Rationalizing observed health and safety legislation: a Pascalian approach.
Explore the source record for details and available documents.
Health Care Reform↗
Biomedical subjects
E A Thompson
Publications and source records attributed to E A Thompson.
Reducing suicide potential among high-risk youth: tests of a school-based prevention program.
This study tested the efficacy of a school-based prevention program for reducing suicide potential among high-risk youth. A sample of 105 youth at suicide risk participated in a three-group, repeated-measures, intervention study. Participants in (1) an assessment plus 1-semester experimental program, (2) an assessment plus 2-semester experimental program, and (3) an assessment-only group were compared, using data from preintervention, 5-month, and 10-month follow-up assessments. All groups showed decreased suicide risk behaviors, depression, hopelessness, stress, and anger; all groups also reported increased self-esteem and network social support. Increased personal control was observed only in the experimental groups, and not in the assessment-only control group. The potential efficacy of the experimental school-based prevention program was demonstrated. The necessary and sufficient strategies for suicide prevention, however, need further study as the assessment-only group, who received limited prevention elements, showed improvements similar to those of the experimental groups.
Adolescent↗
Glucocorticoid regulation of G1 cyclin-dependent kinase genes in lymphoid cells.
These experiments were undertaken to study cell cycle-dependent regulation of expression of genes encoding cyclin-dependent kinases (Cdks). P1798 T-lymphoma cells were studied as a model system, since these cells undergo reversible G0 arrest within 24 h after addition of 0.1 microM dexamethasone to mid log phase cultures. G0 arrest is associated with inhibition of expression of several Cdks. The mRNAs encoding Cdk1 and Cdk4 decreased by 80-90% within 24 h. Fifty % inhibition of Cdk4 mRNA occurred within about 4 h, and 50% inhibition of Cdk1 mRNA was observed within 12-14 h. There was a slight decrease (< 50%) in the abundance of the mRNAs encoding Cdk2 and Cdk5. Cdk6 mRNA did not decrease in glucocorticoid-treated cells. Cdk1 and Cdk2 protein levels were reduced by no more than 50-70% within 24 h after the addition of dexamethasone, and the amounts of Cdk5 and Cdk6 protein did not change. However, the amount of Cdk4 protein decreased by > 90% under these circumstances. P1798 cells enter S phase in a synchronous fashion within 16-20 h after removal of dexamethasone. Cdk1, Cdk2, and Cdk5 mRNAs and proteins increased at or after the time that cells began to enter S phase. The mRNA encoding Cdk4 increased much more rapidly after removal of glucocorticoids, and a 5-fold increase in Cdk4 mRNA abundance was observed within 8 h after removal of the steroid. A corresponding increase in Cdk4 protein was observed, indicating that inhibition of Cdk4 expression is more proximal to the glucocorticoid-induced blockade in G1 progression.(ABSTRACT TRUNCATED AT 250 WORDS)
Cyclin-Dependent Kinase 4↗
Monte Carlo likelihood in the genetic mapping of complex traits.
Many of the likelihoods arising in the analysis of complex genetic traits, particularly in linkage analysis, are computationally infeasible. Where exact likelihoods cannot be computed, Monte Carlo estimates of likelihoods may provide a satisfactory alternative. Although simulation on pedigrees is straightforward, simulation conditional upon observed phenotypic data is not. However, recent advances in Markov chain Monte Carlo methods have provided a method well suited to this problem. From realizations of underlying genes, simulated under a genetic model, conditional upon observed data, a Monte Carlo estimate of this likelihood surface can be formed. Various sampler and model modifications are needed to enhance the statistical efficiency of the Monte Carlo estimator; as these methods become increasingly developed, this approach becomes a useful tool in resolving the genes contributing to the phenotypes associated with genetically complex diseases.
Algorithms↗
The macromolecular state of the transcription factor E2F and glucocorticoid regulation of c-myc transcription.
