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Biomedical subjects

S Neil

Publications and source records attributed to S Neil.

10 recordsLinked to original sources

A satisfaction survey of women admitted to a Psychiatric Mother and Baby Unit in the northwest of England.

A Satisfaction Questionnaire for an Inpatient Mother and Baby Unit was developed covering general psychiatric and specific perinatal aspects of the service. In a study of 41 women admitted over one year twenty returned the completed questionnaire. Among respondents overall satisfaction with the service was very high and women preferred it to a general psychiatric ward. Respondents were most dissatisfied with degree of involvement in the planning and the level of decision making about their care which is a recurring theme in surveys of psychiatric inpatients.

Adult↗

Breast cancer management: the perspective of general practitioners in inner and eastern Melbourne.

This study sought to explore general practitioners' (GPs') experience with specialist breast services and to identify their communication, education and resource requirements regarding care of the breast cancer patient, by means of a self-administered questionnaire distributed to 450 GPs in inner and eastern Melbourne. Twenty-three per cent of questionnaires were returned. On average, GPs had one patient newly diagnosed with breast cancer per year. GPs were most likely to refer symptomatic patients to a private specialist breast surgeon. Their referral pattern was largely influenced by previous experience of referral to the service. Communication with specialist breast services was generally satisfactory during the initial stages of diagnosis and treatment; however discharge communication, phone communication with specialists, and admission notification was less satisfactory. When given a list of topics in which GPs may require further education, 65% of respondents identified "Recent advances in breast cancer management" as an area of interest, and the majority requested a directory listing breast services in their local area.

Breast Neoplasms↗

Indigenous NGO involvement in TB treatment programmes in high-burden settings: experiences from the Northern Cape province, South Africa.

Effective tuberculosis (TB) treatment delivery in high-burden countries increasingly requires a multisectoral approach. This paper examines the role two local non-governmental organisations (NGOs) play in TB care delivery in a high-burden setting, the Northern Cape province, South Africa. NGOs played a complementary role to the formal health sector in effecting TB treatment delivery by training facilitators and recruiting and training lay volunteers for directly observed treatment. One key challenge was the paucity of systematised information to enable rigorous evaluation of the effectiveness of NGO contribution, which led to inadequate funding, as potential donors were sceptical about supporting activities whose value they could not assess. In high disease burden settings, where auxiliary actors can play useful roles in effective service delivery, it is important for NGOs to document and self-evaluate their role. One way of building this capacity is through technical support by government and development partners.

Antitubercular Agents↗

Postentry restriction to human immunodeficiency virus-based vector transduction in human monocytes.

Cells of the monocyte lineage can be infected with human immunodeficiency virus type 1 (HIV-1) both during clinical infection and in vitro. The ability of HIV-1-based vectors to transduce human monocytes, monocyte-derived macrophages, and dendritic cells (DCs) was therefore examined, in order to develop an efficient protocol for antigen gene delivery to human antigen-presenting cells. Freshly isolated monocytes were refractory to HIV-1-based vector transduction but became transducible after in vitro differentiation to mature macrophages. This maturation-dependent transduction was independent of the HIV-1 accessory proteins Vif, Vpr, Vpu, and Nef in the packaging cells and of the central polypurine tract in the vector, and it was also observed with a vesicular stomatitis virus-pseudotyped HIV-1 provirus, defective only in envelope and Nef. The level and extent of reverse transcription of the HIV-1-based vector was similar after infection of immature monocytes and of mature macrophages. However, 2LTR vector circles could not be detected in monocytes, suggesting a block to vector nuclear entry in these cells. Transduction of freshly isolated monocytes exposed to HIV-1-based vector could be rescued by subsequent differentiation into DCs. This rescue was induced by fetal calf serum in the DC culture medium, which promoted vector nuclear entry.

Antigen-Presenting Cells↗

Retrovirus targeting by tropism restriction to melanoma cells.

