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Biomedical subjects

S Harrison

Publications and source records attributed to S Harrison.

At least 91 records · Page 5Linked to original sources
PubMed1994

Site-specific transgene insertion: an approach.

Methods to improve the production of transgenic animals are being developed. Conventional transgenesis, involving microinjection of DNA into fertilized eggs, has a number of limitations. These result from the inability to control both the site of transgene insertion and the number of gene copies inserted. The approach described seeks to overcome these problems and to allow single copy insertion of transgenes into a defined site in animal genomes. The method involves the use of embryonic stem cells, gene targeting and the FLP recombinase system.

Animals↗
PubMed1994

Knowledge into practice: what's the problem?

It is now widely accepted that there is a problem in putting research findings into routine clinical practice. Approaches the topic by identifying the conditions which would have to be met for the "perfect" implementation of such findings, and by outlining some of the research findings concerning each of these. Concludes that research to date has concentrated on certain of these conditions at the expense of others.

Communication↗
PubMed1994

Sequence requirements of the Epstein-Barr virus latent origin of DNA replication.

The Epstein-Barr virus (EBV) latent origin of DNA replication (oriP) is composed of two elements that contain binding sites for the sole viral gene product required for latent cycle replication, EBNA-1. One of these elements, region I, functions as an EBNA-1-dependent enhancer for RNA polymerase II-transcribed genes, may play a role in plasmid segregation, and is required for origin function in B cells latently infected with EBV. The second element, region II, contains or is very near the site of initiation of DNA replication. A genetic approach was taken to determine the contribution of the EBNA-1 binding sites in oriP to origin function. Although region I is required for the transient replication of plasmids bearing region II in EBV-infected B cells, a plasmid lacking region I but containing region II, was observed to replicate transiently in both D98/Raji and HeLa cells expressing EBNA-1. Thus, binding of EBNA-1 to region I is not absolutely required for the molecular events that lead to initiation of DNA replication at region II. Site-directed mutagenesis of the four EBNA-1-binding sites in region II, individually and in various combinations, demonstrated that only two EBNA-1-binding sites are required for region II function. The results obtained with these mutants, together with the analysis of the replicative ability of plasmids containing insertions between EBNA-1-binding sites, suggested that the spatial relationship of the two sites is critical. Mutants that contain only two EBNA-1-binding sites separated by 26 to 31 bp in region II were not maintained as plasmids over many cell generations and were greatly reduced in their ability to replicate transiently in D98/Raji cells. The EBNA-1-induced bending or untwisting of the DNA in EBNA-1-binding sites 1 and 4 in region II did not, however, demonstrate this spatial constraint. It may be concluded from these results that specific protein-protein interactions between EBNA-1 and/or between EBNA-1 and a cellular protein(s) are required for origin function.

Antigens, Viral↗
PubMed1994

Health services research--what it is, how to do it, and why it matters.

The term 'Health Services Research' (HSR) has achieved only recent currency in the UK. The purpose of this short article is to explain what it is, to say how it differs from clinical research even when using similar methods, and to argue that it is likely to become of rapidly increasing importance to health policy-makers and managers.

Health Policy↗
PubMed1994

The dynamics of health care organisation in Britain.

The National Health Service provides a 'policy puzzle' to British governments: how to cope with rising demands in a service which is extremely popular with the public, whilst maintaining economic orthodoxy with regard to public expenditure. The limited number of options for reconciling these tensions has provided the menu from which successive recent policies for organising and managing the Service have been drawn, and from which governments will continue to have to choose over the next few years.

Health Expenditures↗
PubMed1993

Role of the dorsal prestriate cortex in visuospatial configural discrimination by monkeys.

