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Biomedical subjects

C Snell

Publications and source records attributed to C Snell.

7 recordsLinked to original sources
PubMed2006

SOCS3 negatively regulates LIF signaling in neural precursor cells.

Cytokines that signal through the LIFRbeta/gp130 receptor complex, including LIF and CNTF, promote the self-renewal of embryonic and adult neural precursor cells (NPCs). In non-CNS tissues, the protein suppressor of cytokine signaling-3 (SOCS3) negatively regulates signaling through gp130. Here, we analyze the role of SOCS3 in inhibiting LIF signaling in NPCs in vitro. SOCS3 is rapidly expressed by NPCs in response to LIF stimulation, with this expression largely dependent on recruitment of STAT proteins to the activated gp130 receptor. Proliferating NPC cultures can be generated from SOCS3 knockout (SOCS3KO/KO) embryos and display prolonged STAT3 phosphorylation and induction of the GFAP gene in response to LIF. In comparison with SOCS3 wild-type (SOCS3WT/WT) NPCs, SOCS3KO/KO cultures display enhanced self-renewal capacity. However, the clonal potential of SOCS3WT/WT but not SOCS3KO/KO NPCs is enhanced by exogenous LIF. Thus, SOCS3 acts as a negative regulator of LIF signaling in NPCs.

Animals↗
PubMed2005

Oligodendrocytes exhibit selective expression of suppressor of cytokine signaling genes and signal transducer and activator of transcription 1 independent inhibition of interferon-gamma-induced toxicity in response to leukemia inhibitory factor.

Multiple sclerosis is an autoimmune disease of the CNS that results in the death of oligodendrocytes, the myelinating cells of the CNS. Previous studies have indicated that the cytokine leukemia inhibitory factor prevents the cytotoxic effects of interferon-gamma on oligodendrocytes in vitro, and the death of oligodendrocytes in an animal model of multiple sclerosis. Members of a recently characterized family of proteins, the suppressors of cytokine signaling, have been demonstrated to mediate negative cross-talk between cytokines, with induction of suppressors of cytokine signaling proteins by one cytokine inhibiting the activity of a second. Here, we assess whether induction of members of the suppressors of cytokine signaling family could explain the antagonistic biological effects of leukemia inhibitory factor and interferon-gamma upon oligodendrocytes. It is found that leukemia inhibitory factor rapidly and strongly induces the expression of suppressors of cytokine signaling-3 in cultured rat oligodendrocytes, whereas interferon-gamma weakly induces the expression of both suppressor of cytokine signaling-1 and 3. Pre-treatment of oligodendrocytes with leukemia inhibitory factor does not prevent the subsequent phosphorylation of signal transducer and activator of transcription-1 by interferon-gamma indicating that the leukemia inhibitory factor inhibition of interferon-gamma toxicity in oligodendrocytes is mediated by a suppressor of cytokine signaling-3 independent mechanism.

Animals↗
PubMed2004

Minors' tobacco possession law violations and intentions to smoke: implications for tobacco control.

OBJECTIVES: To test: (1) whether citation under the Minors in Possession (MIP) law, vicarious citation (knowing someone who was cited), and threat of driving licence suspension are associated with decreased intentions to smoke next year; and (2) whether the policy is differentially enforced. SUBJECTS: 28,249 white, Hispanic, and African American students in grades 6-12 (11-18 years old) participated in the study. METHOD: The 86 item anonymous Texas Youth Tobacco Survey was completed by students attending 37 schools in 14 east and central Texas communities. RESULTS: Hierarchical linear modelling showed that MIP citation was unrelated to the future smoking intentions of most youth. However, there was a negative association between citation and smoking intentions for ever daily smoking youth at four schools. Threat of licence suspension was associated with a lower likelihood of future smoking intentions among ever daily smoking youth and vicarious citation did not deter youth from future smoking. African American and Hispanic youth had a higher probability of being cited than their peers. CONCLUSIONS: Threat of driving licence suspension has the intended effect upon youth who are/were committed smokers and MIP citation has the intended effect upon committed smokers at only four schools. However, differential enforcement of the law based on ethnicity may be occurring. Before drawing firm conclusions, current findings must be replicated with longitudinal data to determine the consequences of citation on subsequent tobacco use.