Glucocorticoids inhibit transcription of the proto-oncogene c-myc in lymphoid cells of thymic origin. To determine if this effect is associated with changes in the properties of the transcription factor E2F, extracts were prepared from control and glucocorticoid-treated P1798 murine T lymphoma cells, and the macromolecular state of E2F was assessed by gel-mobility shift. Control extracts exhibit two predominant gel-mobility shift entities of which one corresponds to "free" E2F. A second entity, complex C, has properties similar to those described for the complex containing E2F, p107, cyclin A, and Cdk2. Complex C disappears after addition of dexamethasone and is replaced by complex D. The mobility of this complex and its sensitivity to SV40 T antigen suggest that complex D corresponds to an E2F-p105Rb-1 complex. Extracts from control and glucocorticoid-treated cells yield identical DNase I protection patterns on the c-myc P2 promoter. Furthermore, such extracts transcribe the c-myc P2 promoter in vitro with equal activity. The relative abundance of the E2F complexes was measured after addition of dexamethasone. Complex C disappears as cells withdraw from S phase, and complex D appears at this time. The genes encoding thymidine kinase (Tk-1) and p34cdc2 (cdc2) are regulated with kinetics similar to those observed for changes in the macromolecular state of E2F. However, regulation of c-myc expression occurs long before any change in E2F. The macromolecular state of E2F may regulate expression of genes at the G1/S boundary. However, the data are not consistent with the hypothesis that association of E2F with tumor suppressor gene products such as p107 or p105Rb-1 is relevant to glucocorticoid regulation of c-myc transcription.
Animals↗
Failure of methotrexate treatment for term placenta percreta.
Placenta percreta is a severe condition associated with maternal morbidity and mortality even when surgery is performed electively. Methotrexate has been suggested as a possible treatment modality for adherent placenta to avoid catastrophic surgery. The purpose of this report is to present a case where the placenta was left in situ to avoid cystectomy at the time of cesarean section, with subsequent failure of treatment with methotrexate.
Adult↗
Transforming growth factor-beta inhibits rat intestinal cell growth by regulating cell cycle specific gene expression.
Transforming growth factor-beta 1 (TGF-beta 1) inhibits the growth of intestinal cells, but the mechanisms involved are unknown. Using a rat intestinal crypt cell line (IEC-6), we determined the site of action in the cell cycle that TGF-beta 1 acts to suppress proliferation. We also examined the effect of TGF-beta 1 on the expression of proliferation-associated "immediate early" genes (zif268, jun-B, c-myc) during the early G1 phase and the cdc2 gene during the transition from the G1 phase to the S phase of the cell cycle. Cell cycle progression was determined by incorporation of 3H-thymidine, and gene expression was analyzed by Northern blot analysis. We found that TGF-beta 1 acts to inhibit proliferation of rat intestinal crypt cells by blocking cell cycle progression at the middle G1 phase. The genes activated during G1 can be divided into TGF-beta 1 insensitive (zif268, jun-B, and c-myc) and TGF-beta 1 sensitive (the cdc2 gene). TGF-beta 1 suppresses the induction of the cdc2 gene during the G1/S transition without inhibiting the activation of immediate early genes during the early G1 phase.
Animals↗
Expression of c-Myc in glucocorticoid-treated fibroblastic cells.
Glucocorticoids inhibit proliferation of L929 fibroblastic cells in culture. Inhibition of proliferation is reversible and is not associated with changes in the plating efficiency of the cells. Flow cytometric analysis indicates that glucocorticoid-treated cells exhibit a decrease in the percentage of cells with DNA content > 2 N. Thymidine kinase expression is inhibited as cells with 2 N DNA content accumulate. These observations indicate that glucocorticoids arrest proliferation of L929 cells in the G1 phase of the cell cycle. The abundance of c-Myc mRNA does not decrease in glucocorticoid-treated cells, and c-Myc protein content in dexamethasone-treated cells is approximately the same as that detected in mid-log phase cells. Nuclear run-on transcription of c-Myc is not inhibited by glucocorticoids. These observations indicate that glucocorticoid regulation of fibroblastic cell proliferation does not involve inhibition of c-Myc transcription. Although regulation of c-Myc expression is central to the mechanism whereby glucocorticoids regulate proliferation of lymphoid cells, it is clear that different mechanisms must be involved in glucocorticoid regulation of fibroblastic cell proliferation.
Animals↗
Feedback control of the metaphase-anaphase transition in sea urchin zygotes: role of maloriented chromosomes.
To help ensure the fidelity of chromosome transmission during mitosis, sea urchin zygotes have feedback control mechanisms for the metaphase-anaphase transition that monitor the assembly of spindle microtubules and the complete absence of proper chromosome attachment to the spindle. The way in which these feedback controls work has not been known. In this study we directly test the proposal that these controls operate by maloriented chromosomes producing a diffusible inhibitor of the metaphase-anaphase transition. We show that zygotes having 50% of their chromosomes (approximately 20) unattached or monoriented initiate anaphase at the same time as the controls, a time that is well within the maximum period these zygotes will spend in mitosis. In vivo observations of the unattached maternal chromosomes indicate that they are functionally within the sphere of influence of the molecular events that cause chromosome disjunction in the spindle. Although the unattached chromosomes disjoin (anaphase onset without chromosome movement) several minutes after spindle anaphase onset, their disjunction is correlated with the time of spindle anaphase onset, not the time their nucleus breaks down. This suggests that the molecular events that trigger chromosome disjunction originate in the central spindle and propagate outward. Our results show that the mechanisms for the feedback control of the metaphase-anaphase transition in sea urchin zygotes do not involve a diffusible inhibitor produced by maloriented chromosomes. Even though the feedback controls for the metaphase-anaphase transition may detect the complete absence of properly attached chromosomes, they are insensitive to unattached or mono-oriented chromosomes as long as some chromosomes are properly attached to the spindle.
