Biomedical subjects

Ian Robbins

Publications and source records attributed to Ian Robbins.

12 recordsLinked to original sources

PubMed2006

Counterfactual thinking and posttraumatic stress reactions.

Preoccupation with alternative outcomes (counterfactual thinking) is a central component of the ruminations of trauma victims. The questions investigated were whether such thinking should be distinguished from general rumination and whether elements of counterfactual thinking might relate to the process of adjustment. A sample of assault victims was interviewed. They completed a battery of self-report scales and thought-listing procedures. Frequency of counterfactual thinking was closely associated with continuing levels of posttraumatic distress. However, high availability of counterfactuals (as indexed by verbal fluency) was related to potentially adaptive outcomes, such as the generation of behavioral plans. In addition, as expected, levels of different aspects of counterfactual thinking were moderated by metacognitive control strategies as a function of time since the trauma.

Adult↗

PubMed2006

Overseas nurses' experiences of equal opportunities in the NHS in England.

PURPOSE: To explore the experiences of overseas black and minority ethnic nurses in the National Health Service (NHS) in the south of England. METHODS: Semi-structured in-depth interviews were conducted with 12 overseas black and minority ethnic nurses. All interviews were taped, transcribed verbatim and analysed using thematic analysis. All transcripts were read and re-read to elicit general themes. FINDINGS: Qualitative data analysis was undertaken using Van Manen framework and this enabled a number of themes to be identified that were part of overseas black and minority ethnic nurses' experience, however, two main themes would be discussed in this study. Firstly, unequal opportunities in career advancement and secondly, unequal opportunities for skill development and training. Both themes affected overseas nurses chances of promotion in the NHS. RESEARCH LIMITATION/IMPLICATIONS: The study has identified a notably gap in the implementation of equal opportunity policies and suggests that a more transparent implementation of such policies is needed in the NHS in the UK where this study was conducted. Additionally, more research is needed to determine whether overseas nurses in other areas experience similar problems. PRACTICAL IMPLICATIONS: The findings of this study could encourage managers to re-examine their equal opportunity policies in the light of these findings. Although this study has explored overseas nurses experiences, the findings cannot be generalised to the wider population. ORIGINALITY VALUE: The differences experienced by overseas nurses in relation to career opportunities and skill development and training.

Adult↗

PubMed2005

The regulated expression of c-IAP1 and c-IAP2 during the rat seminiferous epithelial cycle plays a role in the protection of germ cells from Fas-mediated apoptosis.

The inhibitor of apoptosis proteins, c-IAP1 and c-IAP2, are highly expressed in rat testis and potentially play a regulatory role in testicular apoptosis. To better understand their functions during spermatogenesis, we have analyzed their spatio-temporal distribution in rat testis, how their expression is controlled by the paracrine stem-cell factor (SCF) and how they affect Fas-mediated apoptosis. Both c-IAP1 and c-IAP2 showed cycles of transcriptional expression, throughout the seminiferous epithelial cycle. c-IAP1 protein showed a diffuse nuclear distribution in type B spermatogonia, preleptotene, leptotene, and zygotene spermatocytes. In pachytene spermatocytes, c-IAP1 colocalized with SUMO-1 in the XY-body. c-IAP2 protein was cytoplasmic in spermatocytes, from stage VI pachytene onwards, round spermatids, elongated spermatids and Leydig cells. Its expression was upregulated by SCF. Inhibition of IAP activity resulted in a greater sensitivity of germ cells to Fas-mediated apoptosis. These results suggest an important role for IAPs in the regulation of spermatogenic apoptosis.

Animals↗

PubMed2005

Local RNA target structure influences siRNA efficacy: a systematic global analysis.

The efficiency with which small interfering RNAs (siRNAs) down-regulate specific gene expression in living cells is variable and a number of sequence-governed, biochemical parameters of the siRNA duplex have been proposed for the design of an efficient siRNA. Some of these parameters have been clearly identified to influence the assembly of the RNA-induced silencing complex (RISC), or to favour the sequence preferences of the RISC endonuclease. For other parameters, it is difficult to ascertain whether the influence is a determinant of the siRNA per se, or a determinant of the target RNA, especially its local structural characteristics. In order to gain an insight into the effects of local target structure on the biological activity of siRNA, we have used large sets of siRNAs directed against local targets of the mRNAs of ICAM-1 and survivin. Target structures were classified as accessible or inaccessible using an original, iterative computational approach and by experimental RNase H mapping. The effectiveness of siRNA was characterized by measuring the IC50 values in cell culture and the maximal extent of target suppression. Mean IC50 values were tenfold lower for accessible local target sites, with respect to inaccessible ones. Mean maximal target suppression was improved. These data illustrate that local target structure does, indeed, influence the activity of siRNA. We suggest that local target screening can significantly improve the hit rate in the design of biologically active siRNAs.

