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Biomedical subjects

M Coleman

Publications and source records attributed to M Coleman.

At least 73 records · Page 4Linked to original sources
PubMed1999

Increased level and duration of expression in muscle by co-expression of a transactivator using plasmid systems.

Skeletal muscle is an attractive target for gene therapies to treat either local or systemic disorders, as well as for genetic vaccination. An ideal expression system for skeletal muscle would be characterized by high level, extended duration of expression and muscle specificity. Viral promoters, such as the cytomegalovirus (CMV) promoter, produce high levels of transgene expression, which last for only a few days at high levels. Moreover, many promoters lack muscle tissue specificity. A muscle-specific skeletal alpha-actin promoter (SkA) has shown tissue specificity but lower peak activity than that of the CMV promoter in vivo. It has been reported in vitro that serum response factor (SRF) can stimulate the transcriptional activity of some muscle-specific promoters. In this study, we show that co- expression of SRF in vivo is able to up-regulate SkA promoter-driven expression about 10-fold and CMV/SkA chimeric promoter activity by five-fold in both mouse gastrocnemius and tibialis muscle. In addition, co-expression of transactivator with the CMV/SkA chimeric promoter in muscle has produced significantly enhanced duration of expression compared with that shown by the CMV promoter-driven expression system. A dominant negative mutant of SRF, SRFpm, abrogated the enhancement to SkA promoter activity, confirming the specificity of the response. Since all the known muscle-specific promoters contain SRF binding sites, this strategy for enhanced expression may apply to other muscle-specific promoters in vivo.

Actins↗
PubMed1999

Medication management: an exploratory study into the role of community mental health nurses.

The recent emphasis on community care for those with mental illness has changed working patterns and modified inter-professional role boundaries within multi-disciplinary teams. Clients with serious mental illness are usually prescribed medications, which have a wide range of side effects. However, it is uncertain who is responsible for monitoring clients for the side effects of their medications, ensuring clients' and carers' understandings of their prescribed medications and optimizing compliance with medication. This paper discusses the findings of the first phase of an ongoing study designed to assess the role of community mental health nurses (CMHNs) in managing clients' medication and the provision of appropriate continuing professional education. Our respondents were 14 CMHNs, seven of whom were preparing to undertake a pharmacology module as part of a higher education diploma, and seven who were to act as comparators. Data from questionnaires, interviews and clinical observations were triangulated. All respondents felt that issues surrounding clients' medication were not accorded a sufficiently high profile and that it was, in part, their responsibility to expand their roles to meet these unmet needs of clients. Administering and managing clients' medications were considered to be the main area of 'occupational territory' which distinguished CMHNs from social workers. However, the nurses felt that their practice was limited by lack of appropriate educational preparation.

Community Mental Health Services↗
PubMed1999

Mental health nursing policy - an exploratory qualitative study of managers' opinions.

During the 1990s, much of the legislation and policy that pertains to mental health services has sought to direct them towards a virtually exclusive concern with the seriously mentally ill, typified by the following recommendation from a recent Department of Health review of mental health nursing that stated: 'The essential focus for the work of mental health nurses lies in working with people with serious or enduring mental illness'. On the other hand, pressure from the primary health care sector suggests the need for services to be provided for the less seriously mentally ill, particularly through the auspices of general practice fundholders. Following a review of the literature, a small-scale, exploratory study was initiated to seek answers to the following research question: How is the policy focus urging reorientation to the severely mentally ill viewed by nurse managers who have a responsibility through Mental Health Resource Centres and Community Mental Health Teams, to provide mental health services? The study was based within a Welsh National Health Service (NHS) Trust that employed six nurse managers of Community Mental Health Teams (CMHTs). Four of the managers additionally had responsibility for Community Mental Health Resource Centres (CMHRCs). Of the population of six managers, four composed the sample for the investigation. A qualitative research approach was employed, utilizing semistructured interviews as the data collection tool. Analysis of the data revealed that managers were finding creative solutions in order to meet the conflicting demands placed upon them. The research findings also indicated that many of the obstacles to providing a needs-led service were structural in origin, and could be resolved by central strategic intervention.

