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Biomedical subjects

G Parsons

Publications and source records attributed to G Parsons.

At least 19 recordsLinked to original sources

Autonomic control of bronchial blood flow and airway dimensions during strenuous exercise in sheep.

BACKGROUND: During exercise and recovery the transient and steady-state changes in autonomic activity regulating lower airway blood flow and dimensions are unknown. The aim of this study was to define changes in bronchial blood flow (Q(br)) and dimensions during moderate and strenuous exercise, and to analyse the role of vagal and sympathetic nerves. METHODS: Nine ewes (34-44kg) underwent left thoracotomy during general anaesthesia (thiopentone/isoflurane) and either (5 sheep=Group 1) a pulsed Doppler transducer was placed on the bronchial artery, or (4 sheep=Group 2) a pulsed Doppler transducer was placed on the bronchial artery, and transit-time and single crystal sonomicrometers were mounted on the left main bronchus. These measured continuously Q(br), bronchial circumference (Circ(br)) and wall thickness (Th(br)). Aortic pressure (P(a)) and central venous pressure catheters were placed in the superficial cervical artery and vein. Trained sheep exercised on a horizontal treadmill, i.e. Group 1, moderate exercise 2.2mph over 1.6, 6min recovery, for analysis of changes in Q(br) before and after cholinoceptor blockade; Group 2, strenuous exercise 4.4mph over 2, 10min recovery for analysis of changes in Q(br) and airway dimensions, before and after cholinoceptor plus alpha(1)-, alpha(2)-adrenoceptor blockade. beta-adrenoceptor systems were intact. RESULTS: In Group 1 during moderate exercise P(a) and heart rate (HR) rose. Q(br) and blood flow conductance (C(br)) fell immediately to 83% (P<0.001) before returning toward resting levels, but fell when exercise ceased to 89% (P<0.01) before recovering. Prior cholinoceptor blockade abolished the immediate fall in Q(br) and C(br), but not the recovery vasoconstriction. Later in recovery the bronchial bed dilated progressively over 6min (P<0.05). In Group 2 during strenuous exercise P(a) and HR rose substantially. Q(br) and C(br) fell to 68% and 54% (P<0.001), respectively, and there was early vasoconstriction in recovery. Circ(br) fell immediately and remained at 93% (P<0.01), and did not recover fully when exercise ceased. Th(br) did not change during or after exercise. Prior cholinoceptor plus alpha-adrenoceptor block caused P(a) and Q(br) to fall slightly during exercise, but the bronchovascular constriction during and after exercise was abolished, as was circumferential shortening in the airway. CONCLUSIONS: At exercise onset and steady-state, resetting the arterial baroreflex upward in sheep increases parasympathetic cholinergic vasoconstrictor activity and causes bronchial wall and bronchovascular smooth muscle contraction in concert with sympathetic adrenergic constriction of systemic vascular beds. Whether the known sigmoid baroreflex control of tracheal smooth muscle tension at rest is extended to tracheobronchial smooth muscle and its circulation during exercise is yet to be determined.

Acetylcholine↗

Effects of graded exercise on bronchial blood flow and airway dimensions in sheep.

Exercise stimulus-response relationships for airway blood supply and dimensions have not been described in mammalian species. These relationships are vital for postulates concerning integrated reflex factors normally controlling the airways and which may underlie the asthma syndromes of exercise. This study defines airways stimulus-response relationships in exercising sheep. Ewes between 35 and 40kg were instrumented at left thoracotomy under thiopentone/isoflurane general anaesthesia. Pulsed Doppler ultrasonic transducers were mounted on the bronchial artery, and transit-time plus single-crystal sonomicrometers on the left main bronchus. These recorded simultaneously and continuously bronchial blood flow (Q(br)) and conductance (C(br)), bronchial circumference (Circ(br)) and wall thickness (Th(br)). In Protocol 1 (P1), four sheep ran duplicate 5min protocols on a horizontal treadmill at continuous step-up-and-down speeds of 1min duration, namely, 0.8, 1.6, 2.2, 1.6 and 0.8mph (moderate exercise), followed by 10min recovery. In P2, four sheep ran duplicate 2min protocols at constant 4mph (strenuous exercise), and in P3, one sheep ran duplicate protocols each of 3min at 2.2, 4.4 and 6mph (severe exercise). Regression analysis and repeated measures ANOVA were used to assess differences between times, runs and exercise intensity. In P1, airway effects were directly related to graded exercise effort sustained over 5min. Peak effects occurred at 2.2mph, except for Th(br). Heart rate and P(a) rose (to 156% and 111% of resting, respectively), and Q(br) and C(br) fell (to 83% and 75%; both P<0.001). Circ(br) fell to 96% (P=0.02), and Th(br) rose at low speeds early and late, and thinned at the highest speed. In P2 and P3 for all variables the steady-state effects were systematically greater than for P1 (4.4mph: C(br) to 43%, Circ(br) to 93%; 6.6mph: C(br) to 25%, Circ(br) to 82%). There was no significant recovery hyperaemia, but there was residual post-exercise bronchoconstriction. The exercise stimulus-response relationships from rest to a maximal 6mph for sheep airway circumference and its bronchial circulation are inverse and functionally constrictor.