Anaphase↗
Discriminating suicide ideation among high-risk youth.
This study examined the hypothesis that among one group of high-risk youth--potential high school dropouts--key psychosocial factors would distinguish adolescents endorsing high suicide ideation from those who do not. Survey data compared high-risk youth with high suicide ideation (n = 43) with randomly selected samples of high-risk (n = 43) and "typical" youth (n = 42) without high suicide ideation. Repeat sampling of comparison groups verified results. Compared to high-risk and typical youth without suicide ideation, high-risk youth with high suicide ideation reported more psychosocial distress, problems with drug involvement, and disrupted family relations. They also described more unmet school goals and perceived a greater likelihood of dropping out of school. Discriminant analysis revealed that depression and low self-esteem were most effective in distinguishing between high-risk youth with and without high suicide ideation; family strain, anger, stress, and drug involvement also were differentiating factors. Implications for school-based screening and prevention programs are discussed within the context of the findings.
Adolescent↗
A measure of adolescent potential for suicide (MAPS): development and preliminary findings.
This paper describes an instrument designed to assess the suicide potential of youth 14-18 years of age who are at risk for suicidal behaviors. A comprehensive measurement theory provides the basis for three central constructs in the Measure of Adolescent Potential for Suicide (MAPS): direct suicide risk factors, related risk factors, and protective factors. The MAPS entails an introductory questionnaire followed by a computer-assisted, structured interview. Two samples were used to examine psychometric properties of the MAPS (n = 43; n = 123). Results revealed generally strong validity (content, criterion, construct) and reliability (internal consistency) for the MAPS. Further verification studies with large and diverse samples are warranted.
Adolescent↗
Monte Carlo estimation of mixed models for large complex pedigrees.
In human quantitative genetics, computational complexity restricts the current methods for estimation of mixed models that include major gene effects to data on small pedigrees. However, large complex pedigrees are not uncommon in practice. Also, large pedigrees tend to provide more information on genetic transmission and are more genetically homogeneous than a pooled sample of many nuclear families. We present a Monte Carlo method, using jointly the EM algorithm and the Gibbs sampler, for estimation of mixed models. The approach also provides a Monte Carlo estimate of the asymptotic variance-covariance matrix of the parameters. The methods are conceptually simple, easy to implement, and can handle multiple heritable/nonheritable random components. A numerical example is given to illustrate the methods.
Algorithms↗
Localization of estrogen receptors in interstitial cells of hamster kidney and in estradiol-induced renal tumors as evidence of the mesenchymal origin of this neoplasm.
The mechanism of estrogen-induced and -dependent kidney carcinogenesis in Syrian hamsters and the cell of origin of the tumor are not well understood; they have been investigated in this study by mapping the cellular locations of estrogen receptor (ER) in estrogen-dependent tumors, in kidney tissue of hamsters treated with estradiol for 0.5 and 5.5 months, and in kidneys of age-matched controls. To validate the methods used, receptors have also been localized in uteri of hamsters and rats and in female hamster kidneys. ERs have been identified in cryostat sections by immunocytochemical techniques using an affinity-purified ER antibody, ER-715. Nuclei of tumors were intensely stained for ERs. In estrogen-treated kidneys and in controls, ER protein was identified in interstitial cells and capillaries, in arteries, and in renal corpuscles, particularly in podocytes and in the parietal layers surrounding the renal corpuscles. There was no ER protein in tubular epithelia even when tubuli were surrounded by tumor cells. The ER distribution in female hamster kidneys closely matched that in male kidneys. However, the staining intensity was stronger in female than in male kidneys. In hamster uteri, there was an intense ER-positive reaction in the nuclei of stroma, in stromal vessels, and in the luminal epithelia as demonstrated previously by others in rat uteri. ER mRNA has also been demonstrated by Northern blot analysis in estrogen-treated kidneys which contained tumors but was undetectable in untreated kidneys. The localization of ERs in estrogen-dependent tumors and in interstitial cell types but not in tubular epithelia supports previous conclusions of an interstitial origin of estrogen-induced hamster kidney tumors.