Attitude of Health Personnel↗
PubMed1999

Assessing educational effectiveness: the impact of a specialist course on the delivery of care.

An exploratory study was undertaken in South Wales to assess the changes in clinical practice brought about by a specialized pharmacology module designed for Community Mental Health Nurses (CMHNs), in our institution. The respondents were the seven CMHNs who completed the course in 1997 and returned to clinical practice, and seven CMHN comparators, matched on the basis of work experience and location. In order to assess the impact of the module, the practice, attitudes and knowledge of the respondents were investigated before and after the course and 6 months later, using semistructured interviews, nonparticipant observation and questionnaires. The three data sets were analysed using the constant-comparative method, and relevant themes were identified and refined. While we obtained some objective measures of positive educational impact, these should be considered in relation to contextual and confounding variables. Both reported and observed behaviours indicated that the main benefit from the course was increased awareness and monitoring of the side-effects of medication. Respondents had not implemented change uniformly; several factors determined how they modified working practices, including service pressures and the support of colleagues.

Cohort Studies↗
PubMed1999

More about brows: how poses that change brow position affect perceptions of gender.

The speeded categorisation of gender from photographs of men's and women's faces under conditions of vertical brow and vertical head movement was explored in two sets of experiments. These studies were guided by the suggestion that a simple cue to gender in faces, the vertical distance between the eyelid and brow, could support such decisions. In men this distance is smaller than in women, and can be further reduced by lowering the brows and also by lowering the head and raising the eyes to camera. How does the gender-classification mechanism take changes in pose into account? Male faces with lowered brows (experiment 1) were more quickly and accurately categorised (there was little corresponding 'feminisation' of raised-brow faces). Lowering gaze had a similar effect, but failed to interact with head lowering in a simple manner (experiment 2). We conclude that the initial classification of gender from the facial image may not involve normalisation of the face image to a canonical state (the 'mug-shot view') for expressive pose (brow movement and direction of gaze). For head pose (relative position of the features when the face is not viewed head-on), normalisation cannot be ruled out. Some perceptual mechanisms for these effects, and their functional implications, are discussed.

Adolescent↗
PubMed1999

Genome-wide scan for autism susceptibility genes. Paris Autism Research International Sibpair Study.

Family and twin studies have suggested a genetic component in autism. We performed a genome-wide screen with 264 microsatellites markers in 51 multiplex families, using non-parametric linkage methods. Families were recruited by a collaborative group including clinicians from Sweden, France, Norway, the USA, Italy, Austria and Belgium. Using two-point and multipoint affected sib-pair analyses, 11 regions gave nominal P -values of 0.05 or lower. Four of these regions overlapped with regions on chromosomes 2q, 7q, 16p and 19p identified by the first genome-wide scan of autism performed by the International Molecular Genetic Study of Autism Consortium. Another of our potential susceptibility regions overlapped with the 15q11-q13 region identified in previous candidate gene studies. Our study revealed six additional regions on chromosomes 4q, 5p, 6q, 10q, 18q and Xp. We found that the most significant multipoint linkage was close to marker D6S283 (maximum lod score = 2.23, P = 0.0013).

Adolescent↗
PubMed1999

Preoperative visiting in Wales.

There is clear evidence in the nursing literature that preoperative visits conducted by theatre nurses have a therapeutic benefit for surgical patients. However, it would appear that the actual uptake of this practice is limited (Wicker 1995). The aim of this study is to investigate the prevalence of preoperative visiting in Wales and to identify factors associated with its occurrence or non-occurrence.

Attitude of Health Personnel↗
PubMed1999

Cytokines and cell adhesion molecules in musculoskeletal disorders.

