PubMed Health⌕ Search

Biomedical subjects

Michelle Scott

Publications and source records attributed to Michelle Scott.

4 recordsLinked to original sources

Protection of p27(Kip1) mRNA by quaking RNA binding proteins promotes oligodendrocyte differentiation.

The quaking (Qk) locus expresses a family of RNA binding proteins, and the expression of several alternatively spliced isoforms coincides with the development of oligodendrocytes and the onset of myelination. Quaking viable (Qk(v)) mice harboring an autosomal recessive mutation in this locus have uncompacted myelin in the central nervous system owing to the inability of oligodendrocytes to properly mature. Here we show that the expression of two QKI isoforms, absent from oligodendrocytes of Qk(v) mice, induces cell cycle arrest of primary rat oligodendrocyte progenitor cells and differentiation into oligodendrocytes. Injection of retroviruses expressing QKI into the telencephalon of mouse embryos induced differentiation and migration of multipotential neural progenitor cells into mature oligodendrocytes localized in the corpus callosum. The mRNA encoding the cyclin-dependent kinase (CDK)-inhibitor p27(Kip1) was bound and stabilized by QKI, leading to an increased accumulation of p27(Kip1) protein in oligodendrocytes. Our findings demonstrate that QKI is upstream of p27(Kip1) during oligodendrocyte differentiation.

Animals↗

Adolescents with substance diagnoses in an HMO: factors associated with medical provider referrals to substance abuse and mental health treatment.

This study examines the factors related to referrals of adolescents with substance use disorders to substance abuse or mental health treatment by their medical providers. Administrative and chart review data from the membership of a large private health maintenance organization (HMO) were collected from a probability sample of 400 adolescents, ages 13-18, who were diagnosed with a substance use disorder in 1999. Logistic regression analyses examined referral to substance abuse treatment and referral to mental health treatment in the aggregate and stratified by gender. Documented use of both alcohol and another illicit drug, and legal problems increased likelihood of referral to substance abuse and mental health treatment, whereas diagnoses of alcohol and marijuana use disorders decreased likelihood of referral to substance abuse treatment. Mental health diagnoses played a limited role in both types of referrals, although specific psychosocial problems were associated with increased likelihood of referrals. Treatment history and location of first mention of problem were significant predictors of referral. There were no gender differences in referral rates to either substance abuse or mental health treatment; however predictors of referral differed by gender. These findings extend our knowledge about factors that influence clinicians' treatment referrals of adolescents with substance abuse diagnoses and have implications for influencing clinician referral behavior within health plans.

Adolescent↗

The Columbia Suicide Screen: validity and reliability of a screen for youth suicide and depression.

OBJECTIVE: This study reports on the psychometric properties of a brief, self-administered screening questionnaire, the Columbia Suicide Screen (CSS), intended to identify high school students at risk for suicide. METHOD: Seventeen hundred twenty-nine 9th- to 12th-grade students completed the CSS and Beck Depression Inventory during school hours in 1991 to 1994. Three hundred fifty-six students who screened positively and 285, group matched on age, gender, and ethnicity, who screened negatively were examined on the Diagnostic Interview Schedule for Children (DISC), version 2.3, to assess validity. The DISC-based suicide risk criterion was suicidal ideation or prior suicide attempt and a DSM-III-R diagnosis of major depression or dysthymia or substance use. Test-retest reliability was assessed in a subsample of 85. RESULTS: The most balanced algorithm had a sensitivity of 0.75, specificity 0.83, and positive predictive value 16%. Suicidal ideation and prior attempt item reliabilities (kappa) were 0.48 and 0.58, respectively. Eight-day test-retest reliability for the most balanced scoring algorithm was 0.32. CONCLUSIONS: The CSS demonstrated good sensitivity and reasonable specificity identifying students at risk for suicide. A second-stage evaluation would be needed to reduce the burden of low specificity.

Adolescent↗

Human ING1 proteins differentially regulate histone acetylation.

ING1 proteins are nuclear, growth inhibitory, and regulate apoptosis in different experimental systems. Here we show that similar to their yeast homologs, human ING1 proteins interact with proteins associated with histone acetyltransferase (HAT) activity, such as TRRAP, PCAF, CBP, and p300. Human ING1 immunocomplexes contain HAT activity, and overexpression of p33(ING1b), but not of p47(ING1a), induces hyperacetylation of histones H3 and H4, in vitro and in vivo at the single cell level. p47(ING1a) inhibits histone acetylation in vitro and in vivo and binds the histone deacetylase HDAC1. Finally, we present evidence indicating that p33(ING1b) affects the degree of physical association between proliferating cell nuclear antigen (PCNA) and p300, an association that has been proposed to link DNA repair to chromatin remodeling. Together with the finding that human ING1 proteins bind PCNA in a DNA damage-dependent manner, these data suggest that ING1 proteins provide a direct linkage between DNA repair, apoptosis, and chromatin remodeling via multiple HAT.ING1.PCNA protein complexes.

Acetylation↗