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Biomedical subjects

M J Wright

Publications and source records attributed to M J Wright.

At least 55 records · Page 3Linked to original sources

beta-Galactosidase staining following intracoronary infusion of cationic liposomes in the in vivo rabbit heart is produced by microinfarction rather than effective gene transfer: a cautionary tale.

The myocardium is a potential target for the expression of exogenous genes to treat inherited and acquired diseases. Although adenovirus-mediated gene transfer has resulted in high-level gene transfer in vivo via direct intramyocardial injection and via a percutaneous intra-arterial route, the time-course of gene expression is limited by host immune responses. It was the aim of this study to test whether cationic liposome-mediated gene transfer, which does not suffer from the aforementioned problems, was feasible in the adult rabbit myocardium via a percutaneous transluminal approach. Doses of plasmid DNA encoding lacZ from 200-800 micrograms complexed to cationic liposomes resulted in X-gal conversion at day 3 with associated myocardial damage. We hypothesised that the damage was associated with macro-aggregates of cationic liposomes-DNA occluding the microcirculation. When such aggregates were excluded no X-gal conversion was seen in vivo. In order to show that X-gal conversion occurs in areas of infarction in the myocardium we caused closed chest infarction by deploying a platinum micro-embolisation coil in the circumflex coronary artery. At day 3 X-gal conversion was observed in the territory supplied by the occluded artery. Thus, microinfarction causes the false positive appearance of gene transfer when using a lacZ reporter gene.

Animals↗

Coherence and motion transparency in rigid and nonrigid plaids.

Under a wide range of conditions, stimuli composed of two superimposed grating components with unequal rotation velocities (differing in sign and/or magnitude) gave a striking percept of a single, coherent, nonrigidly deforming plaid surface. Conversely, component angular velocities of the same sign and magnitude yielded rigidly rotating plaids. Rigidity and motion coherence were shown to be independent percepts, and coherent plaids were categorised unambiguously as rigid or nonrigid. Coherence and motion transparency were found to depend upon the relative orientation of components, and polar plots showed two lobes of high coherence for narrow intercomponent angles. There was a slight tendency for plaids with unequal component rotations to appear less coherent, but this was nonsignificant, once the effect of intercomponent angle was taken into account. Changes in the relative spatial frequency of components, relative contrast of components, and repeated presentation produced equivalent effects on coherence for rigid and nonrigid types of plaid motion. Manipulation of the terminators in the display by making the aperture diameters for the two component gratings unequal reduced coherence and increased transparency. The effect was the same for rigid and nonrigid plaids. Coherence in rigid and nonrigid plaids thus depends primarily on local processes and there is no strong interaction between rigidity and coherence.

Humans↗

Firearm injury in Orleans parish: a 24-month perspective.

This study is a retrospective review of all gunshot wounds treated at Charity Hospital, the Orleans Parish designated trauma center, for the 24-month period from November 1993 to November 1995. Its purpose was to define the magnitude of firearm injury in the parish and the impact on the health care system. One-thousand-six-hundred-sixty-nine gunshot wounds were analyzed. Most involved African-American males. Twenty percent were fatal. Two-thousand-forty-three emergent operations were performed. Ten percent of surviving patients had some permanent disability, 6% required institutional care. In 760 patients, initial hospital charges totaled $5,153,516. Extrapolation of these figures to the entire group yields an initial hospital cost of $11,317,392. Transport by the "911" system and in-house trauma team activation were required in most patients. In summary, firearm injury poses a serious economic problem and is a substantial drain on health care providers and their resources.

Adolescent↗

A biologically plausible model of early visual motion processing. I: theory and implementation.

A model of local image encoding is described which explicitly incorporates quantitative data about the number density, bandwidth and receptive field organisation of neurons involved in motion detection. The model solves the problem of extracting local velocity on the basis of inputs tuned to spatiotemporal frequency and sensitive to contrast. The spatiotemporally tuned, opponent motion filters are followed by a compressive non-linearity and comprise a first stage. The inter-stage signals are interpreted as those from single neurons and the second stage is modelled as a neural-network layer. The second stage uses semilinear units and models the effect of lateral, on-centre off-surround, intra-layer connections. Characterisation of the first stage leads to a clarification of the concept of the psychophysical 'channel' and its relation to physiological data. The quantitative parametrisation of the model allows the simulation of several psychophysical phenomena which are reported in a companion paper.