Animals↗
Cyclosporine A inhibits the activity of a TATA box-binding protein that is required for transcription from the adenovirus major late promoter.
Nuclear extracts from P1798 lymphoma cells support transcription from the adenovirus major late promotor (AdMLP) and the human histone H4 promoter. Nuclear extracts prepared from P1798 cells treated with 1 microgram/ml cyclosporine A for 24 h fail to support transcription from AdMLP, whereas transcription from the histone H4 promoter is unimpaired. Both control and cyclosporine-treated extracts contain proteins that interact with synthetic deoxyoligonucleotides that correspond to the CAAT box, TATA box, and upstream stimulatory element of AdMLP. Cyclosporine had no discernible qualitative or quantitative effect upon such DNA-protein interactions, as observed by gel mobility shift assays. Analysis of 5' deletion mutants of AdMLP indicates that deletion of sequences upstream of the TATA box reduces AdMLP transcription by only 50%. This observation suggests that cyclosporine A, which inhibits AdMLP transcription by > 90%, is unlikely to act through changes in the amount or activity of upstream activators such as upstream stimulatory factor- or CAAT box-binding proteins. On the other hand, deletion of TATA box sequences between -50 and -11 base pairs virtually eliminates transcription from AdMLP in vitro. A partially purified TFIID fraction was obtained from control P1798 nuclear extracts. The TFIID fraction reconstitutes transcription from AdMLP when added to extracts from cyclosporine A-treated cells. Recombinant TATA box-binding protein also reconstitutes transcription from AdMLP in cyclosporine A-treated extracts. These results are consistent with the hypothesis that cyclosporine A regulates the activity of a subset of general transcription factors which are required for initiation from some promoters (such as AdMLP) but not from others (such as histone H4).
Adenoviridae↗
Glucocorticoid regulation of thymidine kinase (Tk-1) expression in L929 cells.
Glucocorticoids regulate the proliferation of mouse L cells. Incorporation of [3H]thymidine is inhibited by 70-90% within 24 h after addition of 0.1 microM dexamethasone. This effect on L cells is completely reversible. The expression of the thymidine kinase gene (Tk-1) has been examined in L cells that have been treated with 0.1 microM dexamethasone for 24 h. Dexamethasone inhibits thymidine kinase activity 70-90% after 24 h. This is associated with a 90-95% decrease in Tk mRNA abundance. The decrease in Tk mRNA is not caused by a decrease in transcription of Tk-1, as shown by nuclear run-on transcription assays. Transient expression of the CAT (chloramphenicol acetyltransferase) gene, driven by the Tk-1 promoter, was not affected by dexamethasone, and transcription of stably integrated Tk minigenes in LMTk- cells was not affected by dexamethasone. This effect was observed regardless of whether Tk cDNA was fused to the simian virus 40 promoter or the mouse Tk-1 promoter region. Conversely, expression of thymidine kinase was inhibited when stable Tk+ transformants of LMTk- cells were exposed to glucocorticoids; and inhibition of expression was observed irrespective of the promoter that was used to drive transcription of the Tk minigenes. These data indicate that glucocorticoid regulation of Tk-1 in mouse L cells is, within the limits of detection of the assays used in these studies, entirely due to a posttranscriptional mechanism.
Animals↗
Monte Carlo analysis on a large pedigree.
Monte Carlo methods for linkage and segregation analysis are applied to the HGAR1 pedigree. To address these data, the methods are extended in several ways. The results are compared with those provided by PAP.
Adolescent↗
Culture, ethnicity, and the family: critical factors in childhood chronic illnesses and disabilities.
Explore the source record for details and available documents.
Attitude to Health↗
Immunoreactive growth hormone production by human lymphocyte cell lines.
1. Two human lymphocyte cell lines, a T-cell line and a B-cell line, were shown to produce and secrete immunoreactive growth hormone (irGH). The irGH molecules secreted by the two cell lines appeared to be de novo synthesized and their molecular size was similar to that of pituitary GH as well as irGH secreted by peripheral blood lymphocytes. 2. Affinity-purified irGH molecules had human growth hormone (hGH)-like mitogenic activity on Nb2 cells. These findings indicate that the irGH molecules produced by H9 and IM9 were similar to hGH in structure. 3. However, the irGH messages could not be amplified by polymerase chain reaction (PCR) primers which had been demonstrated to be able to amplify reverse-transcribed hGH messenger RNA successfully, suggesting that the lymphocyte-derived irGH and pituitary hGH are not exactly identical molecules. 4. We conclude that the H9 and IM9 cells produce a growth hormone-related molecule whose structure is different from that in the anterior pituitary.
Animals↗