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Biomedical subjects

J A King

Publications and source records attributed to J A King.

At least 19 recordsLinked to original sources

Proton radiography of a laser-driven implosion.

Protons accelerated by a picosecond laser pulse have been used to radiograph a 500 microm diameter capsule, imploded with 300 J of laser light in 6 symmetrically incident beams of wavelength 1.054 microm and pulse length 1 ns. Point projection proton backlighting was used to characterize the density gradients at discrete times through the implosion. Asymmetries were diagnosed both during the early and stagnation stages of the implosion. Comparison with analytic scattering theory and simple Monte Carlo simulations were consistent with a 3+/-1 g/cm3 core with diameter 85+/-10 microm. Scaling simulations show that protons>50 MeV are required to diagnose asymmetry in ignition scale conditions.

Journal Article↗

Fast-electron transport and heating of solid targets in high-intensity laser interactions measured by K alpha fluorescence.

We present experimental results on fast-electron energy deposition into solid targets in ultrahigh intensity laser-matter interaction. X-ray K alpha emission spectroscopy with absolute photon counting served to diagnose fast-electron propagation in multilayered targets. Target heating was measured from ionization-shifted K alpha emission. Data show a 200 microm fast-electron range in solid Al. The relative intensities of spectrally shifted Al K alpha lines imply a mean temperature of a few tens of eV up to a 100 microm depth. Experimental results suggest refluxing of the electron beam at target rear side. They were compared with the predictions of both a collisional Monte Carlo and a collisional-electromagnetic, particle-fluid transport code. The validity of the code modeling of heating in such highly transient conditions is discussed.

Journal Article↗

Infectious pancreatic necrosis virus in Atlantic salmon, Salmo salar L., post-smolts in the Shetland Isles, Scotland: virus identification, histopathology, immunohistochemistry and genetic comparison with Scottish mainland isolates.

During mid-June 1999 peak mortalities of 11% of the total stock per week were seen at a sea cage site of Atlantic salmon, Salmo salar L., post-smolts in the Shetland Isles, Scotland. Virus was isolated on chinook salmon embryo (CHSE) cells in a standard diagnostic test and infectious pancreatic necrosis virus (IPNV) identified by enzyme-linked immunosorbent assay. IPNV was confirmed as serogroup A by a cell immunofluorescent antibody test using the cross-reactive monoclonal antibody AS-1. Four weeks after the main outbreak, virus titres in surviving moribund fish were assayed at >10(10) TCID50 g(-1) kidney. Histopathology of moribund fish was characterized by pancreatic acinar cell necrosis and a marked catarrhal enteritis of the intestinal mucosa. In the liver, necrosis, leucocytic infiltration and a generalized cell vacuolation were noted. IPNV-specific immunostaining was demonstrated in pancreas, liver, heart, gill and kidney tissue. The nucleotide sequence of the coding region of segment A was determined from the Shetland isolate. A 1180 bp fragment of the VP2 gene of this isolate was compared with a 1979 reference isolate from mainland Scottish Atlantic salmon, La/79 and another more recent mainland isolate, 432/00. Both A2 isolates were derived from carrier fish without signs of IPN and serotyped by a plaque neutralization test. The Shetland isolate shows a different nucleotide and amino acid sequence compared with the two isolates from carrier fish. These latter isolates showed identical amino acid sequences in the fragment examined, despite the 21 years separating the isolations. Sequence comparisons with other A2 (Sp) isolates on the database confirm all three Scottish isolates are A2 (Sp).

Animals↗

Comparative susceptibility of turbot Scophthalmus maximus to different genotypes of viral haemorrhagic septicaemia virus.

Viral haemorrhagic septicaemia (VHS) disease has exerted a significant impact on the development of turbot aquaculture in the British Isles. The source of such outbreaks is believed to be naturally occurring marine isolates of viral haemorrhagic septicaemia virus (VHSV), which are endemic in the marine environment of Northern Europe. Genetic studies have classified these marine VHSV isolates into genotypes based on their geographic rather than host-species origin. This study set out to explore the hypothesis that susceptibility of turbot to VHSV might be genotype specific. Immersion infection of turbot with a range of isolates, selected according to genotype, identified significant differences between susceptibility and genotype. Viruses belonging to Genotypes Ib (Baltic marine isolates) and III (North Sea/E. Atlantic marine isolates) caused significantly higher mortality than isolates from Genotypes Ia (isolates associated with rainbow trout aquaculture) and II (Baltic marine isolates). This study serves to highlight the importance of thoroughly investigating the susceptibility of any given species to the range of pathogens to which they might be exposed prior to considering them resistant to any disease. Furthermore, it highlights different risk factors that might be associated with turbot aquaculture undertaken in different environments. Finally, an increased knowledge of the relative virulence of different isolates in turbot will assist in understanding virulence determinants, which could lead to advances in disease control.