Adolescent↗
PubMed1998

Caring in a managed care environment--a case study in teamwork.

Level of care decisions in managed care require matching the patient's intensity of symptoms with the appropriate placement in the least restrictive setting. In planning appropriate treatment for a patient, the case manager at a managed care organization (MCO) considers "Why now?," examining the patient's diagnosis, as well as other pertinent factors, such as precipitant and the proximal cause for the patient's request for help. Team efforts between the MCO clinicians and the patient's treating clinicians improve the likelihood of patient/treatment outcome.

Adult↗
PubMed1992

Structural and functional evidence for activation of a chick retinoid X receptor by eicosanoids.

The retinoid X receptors (RXR-alpha, RXR-beta and RXR-gamma) are members of the steroid-thyroid hormone receptor superfamily of ligand-dependent transcription factors. They appear to function as auxiliary proteins that regulate high-affinity DNA binding and enhance transcriptional activity through heterodimer formation with other members of the superfamily. The RXR-alpha, RXR-beta and RXR-gamma proteins bind and are activated by the naturally occurring retinoid, 9-cis-retinoic acid. Structural similarities are apparent between retinoic acid and various eicosanoids, raising the possibility that eicosanoids may also activate retinoid receptors in vivo. We present evidence that lipoxygenase metabolites of arachidonic acid at submicromolar concentrations are capable of activating RXR-gamma activity in transient transfection assays. In addition, molecular modelling predicts conformational similarities between some lipoxygenase products and retinoic acid. Consistent with this, hydroxyeicosatetraenoic acids are known to mimic some actions of retinoids in cell-based assays. These observations raise the possibility that eicosanoids, already known to act both as local hormones and as intracellular second messengers, may also have a direct role in transcriptional activation via nuclear receptors.

Animals↗
PubMed1976

Chromatin models. The ionic strength dependence of model histone-DNA interactions: circular dichroism studies of lysine-leucine polypeptide-DNA complexes.

The ionic strength dependence of the complexes between DNA and both random, (Lysx, Leuy)n, and block copolymers, (Lysx)n(Leuy)m, of lysine and leucine, with different amino acid compositions, was studied using circular dichroism (CD) as the probe to detect conformational differences in these complexes relative to native DNA. It was found that the CD spectra of complexes of both the random (Lys84, Leu16)n and block (Lys85)n(Leu15)m copolymers with DNA show a very sharp ionic strength dependence. The maximum altered CD spectrum for the complexes with the block copolymer was found to occur at the same ionic strength as that for poly(L-lysine)-DNA complexes, while the maximum CD change for the random copolymer complex occurred at a slightly lower ionic strength. This sharp dependence of the CD change on the ionic strength was found to be independent of the polymer/DNA ratio, r, for each individual copolymer. The CD spectra for these complexes at optimum NaCl concentration resemble those of the psi spectra of DNA [Jordan, C. F., Lerman, L.S., and Venable, J.H. (1972), Nature (London), New Biol. 236, 67]. The complexes of the random copolymer, (Lys68, Leu32)n, with DNA (r=0.25) at 0.15 M NaCl and below have CD spectra that resemble the A-form DNA spectra. The ionic strength dependence of the CD spectra of this complex is not as sharp as observed with the above polymers and has a broad positive plateau. It is suggested that both the CD spectra of these complexes reflect the phenomena of DNA condensation into a higher order asymmetric structure (folded and compact). The block copolymer, (Lys77)n(Leu23)m, complexes with DNA show very slight alterations in the CD spectra, with respect to native DNA. It appears that the long Leu sequence at one end of such copolymers may be unpropitious for causing the polypeptide-DNA complex to condense into a higher order asymmetric structure. Thus the importance of the distribution of hydrophobic residues, in the copolypeptides of Lys, is shown for causing condensation of complexes with DNA. The relevance of these findings to histone-DNA complexes in chromatin is discussed.

Binding Sites↗