Biomedical subjects

S Whiteside

Publications and source records attributed to S Whiteside.

7 recordsLinked to original sources

PubMed2003

Thought control strategies in obsessive-compulsive disorder: a replication and extension.

Previous research suggests that individuals with OCD use maladaptive strategies to control their unpleasant thoughts (Behav Res Ther (1977) 35, 775). These include worry and self-punishment strategies. In the present study we replicated and extended the previous findings by comparing thought control strategies used by patients with OCD to strategies used by anxious and non-anxious control participants. We also examined changes in thought control strategies for OCD patients who underwent cognitive-behavioral therapy. Compared to controls, OCD patients reported more frequent use of worry and punishment strategies, and less frequent use of distraction. Following successful treatment, OCD patients evidenced increased use of distraction and decreased use of punishment. Findings are discussed in terms of the cognitive model of OCD.

Adult↗

PubMed2003

Is thought-action fusion specific to obsessive-compulsive disorder?: a mediating role of negative affect.

Thought-action fusion (TAF) is a cognitive bias presumed to underlie the development of obsessional problems (i.e. obsessive-compulsive disorder; OCD). Previous studies have found that TAF is related to not only OCD, but also to other anxiety disorders. In the present study we compared levels of TAF in OCD patients and in patients with other anxiety disorders, depression, and healthy controls to examine whether TAF is characteristic of individuals with emotional distress in general, as opposed to anxiety disorders per se. We also examined whether negative affect (i.e. anxiety and depression) mediates the relationship between OCD and TAF. Results indicated that OCD patients were characterized by higher scores on likelihood-self and likelihood-other TAF, but that this difference was predominately due to differences in negative affect. These findings support a model in which negative affect mediates the relationship between OCD and TAF.

Adolescent↗

PubMed2000

Raf induces NF-kappaB by membrane shuttle kinase MEKK1, a signaling pathway critical for transformation.

NF-kappaB is regulated by inhibitor proteins (IkappaBs), which retain NF-kappaB in the cytoplasm. Signal-induced phosphorylation by the IkappaB-kinase complex containing the IkappaB-kinases 1 and 2 (IKK-1/2 or IKK-alpha/beta) and subsequent degradation of the IkappaB proteins are prerequisites for NF-kappaB activation. Many signals induce NF-kappaB, one of them being oncogenic Raf kinase. We investigated whether NF-kappaB induction is critical for Raf-mediated transformation. Here, we demonstrate that inhibition of NF-kappaB interferes with transformation by the Raf-oncogene, and we characterized the mechanism of NF-kappaB induction by activated Raf kinase and the tumor promoter phorbol 12-myristate 13-acetate (PMA). NF-kappaB activation by PMA and Raf critically depends on the IkappaB-kinase complex, most notably on IKK-2. A major signaling pathway induced by Raf is the mitogenic cytoplasmic kinase cascade. However, different inhibitors of this cascade do not affect PMA- and Raf-mediated NF-kappaB activation. Raf does not phosphorylate the IkappaB-kinase proteins directly. Raf rather synergizes with another membrane shuttle kinase MEKK1, and Raf-mediated activation of NF-kappaB is blocked by a dominant negative form of MEKK1. These results suggest that Raf induction of NF-kappaB is relayed by MEKK1, but not by the classical mitogenic cytoplasmic kinase cascade.

Animals↗

PubMed1999

Structural motifs involved in ubiquitin-mediated processing of the NF-kappaB precursor p105: roles of the glycine-rich region and a downstream ubiquitination domain.

The ubiquitin proteolytic system plays a major role in a variety of basic cellular processes. In the majority of these processes, the target proteins are completely degraded. In one exceptional case, generation of the p50 subunit of the transcriptional regulator NF-kappaB, the precursor protein p105 is processed in a limited manner: the N-terminal domain yields the p50 subunit, whereas the C-terminal domain is degraded. The identity of the mechanisms involved in this unique process have remained elusive. It has been shown that a Gly-rich region (GRR) at the C-terminal domain of p50 is an important processing signal. Here we show that the GRR does not interfere with conjugation of ubiquitin to p105 but probably does interfere with the processing of the ubiquitin-tagged precursor by the 26S proteasome. Structural analysis reveals that a short sequence containing a few Gly residues and a single essential Ala is sufficient to generate p50. Mechanistically, the presence of the GRR appears to stop further degradation of p50 and to stabilize the molecule. It appears that the localization of the GRR within p105 plays an important role in directing processing: transfer of the GRR within p105 or insertion of the GRR into homologous or heterologous proteins is not sufficient to promote processing in most cases, which is probably due to the requirement for an additional specific ubiquitination and/or recognition domain(s). Indeed, we have shown that amino acid residues 441 to 454 are important for processing. In particular, both Lys 441 and Lys 442 appear to serve as major ubiquitination targets, while residues 446 to 454 are independently important for processing and may serve as the ubiquitin ligase recognition motif.