Cell Line↗

PubMed2005

Patients' management of migraine and chronic daily headache: a study of the members of the Migraine Action Association (United Kingdom).

BACKGROUND: Many strategies are available to treat and prevent migraine and chronic daily headache (CDH). Broadly these strategies can be divided into four groups, including (i) health care consultations, (ii) medication and alternative remedies, (iii) general (acute and prophylactic) strategies, and (iv) social support. OBJECTIVE: This study aimed to compare headache management between migraine (MO), migraine with aura (MA), and those with CDH over the last 12 months. DESIGN: A postal questionnaire was sent to 887 members of the Migraine Action Association (MAA). The response rate was 60.5% (n=537), and 438 questionnaires were included in the analysis. Migraine (n=117) and MA (n=239) patients were classed according to the International Headache Society (IHS). CDH (n=82) was diagnosed when respondents had 15 or more headache days per month. Descriptive tests, analysis of variances (ANOVAs), chi2, and Kruskal-Wallis tests were used for statistical analysis (P<.05). RESULTS: The three groups did not differ in age, gender, ethnicity, level of education, and employment status. Significant differences in management strategies between the groups were found in the number of respondents who had consulted headache specialists (P=.002) and neurologists (P=.004), the number and types of acute medications (eg, triptans, P=.002), the use of antidepressants (P=.004), and some acute and prophylactic avoidance techniques. Although, no significant differences between the groups were found in the use of other health professionals (eg, GP), alternative health professionals, general acute management, and the use of social support, they all actively used these strategies. CONCLUSIONS: The respondents of this study were active users of management strategies that are based on a combination of health care consultations, medication and alternative remedies, general management, and social support. In comparison to previous findings, the respondents in this study frequently reported higher use of management strategies (such as the use of triptans), which may be related to this group of patients being better informed about headache management than those with headache within the general population. Thus, the findings may not be representative for the general population, but they give an indication of the influence and importance of headache-related education carried out by patient organizations such as the MAA.

Female↗

PubMed2004

Survivin expression in rat testis is upregulated by stem-cell factor.

The inhibitor of apoptosis protein BIRC-5/survivin plays roles in both apoptosis and the regulation of chromosome-segregation/cytokinesis during mitosis. As the population dynamics of male germ cells are regulated by both proliferation (mitosis and meiosis) and apoptotic culling, we hypothesized that BIRC-5/survivin could be central to the regulation of spermatogenesis. We have analyzed BIRC-5/survivin expression throughout the seminiferous epithelial cycle of the rat. BIRC-5/survivin RNA and protein exhibit rhythms of expression throughout the seminiferous epithelial cycle. The highest levels of expression were found, by immunohistochemistry and in situ hybridization, to occur during the long first meiotic prophase of spermatocytes. Cytoplasmic abundance declined at metaphase and reappeared at anaphase. Some BIRC-5/survivin expression was also found to occur in interstitial Leydig cells. BIRC-5/survivin protein levels were up-regulated in vitro by the paracrine, Stem-Cell Factor, that is known to regulate both proliferation and apoptosis of germ cells and Leydig cells.

Animals↗

PubMed2004

The bHLH TAL-1/SCL regulates endothelial cell migration and morphogenesis.

The basic helix-loop-helix tal-1 gene (or scl), known for its fundamental role in embryonic and adult hematopoiesis in vertebrates, is also required for embryonic vascular remodeling. In adults, TAL-1 protein is undetectable in quiescent endothelium but it is present in newly formed vessels including tumoral vasculature, indicating its involvement in angiogenesis. Here, we demonstrate that TAL-1 expression is tightly regulated during in vitro angiogenesis: it is low during the initial step of migration and is upregulated during formation of capillary-like structures. We investigated whether ectopic expression of either wild-type TAL-1 or a dominant-negative mutant lacking the DNA-binding domain (Delta-bas) modulates the activity of human primary endothelial cells in the angiogenic processes of migration, proliferation and cell morphogenesis. Overexpression of either wild-type or Delta-bas TAL-1 affected chemotactic migration of primary endothelial cells without modifying their proliferative properties. Ectopic expression of wild-type TAL-1 accelerated the formation of capillary-like structures in vitro and, in vivo, enhanced vascularisation in mice (Matrigel implants) associated with a general enlargement of capillary lumens. Importantly, transduction of the mutant Delta-bas completely impaired in vitro angiogenesis and strongly inhibited vascularisation in mice. Taken together, our data show that TAL-1 modulates the angiogenic response of endothelial cells by stimulating cell morphogenesis and by influencing their behavior in migration. This study highlights the importance of TAL-1 regulation in postnatal vascular remodeling and provides the first physiological evidence that links TAL-1 activity to endothelial cell morphogenic processes.