Animals↗

Anterior prefrontal involvement in episodic retrieval reflects contextual interference.

Different patterns of prefrontal activation are commonly found in studies of episodic and source memory (typically anterior and lateral) compared to those found in studies of autobiographical memory (typically ventromedial). We investigated a proposal that the former pattern reflects contextual interference when retrieving events that occurred in similar contexts. We used virtual reality to simulate contextually varied life-like events, in which subjects received distinct objects from a number of people in a number of locations. We compared fMRI data from two experiments in which the number of events per context varied. The first experiment (Burgess, N., Maguire, E.A., Spiers, H.J., and O'Keefe, J. 2001. A temporoparietal and prefrontal network for retrieving the spatial context of lifelike events. Neuroimage 14, 439-453) involved 16 objects received from one of two people in one of two locations. The second experiment involved 20 objects, each received from a different person in a different location. The first experiment showed extensive bilateral activation of anterior and lateral prefrontal cortex, as well as a medial temporal and parietal network characteristic of both autobiographical and episodic memory. In the second study, the prefrontal activations were largely absent, while the medial parietal and temporal activations remained, and a ventromedial prefrontal area was additionally activated. Direct comparisons revealed large areas of significantly reduced activation in BA10, with lesser reductions in lateral prefrontal regions. We suggest that involvement of these prefrontal regains in episodic and source memory reflects the use of paradigms involving many events and few sources rather than any fundamental processing requirement of contextual retrieval in the absence of interference.

Adolescent↗

Experimental susceptibility of Atlantic cod, Gadus morhua (L.), and Atlantic halibut, Hippoglossus hippoglossus (L.), to different genotypes of viral haemorrhagic septicaemia virus.

Viral haemorrhagic septicaemia (VHS) is a well-characterized disease of rainbow trout, Oncorhynchus mykiss, which has also caused economic losses in marine turbot farms in the British Isles. We have previously demonstrated that turbot, Scophthalmus maximus, are susceptible to isolates of viral haemorrhagic septicaemia virus (VHSV) that are endemic in the marine environment, highlighting a potential risk to marine aquaculture. Given the increasing interest in the intensive rearing of additional aquaculture species such as Atlantic cod, Gadus morhua, and Atlantic halibut, Hippoglossus hippoglossus, this study aimed at investigating the susceptibility of these species to VHSV. Both species were found to be largely resistant to VHS following immersion challenge with a selection of 18 isolates, representing the known marine VHSV genotypes. Only one and two VHSV-associated mortalities occurred out of a total of 1710 and 1254 halibut and cod, respectively. These findings suggest that there is a low direct risk to the development of commercial cod and halibut aquaculture from the existing endemic reservoir of VHSV. This study, coupled to field observations has, however, highlighted the fact that both species can become infected with VHSV. The known adaptability of RNA viruses, together with the selection pressures associated with intensive aquaculture would thus advocate a cautious approach to VHSV surveillance within these emerging industries.

Animals↗

Sequential pathology after experimental infection with marine viral hemorrhagic septicemia virus isolates of low and high virulence in turbot (Scophthalmus maximus L).

Three marine viral hemorrhagic septicemia virus isolates were used to bath challenge turbot with the purpose of studying mortality and the pathology and antigen distribution over time. Two high-virulence isolates, 860/94, 4p168 and a low-virulence isolate 1p3 from a Baltic Sea herring were used. Organ samples were collected sequentially at 2, 4, 7, 10, 15, 20, 25, and 45 days postinfection. Specimens were processed for virology, histopathology, and immunohistochemistry. Organs during the early stages of infection (from 2 to 7 days) had virus isolation from all three groups only on day 7. Virus titer in kidney and heart sampled at day 25 was higher for the two virulent isolates compared with the low-virulence isolate. The viral distribution in situ of the two more virulent isolates from turbot (860/94) and herring (4p168) resembled viral hemorrhagic septicemia in rainbow trout with regard to the target organs. Early infection of endothelial cells in both kidney and heart was observed. Accumulated mean mortality was 41.5% for the turbot isolate 860/94, 48% for the herring isolate 4p168, and 3.5% for the herring isolate 1p3. This study revealed that the isolates from turbot (860/94) and herring (4p168) induced significantly higher mortality compared with the virus-free control and the herring isolate (1p3). The onset of mortality is markedly later in turbot compared with what is seen in rainbow trout.