This paper reviews the cytokine profiles and various cell adhesion molecules expressed in the more common inflammatory joint conditions such as rheumatoid arthritis, psoriatic arthritis, the spondyloarthropathies (Reiter's syndrome, ankylosing spondylitis), as well as systemic lupus erythematosus, systemic sclerosis, Sjögren's syndrome, giant cell arteritis and polymyositis. Knowledge of the broad range of cytokines produced in these conditions and the expression of cell adhesion molecules that result from cytokine production will assist in the understanding of the pathogenesis of these conditions and may lead to new therapeutic interventions.

Journal Article↗
PubMed1999

Concentrations of activin A, inhibin A and follistatin in human amnion, choriodecidual and placental tissues at term and preterm.

To investigate labour-associated changes in production of activin and related hormones by gestational tissues we prepared extracts from amnion, choriodecidual and placental tissues delivered at term before labour (TNL; n=15), at term after spontaneous labour (TSL; n=15) or preterm (PTD; n=31) and measured concentrations of inhibin A, activin A and follistatin by ELISA. Activin concentrations in placental tissues were significantly (Mann-Whitney U-test; P<0.05) elevated with term labour (pg/mg protein, median; 1313 vs 2591), but in the PTD tissues concentrations were lower than those delivered spontaneously at term (3650 vs 2649). Inhibin concentrations also increased with term labour in the placenta (480 vs 686), but paradoxically decreased in amnion (188 vs 64) and choriodecidua (657 vs 358). Little or no significant changes in follistatin concentrations were observed. Concentrations of all three proteins were significantly correlated between amnion and choriodecidual tissues, and were significantly correlated with each other in most tissues (Spearman's ranked correlation; P<0.05). The activin:inhibin ratio in term amnion and choriodecidual tissues was increased 2 to 3-fold (P<0.0005 by Mann-Whitney U-test) after term labour, with similar trends also observed in the activin:follistatin ratio in placental tissue. These data suggest that a modest increase in placental activin and inhibin production may occur with labour at term. In addition, an increase in activin bioactivity may occur with labour, potentiating any paracrine effects of activin during parturition. The data, however, do not support an association between increased intrauterine activin biosynthesis and preterm delivery.

Activins↗
PubMed1998

Nonviral interferon alpha gene therapy inhibits growth of established tumors by eliciting a systemic immune response.

A plasmid expression system encoding murine IFN-alpha4 and complexed with a protective interactive noncondensing polymeric (PINC) delivery system was used for in vivo immunotherapy treatment of an immunogenic murine renal cell carcinoma, Renca, and a nonimmunogenic mammary adenocarcinoma, TS/A. Mice bearing established tumors were treated with IFN-alpha/polyvinylpyrrolidone (PVP) expression complexes via direct intratumoral injection. Up to 100% inhibition of tumor growth was observed in the treated mice. By using an optimal dose of 96 and 48 microg of formulated IFN-alpha plasmid for the treatment of Renca and TS/A, respectively, 30% (Renca) and 10% (TS/A) of the treated animals remained tumor free. Inhibition of tumor growth was dependent on activation of the immune system. The antitumor activity elicited by IFN-alpha gene therapy was abrogated when mice were selectively depleted of CD8+ T cells. By contrast, depletion of CD4+ T cells resulted in enhanced tumor rejection following IFN-alpha/PVP treatments. Finally, mice that remained tumor free following IFN-alpha gene therapy displayed immune resistance to a subsequent tumor challenge. These data provide evidence that IFN-alpha gene therapy can be used to induce an efficient antitumor response in vivo.

Adenocarcinoma↗
PubMed1998

Detection of threonine structural changes upon formation of the M-intermediate of bacteriorhodopsin: evidence for assignment to Thr-89.