Cynomolgus monkeys (Macaca fascicularis) learned a series of visuospatial configural discriminations in which particular discriminative stimulus objects were rewarded only in particular spatial locations. For example, object X was rewarded if it was on the left but not if it was on the right. After ablation of part of the dorsal prestriate cortex they were impaired in learning discriminations of this kind. The same animals were not impaired in learning visual object discriminations in which spatial position was irrelevant, nor in learning spatial discriminations in which object identity was irrelevant. The results were compared with previously reported results from fornix transection in the same tasks; the deficit following dorsal prestriate ablation in visuospatial configural discrimination learning was similar in severity to that which followed fornix transection. The results show that the dorsal prestriate area has a more general role in visuospatial processing than was known hitherto, and they suggest that it interacts with the hippocampal formation and fornix in visuospatial memory tasks.

Animals↗
PubMed1993

The effect of a range of alcohols on the contraction of guinea-pig ventricular myocytes.

Previous results have shown that ethanol and some anaesthetics have a negative inotropic effect on the heart. This study was undertaken to investigate the influence of a range on n-alcohols (with chain lengths from 2 to 8) on contractility in guinea-pig ventricular myocytes. The results demonstrate that the negative inotropic action of alcohols increases dramatically as the chain length increases. The concentration required to reduce the magnitude of contraction to 50% of control (IC50) was 274 mM, 26 mM, 1.4 mM and 235 microM for ethanol, butanol, hexanol and octanol, respectively. The relationship between the logarithm of IC50 and chain length was linear for all the alcohols tested (up to a chain length of 8).

Alcohols↗
PubMed1993

Influence of Ca2+ channel agonists and antagonists on the post-rest staircase.

It is now generally accepted that the post-rest staircase consists of two phases, an initial fast phase occurring over the first five to six beats followed by a slow phase which occurs over a period of minutes. In this study, the influence of Ca2+ channel antagonists (Cd2+ and nifedipine) and agonists (Bay K 8644 and noradrenaline) on developed tension is investigated to assess the role played by the L-type Ca2+ current (iCa) during post-rest recovery. The results show that, at a range of stimulus frequencies, exposure of guinea-pig papillary muscles to either Cd2+ or nifedipine greatly reduces the fast phase of the staircase and reduces the slow phase of the staircase compared to control (both effects being more prominent at higher stimulus frequencies). Exposure of guinea-pig papillary muscles to Bay K 8644 or noradrenaline potentiated both the fast and slow phases of the staircase with greater proportionate effects observed at higher stimulus frequencies. These results suggest that iCa plays an important role in both phases of the staircase. The first post-rest beat (the rested state contraction) proved very resistant to Ca2+ channel blockade suggesting that iCa plays little role in this contraction which may be the result of entry of Ca2+ into the cell via a relatively Cd2+ insensitive pathway, for example the Na(+)-Ca2+ exchanger.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed1993

Quantitative evaluation of hepatitis C virus RNA in patients with concurrent human immunodeficiency virus infections.

Quantitation of the hepatitis C virus (HCV) provides a powerful epidemiologic and therapeutic method for the evaluation of infected patients. In this study semiquantitative reverse transcriptase polymerase chain reaction (PCR) is compared with a new branched DNA signal amplification methodology. Samples from HCV-infected patients as well as from human immunodeficiency virus-infected patients were evaluated. Reverse transcriptase PCR correlated well with the branched DNA assay (r = 0.7036, P < 0.05). HCV RNA was found to occur at significantly higher titers (P < 0.05) in patients coinfected with the human immunodeficiency virus compared with titers in those infected with HCV alone. Immune status as defined by the CD4+ count was not associated with the observed difference in viral titer.

Base Sequence↗
PubMed1992

Predeposit autologous blood transfusion in patients with colorectal cancer: a feasibility study.

Over a 2-year period, a predeposit autologous blood transfusion service was provided for all patients undergoing elective surgery for left-sided colonic or rectal cancer in one hospital. Of 129 such patients, 28 were suitable for autologous donation. Eight of these received autologous blood only, 13 required no transfusion, and seven needed additional homologous blood. Thus, although predeposit autologous transfusion for patients with colorectal cancer is possible, only a very small proportion are likely to derive any benefit which it might confer.

