Search PubMed⌕ Search

Biomedical subjects

M Harvey

Publications and source records attributed to M Harvey.

At least 55 records · Page 3Linked to original sources

On the mechanism of sodium-proton exchange in crayfish.

In salt depleted crayfish net sodium and proton fluxes were coupled 1:1 as required by the frog skin-turtle bladder model. In addition, three proton pump inhibitors produced equal reductions of both fluxes. It is concluded that the model operates in these animals. Net Na+ and H+ fluxes were very small in tap water adapted animals, but regression analysis clearly showed that they were coupled, though perhaps not 1:1. Proton pump inhibitors, at concentrations that suppressed fluxes in salt-depleted crayfish, had no measureable effect on proton movement in tap water-adapted animals. Two of them (dicyclocarbodiimide and N-ethyl maleimide), caused a small reduction in Na+ influx without affecting proton efflux. These experiments provide no support for operation of the frog-turtle system in adult crayfish adapted to tap water. A 2Na+-H+ exchanger is considered from an energetic point of view. Such a system might be able to couple Na+ and H+ fluxes in dilute, near neutral solutions ([Na+] approximately 1-2 mM; pH 7).

Animals↗

Education for a new role: a review of neonatal nurse practitioner programmes.

A comparison was made of the different educational programmes developed to train Neonatal Nurse Practitioners (ENB A19) in the UK. The structure and character of the programmes were examined in relation to course aims and philosophies, learning outcomes, content, teaching strategies and methods of assessment. Documentation provided by course leaders included hand-books, timetables, teaching staff details and documents concerning supervision and assessment. When viewed closely there are differences between the programmes that are evident in design and curriculum content and which present a quality assurance issue to the institutions validating and running these programmes. The issue of parity and standards is also a critical one for those supporting the development regionally and nationally. Viewed within the broader perspective of post-registration nurse education, these relatively new programmes could be regarded as experiments in which professionals, as teachers and learners, are trying to address the changing boundaries of expertise and professional identities. It is suggested that the nurse practitioner programmes developed for neonatal care could provide a model for similar programmes in other specialties and argued that the experience gained in planning and running these courses could contribute positively to the development of other comparable educational programmes for established and experienced nurses.

Curriculum↗

Impaired fast-spiking, suppressed cortical inhibition, and increased susceptibility to seizures in mice lacking Kv3.2 K+ channel proteins.

Voltage-gated K(+) channels of the Kv3 subfamily have unusual electrophysiological properties, including activation at very depolarized voltages (positive to -10 mV) and very fast deactivation rates, suggesting special roles in neuronal excitability. In the brain, Kv3 channels are prominently expressed in select neuronal populations, which include fast-spiking (FS) GABAergic interneurons of the neocortex, hippocampus, and caudate, as well as other high-frequency firing neurons. Although evidence points to a key role in high-frequency firing, a definitive understanding of the function of these channels has been hampered by a lack of selective pharmacological tools. We therefore generated mouse lines in which one of the Kv3 genes, Kv3.2, was disrupted by gene-targeting methods. Whole-cell electrophysiological recording showed that the ability to fire spikes at high frequencies was impaired in immunocytochemically identified FS interneurons of deep cortical layers (5-6) in which Kv3.2 proteins are normally prominent. No such impairment was found for FS neurons of superficial layers (2-4) in which Kv3.2 proteins are normally only weakly expressed. These data directly support the hypothesis that Kv3 channels are necessary for high-frequency firing. Moreover, we found that Kv3.2 -/- mice showed specific alterations in their cortical EEG patterns and an increased susceptibility to epileptic seizures consistent with an impairment of cortical inhibitory mechanisms. This implies that, rather than producing hyperexcitability of the inhibitory interneurons, Kv3.2 channel elimination suppresses their activity. These data suggest that normal cortical operations depend on the ability of inhibitory interneurons to generate high-frequency firing.

Action Potentials↗

A mesoscale phytoplankton bloom in the polar Southern Ocean stimulated by iron fertilization.

Changes in iron supply to oceanic plankton are thought to have a significant effect on concentrations of atmospheric carbon dioxide by altering rates of carbon sequestration, a theory known as the 'iron hypothesis'. For this reason, it is important to understand the response of pelagic biota to increased iron supply. Here we report the results of a mesoscale iron fertilization experiment in the polar Southern Ocean, where the potential to sequester iron-elevated algal carbon is probably greatest. Increased iron supply led to elevated phytoplankton biomass and rates of photosynthesis in surface waters, causing a large drawdown of carbon dioxide and macronutrients, and elevated dimethyl sulphide levels after 13 days. This drawdown was mostly due to the proliferation of diatom stocks. But downward export of biogenic carbon was not increased. Moreover, satellite observations of this massive bloom 30 days later, suggest that a sufficient proportion of the added iron was retained in surface waters. Our findings demonstrate that iron supply controls phytoplankton growth and community composition during summer in these polar Southern Ocean waters, but the fate of algal carbon remains unknown and depends on the interplay between the processes controlling export, remineralisation and timescales of water mass subduction.

