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Biomedical subjects

S M Murphy

Publications and source records attributed to S M Murphy.

At least 37 records · Page 2Linked to original sources

After axotomy, substance P and vasoactive intestinal peptide expression occurs in pilomotor neurons in the rat superior cervical ganglion.

Autonomic sympathetic postganglionic neurons normally express distinct combinations of neuropeptides which are often highly correlated with the projection of the neurons. When sympathetic postganglionic neurons are axotomized, they can express quite different neuropeptides, notably substance P, vasoactive intestinal peptide or galanin. In this study, we have examined rat sympathetic postganglionic neurons in the superior cervical ganglion that project to the skin, the vasculature of the skeletal muscle or to the submandibular salivary gland, and assessed whether the neuropeptides that they express after axotomy depend on which target tissue they previously innervated. In all three populations, around half of the postganglionic neurons expressed galanin after axotomy. In contrast, only skin-projecting neurons showed a significant increase in the number of neurons that expressed substance P (22%) and vasoactive intestinal peptide (17%) following axotomy. Within the skin-projecting neurons, as judged on the basis of cell body size, substance P and vasoactive intestinal peptide were expressed predominantly in pilomotor neurons, but only rarely were the two neuropeptides present in the same nerve cell body. In conclusion, we have demonstrated that three different neuropeptides, which can be induced by axotomy in postganglionic neurons, follow quite different patterns of expression when they are viewed in relation to the function of the postganglionic neurons in the superior cervical ganglion.

Animals↗

Sexual assault and sexually transmitted infections: an updated review.

The purpose of this review is to provide an overview of sexual assault (in adults). In particular, the aim is to emphasize changes regarding medical, legal and management issues since the subject was reviewed in this journal in 1990. However some aspects will not have changed in the last 10 years.

Adolescent↗

Compartmentation and topology of glucosylceramide synthesis.

Evidence is presented supporting a model for glucosylceramide formation on the apoplastic side of the plasma membrane in plants. Glucosylceramide synthase and sterol glucosyltransferase were both localized to the plasma membrane. Whereas sterol glucosylation was sensitive to proteolytic enzymes, ceramide glucosylation was not. These results are consistent with our model in which steryl glucoside is synthesized on the cytosolic side of the membrane and then translocated across the membrane where it donates glucose to ceramide.

Cell Membrane↗

Chemically distinct preganglionic inputs to iris-projecting postganglionic neurons in the rat: A light and electron microscopic study.

Individual autonomic postganglionic neurons are surrounded by pericellular baskets of preganglionic terminals that are easily identifiable with the light microscope. It has been assumed that the target cell of a pericellular basket of preganglionic terminals is the neuron at the centre of the basket. This assumption has enabled the connectivity of preganglionic neurons to be determined at the light microscopic level. However, if the preganglionic terminals in a pericellular basket make synapses with the dendrites of nearby, but functionally different, postganglionic neurons, then the conclusions of light microscopic studies are far less certain. We have used a serial section ultrastructural study to determine the target of the preganglionic pericellular basket in a situation where the apparent target cell is surrounded by neurons of dissimilar function. In the rat superior cervical ganglion, postganglionic neurons projecting to the iris were identified, using retrograde tracers, as single neurons (i.e., not in clusters). We have used immunohistochemistry to show that iris-projecting neurons are surrounded by preganglionic nerve terminals containing calcitonin gene-related peptide (CGRP). We have demonstrated that the pericellular basket of CGRP-immunoreactive preganglionic terminals provides inputs only to the soma at the centre of the basket and not to the dendrites of surrounding neurons. This suggests that, in autonomic ganglia, light microscopic identification of the preganglionic terminal baskets is likely to be a reliable method for identifying the targets of subclasses of preganglionic neurons.

Animals↗

Test of performances strategies: development and preliminary validation of a comprehensive measure of athletes' psychological skills.