Amino Acid Sequence↗

PubMed1999

Self-reported psychopathy: a validation study.

Two studies are reported examining the reliability and validity of Levenson's Self-Report Psychopathy Scale (LSRP; Levenson, Kiehl, & Fitzpatrick, 1995) in a noninstitutionalized population. The first study used 1,958 undergraduates to examine the factor structure of the LSRP and its relation to serious antisocial behavior and common dimensions of personality. The second study (n = 70) included performance tasks known to discriminate psychopathic from nonpsychopathic prisoners. Results of the studies support the reliability and validity of the LSRP. The 2-factor structure of the inventory was strongly replicated in a series of confirmatory factor analyses. Predicted relations were observed between the LSRP and other self-report instruments of delinquency. In addition, the factors of the LSRP demonstrated the predicted divergent relations to traditional personality traits. Finally, psychopathic undergraduates showed deficits in response modulation similar to those observed in incarcerated psychopaths. Implications for psychopathy in general are also discussed.

Adult↗

PubMed1998

Sequential DNA damage-independent and -dependent activation of NF-kappaB by UV.

NF-kappaB activation in response to UV irradiation of HeLa cells or of primary human skin fibroblasts occurs with two overlapping kinetics but totally different mechanisms. Although both mechanisms involve induced dissociation of NF-kappaB from IkappaBalpha and degradation of IkappaBalpha, targeting for degradation and signaling are different. Early IkappaBalpha degradation at 30 min to approximately 6 h is not initiated by UV-induced DNA damage. It does not require IkappaB kinase (IKK), as shown by introduction of a dominant-negative kinase subunit, and does not depend on the presence of the phosphorylatable substrate, IkappaBalpha, carrying serines at positions 32 and 36. Induced IkappaBalpha degradation requires, however, intact N- (positions 1-36) and C-terminal (positions 277-287) sequences. IkappaB degradation and NF-kappaB activation at late time points, 15-20 h after UV irradiation, is mediated through DNA damage-induced cleavage of IL-1alpha precursor, release of IL-1alpha and autocrine/paracrine action of IL-1alpha. Late-induced IkappaBalpha requires the presence of Ser32 and Ser36. The late mechanism indicates the existence of signal transfer from photoproducts in the nucleus to the cytoplasm. The release of the 'alarmone' IL-1alpha may account for some of the systemic effects of sunlight exposure.

Autocrine Communication↗

PubMed1995

Ubiquitin-mediated processing of NF-kappa B transcriptional activator precursor p105. Reconstitution of a cell-free system and identification of the ubiquitin-carrier protein, E2, and a novel ubiquitin-protein ligase, E3, involved in conjugation.

In most cases, the transcriptional factor NF-kappa B is a heterodimer consisting of two subunits, p50 and p65, which are encoded by two distinct genes of the Rel family. p50 is translated as a precursor of 105 kDa. The C-terminal domain of the precursor is rapidly degraded, forming the mature p50 subunit consisted of the N-terminal region of the molecule. The mechanism of generation of p50 is not known. It has been suggested that the ubiquitin-proteasome system is involved in the process; however, the specific enzymes involved and the mechanism of limited proteolysis, in which half of the molecule is spared, have been obscure. Palombella and colleagues (Palombella, V. J., Rando, O. J., Goldberg, A. L., and Maniatis, T. (1994) Cell 78, 773-785) have shown that ubiquitin is required for the processing in a cell-free system of a truncated, artificially constructed, 60-kDa precursor. They have also shown that proteasome inhibitors block the processing both in vitro and in vivo. In this study, we demonstrate reconstitution of a cell-free processing system and demonstrate directly that: (a) the ubiquitin-proteasome system is involved in processing of the intact p105 precursor, (b) conjugation of ubiquitin to the precursor is an essential intermediate step in the processing, (c) the recently discovered novel species of the ubiquitin-carrier protein, E2-F1, that is involved in the conjugation and degradation of p53, is also required for the limited processing of the p105 precursor, and (d) a novel, approximately 320-kDa species of ubiquitin-protein ligase, is involved in the process. This novel enzyme is distinct from E6-AP, the p53-conjugating ligase, and from E3 alpha, the "N-end rule" ligase.

Animals↗