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G L Smith

Publications and source records attributed to G L Smith.

At least 109 records · Page 6Linked to original sources
PubMed1997

Temperature profiles during resuscitation predict survival following burns complicated by smoke inhalation injury.

Temperature and resuscitation profiles of 15 non-survivors were compared with matched survivors of major burns. All patients were intubated and ventilated for smoke inhalation injury, survived more than 3 days postburn and had a cutaneous burn greater than 15 per cent of the body surface area (mean 32.3 +/- 11.0 per cent SD). Cases were matched for similar ages (within 10 years) and total body surface area burn (within 10 per cent). The rate of core temperature rise following admission to the burn unit was significantly greater in survivors (mean 0.46 +/0 0.18 degree C/h) compared with matched non-survivors (mean 0.30 +/- 0.15 degrees C/h; p < 0.01). Core temperature increased at a rate of 0.27 degrees C/h or greater in all survivors, whereas 7 non-survivors raised their core temperature at a rate less than this. The rate of skin temperature rise was also significantly greater in the survivors (mean 1.35 +/- 0.91 degrees C/h) compared with matched non-survivors (mean 0.63 +/- 0.43 degrees C/h, p < 0.01). In 13/15 survivors, the skin temperature increased at a rate of 0.6 degree C/h or greater, whereas in 8/15 non-survivors skin temperature increased at a rate less than this. There was a negative relationship between initial core temperature and delay from time of burn to admission to the burns unit in non-survivors (correlation coefficient = -0.92; p < 0.01), whereas there was no effect of delay in the survivors. These findings suggest that patients with a high mortality probability can be detected early in their clinical course by means of temperature profiles.

Adult↗
PubMed1997

Diagnosis and management of high-pressure peristaltic contractions in cystoplasties.

OBJECTIVE: To define the aetiology of and therapeutic strategy for high-pressure peristaltic contractions within colo- and caecocystoplasties associated with symptoms of frequency, urgency and urge incontinence. PATIENTS AND METHODS: In a series of over 150 subtotal supratrigonal colo- and caeco-cystoplasties, nine patients were identified with such symptoms. These patients underwent videocystometrography (VCMG) confirming the presence of phasic peristaltic contractions of > 35 cmH2O. RESULTS: In three cases, there was urodynamic evidence of outlet obstruction and symptoms resolved when the obstruction was surgically relieved. In the other six cases, high-pressure peristaltic contractions were present without bladder outlet obstruction. The symptoms did not respond to anticholinergic medication. Three of the six patients had tolerable symptoms which did not warrant further intervention. The other three cases had disabling urge incontinence and underwent ileal patch cystoplasty. The symptoms resolved in all three cases, although later recurred in one patient, probably due to incomplete division of the taenia coli during ileal patch cystoplasty. CONCLUSION: It appears that colonic smooth muscle can develop high-pressure contractions in response to neobladder outlet obstruction. Relieving the obstruction ameliorates symptoms associated with these contractions and reduces the magnitude of the peristaltic waves. Symptoms related to high-pressure peristaltic contractions without neobladder outlet obstruction do not respond to anticholinergic medication but can be successfully treated by ileal patch cystoplasty.

Adult↗
PubMed1997

Vaccinia virus serpin B13R (SPI-2) inhibits interleukin-1beta-converting enzyme and protects virus-infected cells from TNF- and Fas-mediated apoptosis, but does not prevent IL-1beta-induced fever.

The vaccinia virus (VV) strain Western Reserve B13R gene encodes a 38.5 kDa intracellular polypeptide that is non-essential for virus replication in vitro and does not affect virus virulence in a murine intranasal model. The protein has 92% amino acid identity with the cowpox virus cytokine response modifier A (crmA) protein which inhibits the interleukin (IL)-1beta converting enzyme (ICE). Here, we show that extracts from THP-1 cells infected with VV strains expressing B13R prevent the cleavage of in vitro transcribed and translated pro-IL-1beta into mature IL-1beta. Similarly, THP-1 cells infected with VVs expressing B13R process pro-IL-1beta into mature IL-1beta inefficiently in situ. Despite its inhibition of ICE, B13R does not prevent fever in infected mice, a systemic effect mediated by IL-1beta. Instead, fever is controlled by the VV IL-1beta receptor, encoded by gene B15R, and deletion of both the B13R and B15R genes did not increase the febrile response compared to deletion of B15R alone. The B13R protein does, however, block apoptosis mediated by anti-Fas antibodies or by tumour necrosis factor (TNF) and cycloheximide. Using DNA fragmentation, chromium release and microscopic analyses it was shown that cells infected with wild-type VV strain WR, or a revertant virus in which the B13R gene had been re-inserted into the B13R deletion mutant, are more resistant than uninfected cells or deletion mutant-infected cells to apoptosis mediated by anti-Fas and TNF.