The behavior of threonine residues in the bacteriorhodopsin (bR) photocycle has been investigated by Fourier transform infrared difference spectroscopy. L-Threonine labeled at the hydroxyl group with 18O (L-[3-(18)O]threonine) was incorporated into bR and the bR-->M FTIR difference spectra measured. Bands are assigned to threonine vibrational modes on the basis of 18O induced isotope frequency shifts and normal mode calculations. In the 3500 cm-1 region, a negative band is assigned to the OH stretch of threonine. In the 1125 cm-1 region, a negative band is assigned to a mixed CH3 rock/CO stretch mode. The frequency of both these bands indicates the presence of at least one hydrogen bonded threonine hydroxyl group in light adapted bR which undergoes a change in structure by formation of the M intermediate. Spectral changes induced by the substitution Thr-89-->Asn but not Thr-46-->Asn or Asp-96-->Asn are consistent with the assignment of these bands to Thr-89. These results along with another related study on the mutant Thr-89-->Asn indicate that the active site of bR includes Thr-89 and that its interaction with the retinylidene Schiff base and Asp-85 may play an important role in regulating the color of bacteriorhodopsin and the transfer of a proton to the Schiff base.

Bacteriorhodopsins↗
PubMed1998

Augmented therapy of extensive Hodgkin's disease: radiation to known disease or prolongation of induction chemotherapy did not improve survival--results of a Cancer and Leukemia Group B study.

PURPOSE: This prospective randomized trial in extensive untreated Hodgkin's disease was undertaken to assess the potential benefit of augmented therapy (12 months chemotherapy or radiation to known disease) compared to standard 6 months chemotherapy. PATIENT AND METHODS: A total of 258 patients, mostly Stage IV, were randomized to four treatment regimens consisting of six cycles of CCNU, vinblastine, procarbazine, and prednisone (CVPP); 12 cycles of CVPP; six cycles of CVPP followed by 25 Gy radiotherapy; or three cycles CVPP, 25 Gy radiotherapy, and three cycles CVPP. RESULTS: Complete remissions were achieved in 65% of all patients. A 58% overall 5-year survival rate was obtained. Relapses in irradiated areas of known disease occurred in only 6% of responding patients. There was, however, no statistical difference in response frequency, disease-free survival, or overall survival among the four regimens. Elderly patients responded less frequently. CONCLUSION: While radiotherapy provided control of local (known) disease, no impact on overall survival was apparent. Likewise, doubling the duration of chemotherapy did not improve response or survival. Augmentation of therapy with either radiotherapy or more chemotherapy in this study was of no benefit compared to the standard 6 months of treatment.

Adult↗
PubMed1998

Pathogenic mechanisms in the rheumatoid nodule: comparison of proinflammatory cytokine production and cell adhesion molecule expression in rheumatoid nodules and synovial membranes from the same patient.

OBJECTIVE: To investigate the production of proinflammatory cytokines and expression of cell adhesion molecules in the rheumatoid nodule. METHODS: Cytokine content (tumor necrosis factor alpha [TNFalpha], interleukin-1beta [IL-1beta], and IL-1 receptor antagonist [IL-1Ra]), at the messenger RNA (mRNA) and protein levels, and cell adhesion molecule expression were studied in 16 rheumatoid nodules and 6 synovial membranes. RESULTS: Macrophages in the rheumatoid nodules contained TNFalpha, IL-1beta, and IL-1Ra mRNA and protein, particularly in perivascular cells of the stroma and in the palisading layer. All cell adhesion molecules studied were expressed in both the rheumatoid nodules and synovial membranes, with increased expression of E-selectin in the rheumatoid nodule compared with the synovial membrane, and with the absence of vascular cell adhesion molecule 1 expression on cells of the palisading layer in the rheumatoid nodule. CONCLUSION: The presence of similar proinflammatory cytokines and cell adhesion molecules in the rheumatoid nodule and synovial membrane suggests that similar pathogenic processes result in the chronic inflammation and tissue destruction in these lesions.

Adult↗