We report the initial stages of validation of the 64-item Test of Performance Strategies, a self-report instrument designed to measure the psychological skills and strategies used by athletes in competition and during practice. Data were obtained from a sample of 472 athletes competing across a range of performance standards in a wide variety of sports. Exploratory factor analyses of their responses produced eight competition strategy subscales and eight practice strategy subscales, each consisting of four items. Internal consistencies of the subscales ranged from 0.66 to 0.81 (x = 0.75). Correlations among strategies were examined within and between performance contexts. Subgroups defined by age, sex and current standard of performance in sport differed significantly in their psychological skills and strategies.

Adaptation, Psychological↗

Examination of particulate macroporous hydrogels in an extracorporeal rat haemoperfusion model.

A series of macroporous hydrogels has been synthesized, selected from a range of such materials in which the presence of functional groups has been shown to produce sorbent properties with respect to molecules having clinical significance in the field of liver support. The use of freeze thaw polymerization, together with inverse suspension polymerization in hexane, or in brine, enables macroporous beads ranging in size from 150 to 2000 microm, to be prepared from functional monomers exhibiting a range of chemical functionalities and aqueous solubilities. In order to investigate the behaviour of these rigid porous hydrophilic substrates in haemoperfusion, a rat model was used to explore various aspects of whole blood response. The materials were incorporated into an extracorporeal circuit linking the right carotid artery and left jugular vein of male Sprague-Dawley rats. Erythrocyte, leucocyte and platelet levels were monitored over a 240 min haemoperfusion period. The most significant observation is that, apart from the strongly acidic polyacrylic acid substrate. matrix chemistry has relatively little effect on leucocyte or platelet response. The most important factors appear to be surface area, pore size and surface rugosity, which do produce measurable, but not dramatic differences. This is encouraging for future work, since these variables may be manipulated by polymerization conditions.

Acrylates↗

Large scale implementation of a respiratory therapist-driven protocol for ventilator weaning.

We prospectively investigated the large-scale implementation of a respiratory-therapist-driven protocol (TDP) that included 117 respiratory care practitioners (RCPs) managing 1,067 patients with respiratory failure over 9,048 patient days of mechanical ventilation. During a 12-mo period, we reintroduced a previously validated protocol that included a daily screen (DS) coupled with spontaneous breathing trials (SBTs) and physician prompt, as a TDP without daily input from a physician or "weaning team." With graded, staged educational interventions at 2-mo intervals, RCPs had a 97% completion rate and a 95% correct interpretation rate for the DS. The frequency with which patients who passed the DS underwent SBTs increased throughout the implementation process (p < 0.001). As the year progressed, RCPs more often considered SBTs once patients had passed a DS (p < 0.001), and physicians ordered more SBTs (46 versus 65%, p = 0.004). Overall, SBTs were ordered more often on the medicine than on the surgical services (81 versus 63%, p = 0.001), likely reflecting medical intensivists' prior use of this protocol. Important barriers to protocol compliance were identified through a questionnaire (89 respondents, 76%), and included: Physician unfamiliarity with the protocol, RCP inconsistency in seeking an order for an SBT from the physician, specific reasons cited by the physician for not advancing the patient to a SBT, and lack of stationary unit assignments by RCPs performing the protocol. We conclude that implementation of a validated weaning strategy is feasible as a TDP without daily supervision from a weaning physician or team. RCPs can appropriately perform and interpret DS data more than 95% of the time, but significant barriers to SBTs exist. Through a staged implementation process, using periodic reinforcement of all participants in ventilator management, improved compliance with this large-scale weaning protocol can be achieved.

Clinical Protocols↗

A care package for managing female sexual assault in genitourinary medicine.

This paper describes the development of a designated in-house service for the management of adult female victims of sexual assault within the Department of Genitourinary Medicine (GUM) at St Mary's Hospital, London. This was set up in 1994 as a need was identified by medical, nursing, psychological and health advising staff for an appropriate streamlined service which would provide comprehensive sexual health screening, psychological support and therapy and adequate medico-legal documentation within the limitations of a busy GUM clinic. A structured package of care consisting of medical and psychological protocols with training for relevant staff and a specialist in-house referral clinic was introduced. Fifty-four patients were seen during the first 17 months of the service, the notes of 48 of these were examined and relevant epidemiological and audit data are presented here. By auditing the quality of documentation before and after the introduction of the protocols specifically looking at the appropriateness and comprehensiveness of the sexually transmitted diseases screen and the medico-legal documentation it was clear that the quality of care to these patients was improved. We present here the development of these protocols, a detailed description of the protocols themselves and the method of their implementation.