Animals↗
PubMed1997

Antibodies against vaccinia virus do not neutralize extracellular enveloped virus but prevent virus release from infected cells and comet formation.

Vaccinia virus (VV) produces two antigenically and structurally distinct infectious virions, intracellular mature virus (IMV) and extracellular enveloped virus (EEV). EEV is important for the efficient dissemination of virus both in vivo and in vitro where it causes formation of comet-shaped virus plaques. Here, we show that EEV, in contrast to IMV, is resistant to neutralization by antibodies bound to its surface. However, antibodies against EEV can prevent comet formation in cell culture. To explain this apparent paradox, we investigated the mechanism by which antibodies inhibit comet formation and demonstrated that antibodies prevent EEV release from infected cells, and consequently comet formation, by agglutination of the virus on the cell surface. Two complementary observations allow this conclusion: first, electron microscopy showed that infected cells incubated with medium containing anti-vaccinia virus antibodies have virus aggregates on their surface; second, culture medium from these cells contained a 4 log10 fold reduction in the physical particle/ml titre in comparison with control culture. A mechanism by which antibodies to EEV proteins provide immunological protection is thus restriction of EEV release rather than neutralization of free EEV particles.

Agglutination↗
PubMed1997

Vaccinia virus immune evasion.

Vaccinia virus and other poxviruses express a wide variety of proteins which are non-essential for virus replication in culture but help the virus to evade the host response to infection. Examples include proteins which oppose apoptosis, synthesise steroids, capture chemokines, counteract complement, interfere with interferon and intercept interleukins. This review provides an overview of such proteins, with an emphasis on work from our laboratory, and illustrates how the study of these proteins can increase our understanding of virus pathogenesis, the function of the immune system and how to make safer and more immunogenic poxvirus-based vaccines.

Animals↗
PubMed1997

The effect of cromakalim on intracellular [Ca2+] in isolated rat skeletal muscle during fatigue and metabolic blockade.

The effects of the ATP-sensitive K+ channel (KATP channel) opener cromakalim on excitation-contraction (E-C) coupling were studied in skeletal muscle during fatiguing and non-fatiguing activity. Intracellular calcium concentration ([Ca2+]i) was monitored using the fluorescent indicator fura-2 in isolated single skeletal muscle fibres enzymatically dissociated from rat flexor digitorum brevis. A protocol of tetanic stimulation (50 Hz for 300 ms) with progressively shorter durations between tetani was used to induce E-C coupling failure in these cells. Cromakalim (100-800 microM) had little effect on peak [Ca2+]i during twitch and non-fatiguing tetanic stimulation. However, with 0.4 s between tetani, 100 microM cromakalim decreased peak tetanic [Ca2+]i from 1.47 +/- 0.11 microM to 8.35 +/- 55 nM, but did not affect resting [Ca2+]i (control, 220 +/- 40 nM; with cromakalim, 171 +/- 33 nM). Cyanide (2 mM) decreased tetanic [Ca2+]i and increased resting [Ca2+]i during the stimulus protocol; with 0.4 s between tetani, peak [Ca2+]i was 820 +/- 50 nM and resting [Ca2+]i was 443 +/- 32 nM. The ability of cromakalim to inhibit E-C coupling was enhanced by the presence of cyanide. Complete blockade of metabolism by cyanide and iodoactetate (0.1 mM) caused a marked rise in resting [Ca2+]i and inhibition of the tetanic rise of [Ca2+]i. With cromakalim (100 microM) present, E-C coupling failed during metabolic blockade but without a significant increase in resting [Ca2+]i. These results are consistent with a role for the KATP channel in the failure of Ca2+ release during fatigue.

Adenosine Triphosphate↗
PubMed1997

A novel virus binding assay using confocal microscopy: demonstration that the intracellular and extracellular vaccinia virions bind to different cellular receptors.

Vaccinia virus (VV) produces two antigenically and structurally distinct infectious virions, intracellular mature virus (IMV) and extracellular enveloped virus (EEV), which bind to unidentified and possibly different cellular receptors. Studies of VV binding have been hampered by having two infectious virions and by the rupture of the EEV outer membrane in the majority of EEV virions during purification. To overcome these problems, we have developed a novel approach to study VV binding that is based on confocal microscopy and does not require EEV purification. In this assay, individual virus particles adsorbed to the cell are simultaneously distinguished and quantified by double immunofluorescence labelling with antibody markers for EEV and IMV. By this method, we show unequivocally that IMV and EEV bind to different cellular receptors. Three independent observations allow this conclusion. First, the efficiencies with which IMV and EEV bind to different cell lines are unrelated; second, cell surface digestion with some enzymes affects IMV and EEV binding differently; and third, the binding of a monoclonal antibody to cells prevents IMV binding but not EEV binding. This technique may be widely applicable for studying the binding of different viruses.