Animals↗

Ion acceleration from the shock front induced by hole boring in ultraintense laser-plasma interactions.

Ion-acceleration processes have been studied in ultraintense laser plasma interactions for normal incidence irradiation of solid deuterated targets via neutron spectroscopy. The experimental neutron spectra strongly suggest that the ions are preferentially accelerated radially, rather than into the bulk of the material from three-dimensional Monte Carlo fitting of the neutron spectra. Although the laser system has a 10(-7) contrast ratio, a two-dimensional magnetic hydrodynamics simulation shows that the laser pedestal generates a 10 mum scale length in the coronal plasma with a 3 mum scale-length plasma near the critical density. Two-dimensional particle-in-cell simulations, incorporating this realistic density profile, indicate that the acceleration of the ions is caused by a collisionless shock formation. This has implications for modeling energy transport in solid density plasmas as well as cone-focused fast ignition using the next generation PW lasers currently under construction.

Journal Article↗

Genetic population structure of marine viral haemorrhagic septicaemia virus (VHSV).

The nucleotide sequences of a specific region of the nucleoprotein gene were compared in order to investigate the genetic population structure of marine viral haemorrhagic septicaemia virus (VHSV). Analysis of the sequence from 128 isolates of diverse geographic and host origin renders this the most comprehensive molecular epidemiological study of marine VHSV conducted to date. Phylogenetic analysis of nucleoprotein gene sequences confirmed the existence of the 4 major genotypes previously identified based on N- and subsequent G-gene based analyses. The range of Genotype I included subgroups of isolates associated with rainbow trout aquaculture (Genotype Ia) and those from the Baltic marine environment (Genotype Ib) to emphasise the relatively close genetic relationship between these isolates. The existence of an additional genotype circulating within the Baltic Sea (Genotype II) was also confirmed. Genotype III included marine isolates from around the British Isles in addition to those associated with turbot mariculture, highlighting a continued risk to the development of this industry. Genotype IV consisted of isolates from the marine environment in North America. Taken together, these findings suggest a marine origin of VHSV in rainbow trout aquaculture. The implications of these findings with respect to the future control of VHSV are discussed. The capacity for molecular phylogenetic analysis to resolve complex epidemiological problems is also demonstrated and its likely future importance to disease management issues highlighted.

Animals↗

K(alpha) fluorescence measurement of relativistic electron transport in the context of fast ignition.

Electron transport within solid targets, irradiated by a high-intensity short-pulse laser, has been measured by imaging K(alpha) radiation from high- Z layers (Cu, Ti) buried in low- Z (CH, Al) foils. Although the laser spot is approximately 10 microm [full width at half maximum (FWHM)], the electron beam spreads to > or =70 microm FWHM within <20 microm of penetration into an Al target then, at depths >100 microm, diverges with a 40 degree spreading angle. Monte Carlo and analytic models are compared to our data. We find that a Monte Carlo model with a heuristic model for the electron injection gives a reasonable fit with our data.

Journal Article↗

Acute ventilator-induced vascular permeability and cytokine responses in isolated and in situ mouse lungs.

To determine the influence of experimental model and strain differences on the relationship of vascular permeability to inflammatory cytokine production after high peak inflation pressure (PIP) ventilation, we used isolated perfused mouse lung and intact mouse preparations of Balb/c and B6/129 mice ventilated at high and low PIP. Filtration coefficients in isolated lungs and bronchoalveolar lavage (BAL) albumin in intact mice increased within 20-30 min after initiation of high PIP in isolated Balb/c lungs and intact Balb/c, B6/129 wild-type, and p55 and p75 tumor necrosis factor (TNF) dual-receptor null mice. In contrast, the cytokine response was delayed and variable compared with the permeability response. In isolated Balb/c lungs ventilated with 25-27 cmH(2)O PIP, TNF-alpha, interleukin (IL)-1 beta, IL-1 alpha, macrophage inflammatory protein (MIP)-2, and IL-6 concentrations in perfusate were markedly increased in perfusate at 2 and 4 h, but only MIP-2 was detectable in intact Balb/c mice using the same PIP. In intact wild-type and TNF dual-receptor null mice with ventilation at 45 cmH(2)O PIP, the MIP-2 and IL-6 levels in BAL were significantly increased after 2 h in both groups, but there were no differences between groups in the BAL albumin and cytokine concentrations or in lung wet-to-dry weight ratios. TNF-alpha was not be detected in BAL fluids in any group of intact mice. These results suggest that the alveolar hyperpermeability induced by high PIP ventilation occurs very rapidly and is initially independent of TNF-alpha participation and unlikely to depend on MIP-2 or IL-6.

