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Biomedical subjects

S M Murphy

Publications and source records attributed to S M Murphy.

At least 55 records · Page 3Linked to original sources

Thyrotropin-releasing hormone-immunoreactive varicosities synapse on rat phrenic motoneurons.

The relationship between retrogradely labelled or intracellularly filled phrenic motoneurons and varicosities containing thyrotropin-releasing hormone immunoreactivity was investigated in rats by light and electron microscopy. Phrenic motoneurons were identified via retrograde tracing from the diaphragm with cholera toxin B subunit, which was followed by immunocytochemistry to visualise retrogradely labelled motoneurons and thyrotropin-releasing hormone-immunoreactive nerve fibres in their vicinity. At the light microscopic level, varicose thyrotropin-releasing hormone-immunoreactive nerve fibres were distributed sparsely in the phrenic motor nucleus, with some axons surrounding retrogradely labelled motoneurons. In separate intracellular experiments, four phrenic motoneurons identified by antidromic activation from the C5 phrenic nerve root were subsequently filled with Neurobiotin, and nerve fibres that contained thyrotropin-releasing hormone immunoreactivity were identified by immunocytochemistry. The numbers and locations of thyrotropin-releasing hormone-immunoreactive varicosities that were closely appeared to the intracellularly labelled motoneurons were mapped using a camera lucida technique. Close appositions by thyrotropin-releasing hormone-immunoreactive varicosities were seen on somata as well as on proximal and distal dendrites. The closely apposed varicosities were usually present in tight clusters, which were formed by single varicose axons. However, the distribution was nonuniform, in that some dendrites did not receive any close appositions. Ultrastructural analysis of random ultrathin sections through retrogradely labelled neurons showed that varicosities with thyrotropin-releasing hormone immunoreactivity made 1.8% of all synapses and direct contacts on somata and 2.3% of synapses and contacts with dendrites of the retrogradely labelled phrenic motoneurons. The results of these experiments suggest that thyrotropin-releasing hormone-immunoreactive varicosities provide similar numbers of inputs to both the somata and dendrites of phrenic motoneurons. These thyrotropin-releasing hormone-containing inputs seen via light and electron microscopy could modulate the excitability of phrenic motoneurons.

Animals↗

Tetanus immunity in elderly people.

The aims of this study were to document the level of tetanus immunity in elderly people; to assess the value of immunization history in predicting tetanus immune status and to determine the response to tetanus immunization in elderly people compared with younger subjects. One-hundred day-hospital attenders (group 1), 100 long-term-care residents (group 2) and 50 young subjects (group 3) were recruited. Protective titres of tetanus antitoxin antibodies were detected in 20% of group 1, 45% of group 2 and 80% of group 3. Tetanus immunization history was a poor predictor of immune status in older people with a positive predictive value of 50% and a negative predictive value of 76%. The response to tetanus immunization was slower and of lower magnitude in older people. However, 36 of 37 older subjects developed protective levels of tetanus antitoxin antibodies on completion of a primary immunization programme.

Adult↗

Effect of trauma on implantation of metastatic tumor in bone in mice.

We studied the influence of surgical trauma to the iliac bone on the implantation of I.V. injected tumor cells, which formed tumor in the surgical wounds of 27/84 mice (32%). None of these mice or nonsurgical mice developed tumor in the opposite or uninjured pelvic bone (P < 0.0001). When different numbers (10(5), 5 x 10(5), and 10 x 10(5)) of TA3Ha cells were injected I.V. immediately after surgery, the frequency of tumor formation showed an increase (respectively, 32%, 63%, 71%). As the interval between induction of trauma and tumor cell injection was increased from 0 to 15 days, the frequency of tumor formation declined from 32% to 0%. These results suggest that the healing wound is a privileged site for experimental metastasis, particularly in the early stages. It is likely that the proteins in the blood clotting cascade are involved in local tumor implantation.

Animals↗

Imagery interventions in sport.