Adaptation, Psychological↗

A one-year survey of gonococcal infection seen in the genitourinary medicine department of a London district general hospital.

The results of a one-year clinical, epidemiological and microbiological survey of gonococcal infection presenting to the Patrick Clements Clinic (PCC), a London district general hospital (DGH) genitourinary medicine (GUM) clinic, are presented. Clinical and epidemiological patient data were collected by a combination of questionnaire and retrospective case-note review. Microscopy performance within the PCC, outcome of treatment, return for tests of cure and efficacy of contact tracing were assessed. Isolates were tested for susceptibility to penicillin, tetracycline and ciprofloxacin. The study showed the PCC continues to diagnose and treat over 200 cases of gonorrhoea per year. High level resistance to penicillin, tetracycline and ciprofloxacin was documented among the year's isolates and antibiotic resistance was linked to acquisition of gonorrhoea overseas. Despite interviewing 183 patients concerning health advice and contact tracing issues, only 55% of new episodes re-attended for a first test of cure. In addition, only 29% of reported sexual contacts attended GUM clinics for investigation and treatment.

Adolescent↗

Synaptic organisation of lumbar sympathetic ganglia of guinea pigs: serial section ultrastructural analysis of dye-filled sympathetic final motor neurons.

The authors serially sectioned seven dye-filled neuronal somata and more than 1.6 mm of their dendrites from the lumbar sympathetic ganglia of guinea pigs and examined them ultrastructurally to determine the distribution of preganglionic synaptic inputs to their dendrites and cell bodies. Most of the surface of the neurons was covered with Schwann cells. Apposing boutons were rare, with an average density of one axosomatic bouton per 125 microm2 of somatic membrane and one axodendritic bouton per 25 microm of dendrite. Many dendritic segments that were more than 50 microm long completely lacked any apposing boutons. Although the average density of apposing boutons was low, local densities could be high, so that clusters of up to four adjacent boutons occurred on cell bodies and dendrites alike. The spatial arrangement of the apposing boutons for each of the cells examined here was not significantly different from a random distribution. Consequently, the number of apposing boutons observed for any neuron was simply proportional to the amount of neuronal surface sampled in the serial section run. About 50% of boutons directly apposing the neurons lacked any detectable presynaptic specialisations. When they were present, the presynaptic densities had a mean length of about 220 nm, with no difference between boutons that made axosomatic or axodendritic appositions. By applying these data to complete reconstructions of the dendritic trees of dye-filled sympathetic neurons at the light microscopic level, the authors estimated that few neurons in the lumbar sympathetic chain of guinea pigs would receive more than 200 synapses or apposing boutons and that many of them would receive less than 100 synapses. Up to 50% of these boutons would be predicted to make axosomatic contacts. These new observations provide a strong morphological framework for a better understanding of how sympathetic final motor neurons process their preganglionic synaptic inputs.

Animals↗

Synaptic organisation of neuropeptide-containing preganglionic boutons in lumbar sympathetic ganglia of guinea pigs.

Within the lumbar sympathetic ganglia of guinea pigs, the endings of different populations of neuropeptide-containing preganglionic neurons form well-defined pericellular baskets of boutons around target neurons in specific functional pathways. We have used multiple-labelling immunofluorescence, confocal microscopy, and ultrastructural immunocytochemistry to investigate synaptic organisation within pericellular baskets labelled for immunoreactivity to calcitonin gene-related peptide (CGRP), substance P (SP), or the pro-enkephalin-derived peptide, met-enkephalin-arg-gly-leu (MERGL) in relation to their target neurons. Different functional populations of neurons, identified by their neurochemical profile, showed a significant degree of spatial clustering and predicted well the distribution of specific classes of pericellular baskets. Most of the boutons in a basket were completely surrounded by Schwann cell processes and did not form synapses. The synapses that were present were made mostly onto dendrites enclosed by the Schwann cell sheath surrounding the neuron within the basket. These dendrites probably originated from neurochemically similar neighbouring neurons. Nevertheless, some of the boutons in the baskets did form synapses with the cell body or proximal dendrites of the neuron they surrounded. Occasionally, cell bodies received a relatively high number of synapses and close appositions from boutons in a pericellular basket. Synaptic convergence of two immunohistochemically distinct types of preganglionic inputs was found in baskets of SP-immunoreactive or MERGL-immunoreactive, but not CGRP-immunoreactive, boutons. Taken together, our results show that the appearance of pericellular baskets is primarily due to the packing of the target neurons. The grouping of functionally similar classes of neurons with their pathway-specific projections of peptide-containing preganglionic neurons suggests that peptides could exert their effects in relatively well-defined zones within the ganglia.