Acute Disease↗

A neuroanatomical and neuroendocrinological study into the relationship between social status and the GnRH system in cooperatively breeding female Damaraland mole-rats, Cryptomys damarensis.

The gonadotrophin-releasing hormone (GnRH) system in female Damaraland mole-rats, Cryptomys damarensis, has been investigated to map the distribution of GnRH-immunoreactive (GnRH-IR) structures in the brain of this species and to assess whether changes in this system may mediate the inhibitory effect of social cues on fertility. The distribution of GnRH-IR cell bodies and fibres was similar to that of other mammals, forming a loose continuum along a septo-preoptico-infundibular pathway. GnRH-IR cell bodies were more abundant in the vicinity of the organum vasculosum of the lamina terminalis than in the medial basal hypothalamus. GnRH-IR cells and fibres were also found in the subfornical organ. The cell bodies were typically unipolar or bipolar. No differences were found in the morphology or size of the cell bodies or in the number of cells between non-reproductive females and reproductive females living together in a colony. However, GnRH concentrations, measured in the brain by radioimmunoassay, were significantly higher in non-reproductive females than in reproductive females; this finding was complemented by the reduced immunoreactivity for GnRH in the median eminence and proximal pituitary stalk of reproductive females. In contrast, the concentrations of GnRH measured by radioimmunoassay in non-reproductive and reproductive males did not differ. These results are consistent with the hypothesis that GnRH release is inhibited in the non-reproductive females but not in the non-reproductive males of this species.

Animals↗

Changes in MRI signal intensity during hypercapnic challenge under conscious and anesthetized conditions.

Most functional magnetic resonance imaging (fMRI) studies in animals are conducted under anesthesia to minimize motion artifacts. However, methods and techniques have been developed recently for imaging fully conscious rats. Functional MRI studies on conscious animals report enhanced BOLD signal changes as compared to the anesthetized condition. In this study, rats were exposed to different concentrations of carbon dioxide (CO(2)) while conscious and anesthetized to test whether cerebrovascular reactivity may be contributing to these enhanced BOLD signal changes. Hypercapnia produced significantly greater increases in MRI signal intensity in fully conscious animals (6.7-13.3% changes) as when anesthetized with 1% isoflurane (3.2-4.9% changes). In addition, the response to hypercapnia was more immediate in the conscious condition (< 30s) with signal risetimes twice as fast as in the anesthetized state (60s). Both cortical and subcortical brain regions showed a robust, dose- dependent increase in MRI signal intensity with hypercapnic challenge while the animals were conscious but little or no change when anesthetized. Baseline variations in MRI signal were higher while animals were conscious but this was off set by greater signal intensity changes leading to a greater contrast-to-noise ratio, 13.1 in conscious animals, as compared to 8.0 in the anesthetized condition. In summary, cerebral vasculature appears to be more sensitive to hypercapnic challenge in the conscious condition resulting in enhanced T2* MRI signal intensity and the potential for better BOLD signal changes during functional imaging.

Anesthesia↗

An evaluation of current diagnostic tests for the detection of infectious salmon anaemia virus (ISAV) following experimental water-borne infection of Atlantic salmon, Salmo salar L.

Four commonly used diagnostic tests [reverse transcription polymerase chain reaction (RT-PCR), indirect fluorescent antibody test (IFAT), virus culture and light microscopy] were evaluated for their ability to detect infectious salmon anaemia virus (ISAV) or tissue pathology following experimental infection of Atlantic salmon. Fish were infected with ISAV by water-borne exposure which mimics the route of natural infection. Forty-five per cent of pre-clinical fish tested yielded positive results by RT-PCR for at least one of the organs tested (kidney, heart, gill, liver, blood). No significant difference was detected between organs in the number or time of first occurrence of positive result. Virus culture identified a total of 14% of pre-clinical fish as ISAV-infected. The presence of ISAV in heart tissue was particularly notable (13% of fish sampled) as was the inability to culture virus from spleen tissue. In the case of IFAT, 15% of fish sampled were positive, although tissue other than kidney proved unsuitable for use in this method. Only limited ISAV-specific pathology was detectable by histological examination of fish prior to the onset of clinical disease. These findings reveal important information regarding the optimal choice of both tissue sample and diagnostic test for the routine diagnosis of ISAV.