Atmosphere↗

Refixation frequency and memory mechanisms in visual search.

Visual search-looking for a target object in the presence of a number of distractor items-is an everyday activity for humans (for example, finding the car in a busy car park) and animals (for example, foraging for food). Our understanding of visual search has been enriched by an interdisciplinary effort using a wide range of research techniques including behavioural studies in humans [1], single-cell electrophysiology [2], transcranial magnetic stimulation [3], event-related potentials [4] and studies of patients with focal brain injury [5]. A central question is what kind of information controls the search process. Visual search is typically accompanied by a series of eye movements, and investigating the nature and location of fixations helps to identify the kind of information that might control the search process. It has already been demonstrated that objects are fixated if they are visually similar to the target [6]. Also, if an item has been fixated, it is less likely to be returned to on the subsequent saccade. This automatic process is referred to as inhibition of return (IOR [7,8]). Here, we investigated the role of memory for which items had been fixated previously. We found that, during search, subjects often refixated items that had been previously fixated. Although there were fewer return saccades than would be expected by chance, the number of refixations indicated limited functional memory, indeed the memory effects that were present may primarily be a result of IOR.

Humans↗

The expression of the ADAMs proteases in prostate cancer cell lines and their regulation by dihydrotestosterone.

The ADAMs are a multi-functional gene family, some of which have been shown to play a role in diverse biological processes such as fertilization, myogenesis, neurogenesis and the activation of growth factors/immune regulators such as TNF-alpha. So-named because they possess both A Disintegrin And Metalloprotease domain, the ADAMs have potential implications for the metastasis of human tumour cells via cell adhesion and protease activities. However, no studies have yet comprehensively examined the expression or regulation of ADAMs in solid tumours. Therefore, the aim of this study was to examine the expression of the ADAMs in human prostate cancer cell lines and to examine their possible regulation by androgen, a primary hormonal regulator of prostate cancer cell proliferation and metastasis. Applying RT-PCR, ADAM-9, -10, -11, -15 and -17 mRNA expression was found in the androgen-dependent prostate cancer cell lines, LNCaP and ALVA-41 and the androgen-independent cell lines, DU-145 and PC-3. Northern blotting of LNCaP cell total RNA revealed transcripts for ADAM-9 (3.8 kb), ADAM-10 (4.4, 3.2 and 0.54 kb), ADAM-15 (3 kb) and ADAM-17 (4 and 2.6 kb). ADAM-11 transcript was not detected by Northern blotting possibly due to low levels of ADAM-11 mRNA expression. This is the first report of ADAM expression in prostate cancer cell lines. Since androgens are implicated in prostate cancer cell growth and maintenance, the regulation of ADAMs by dihydrotestosterone (DHT) was investigated in the androgen-dependent cell line LNCaP. It was shown by quantitative RT-PCR using continuous fluorescence monitoring that ADAM-10 mRNA expression was regulated in a bell shaped, dose-dependent manner by DHT. Maximum stimulation was observed at 1.0 nM DHT (5-fold significant increase). For ADAM-9 mRNA, a significant upregulation was found at 1.0 and 10 nM (1.5-1.7-fold increase). In contrast, ADAM-17 mRNA, was significantly inhibited at 0.1 and 1.0 nM (1.7-fold decrease). This is the first report, to our knowledge, illustrating hormonal regulation of ADAM mRNA. The novel data described here also provide a strong stimulus to the development of specific quantitative and functional assays for particular ADAMs. These assays, which are not yet available, are required to enable subsequent investigation, both in vitro and in vivo, of the specific roles of each ADAM in prostate cancer cell proliferation, cell motility and invasion.

Blotting, Northern↗

Experiments with longitudinally polarized electrons in a storage ring using a siberian snake

We report on first measurements with polarized electrons stored in a medium-energy ring and with a polarized internal target. Polarized electrons were injected at 442 MeV (653 MeV), and a partial (full) Siberian snake was employed to preserve the polarization. Longitudinal polarization at the interaction point and polarization lifetime of the stored electrons were determined with laser backscattering. Spin observables were measured for electrodisintegration of polarized 3He, with simultaneous detection of scattered electrons, protons, neutrons, deuterons, and 3He nuclei, over a large phase space.