The use of imagery processes in the regulation and enhancement of sports performance is examined in this review paper. Research studies in this area are reviewed and four general categories of research are identified: 1) mental practice, 2) precompetition imagery, 3) comparisons of successful and unsuccessful competitors, and 4) mediating variables. The conclusion is reached that mental practice research has produced equivocal results and the reasons for this are examined. The argument is made that the mental practice model for research into imagery processes in sports is nonproductive. Suggestions for future research directions are offered and guidelines for productive imagery research in sport are provided.

Humans↗

Treatment of cryptococcosis with liposomal amphotericin B (AmBisome) in 23 patients with AIDS.

OBJECTIVE: To determine the safety and efficacy of liposomal amphotericin B (AmBisome) in the primary treatment of AIDS-associated cryptococcosis. DESIGN: A Phase II, multicentre, European, non-comparative, open study to assess the use of AmBisome in 23 patients (26 enrolments) with cryptococcosis. Dose requirements, mycological response and toxicity were documented. SETTING: Hospital-based HIV units. PATIENTS: Twenty-three HIV-1-seropositive patients. RESULTS: Drug toxicity, assessed in 25 enrolments, was well-tolerated with little renal, hepatic or haematological toxicity. Eighteen out of 23 (78%) enrolments responded clinically. Nineteen enrolments had cryptococcal meningitis: sterilization of spinal fluid was achieved in 12 out of the 18 (67%) who were mycologically evaluable. Fourteen out of the 19 (74%) responded clinically. CONCLUSION: AmBisome is well-tolerated and may be an effective formulation in the treatment of cryptococcosis.

AIDS-Related Opportunistic Infections↗

Suppression of c-Src activity by C-terminal Src kinase involves the c-Src SH2 and SH3 domains: analysis with Saccharomyces cerevisiae.

The kinase activity of c-Src is normally repressed in vertebrate cells by extensive phosphorylation of Y-527. C-terminal Src kinase (CSK) is a candidate for the enzyme that catalyzes this phosphorylation. We have used budding yeast to study the regulation of c-Src activity by CSK in intact cells. Expression of c-Src in Saccharomyces cerevisiae, which lacks endogenous c-Src and Y-527 kinases, induces a kinase-dependent growth inhibition. Coexpression of CSK in these cells results in phosphorylation of c-Src on Y-527 and suppression of the c-Src phenotype. CSK does not fully suppress the activity of c-Src mutants lacking portions of the SH2 or SH3 domains, even though these mutant proteins are phosphorylated on Y-527 by CSK both in vivo and in vitro. These results suggest that both the SH2 and SH3 domains of c-Src are required for the suppression of c-Src activity by Y-527 phosphorylation.

CSK Tyrosine-Protein Kinase↗

Outpatient follow-up in women with HIV infection in Parkside Health Authority (UK).

OBJECTIVE: To describe patterns of attendance for follow-up among HIV infected women in Parkside, UK and their correlates. DESIGN: Retrospective cohort study. SUBJECTS: 103 HIV infected women. MAIN OUTCOME MEASURES: Whether patients attended for follow-up between three and 18 months. RESULTS: 31% of women were married and 46% had children. Women born in sub-Saharan Africa were significantly less likely to attend for follow-up after three months (56%) than women born in other areas who had acquired HIV either heterosexually (82%) or through injecting drug use (81%). This pattern persisted on multivariate analysis controlling for whether women were symptomatic, had had a previous positive test, were married or had children. CONCLUSIONS: HIV positive sub-Saharan African women are less likely to reattend for follow-up than women with heterosexually acquired HIV from other areas or those who acquired infection through intravenous drug use. Further studies are needed to identify barriers to follow-up for women and to shape the development of more appropriate and accessible services for HIV infected women, especially those of sub-Saharan African origin.

Adult↗

Polymer membranes in clinical sensor applications. I. An overview of membrane function.