Animals↗
PubMed1997

Cholesterol granuloma of the breast presenting as an intracystic papilloma.

Cholesterol granuloma of the breast is a rare benign condition. It is often clinically and radiologically indistinguishable from breast carcinoma. A case of cholesterol granuloma which manifested as an intracystic papilloma on ultrasound is described. This unusual ultrasonographic appearance has not previously been reported.

Adenoma↗
PubMed1997

Complication of ventricular demand pacing after orthotopic heart transplantation: unusual case of pacemaker syndrome in an infant.

BACKGROUND: Sinus node dysfunction is the most common indication for antibradycardiac permanent pacing after heart transplantation. Lack of atrioventricular synchrony during pacing can result in symptoms ranging from mild chest discomfort to severe manifestations such as dyspnea, hypotension, and cardiovascular collapse, all of which are ascribed to pacemaker syndrome. In infants pacemaker syndrome is often only recognized in the face of marked hemodynamic compromise. RESULTS: This report details an unusual account of pacemaker syndrome in an infant after orthotopic heart transplantation. CONCLUSIONS: Careful assessment of atrioventricular synchrony is important after infant transplantation.

Angina Pectoris↗
PubMed1996

A mechanism for the inhibition of fever by a virus.

Poxviruses encode proteins that block the activity of cytokines. Here we show that the study of such virulence factors can contribute to our understanding of not only virus pathogenesis but also the physiological role of cytokines. Fever is a nonspecific response to infection that contributes to host defense. Several cytokines induce an elevation of body temperature when injected into animals, but in naturally occurring fever it has been difficult to show that any cytokine has a critical role. We describe the first example of the suppression of fever by a virus and the molecular mechanism leading to it. Several vaccinia virus strains including smallpox vaccines express soluble interleukin 1 (IL-1) receptors, which bind IL-1 beta but not IL-1 alpha. These viruses prevent the febrile response in infected mice, whereas strains that naturally or through genetic engineering lack the receptor induce fever. Repair of the defective IL-1 beta inhibitor in the smallpox vaccine Copenhagen, a more virulent virus than the widely used vaccine strains Wyeth and Lister, suppresses fever and attenuates the disease. The vaccinia-induced fever was inhibited with antibodies to IL-1 beta. These findings provide strong evidence that IL-1 beta, and not other cytokines, is the major endogenous pyrogen in a poxvirus infection.

Animals↗
PubMed1996

Ligation of double-stranded and single-stranded [oligo(dT)] DNA by vaccinia virus DNA ligase.

Vaccinia virus DNA ligase has been expressed in Escherichia coli, purified, and biochemically characterized. The enzyme ligates double-stranded (ds) DNA substrates with either cohesive or blunt-end termini and the latter reaction is stimulated by PEG. Vaccinia virus DNA ligase can also ligate oligo(dT) when annealed to either a poly(dA) or a poly(rA) backbone and, remarkably, free oligo(dT). This ligation of a single-stranded (ss) substrate is unique among eukaryotic DNA ligases. The enzyme requires high ATP concentrations with a Km for the overall ligation of a ssDNA substrate of 0.8 mM. The salt, divalent cation, temperature, and pH requirements of the enzyme for the optimal ligation of ss and ds substrate are described.

Adenosine Triphosphate↗
PubMed1996

Comparative effects of inorganic phosphate and oxalate on uptake and release of Ca2+ by the sarcoplasmic reticulum in saponin skinned rat cardiac trabeculae.

