Biomedical subjects
Publications and source records attributed to Jane Collins.
Microarray screening of polymer libraries for cellular adhesion was developed utilising a thin film of agarose to allow unsurpassed localisation of cell binding onto the array substrate and the discovery of cell specific polymers.
Tristetraprolin (TTP) is the only trans-acting factor shown to be capable of regulating AU-rich element-dependent mRNA turnover at the level of the intact animal; however, the mechanism by which TTP mediated RNA instability is unknown. Using an established model system, we performed structure/function analysis with TTP as well as examined the current hypothesis that TTP function is regulated by p38-MAPKAP kinase 2 (MK2) activation. Deletion of either the N- or C-terminal domains inhibited TTP function. Extensive mutagenesis, up to 16%, of serines and threonines, some of which were predicted to mediate proteasomal targeting, did not alter human TTP function. Mutation of the conserved MK2 phosphorylation sites enhanced human TTP function in both resting and p38-stress-activated protein kinase-MK2-activated cells. However, p38-stress-activated protein kinase-MK2 activation did not alter the activity of either wild-type or mutant TTP. TTP localized to the stress granules, with arsenite treatment reducing this localization. In contrast, arsenite treatment enhanced stress granule localization of the MK2 mutant, consistent with the involvement of additional pathways regulating this event. Finally, we determined that, in response to LPS stimulation, human TTP moves onto the polysomes, and this movement occurs in the absence of 14-3-3. Taken together, these data indicate that, although p38 activation alters TTP entry into the stress granule, it does not alter TTP function. Moreover, the interaction of TTP with 14-3-3, which may limit entry into the stress granule, is not involved in the downstream message stabilization events.
Apoptosis of hepatic stellate cells (HSC) has previously been shown to occur during spontaneous resolution of experimental liver fibrosis. TIMP-1 has also been shown to have a key role because of its ability to inhibit apoptosis of HSC via matrix metalloproteinase (MMP) inhibition. This has led to further study of novel substrates for MMPs that might impact on HSC survival. N-Cadherin is known to mediate cell-cell contacts in fibroblasts. In this study we demonstrate that N-Cadherin is expressed by activated rat HSC. Furthermore, during apoptosis of HSC, the N-Cadherin is cleaved into smaller fragments. Apoptosis of HSC may be inhibited by TIMP-1. This is associated with reduced fragmentation of N-Cadherin. N-Cadherin may have an important role in supporting HSC survival while N-Cadherin cleavage may play a part in promoting HSC apoptosis in recovery from liver fibrosis.
OBJECTIVES: To review the characteristics of psychiatric screening tools currently available in addiction treatment services for rapid assessment of comorbid pathology and to introduce the Centre for Addictions and Mental Health Concurrent Disorders Screener (CAMH-CDS), a computer-administered questionnaire that screens for the occurrence of 11 Axis I disorders plus all substance use disorders, as well as for a history of conduct disorder. METHODS: We describe the structure, contents, and application of the CAMH-CDS. We undertook a sensitivity and specificity trial involving 171 subjects, a test-retest reliability study with 301 participants, and an open-label concordance study with 656 respondents. All subjects were regular clients of a major addiction treatment facility. RESULTS: The CAMH-CDS was easily and effectively used by addiction counsellors with limited or no mental health training. It has a low rate of false-negative responses, and it yields excellent test-retest reliability figures. It is highly sensitive to identifying persons with psychiatric disturbances; however, its ability to discriminate among specific disorders appears to be more limited. CONCLUSIONS: The CAMH-CDS can be reliably used to rule out the presence of psychiatric comorbidity in addiction service populations. As with other psychiatric screening instruments, its sensitivity values are stronger than its specificity values. The use of nonstructured clinical evaluations as the gold standard for diagnosis and a likely variance in the patients' symptom reports between the 2 examinations may have contributed to the latter finding.