Aged↗
PubMed1992

Control of contamination of the operative team in total joint arthroplasty.

Reports of percutaneous transmission of blood-borne disease emphasize the need for control of intraoperative contamination. In a randomized prospective study, surgeons and surgical assistants involved in total hip and total knee arthroplasty adopted the following protocol: total body exhaust with hood, aspirator, knee-length impermeable gowns, foot covers, including knee-high covers and waterproof covers, and one of three combinations of gloving protocols: latex/latex changed hourly, latex/cloth, or latex/cloth/latex. All inner gloves were tested by a leak test. All needles and sharp instruments were passed on trays, and all contaminations and perforations were recorded. Each surgeon and assistant was inspected twice for contamination. There were no needle sticks, and only one of 267 personnel had head, neck, body, leg, or foot contamination. Perforation rates of inner gloves were 9.2% for latex/latex, 7.9% for latex/cloth, and 4.3% for latex/cloth/latex.

Blood↗
PubMed1992

The career development internship program. Pathway to enhanced nursing practice.

Nurse administrators can enhance nursing practice and improve patient care by providing clinical nurses with ways to develop and share their expertise in areas such as education, management, quality assurance, advanced clinical practice, and research. The authors describe the Career Development Internship Program that grew out of the Management Internship Program. This creative program allows for professional growth in specific fields while also developing leadership capability.

Career Mobility↗
PubMed1992

Sexual dimorphism and growth hormone regulation of a hybrid gene in transgenic mice.

The sexually dimorphic expression of the urinary protein genes of mice (Mup genes) in the liver is mediated by the different male and female temporal patterns of circulating GH. Normal females were induced to male levels when GH was administered by injection to mimic the male GH pattern, showing that expression at the male level does not require a male sex steroid status in addition to intermittent GH. Two Mup-alpha 2u-globulin hybrid transgenes with different Mup gene promoters showed sexually dimorphic expression, and their expression in females increased to male levels upon testosterone treatment. GH-deficient (lit/lit) mice did not express these transgenes, and GH-deficient females did not respond to testosterone treatment, showing that GH was required for induction. Both normal and GH-deficient females were induced to male levels when GH was administered by injection. This is the first report of a transgene responsive to GH. A transgene consisting of a Mup promoter fused to a Herpes simplex virus thymidine kinase reporter sequence also showed sexual dimorphism, although to a lesser degree. It was expressed at the same level in normal females and GH-deficient mice of both sexes and was induced when GH-deficient mice were treated with GH. We propose that this transgene has a basal constitutive expression, possibly due to the absence of any rodent DNA downstream of the promoter. Since expression of the transgene was significantly induced by GH, the GH response is due at least in part to sequences in the promoter region.

Alpha-Globulins↗
PubMed1991

Auditory-visual associations, hemispheric specialization and temporal-frontal interaction in the rhesus monkey.

Monkeys (Macaca mulatta) learned preoperatively to associate each of 6 auditory stimuli with 1 of 6 visual stimuli. Ablation of the left prefrontal cortex in a group of 3 monkeys produced a substantial impairment in performance of the task, though performance was still above chance. Ablation of the right prefrontal cortex in a second group of 3 monkeys was without effect. Subsequently the superior temporal gyrus (auditory cortex) was removed in each animal unilaterally in the hemisphere contralateral to the existing prefrontal ablation. Ablation of the left auditory cortex produced a severe impairment, but ablation of the right auditory cortex was without effect. Finally, forebrain commissurotomy in the animals with left prefrontal and right temporal ablation reduced their performance virtually to chance level. These results are consistent with previous findings indicating a left hemisphere specialization for audition in the monkey, and they give strong support to the idea, derived from previous experiments on difficult associative learning in the monkey, that auditory-visual association depends on a convergence of auditory and visual information in the prefrontal cortex.

Animals↗