Animals↗

PubMed2004

An analysis of information available to relatives in intensive care.

The Comprehensive Critical Care Review published by the Government in 2000 acknowledges that patients are part of family units and critical illness has an extended impact. It outlines information that should be provided to relatives and suggests recommendations be implemented within 3-5 years. The aim of this study was to gauge an overall view of provisions available across general Intensive Care Units in England for relatives, by conducting an analysis of information available and unit policies, and to see the extent that government guidelines have been adhered to. Two hundred and ten units were approached for copies of policy documents and leaflets. There was a 56% response rate. Results were collated and analysed for basic descriptive statistics using software package SPSS version 11.5. The Gunning's Fog Index was performed on 20% of leaflets to measure readability. All leaflets measured above the recommended level. Sixteen percent of units do not have a leaflet and therefore do not comply with the Department of Health recommendations. Huge variation exists nationally over the amount and quality of information that relatives have access to and receive. Only 9% of units had an official policy on how to deal with relatives. The implications of this are discussed.

England↗

PubMed2003

Cationic phosphoramidate alpha-oligonucleotides efficiently target single-stranded DNA and RNA and inhibit hepatitis C virus IRES-mediated translation.

A potential means to improve the efficacy of steric-blocking antisense oligonucleotides (ON) is to increase their affinity for a target RNA. The grafting of cationic amino groups to the backbone of the ON is one way to achieve this, as it reduces the electrostatic repulsion between the ON and its target. We have examined the duplex stabilising effects of introducing cationic phosphoramidate internucleoside linkages into ON with a non-natural alpha-anomeric configuration. Cationic alpha-ON bound with high affinity to single-stranded DNA and RNA targets. Duplex stabilisation was proportional to the number of cationic modifications, with fully cationic ON having particularly high thermal stability. The average stabilisation was greatly increased at low ionic strength. The duplex formed between cationic alpha-ON and their RNA targets were not substrates for RNase H. The penalty in T(m) inflicted by a single mismatch, however, was high; suggesting that they are well suited as sequence-specific, steric-blocking, antisense agents. Using a well-described target sequence in the internal ribosome entry site of the human hepatitis C virus, we have confirmed this potential in a cell-free translation assay as well as in a whole cell assay. Interestingly, no vectorisation was necessary for the cationic alpha-ON in cell culture.

Amides↗

PubMed2003

Oligonucleotide-based strategies to inhibit human hepatitis C virus.

Hepatitis C virus (HCV) infection represents a worldwide problem, and current antiviral regimens are not satisfactory. The need to develop novel, specific, anti-HCV antiviral drugs is clear. Antisense oligonucleotides (AS-ON), ribozymes, and more recently, small interfering RNAs (siRNAs) have been widely used to control gene expression, and several clinical trials are in progress. The potential to use AS-ON as tools to control HCV infection, either by promoting an RNase H mediated cleavage of viral genomic RNA or by interfering with the assembly of a translation initiation complex on the internal ribosome entry site (IRES) is reviewed. Extensive knowledge of IRES structure and conservation among HCV genotypes have rendered the HCV IRES (and, in particular, its IIId loop) particularly attractive for antisense approaches. Encouraging data have been obtained with IRES-targeted RNase H-competent and incompetent ON analogs. We demonstrate here that very short steric blocking ONs can inhibit the formation of translation preinitiation complexes on the IRES and block IRES-mediated translation in a cell-free translation assay and in a transfected hepatoma cell line.

Antiviral Agents↗

PubMed2003

Cellular uptake and intracellular fate of antisense oligonucleotides.

Antisense oligonucleotides and short interfering RNAs are routinely used for gene function analysis and are being developed for clinical applications. The mechanism underlying internalization of free oligonucleotides into cells is poorly understood and inefficient in most cases. Antisense oligonucleotide delivery into ex vivo cells is routinely improved by the addition of cationic lipids. New chemical modifications and vectors allowing improved cellular delivery in vivo are being developed.

Animals↗

PubMedDate not supplied

Relatives' experiences of critical care.

This exploratory study investigates relatives' overall experiences of the critical care environment and how staff perceived these experiences. Traditionally, research in Critical Care concentrated on patients' psychological well-being or relatives' immediate needs. There is little research that addresses the relative's overall experience of events. Critical Care Units are possibly the most daunting units in hospitals. Having a family member admitted to a Critical Care Unit could qualify as a traumatic-enough stressor to induce post-traumatic stress symptoms in relatives. A convenience sample of eight relatives and five staff participated in the study. The study used qualitative methods and drew on techniques of grounded theory. While staff perceived relatives' experiences accurately; issues arose, from both staff and relatives perspective, with regard to accurate dissemination of information. Further research into the communication processes used within Critical Care Units is required in addition to developing best practice in this area.

Adaptation, Psychological↗