Animals↗

Rabies human diploid cell vaccine elicits cross-neutralising and cross-protecting immune responses against European and Australian bat lyssaviruses.

The ability of antibodies elicited against the rabies human diploid cell vaccine (HDCV) to neutralise European bat Lyssaviruses (EBLV types-1 and -2), Australian bat Lyssavirus and classical rabies virus (RABV) has been evaluated using modified fluorescent antibody virus neutralisation (mFAVN) assays. Ninety-six percent (48 of 50) of the human post-vaccinated sera tested cross-neutralised these viruses (>or=0.5 IU/ml). Cross-protection experiments using inbred mice (RIII, k/k haplotype) were also assessed. Mice were given HDCV (twice by the intra-peritoneal route) and challenged (intra-cranially or peripherally) with a lethal dose (25 MLD(50)) of the individual viruses. The vaccine conferred statistically significant protection in 80--100% of animals challenged via the peripheral route. Levels of protection were lower following intra-cranial (i.c.) challenge. Our data provides strong evidence for broad spectrum cross-neutralisation and cross-protection of phylogroup I lyssaviruses using rabies HDCV.

Animals↗

Intracerebral transplantation of adult mouse neural progenitor cells into the Niemann-Pick-A mouse leads to a marked decrease in lysosomal storage pathology.

Niemann-Pick disease is caused by a genetic deficiency in acid sphingomyelinase (ASM) leading to the intracellular accumulation of sphingomyelin and cholesterol in lysosomes. In the present study, we evaluated the effects of direct intracerebral transplantation of neural progenitor cells (NPCs) on the brain storage pathology in the ASM knock-out (ASMKO) mouse model of Type A Niemann-Pick disease. NPCs derived from adult mouse brain were genetically modified to express human ASM (hASM) and were transplanted into multiple regions of the ASMKO mouse brain. Transplanted NPCs survived, migrated, and showed region-specific differentiation in the host brain up to 10 weeks after transplantation (the longest time point examined). In vitro, gene-modified NPCs expressed up to 10 times more and released five times more ASM activity into the culture media compared with nontransduced NPCs. In vivo, transplanted cells expressed hASM at levels that were barely detectable by immunostaining but were sufficient for uptake and cross-correction of host cells, leading to reversal of distended lysosomal pathology and regional clearance of sphingomyelin and cholesterol storage. Within the host brain, the area of correction closely overlapped with the distribution of the hASM-modified NPCs. No correction of pathology occurred in brain regions that received transplants of nontransduced NPCs. These results indicate that the presence of transduced NPCs releasing low levels of hASM within the ASMKO mouse brain is necessary and sufficient to reverse lysosomal storage pathology. Potentially, NPCs may serve as a useful gene transfer vehicle for the treatment of CNS pathology in other lysosomal storage diseases and neurodegenerative disorders.

Animals↗

Isolation of a European bat lyssavirus type 2 from a Daubenton's bat in the United Kingdom.

European bat lyssavirus type 2 (EBLV-2) has been isolated once previously from a bat in the UK in June 1996. In September 2002, a Daubenton's bat (Myotis daubentonii) found in Lancashire developed abnormal behaviour, including unprovoked aggression, while it was in captivity. Brain samples from the bat were tested for virus of the Lyssavirus genus, which includes EBLV-2 (genotype 6), and classical rabies virus (genotype 1). A positive fluorescent antibody test confirmed that it was infected with a lyssavirus, and PCR and genomic sequencing identified the virus as an EBLV-2a. Phylogenetic comparisons with all the published sequences from genotype 6 showed that it was closely related to the previous isolate of EBLV-2 in the UK and suggested links to isolates from bats in The Netherlands. The isolation of EBLV-2 from a bat found on the west coast of England provides evidence that this virus may be present within the UK Daubenton's bat population at a low prevalence level.

Amino Acid Sequence↗

Risk factors associated with travel to rabies endemic countries.

Increased travel to exotic destinations around the world is escalating the risk that an emerging virus may be imported into the UK. Rabies should be considered in the differential diagnosis of any encephalitic illness presenting in an appropriate epidemiological context. Molecular diagnostic tests that can rapidly discriminate rabies from other suspected infections will influence the use of anti-rabies prophylaxis for potential contacts with the victim. In 2001, the UK had two confirmed human rabies cases, imported from the Philippines and Nigeria, respectively. In case one, hemi-nested reverse transcriptase polymerase chain reaction (hn-RT-PCR) and automated sequencing confirmed the presence of rabies virus (RABV) within both the saliva and skin specimens within 36 h of sample submission. Subsequent phylogenetic analysis using a partial sequence of the nucleoprotein (N-) gene segment demonstrated that the virus was closely related to that of canine variants currently circulating in the Philippines. In the second case, the fluorescent antibody test and reverse transcriptase polymerase chain reaction (RT-PCR) confirmed the diagnosis on post-mortem tissue. Phylogenetic analysis of two genomic segments of this isolate confirmed that it was a classical RABV (genotype 1) of the Africa 2 subgroup. These cases have highlighted the capability of molecular diagnostic tests for the rapid identification and subsequent genotyping of RABV to host and geographical location. In the first instance, rabies diagnosis often rests on clinical and epidemiological grounds. Negative tests, even late in the illness, do not exclude the diagnosis as these tests are never optimal and are entirely dependent on the nature and quality of the sample supplied. For this reason, rapid molecular detection and virus typing will be essential in considering the appropriate medical treatment regimen for a patient. In addition, an early diagnosis may decrease the number of unnecessary contacts with the patient and reduce the requirement for invasive and costly interventions. Rabies should form part of a differential diagnosis for any patient presenting with a history of travel to a rabies endemic country and displaying an undiagnosed encephalopathy.