Anemia↗

Identification of a heparin-binding motif on adeno-associated virus type 2 capsids.

Infection of cells with adeno-associated virus (AAV) type 2 (AAV-2) is mediated by binding to heparan sulfate proteoglycan and can be competed by heparin. Mutational analysis of AAV-2 capsid proteins showed that a group of basic amino acids (arginines 484, 487, 585, and 588 and lysine 532) contribute to heparin and HeLa cell binding. These amino acids are positioned in three clusters at the threefold spike region of the AAV-2 capsid. According to the recently resolved atomic structure for AAV-2, arginines 484 and 487 and lysine 532 on one site and arginines 585 and 588 on the other site belong to different capsid protein subunits. These data suggest that the formation of the heparin-binding motifs depends on the correct assembly of VP trimers or even of capsids. In contrast, arginine 475, which also strongly reduces heparin binding as well as viral infectivity upon mutation to alanine, is located inside the capsid structure at the border of adjacent VP subunits and most likely influences heparin binding indirectly by disturbing correct subunit assembly. Computer simulation of heparin docking to the AAV-2 capsid suggests that heparin associates with the three basic clusters along a channel-like cavity flanked by the basic amino acids. With few exceptions, mutant infectivities correlated with their heparin- and cell-binding properties. The tissue distribution in mice of recombinant AAV-2 mutated in R484 and R585 indicated markedly reduced infection of the liver, compared to infection with wild-type recombinant AAV, but continued infection of the heart. These results suggest that although heparin binding influences the infectivity of AAV-2, it seems not to be necessary.

Amino Acid Motifs↗

The proseal laryngeal mask: results of a descriptive trial with experience of 300 cases.

BACKGROUND: The ProSeal laryngeal mask airway (PLMA) is a new laryngeal mask device with a modified cuff and a drainage tube. METHODS: We assessed the PLMA in 300 anaesthetized adults either paralysed or breathing spontaneously. We assessed insertion characteristics, airway seal pressures, haemodynamic response to insertion, ease of gastric tube placement, gastric insufflation, and postoperative sore throat. RESULTS: Insertion was successful in 294 patients (98%) and graded as easy in 274 patients (91%). We found no difference in ease of insertion or success rate with either the introducer or the finger insertion method, or in paralysed or non-paralysed patients. Mean airway seal pressure was 29 cm H2O, and 59 patients (20%) had seal pressures greater than 40 cm H2O. No gastric insufflation was detected. Gastric tube placement was successful in 290 of 294 patients (98.6%). There was no cardiovascular response to insertion, with a small reduction in heart rate 5 min after insertion and significant decreases in mean arterial pressure at 1 and 5 min after insertion. Sore throat was noted in 23% patients after operation and in 16% of patients after 24 h, with 90% of the sore throats described as mild. CONCLUSIONS: The PLMA is a reliable airway management device that can give an effective glottic seal in paralysed and non-paralysed patients. The device allows the easy passage of a gastric tube, causes a minimal haemodynamic response to insertion, and an acceptable incidence of sore throat.

Adolescent↗

Distribution of viral haemorrhagic septicaemia virus in wild fish species of the North Sea, north east Atlantic Ocean and Irish Sea.

A surveillance programme was initiated on the occurrence and distribution of viral haemorrhagic septicaemia virus (VHSV) in wild marine fish. Six research cruises were undertaken in an 18 mo period during 1997 and 1998, covering the North Sea, the Atlantic waters off the north and west coasts of Scotland and the Irish Sea. A total of 19,293 fish were sampled from 23 different species including cod, haddock, Norway pout, herring and sprat. Individual fish lengths were recorded and the fish were checked for lesions, haemorrhaging and other signs of disease. Pools of organ samples were taken for virus assay. The majority of fish sampled did not display clinical signs indicative of viral haemorrhagic septicaemia. A small number of cod were found with skin lesions and haddock with skin haemorrhaging. Of the 2081 organ and skin sample pools collected, 21 tested positive for VHSV by tissue culture and enzyme-linked immunosorbent assay. Seventeen of the isolates originated from Norway pout Trisopterus esmarkii, one from cod Gadus morhua (skin lesion), one from herring Clupea harengus, one from whiting Merlangius merlangus, and one from a previously unreported host species, poor cod Trisopterus minutus.

Animals↗