Targeted vectors will be necessary for many gene therapy applications. To target retroviruses to melanomas, we fused a single-chain variable fragment antibody (scFv) directed against the surface glycoprotein high-molecular-weight melanoma-associated antigen (HMW-MAA) to the amphotropic murine leukemia virus envelope. A proline-rich hinge and matrix metalloprotease (MMP) cleavage site linked the two proteins. The modified viruses bound only to HMW-MAA-expressing cells, as inclusion of the proline-rich hinge prevented viral binding to the amphotropic viral receptor. Following attachment to HMW-MAA, MMP cleavage of the envelope at the melanoma cell surface removed the scFv and proline-rich hinge, allowing infection. Complexing of targeted retroviruses with 2, 3-dioleoyloxy-N-[2(spermine-carboxamido)ethyl]N, N-dimethyl-1-propanaminium trifluoroacetate-dioleoyl phosphatidylethanolamine liposomes greatly increased their efficiency without affecting their target cell specificity. In a cell mixture, 40% of HMW-MAA-positive cells but less than 0.01% of HMW-MAA-negative cells were infected. This approach can therefore produce efficient, targeted retroviruses suitable for in vivo gene delivery and should allow specific gene delivery to many human cell types by inclusion of different scFv and protease combinations.

Antibodies, Neoplasm↗

Transcytosis and surface presentation of IL-8 by venular endothelial cells.

Chemokines have been convincingly implicated in actuating inflammatory leukocyte emigration. To affect the circulating leukocytes, tissue-derived chemokines have to traverse the endothelial cells (ECs). This was thought to be accomplished by chemokine diffusion through the intercellular gaps. On the contrary, we show by electron microscopy that the prototype chemokine IL-8 is internalized by venular ECs abluminally and transcytosed to the luminal surface. Here, it is presented to the adherent leukocytes on the EC membrane, predominantly in association with the EC projections. The intact C terminus of IL-8, the molecule's "immobilization" domain, is required for the EC binding, transcytosis, and consequently, the in vivo proemigratory activity of IL-8, indicating that the described subcellular interactions of IL-8 with the ECs are functionally relevant.

Animals↗

The detection of contiguous gene deletions at the neurofibromatosis 1 locus with fluorescence in situ hybridization.

Neurofibromatosis type 1 (NF1) is a common genetic disorder characterized primarily by the development of multiple neurofibromas and pigmentary changes. The recent identification of contiguous gene deletions in NF1, a previously unrecognized molecular basis for this disorder, raises important questions regarding deletion frequency in the patient population and the role that contiguous genes may play in the physical manifestations of NF1 patients. To facilitate the identification of patients with large NF1 deletions, we have isolated clones carrying large genomic segments from the NF1 locus and tested their efficacy as probes for fluorescence in situ hybridization (FISH). Clone P1-9 spans approximately 65 kb of the NF1 gene, including exons 2-11, and clone P1-12 carries approximately 55 kb of NF1 intron 27B. FISH studies performed with P1-9, P1-12, and a set of overlapping 1F10 cosmid clones mapping telomeric to the NF1 locus identified large deletions in two new neurofibromatosis type 1 patients who, like previously characterized deletion patients, had mildly dysmorphic facial features and large numbers of cutaneous neurofibromas.

Chromosome Aberrations↗

Genomic organization of the neurofibromatosis 1 gene (NF1).

Neurofibromatosis 1 maps to chromosome band 17q11.2, and the NF1 locus has been partially characterized. Even though the full-length NF1 cDNA has been sequenced, the complete genomic structure of the NF1 gene has not been elucidated. The 5' end of NF1 is embedded in a CpG island containing a NotI restriction site, and the remainder of the gene lies in the adjacent 350-kb NotI fragment. In our efforts to develop a comprehensive screen for NF1 mutations, we have isolated genomic DNA clones that together harbor the entire NF1 cDNA sequence. We have identified all intron-exon boundaries of the coding region and established that it is composed of 59 exons. Furthermore, we have defined the 3'-untranslated region (3'-UTR) of the NF1 gene; it spans approximately 3.5 kb of genomic DNA sequence and is continuous with the stop codon. Oligonucleotide primer pairs synthesized from exon-flanking DNA sequences were used in the polymerase chain reaction with cloned, chromosome 17-specific genomic DNA as template to amplify NF1 exons 1 through 27b and the exon containing the 3'-UTR separately. This information should be useful for implementing a comprehensive NF1 mutation screen using genomic DNA as template.

Amino Acid Sequence↗