Animals↗

Rabies antibody testing and the UK Pet Travel Scheme.

The Pet Travel Scheme (PETS) commenced on February 28, 2000, allowing pet dogs and cats from named countries to enter the UK without spending six months in quarantine as long as they met specific criteria. Since the start of the scheme to the end of February 2002, more than 45,000 animals have successfully entered the UK under PETS. In this article, Dr Tony Fooks and colleagues consider the results of serological testing under the scheme at the Veterinary Laboratories Agency and look to future developments.

Animals↗

Changes in short-term power output in 10- to 12-year-olds.

In this study, we used multi-level regression modelling to assess the influence of age, sex, body size, skinfold thicknesses, maturity, thigh muscle volume and isokinetic leg strength on the development of load- and inertia-adjusted peak (1 s) and mean power (30 s) determined using the Wingate anaerobic test. Fifteen males and 19 females were measured twice, first aged 10.0 +/- 0.3 years and then aged 11.8 +/- 0.3 years. Initial models identified body mass and height as significant explanatory variables (P < 0.05) for peak power and mean power, with an additional age effect for the former. No significant differences between the sexes or maturity effects were observed for either peak or mean power (P > 0.05). The introduction of sum of skinfolds improved the fit of the model and rendered the height term non-significant for both peak and mean power (P> 0.05). An age effect became apparent for mean power. When isokinetic leg strength and thigh muscle volume were entered into the model, the latter exerted a significant effect on both peak and mean power (P< 0.05), whereas isokinetic leg strength was not a significant explanatory variable for either (P> 0.05). In conclusion, thigh muscle volume exerts a positive influence on young people's short-term power output, which is additional to the effects of body mass, sum of skinfolds and age.

Age Factors↗

Use of a dual monoclonal solid phase and a polyclonal detector to create an immunoassay for the detection of human cardiac troponin I.

OBJECTIVES: We report the development of a fully automated, random access, chemiluminescent immunoassay, for the detection of human cardiac Troponin I (cTnI) in serum and plasma for use on the ACS:180(R) System. DESIGN AND METHODS: This assay format uses a combination of two monoclonal antibodies covalently coupled to paramagnetic (PMP) particles as a solid phase and an affinity purified polyclonal antibody, specific to the N-terminal domain of cTnI (peptide-3 region) labeled with a chemiluminescent compound as the detector antibody. The assay offers excellent low-end sensitivity and precision. RESULTS: No interferences are observed from by blood components such as HAMA and drugs used in cardiac therapy. Patient samples tested on the ACS:180 cTnI assay showed good correlation with the Stratus cTnI assay (ACS: cTnI = 1. 02*Stratus + 0.05 g/L, r = 0.96, n = 1170). CONCLUSION: Paired with the other ACS:180 cardiac assays, myoglobin and CKMBII, the ACS:180 system now offers an excellent panel of cardiac assay for use in rapid and accurate diagnosis of a myocardial event.

Antibodies, Monoclonal↗

Are people with intellectual disabilities just another customer? Interviews with business owners and staff.

Descriptive information on the views of business people towards the presence of persons with intellectual disabilities as customers was reported. We interviewed 89 individuals representing a range of shops and local amenities in four urban and four country regions in Queensland, Australia. We also systematically examined the influence of degree of intellectual disabilities by interviewing employees in shops near community residential facilities for persons with mild/moderate and those near facilities for persons with severe/profound intellectual disabilities. A third group of businesses not located near any such residential facilities served as a control group. Overall, results suggest that business people had few special concerns related to interactions with customers who have intellectual disabilities.

Adult↗

Newcastle disease outbreaks in domestic fowl and turkeys in Great Britain during 1997.

Between January 6 and April 23, 1997, 11 outbreaks of Newcastle disease were confirmed in Great Britain, four in broiler chickens and seven in turkeys. Although the viruses isolated gave intracerebral pathogenicity indices in day-old chicks between 1.65 and 1.95, the clinical signs of disease in field infections were variable and not always associated with high mortality, especially in turkeys. Epidemiological investigations indicated that the majority of the outbreaks occurred as a result of secondary spread by human agency from two or more primary infected flocks. The presence of similar outbreaks in Scandinavian countries in 1996 and the unusual patterns of movement of migratory birds at the end of 1996 and beginning of 1997 suggest they may have been responsible for the primary introduction of the causative virus into Great Britain.

Animals↗