Journal Article↗

Effects of visible and invisible cueing procedures on perceptual judgments in young and elderly subjects.

Healthy subjects were tested in two experiments to examine the effects of lateralized cues on line bisection and landmark judgments. The studies were designed to investigate whether bisection and landmark biases induced by cueing are simply a result of a direct perceptual lengthening of the cued part of the line caused by the fact that the cue is visible, thus creating a composite 'line plus cue' or whether cueing induces an attentional bias operating on judgments of spatial extent by either reducing the magnitude of the parts of the stimulus receiving 'less' attention or magnifying those parts receiving 'more'. Lateralized cues were either visible letter cues or invisible marks drawn with a leadless pencil either by the subject him/herself (Experiment 1) or the experimenter (Experiment 2). Comparable to a previous study (Mattingley, Pierson, Bradshaw, Phillips and Bradshaw, 1993, Neuropsychologia, 31, 1201-1215), the first experiment showed that only visible cues affected line bisection and landmark judgments thus favouring the perceptual explanation. The second study, however, revealed bisection and judgment biases for invisible as well as visible cues with the attended part of the line appearing subjectively longer. These results indicate that attentional modulations can increase the salience of a line in a similar vein to physical changes. It seems likely that the requirement of a motor response in Experiment 1 cancelled out all attentional properties supposedly induced by placing that invisible cue.

Adult↗

Reaching movements may reveal the distorted topography of spatial representations after neglect.

It has been proposed that patients with spatial neglect fail to respond appropriately toward stimuli opposite their brain lesion because they have an impairment of directing attention. However, a disorder of 'intention' - or movement initiation - has also been demonstrated in this condition. Recently, the paths of neglect patients' reaches have been shown to be abnormally curved, but it is unclear whether this impairment is visual or motor. Here, we show for the first time that reaches to and from identical positions executed by three patients recovering from neglect are significantly more curved to visually defined targets compared to when the same targets are defined proprioceptively. These findings indicate that abnormal hand paths in neglect result from an impairment in the visual representation of space used to guide reaches but without any general failure of spatial representation of target position. Furthermore, the curved hand paths reveal how the topography of that representation is distorted in spatial neglect.

Aged↗

Heritability of elevated factor VIII antigen levels in factor V Leiden families with thrombophilia.

Factor VIII activity (factor VIII:C) and factor VIII antigen (factor VIII:Ag) levels above 150 IU/dl are associated with a five- to sixfold increased risk of venous thrombosis compared with levels < 100 IU/dl. These high levels are present in 25% of patients with a first episode of deep-vein thrombosis and in 11% of healthy controls. von Willebrand factor (VWF) and blood group are important determinants of the factor VIII level in plasma and therefore contribute to thrombotic risk, while factor VIII appears to be the final effector. Previously, we found familial clustering of factor VIII:C levels in women, which remained after adjustment for VWF and blood group. In the present study, we analysed the familial influence on factor VIII:Ag levels exceeding 150 IU/dl in 12 large families with thrombophilia in which high factor VIII:Ag levels contribute to thrombotic risk. As expected, blood group was a main determinant of the plasma factor VIII level: 58 relatives (32%) had factor VIII levels above 150 IU/dl and 50 (86%) of these had blood group non-O. After adjustment for blood group and age, we found an association between factor VIII:Ag levels in sister pairs (0.35, P = 0.003), brother pairs (0.35, P = 0.003), brother-sister pairs (0.35, P < 0.001) and in mother-son pairs (0.45, P = 0.02), but not in father-daughter or father-son pairs. The familial aggregation test was strongly positive for factor VIII:Ag levels (P < 0.001) and remained so after adjustment for the influence of blood group. We conclude that high factor VIII:Ag levels are a highly prevalent risk factor for venous thrombosis and contribute to risk in families with thrombophilia, and that these high levels are likely to be genetically determined by factors other than just blood group.

Adolescent↗

The coordination of bimanual prehension movements in a centrally deafferented patient.

Many everyday tasks require that we use our hands co-operatively, for example, when unscrewing a jar. For tasks where both hands are required to perform the same action, a common motor programme can be used. However, where each hand needs to perform a different action, some degree of independent control of each hand is required. We examined the coordination of bimanual movement kinematics in a female patient recovering from a cerebrovascular accident involving anterior regions of the parietal lobe of the right hemisphere, which resulted in a dense hemianaesthesia of her left arm. Our results indicate that unimanual movements executed by our patient using her non-sensate hand are relatively unimpaired. In contrast, during bimanual movements, reaches executed by our patient using her non-sensate hand show gross directional errors and spatiotemporal irregularities, including the inappropriate coupling of movement velocities. These data are discussed with reference to the role played by limb proprioception in the planning and control of prehension movements.