1. Ventricular trabeculae from the right ventricle of rat heart were suspended in a 6 microliters bath and "skinned' with saponin (50 mg ml-1). Preparations were perfused with solutions mimicking the intracellular milieu and the [Ca2+] within the bath was monitored continuously using fura-2. 2. Application of 20 mM caffeine released Ca2+ from the sarcoplasmic reticulum (SR), resulting in a transient increase in the fura-2 fluorescence ratio. Caffeine-induced Ca2+ transients were smaller in the presence of 30 or 60 mM inorganic phosphate (Pi). This depressive effect of Pi on SR function was reversed by 10 mM creatine phosphate (CP). Caffeine-induced Ca2+ transients were also reduced in the presence of 10 mM oxalate, although this effect was not reversed by CP. 3. When perfusion was stopped in the presence of 30 or 60 mM Pi, the [Ca2+] within the bath remained constant. However, when the flow was stopped in the presence of 60 mM Pi and 10 mM CP, a prolonged decrease in [Ca2+] occurred, consistent with precipitation of calcium phosphate within the SR. A similar decrease in [Ca2+] was observed when perfusion was stopped in the presence of 2 or 20 mM oxalate, in the absence or presence of CP. 4. The SR was Ca2+ depleted by withdrawal of ATP and exposure to 20 mM caffeine. Perfusion was then stopped and ATP reapplied, resulting in a maintained decrease in [Ca2+] within the bath, due to SR Ca2+ uptake. Net Ca2+ uptake was markedly reduced in the presence of 30 mM Pi. In contrast, 20 mM oxalate increased Ca2+ uptake and the [Ca2+] within the bath continued to fall over 2-3 min. 5. Introduction of Pi released Ca2+ from the SR. Ryanodine (100 microM) abolished caffeine-induced Ca2+ release while Pi-induced Ca2+ release was unaffected. Pi-induced Ca2+ release was reduced in the constant presence of 20 mM caffeine or 10 mM CP and was abolished completely by disruption of the SR membrane with Triton X-100. Pi-induced Ca2+ release occurred after abolition of SR Ca2+ uptake by ATP withdrawal. 6. These results suggest that the Pi-induced decrease in releasable Ca2+ does not result from precipitation of calcium phosphate within the SR lumen. Pi inhibits net SR Ca2+ uptake, but this appears to result from activation of a ryanodine-insensitive Ca2+ efflux pathway rather then inhibition of Ca2+ uptake. Possible mechanisms are considered, including reversal of the SR Ca2+ pump.

Animals↗
PubMed1996

Soluble interferon-gamma receptors encoded by poxviruses.

Poxviruses encode a broad range of proteins that counteract the formidable attack of the immune response initiated in the host after infection, among which are proteins that mimic the extracellular binding domain of host cytokine receptors and are secreted from virus-infected cells. A soluble interferon-gamma receptor (IFN-gamma R) is produced early after infection and efficiently blocks the binding of IFN-gamma to cellular receptors, thus inhibiting both the anti-viral and immune functions of IFN-gamma. An IFN-gamma R is highly conserved among members of the poxvirus family, suggesting a major role in viral pathogenesis. The highly species-specific nature of the IFN system enables questions concerning the evolutionary relationship between poxviruses and their hosts to be addressed. The IFN-gamma R encoded by myxoma virus, a natural pathogen of rabbits, is specific for rabbit IFN-gamma. However, the IFN-gamma R encoded by orthopoxviruses (vaccinia, cowpox, camelpox, ectromelia) shows a novel, broad species specificity suggesting that these viruses have evolved in several species. The implications for the unknown origin and natural host(s) of vaccinia virus are discussed.

Animals↗
PubMed1996

Receptors for gamma-interferon encoded by poxviruses: implications for the unknown origin of vaccinia virus.

Poxviruses encode soluble interferon-gamma receptors (IFN-gamma Rs) that inhibit IFN-gamma activity and play a major role in virus pathogenesis. In contrast to the highly species specific cellular homologues, the vaccinia IFN-gamma R has novel broad species specificity. This has implications for the unknown origin and natural host(s) of vaccinia virus, the vaccine used for smallpox eradication.

Antigens, CD↗
PubMed1996

Virus proteins that bind cytokines, chemokines or interferons.

Some viruses express proteins to evade non-specific host defences such as complement, interferons and the inflammatory response. Recent notable discoveries are the broad species specificity of orthopoxvirus interferon receptors, herpesvirus and poxvirus proteins related to chemokine receptors and proteins that bind more than one cytokine, interferon or chemokine.

Animals↗
PubMed1996

Detrusor myopathy: an accurate predictor of bladder hypocompliance and contracture in interstitial cystitis.

OBJECTIVE: To determine whether any histological characteristics within the detrusor in cases of early interstitial cystitis (IC) predict the subsequent development of severe symptoms due to bladder contracture. PATIENTS AND METHODS: The detrusor muscle component of bladder biopsies from 21 patients with IC was examined in sections stained with haematoxylin and eosin. Videocystometrography was performed at least 2 months after the biopsy and the patients were then followed up clinically for at least 3 years. RESULTS: The detrusor appeared normal in 13 patients; in eight there was evidence of detrusor myopathy. Patients with biopsies confirming detrusor myopathy were significantly more likely to have hypocompliant bladders than those with normal detrusor muscle histology (P < 0.02). Over the following 3 years, six of the eight patients with detrusor myopathy developed progressively severe symptoms and required subtotal cystectomy and enterocystoplasty. None of the 13 patients without detrusor myopathy required bladder substitution. CONCLUSION: In IC, detrusor myopathy is associated with bladder hypocompliance. Patients with detrusor myopathy appear to have more severe disease and are more likely to progress to bladder contracture requiring substitution enterocystoplasty.

Contracture↗