Animals↗

The mammalian gamma-tubulin complex contains homologues of the yeast spindle pole body components spc97p and spc98p.

gamma-Tubulin is a universal component of microtubule organizing centers where it is believed to play an important role in the nucleation of microtubule polymerization. gamma-Tubulin also exists as part of a cytoplasmic complex whose size and complexity varies in different organisms. To investigate the composition of the cytoplasmic gamma-tubulin complex in mammalian cells, cell lines stably expressing epitope-tagged versions of human gamma-tubulin were made. The epitope-tagged gamma-tubulins expressed in these cells localize to the centrosome and are incorporated into the cytoplasmic gamma-tubulin complex. Immunoprecipitation of this complex identifies at least seven proteins, with calculated molecular weights of 48, 71, 76, 100, 101, 128, and 211 kD. We have identified the 100- and 101-kD components of the gamma-tubulin complex as homologues of the yeast spindle pole body proteins Spc97p and Spc98p, and named the corresponding human proteins hGCP2 and hGCP3. Sequence analysis revealed that these proteins are not only related to their respective homologues, but are also related to each other. GCP2 and GCP3 colocalize with gamma-tubulin at the centrosome, cosediment with gamma-tubulin in sucrose gradients, and coimmunoprecipitate with gamma-tubulin, indicating that they are part of the gamma-tubulin complex. The conservation of a complex involving gamma-tubulin, GCP2, and GCP3 from yeast to mammals suggests that structurally diverse microtubule organizing centers such as the yeast spindle pole body and the animal centrosome share a common molecular mechanism for microtubule nucleation.

3T3 Cells↗

Pre-embedding staining for GAD67 versus postembedding staining for GABA as markers for central GABAergic terminals.

Pre-embedding immunocytochemistry for the active form of glutamate decarboxylase (GAD67) and postembedding staining for gamma-aminobutyric acid (GABA) were compared as markers for central GABAergic terminals in the phrenic motor nucleus, in which phrenic motor neurons had been retrogradely labeled with cholera toxin B-horseradish peroxidase. Nerve terminals with or without GAD67 immunoreactivity were identified in one ultrathin section. GABA was localized with immunogold in an adjacent section after etching and bleaching. GABA labeling density was assessed over 519 GAD67-positive and GAD67-negative nerve terminals in the phrenic motor nucleus. Frequency histograms showed that statistically higher densities of gold particles occurred over most GAD67-positive terminals. However, some GAD67-negative terminals also showed high densities of gold particles, and some GAD67-positive terminals showed low densities. Preabsorption of the anti-GABA antibody with a GABA-protein conjugate, but not with other amino acid-protein conjugates, significantly reduced gold labeling over both GAD67-positive and GAD67-negative terminals. These results show that the presence of GAD67 immunoreactivity correlates strongly with high densities of immunogold labeling for GABA in nerve terminals in the phrenic motor nucleus. Preabsorption controls indicate that authentic GABA was localized in the postembedding labeling procedure. Only a small proportion of intensely GABA-immunoreactive terminals lack GAD67, suggesting that both GAD67 and GABA are reliable markers of GABAergic nerve terminals.

Animals↗

Vesicle shape and amino acids in synaptic inputs to phrenic motoneurons: do all inputs contain either glutamate or GABA?

