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Biomedical subjects

S L Hart

Publications and source records attributed to S L Hart.

69 records · Page 4Linked to original sources
PubMed1975

The effects of drugs on human foetal intestine.

The longitudinal muscle of human foetal intestine, of gestational age between eight and twenty-six weeks, has been studied in vitro using standard pharmacological methods. Muscarinic receptors and adrenoceptors have been identified in both the small and large intestine. The muscarinic receptors are similar to those of adult tissue whereas the adrenoceptor population of foetal intestine differs from that reported for adult tissue. In the foetal small intestine there is a predominance of beta receptors and the foetal colon contains alpha receptors which are involved in a contractile response to sympathomimetic amines. The responses to nicotine show that cholinergic and adrenergic fibres are present in the intestinal wall of the 12-week foetus.

Acetylcholine↗
PubMed1974

The actions of prostaglandins E2 and F2alpha on human foetal intestine.

Human foetal small and large intestine responded to prostaglandins E(2) and F(2alpha), the gestational age of the tissue being between 14 and 26 weeks. The predominant response to both prostaglandins was a contraction of each region of the intestine studied. The response to both prostaglandins was antagonized selectively by poly.phloretin phosphate.

Abortion, Induced↗
PubMed1971

Adrenoceptors in the human foetal small intestine.

Human foetal small intestine was shown to contain both alpha- and beta-adrenoceptors with a predominance of beta-adrenoceptors. The tissue examined was obtained from foetuses of gestational age between 8 and 26 weeks.

Acetylcholine↗
PubMedDate not supplied

Non-viral, integrin-mediated gene transfer into fibroblasts from patients with lysosomal storage diseases.

BACKGROUND: Non-viral vectors consisting of Lipofectin/integrin-targeting peptide/DNA (LID) complexes have great potential for gene therapy, as they are safe, simple, and able to package large DNA molecules. In this study, these vectors were evaluated in vitro for the therapy of lysosomal storage disorders. METHODS: Non-viral vectors were designed to deliver therapeutic genes by integrin-mediated uptake into fibroblasts from patients with the lysosomal storage disorders fucosidosis and Fabry disease, which result from deficiencies of alpha-L-fucosidase and alpha-galactosidase A, respectively. The vectors consisted of a complex (LID) of Lipofectin and a peptide containing an integrin-targeting domain and a poly-lysine domain to which was bound plasmid DNA, containing alpha-L-fucosidase (LID-alpha-Fuc) or alpha-galactosidase A (LID-alpha-Gal). RESULTS: Patients' fibroblasts transfected with LID-alpha-Fuc and LID-alpha-Gal produced the corresponding enzyme at levels which were 10-40% of the total activity in cultures of normal fibroblasts. However, 95-98% of this activity was secreted. Transfection of endothelial cells, the main target cells in Fabry disease, with an LID-alpha-Gal produced a total alpha-galactosidase activity 65% higher than that in untransfected cultures after 6 days, 67% of the activity being secreted. Although transfection of fibroblasts with LID complexes also caused small changes in the distribution of endogenous lysosomal enzymes, it did not appear to affect the viability of the cells. CONCLUSIONS: The integrin-mediated transfer of genes encoding lysosomal enzymes into cells results in the secretion of large amounts of normal enzyme that could be taken up by other cells. This could be a useful strategy for enzyme-replacement therapy.

Cell Line↗
PubMedDate not supplied

In vivo myocardial gene transfer: optimization, evaluation and direct comparison of gene transfer vectors.

The purpose was to determine the relative efficiency, toxicity and duration of expression following gene delivery by intramyocardial injection of naked DNA, naked DNA complexed to cationic liposomes, naked DNA complexed to cationic liposomes with integrin-targetting peptide, recombinant (E1-/E3-) adenovirus, recombinant adeno-associated virus and recombinant (ICP27-) herpes simplex virus. All vectors incorporated a LacZ reporter driven by a promoter containing the hCMV-IE promoter/enhancer. Efficiency was scored by counting positive cells in five standard microscopic sections harvested from the left ventricular apex. Rabbit hearts (n = 100) were examined from 2 to 56 days after injection. Uncomplexed and complexed naked DNA were very inefficient with less than one positive cell visible per heart. The viral vectors all resulted in robust gene expression with adenovirus being the most efficient by at least one order of magnitude before 21 days. However, despite disparate titres, the efficiency beyond 21 days of adenovirus and adeno-associated virus were comparable. In contrast to adeno-associated virus, both adenovirus and herpes-simplex virus were associated with a marked inflammatory response. Despite reporter gene activity appearing only after 21 days, adeno-associated virus shows comparative promise as a myocardial gene delivery vector.

Adenoviridae↗
PubMedDate not supplied

Learning-disabled people's experience of general hospitals.

As more people with learning disability move from long-stay hospitals into the community, contact with general hospital services will increase. Yet, how people with learning disability experience general hospital settings has remained a largely unresearched area. Despite the Department of Health's (DoH's) 1992 guidelines regarding learning-disabled people's access to hospitals, research reveals several areas where the needs of people with learning disability have not been considered. This small-scale study sought to hear from learning-disabled people themselves about their hospital experiences. Thirteen interviews were conducted over 3 months. The interviews were then transcribed and, using grounded theory, a series of key concepts developed. Findings highlighted that, particularly in the areas of 'fears about treatment', 'communication', 'general nursing', 'consent to treatment' and 'doctors', learning-disabled people had a lot to say, much of which was critical of service provision.

Adolescent↗
PubMedDate not supplied

Pulmonary gene therapy. Realistic hope for the future, or false dawn in the promised land?

Pulmonary gene therapy offers the hope of treatment for conditions such as cystic fibrosis, lung cancer, pulmonary fibrosis and acute respiratory distress syndrome for which current therapy is inadequate. Although initial clinical trials in cystic fibrosis and non-small cell lung cancer have shown promise the results have not been as good as might have been anticipated. However, clinical improvement has been demonstrated in conditions such as haemophilia [82], cardiovascular disease [83], head and neck cancer [84] and X-linked severe combined immunodeficiency disease [85]. The lack of success of pulmonary gene therapy is due, in part on the physical barriers to transfection perfected by the lung to prevent toxicity from inhaled particles, and partly due to the poor transfection efficiency of non-viral systems, and the immunogenicity of viral systems, of gene transfer. The LID vector goes some way to addressing the problems associated with current gene delivery strategies. With continued improvements in the properties of both viral and non-viral gene delivery systems leading to improved transfection efficiency with reduced toxicity, as well as the development of strategies aimed at reducing the physical barriers to pulmonary transfection, and targeting gene delivery systems to the site of injury, it is likely that pulmonary gene therapy will be used successfully to ameliorate a number of devastating pulmonary conditions.

Adenoviridae↗