Fourier Analysis↗

A biologically plausible model of early visual motion processing. II: psychophysical application.

We test the model of early visual processing introduced in the companion paper by simulating a range of psychophysical phenomena. We present new data concerning our ability to discriminate the speed of drifting gratings when spatiotemporally apertured in a variety of ways. We shall investigate the role played by the aperture in modifying the grating's behaviour from its idealisation as a pure Fourier component and show that this is not negligible. Other phenomena which we simulate and explain relate to the way perceived velocity is influenced by contrast and spatial frequency. Many of our explanations are couched in terms of the relative number of cells occurring within each locale of the Fourier domain. This use of the cell density map is a unifying concept and avoids the necessity for a range of separate mechanisms. We argue that a neurophysiologically detailed model is necessary in order to explain psychophysical data (Weber fractions) which vary over less than an order of magnitude, and small deviations from veridical encoding of velocity.

Artifacts↗

A model for the spatial integration and differentiation of velocity signals.

We present a model of optic flow processing which is able to reconcile the integrative, cooperative phenomena of motion capture and coherence with the differentiation of velocity signals in motion segmentation and transparency. The model uses a Markov random field to compute the behaviour of coextensive topographic neural maps of retinotopy and velocity. We have used the model to simulate the psychophysics of motion coherence, motion capture and transparency. Further, it exhibits motion segmentation without extra postulates. The model is robust and able to display all types of motion percept with the same parameter set.

Humans↗

Myocardial protection after monophosphoryl lipid A: studies of delayed anti-ischaemic properties in rabbit heart.

1. Monophosphoryl lipid A (MLA) is a non-pyrogenic derivative of Salmonella lipopolysaccharide. Administration of this agent at high doses to rats and at low doses to dogs was previously shown to confer marked protection against ischaemia-reperfusion 24 h later, although the cellular mechanisms of this delayed protection are obscure. We hypothesized that MLA pretreatment causes the induction of the 70 kDa cytoprotective stress protein HSP70i in the myocardium. If this were the case, protection against ischaemia-reperfusion injury would be observed both in vitro and in vivo. 2. Rabbits were pretreated with MLA 0.035 mg kg-1, i.v. or vehicle solution. For the in vitro study, hearts were isolated 24 h later and Langendorff-perfused with Krebs-Henseleit buffer at 37 degrees C. Global ischaemia was induced for 20 min followed by 120 min reperfusion. Recovery of post-ischaemic left ventricular function and lactate dehydrogenase efflux was similar in MLA and vehicle pretreated hearts and there was no significant difference in the percentage of infarction of the left ventricle determined by triphenyltetrazolium staining (MLA 22.4 +/- 5.2%, vehicle 24.8 +/- 5.1%). 3. When 30 min regional ischaemia and 120 min reperfusion was instituted in pentobarbitone-anaesthetized rabbits 24 h after pretreatment with MLA or vehicle, the percentage infarction within the risk zone was reduced from 42.6 +/- 5.7% in vehicle pretreated animals to 19.6 +/- 4.4% in MLA pretreated animals (P < 0.01). 4. Determination of myocardial HSP70i content by Western blot analysis showed that MLA treatment did not increase HSP70i immunoreactivity. 5. We conclude that MLA at this dose confers protection only against ischaemia-reperfusion injury in vivo and that this protection is not related to induction of HSP70i. Because protection was observed only in vivo it seems possible that the delayed protection conferred by MLA is mediated by effects on humoral or blood-borne factors.

Adjuvants, Immunologic↗

Natural history of trisomy 18.

It has been suggested that survival in babies with trisomy 18 may be better than previously recognised, and that cardiac surgery may be justified. A population based study spanning seven years in one English health region is presented. The fetal prevalence at 18 weeks was 1 in 4274 and birth prevalence 1 in 8333 live births. Trisomy 18 was detected antenatally in 43% of cases, but almost 90% of those born without a diagnosis were known to be growth retarded in utero. More than 50% of liveborn infants were delivered by caesarean section. The median survival of those born alive was 3 days with no babies living longer than one year. Cardiac malformations were not universal but were present in more than 87% of those for whom there were data. However, in only three cases were cardiac problems implicated in the death of the infants. Cardiac surgery is not likely to improve the survival of infants with trisomy 18 and at present cannot be justified. The most common mode of death was central apnoea.

Adult↗