Aged↗

catena-Poly

Explore the source record for details and available documents.

Journal Article↗

Relationships between adolescents' attachment styles and family functioning.

This study examined the relationship between university students' perceptions of their familial attachment and the manner in which their families cope with life's difficulties. It was hypothesized that individuals with high levels of secure attachment would perceive their families as using more active coping strategies (e.g., mobilizing the family to deal with a problem and making efforts to acquire social support). The results supported this hypothesis. Further, individuals with high levels of anxious/ambivalent attachment perceived their families as using a passive appraisal coping strategy, possibly because of a desire to avoid confrontation for fear of disturbing family accord. The findings are discussed in terms of individuals' dispositional coping styles formed as a function of type of familial attachment, as well as situational factors that might serve to mitigate the use of their basic coping strategies.

Adolescent↗

Antitransferrin receptor antibody-RNase fusion protein expressed in the mammary gland of transgenic mice.

Antibodies fused to human enzymes offer an alternative to specifically targeting tumors with antibodies linked to plant or bacterial toxins. Since large amounts of these reagents can be administered without eliciting non-specific toxicities, efficient methods of production are needed. The goal of this work was to express a complex immunoenzyme fusion protein (immunotoxin) in the mammary gland of transgenic mice. A chimeric mouse/human antibody directed against the human transferrin receptor (E6) was fused at its CH2 domain to the gene for a human angiogenic ribonuclease, angiogenin (Ang). It was expressed in the mammary gland of mice and secreted into mouse milk. Expression levels in milk were approximately 0.8 g/l. The chimeric protein retained antibody binding activity and protein synthesis inhibitory activity equivalent to that of free Ang. It was specifically cytotoxic to human tumor cells in vitro.

Animals↗

Effects of dopamine and aminophylline on contrast-induced acute renal failure after coronary angioplasty in patients with preexisting renal insufficiency.

In phase 1 of this study, 60 patients undergoing coronary angioplasty were randomized to receive saline, dopamine, or aminophylline; the overall incidence of contrast-induced renal failure was 38%, without difference among the 3 groups. In phase 2 of this study, 72 patients with established contrast-induced renal failure were randomized to receive saline or dopamine; dopamine had a deleterious effect on the severity of renal failure, prolonging the course.

Acute Kidney Injury↗

Residual perceptual distortion in 'recovered' hemispatial neglect.

In most neglect patients, line bisection errors become smaller on repeated tests over the months following the lesion. We have tried to determine in two typical patients whether this is because of a real reduction in the perceptual distortions that appear to underlie line bisection errors in neglect, or whether it reflects a learned behavioural strategy to counteract those perceptual biases. We tested the patients on two occasions (2 and 12 months post-stroke), on line bisection and also on the 'Landmark' task. The data indicated that at the first testing session both patients showed strong 'perceptual' neglect, making large rightward errors in the standard bisection task and uniformly leftward pointing in the Landmark task. On the second occasion, as expected, both patients showed a marked recovery when tested with the line bisection task, making only very small errors. In contrast, their landmark performance was still markedly biased in the same direction as before. These findings suggest that despite their apparent recovery on the bisection task, both patients still experience some form of perceptual distortion of horizontal lines. It is suggested that the Landmark task may provide a sensitive means for identifying real recovery of the underlying perceptual deficit.

Adaptation, Psychological↗

Factor-based prototypes of the Millon Adolescent Clinical Inventory in adolescents referred for residential treatment.

Although well received by the clinical community, there have been few published reports on the use of the Millon Adolescent Clinical Inventory (MACI). There have been no published studies describing use of the MACI with a residential treatment population. In addition, there have been no published reports investigating the factor structure of the MACI. A principal components factor analysis was performed for all MACI scales and sex for 251 adolescents referred to a residential treatment facility. Five factors were found accounting for 77.4% of the variance. Factor-based prototypes were generated from these results: Factor 1 defines a prototype for Defiant Externalizers, Factor 2 for Intrapunitive Ambivalent Types, Factor 3 for Inadequate Avoidants, Factor 4 for Self-Deprecating Depressives, and Factor 5 for Reactive Abused Types. Prototype descriptions and clinical vignettes are included for each of the 5 factor-based prototypes. These results are consistent with our clinical experience with this population. Prototype analysis may offer a powerful way of enhancing the utility of the MACI in clinical settings.

Adolescent↗