xanthophore precursors and that fms promotes the normal patterning of melanocyte death and migration during adult stripe formation. Finally, we show that fms is required for the appearance of a late developing, kit-independent subpopulation of adult melanocytes. These findings reveal an unexpected role for fms in pigment pattern development and demonstrate that parallel neural crest-derived pigment cell populations depend on the activities of two essentially paralogous genes, kit and fms.

Animals↗

Zebrafish kit mutation reveals primary and secondary regulation of melanocyte development during fin stripe regeneration.

Fin regeneration in adult zebrafish is accompanied by re-establishment of the pigment stripes. To understand the mechanisms underlying fin stripe regeneration and regulation of normal melanocyte stripe morphology, we investigated the origins of melanocytes in the regenerating fin and their requirement for the kit receptor tyrosine kinase. Using pre-existing melanin as a lineage tracer, we show that most fin regeneration melanocytes develop from undifferentiated precursors, rather than from differentiated melanocytes. Mutational analysis reveals two distinct classes of regeneration melanocytes. First, an early regeneration class develops dependent on kit function. In the absence of kit function and kit-dependent melanocytes, a second class of melanocytes develops at later stages of regeneration. This late kit-independent class of regeneration melanocytes has little or no role in wild-type fin stripe development, thus revealing a secondary mode for regulation of fin stripes. Expression of melanocyte markers in regenerating kit mutant fins suggests that kit normally acts after mitf and before dct to promote development of the primary kit-dependent melanocytes. kit-dependent and kit-independent melanocytes are also present during fin stripe ontogeny in patterns similar to those observed during regeneration.

Animals↗

Improving Preschoolers' self-regulation of energy intake.

BACKGROUND: Children exhibit individual differences in their ability to self-regulate energy intake. Feeding strategies that focus on external signals, like the time of day or amount of food left on a plate, tend to diminish children's ability to respond to internal cues of hunger and fullness. OBJECTIVES: We investigated whether children could be taught to focus on internal cues of hunger and satiety, and consequently improve their self-regulation of energy intake. We explored whether parents' eating behaviors and adiposity were related to their children's self-regulation skills and adiposity. DESIGN: In a pretest and posttest design, preschoolers participated in single-meal protocols to assess their individual ability to self-regulate food intake. During a 6-week intervention period, children took part in individual and group activities designed to help them recognize internal cues. Parents completed questionnaires regarding adult dietary restraint and disinhibition. RESULTS: At baseline, we found a large individual variability in children's regulation: some children overate, some regulated accurately, and others underate. At baseline, children's eating related to their adiposity and to mothers' disinhibition: heavier children and children whose mothers' reported difficulty controlling food intake showed less evidence of self-regulation. Both overeaters and undereaters responded to the intervention, improving their ability to self-regulate, and children's eating was no longer significantly related to mother's eating. CONCLUSIONS: Children's disregulated energy intake is related to mothers' weight status and mothers' perceived control over eating. Cues can be provided that help children to focus on internal signals and improve their ability to self-regulate energy intake.

Anthropometry↗

Human and behavioral factors contributing to spine-based neurological cockpit injuries in pilots of high-performance aircraft: recommendations for management and prevention.

In high-performance aircraft, the need for total environmental awareness coupled with high-g loading (often with abrupt onset) creates a predilection for cervical spine injury while the pilot is performing routine movements within the cockpit. In this study, the prevalence and severity of cervical spine injury are assessed via a modified cross-sectional survey of pilots of multiple aircraft types (T-38 and F-14, F-16, and F/A-18 fighters). Ninety-five surveys were administered, with 58 full responses. Fifty percent of all pilots reported in-flight or immediate post-flight spine-based pain, and 90% of fighter pilots reported at least one event, most commonly (> 90%) occurring during high-g (> 5 g) turns of the aircraft with the head deviated from the anatomical neutral position. Pre-flight stretching was not associated with a statistically significant reduction in neck pain episodes in this evaluation, whereas a regular weight training program in the F/A-18 group approached a significant reduction (mean = 2.492; p < 0.064). Different cockpit ergonomics may vary the predisposition to cervical injury from airframe to airframe. Several strategies for prevention are possible from both an aircraft design and a preventive medicine standpoint. Countermeasure strategies against spine injury in pilots of high-performance aircraft require additional research, so that future aircraft will not be limited by the human in control.

Adult↗

Gene duplication of zebrafish JAK2 homologs is accompanied by divergent embryonic expression patterns: only jak2a is expressed during erythropoiesis.

Members of the JAK family of protein tyrosine kinase (PTK) proteins are required for the transmission of signals from a variety of cell surface receptors, particularly those of the cytokine receptor family. JAK function has been implicated in hematopoiesis and regulation of the immune system, and recent data suggest that the vertebrate JAK2 gene may play a role in leukemia. We have isolated and characterized jak cDNAs from the zebrafish Danio rerio. The zebrafish genome possesses 2 jak2 genes that occupy paralogous chromosome segments in the zebrafish genome, and these segments conserve syntenic relationships with orthologous genes in mammalian genomes, suggesting an ancient duplication in the zebrafish lineage. The jak2a gene is expressed at high levels in erythroid precursors of primitive and definitive waves and at a lower level in early central nervous system and developing fin buds. jak2b is expressed in the developing lens and nephritic ducts, but not in hematopoietic tissue. The expression of jak2a was examined in hematopoietic mutants and found to be disrupted in cloche and spadetail, suggesting an early role in hematopoiesis. Taken together with recent gene knockout data in the mouse, we suggest that jak2a may be functionally equivalent to mammalian Jak2, with a role in early erythropoiesis.

Alleles↗

Radiation hybrid mapping of the zebrafish genome.

The zebrafish is an excellent genetic system for the study of vertebrate development and disease. In an effort to provide a rapid and robust tool for zebrafish gene mapping, a panel of radiation hybrids (RH) was produced by fusion of irradiated zebrafish AB9 cells with mouse B78 cells. The overall retention of zebrafish sequences in the 93 RH cell lines that constitute the LN54 panel is 22%. Characterization of the LN54 panel with 849 simple sequence length polymorphism markers, 84 cloned genes and 122 expressed sequence tags allowed the production of an RH map whose total size was 11,501 centiRays. From this value, we estimated the average breakpoint frequency of the LN54 RH panel to correspond to 1 centiRay = 148 kilobase. Placement of a group of 235 unbiased markers on the RH map suggests that the map generated for the LN54 panel, at present, covers 88% of the zebrafish genome. Comparison of marker positions in RH and meiotic maps indicated a 96% concordance. Mapping expressed sequence tags and cloned genes by using the LN54 panel should prove to be a valuable method for the identification of candidate genes for specific mutations in zebrafish.

Animals↗