Polymer membranes are used in a wide variety of molecular sensing devices many of which are of potential clinical interest. The role of the polymer and the physical properties required of it are, however, rarely clearly defined. An extensive review is presented of the range of polymers whose use as membranes is described in the sensor literature. This forms the basis of an overview of membrane function in potentiometric amperometric and fibre optic sensors. In particular, the interaction of permeability, permselectivity and transmembrane potential is highlighted, together with the role of polymer membranes as matrices for the immobilization of reactive chemical and biological agents.

Biocompatible Materials↗

Polymer membranes in clinical sensor applications. II. The design and fabrication of permselective hydrogels for electrochemical devices.

Hydrogels, particularly the tough, low water content materials, have potential advantages in the field of clinical biosensors because of their established use as medical polymers. The factors that control transport behaviour in these polymers are discussed with particular reference to ion selectivity. The nature of the transport behaviour in relation to coated wire electrode performance is presented and an extension of these permselectivity studies to the fabrication of miniaturized devices, such as ISFETs, is described. Linear soluble hydrogel polymers, coated on to sensor substrates, may be converted to insoluble membranes using solid photosensitive aromatic monomers, such as N-vinyl carbazole. Photolithographic patterning is achieved using a UV source together with appropriate masking, followed by an oxygen plasma etch process. Gas plasma etching, which selectively removes uncross-linked (masked) areas forms the basis of an all dry, low-temperature patterning process capable of giving micrometre-scale resolution. This novel photographic process, which does not damage or extract enzymes or ionophores, can advantageously be extended to the fabrication of poly(vinylchloride)-based membranes.

Biocompatible Materials↗

Polymer membranes in clinical sensor applications. III. Hydrogels as reactive matrix membranes in fibre optic sensors.

The potential of hydrogel copolymer membranes in clinical sensors, based on fibre optics, is addressed. The particular properties of the membranes of relevance in this application are the ease of refractive index modulation and the potential of the hydrogel to act as a permselective barrier in which a colorimetric agent may be immobilized. The results presented illustrate the complexity of colorimetric and refractive index effects together with their dependence on pH and tonicity for hydrogels of a given composition range. The incorporation of an acryloyl-functionalized reagent (bromopyrogallol red) is used to illustrate the way in which a working pH sensor based on these combined properties may be designed and fabricated.

Biocompatible Materials↗

Rebound cue state following a single dose of haloperidol.

It has been reported that chronic administration of haloperidol produces an amphetamine-like rebound cue state. The experiments reported here were designed to assess whether a similar rebound phenomenon would result from a single dose of haloperidol. Rats were trained to discriminate .5 mg/kg amphetamine from distilled water. Five groups were formed to allow testing of haloperidol's effect at 12, 18, 24, 30, and 36 hr postinjection. Each animal was given 0, .5, 1.0, and 1.5 mg/kg haloperidol at its appropriate injection time in a counterbalanced fashion with one week between each test. A shift in the dose-response function of amphetamine that occurred during these weeks, however, precluded appropriate analysis of haloperidol's effects. Given this result, a second experiment was conducted using a between-subjects design. Half of the animals were injected with 1 mg/kg haloperidol 23 hr prior to testing, whereas the others were injected with distilled water. When tested, the haloperidol group responded 33% of the time on the amphetamine-correct lever, whereas the control group responded at 20%. The observation of posthaloperidol rebound in the between-subjects study and the failure to find significant temporal patterns of rebound phenomena using a within-subjects design have both theoretical and methodological importance.

Amphetamine↗

Experience with liposomal amphotericin B (AmBisome) in cryptococcal meningitis in AIDS.

Three patients with AIDS who had cryptococcal meningitis were treated with liposomal amphotericin B after unsuccessful treatment with fluconazole and conventional amphotericin B. One patient responded but relapsed nine weeks later; he responded to a second course of treatment but again relapsed and subsequently died. Another patient deteriorated despite an improvement in cryptococcal antigen titres. The third patient was found to have culture negative CSF and treatment was therefore stopped. None of the patients suffered any adverse effects and renal function improved in all after conventional amphotericin was stopped and liposomal amphotericin B commenced.

Acquired Immunodeficiency Syndrome↗