Varicosities that made synapses or direct contacts with retrogradely labelled rat phrenic motoneurons were examined for their content of immunoreactivity for either glutamate or glutamate decarboxylase, the enzyme involved in synthesis of gamma-aminobutyric acid (GABA). Phrenic motoneurons were identified by retrograde tracing from the diaphragm with cholera toxin B subunit conjugated to horseradish peroxidase. Cell bodies and medium-sized to large dendrites were labelled. Preembedding immunocytochemistry identified glutamate decarboxylase-immunoreactive nerve fibres; glutamate-immunoreactive nerve terminals were identified using postembedding immunogold labelling of ultrathin sections. The presence of glutamate- or glutamate decarboxylase immunoreactivity in nerve terminals was correlated with the morphology of the synaptic vesicles. Two major classes of nerve terminals were identified. Nerve terminals with round (presumably spherical) synaptic vesicles (S terminals) comprised 55% of synapses and contacts on phrenic motoneuron somata and 58% of synapses and direct contacts with dendrites. Nerve terminals with flattened synaptic vesicles (F terminals) comprised 42% of synapses direct contacts with somata and 41% of synapses and direct contacts with dendrites. Analysis of immunogold-labelled sections showed that S terminals contained statistically higher levels of glutamate immunoreactivity than F terminals. At the light microscope level, many glutamate decarboxylase-immunoreactive nerve terminals surrounded retrogradely labelled motoneurons. Varicosities with glutamate decarboxylase immunoreactivity made 33% of all synapses and direct contacts on somata, and 33% of synapses and direct contacts with dendrites of the retrogradely labelled phrenic motoneurons. Flattened synaptic vesicles were present in those glutamate decarboxylase-immunoreactive nerve terminals in which synaptic vesicle morphology could be judged. An additional 10% of all nerve terminals were of the F type, but were not glutamate decarboxylase-immunoreactive. Three percent of terminals on somata and 1% of nerve terminals on dendrites could not be classified as S or F types. These findings suggest that more than 90% of all inputs to phrenic motoneuron cell bodies and proximal dendrites could contain either GABA or glutamate. Some of these glutamatergic and GABAergic nerve fibres undoubtedly represent the source of inspiratory drive to, or expiratory inhibition of, phrenic motoneurons.

Animals↗

Cytoskeleton: microtubule nucleation takes shape.

The centrosomal protein gamma-tubulin is part of a ring-shaped complex that can induce microtubule polymerization. This complex may explain how the centrosome nucleates microtubule polymerization, and thereby organizes the microtubule cytoskeleton.

Animals↗

Cognitive behavioral strategies in athletic performance enhancement.

While we might debate the role of sport in our culture, its influence is certainly pervasive. Each day millions of Americans engage in some form of competition, training, or physical exercise. Such popularity and the value our culture places on competition have made sport a valid area of psychological inquiry. Within the cognitive behavioral model, sport psychology and, specifically, athletic performance enhancement have experienced vigorous growth over the past two decades. Behavior change strategies familiar to most cognitive behaviorists form the core of virtually all athletic performance enhancement interventions. Goal setting, imagery or mental rehearsal, relaxation training, stress management, self-monitoring, self-instruction, cognitive restructuring, and modeling interventions dominate this literature. Our examination of these performance enhancement programs, both through a qualitative review and the Whelan et al. (1989) meta-analysis, supports the efficacy of cognitive behavioral interventions for the enhancement of sport performance. First, the average effect size across the empirical literature indicates that these interventions are reliably effective. Furthermore, this positive result is observed across variations in treatment conditions, control conditions, and across different types of dependent measures. Evidence on goal setting, imagery, arousal management, cognitive self-regulation, and packaged programs specifically support the behavior change efficacy of these interventions. These findings are encouraging, but much work needs to be done. Few investigators cited in this review attend to crucial internal and external validity issues. Attention to treatment integrity, including training of behavior change agents, verification of intervention implementation, and verification of reception of the treatment, is sorely lacking. Psychological skill development and its relationship to performance improvements are rarely checked. Now that cognitive behavioral interventions appear to be reliably effective at posttreatment, we must have meaningful evaluation of maintenance of psychological skill and performance changes. Six-month, 12-month, and longer follow-up evaluations are necessary. We must also begin more detailed evaluations of these effective interventions.(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