Structure-specificity features of HSV-1 thymidine kinases.
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Amino Acid Sequence↗
Biomedical subjects
A Buchan
Publications and source records attributed to A Buchan.
An outbreak of herpes rugbiorum managed by vaccination of players and sociosexual contacts.
An outbreak of herpes rugbiorum involved nine players including the scrum half and the full back. The infection was characterized by significant constitutional upset with decreased levels of general fitness and match performance for 1-4 months following the outbreak; one player had herpetic lesions on his right eyelid and corneum. Every infected player, 15 non-infected players and five sociosexual contacts received two vaccinations with intracellular subunit vaccine NFU. Ac. HSV-1 (S-MRC5). None of the players or contacts developed cutaneous herpetic recurrence during a follow-up period of 3 years; the player with ocular disease had one recurrence at 30 months following the original episode. These findings encourage consideration of prophylactic or post-exposure vaccination of participants in rugby or other contact sports with this or other appropriate herpes simplex vaccine.
Adolescent↗
An early loss in membrane protein kinase C activity precedes the excitatory amino acid-induced death of primary cortical neurons.
Several lines of evidence indicate that a rapid loss of protein kinase C (PKC) activity may be important in the delayed death of neurons following cerebral ischemia. However, in primary neuronal cultures, cytotoxic levels of glutamate have been reported not to cause a loss in PKC as measured by immunoblot and conventional activity methods. This apparent contradiction has not been adequately addressed. In this study, the effects of cytotoxic levels of glutamate, NMDA, and alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) on membrane PKC activity was determined in cortical neurons using an assay that measures only PKC that is active in isolated membranes, which can be used to differentiate active enzyme from that associated with membranes in an inactive state. A 15-min exposure of day 14-18 cortical neurons to 100 microM glutamate, AMPA, or NMDA caused a rapid and persistent loss in membrane PKC activity, which by 4 h fell to 30-50% of that in control cultures. However, the amount of enzyme present in these membranes remained unchanged during this period despite the loss in enzyme activity. The inactivation of PKC activity was confirmed by the fact that phosphorylation of the MARCKS protein, a PKC-selective substrate, was reduced in intact neurons following transient glutamate treatment. By contrast, activation of metabotropic glutamate receptors by trans-(1S,3R)-1-amino-1,3-cyclopentanedicarboxylic acid was not neurotoxic and induced a robust and prolonged activation of PKC activity in neurons. PKC inactivation by NMDA and AMPA was dependent on extracellular Ca2+, but less so on Na+, although cell death induced by these agents was dependent on both ions. The loss of PKC activity was likely effected by Ca2+ entry through specific routes because the bulk increase in intracellular free [Ca2+] effected by the Ca2+ ionophore ionomycin did not cause the inactivation of PKC. The results indicate that the pattern of PKC activity in neurons killed by glutamate, NMDA, and AMPA in vitro is consistent with that observed in neurons injured by cerebral Ischemia in vivo.
Animals↗
Growth of herpes simplex type 1 on skin explants of atopic eczema.
In a novel approach to looking at why some children with atopic eczema are susceptible to cutaneous herpes simplex virus (HSV) infections, this study evaluates the hypothesis that HSV replicates more easily on eczematous than normal skin. Growth of HSV on eczematous skin explants was compared with growth on explants from three control groups (psoriasis, Darier's disease and normal skin) over a 2-day period. Growth of HSV was significantly less on normal skin than in atopic eczema, psoriasis and Darier's disease. Virus replicated more quickly, and grew to higher titre within 24h, in eczematous and psoriatic explants than in normal skin. A defect in skin barrier function and host defence factors including local cytokine secretion are discussed as possible mechanisms in causing the increased susceptibility of children with atopic eczema to HSV infection.
Adolescent↗
Immunological studies of herpes simplex virus infection in children with atopic eczema.
This study examines the role of immune defence mechanisms in herpes simplex virus (HSV) infections in atopic eczema and whether impairment of these mechanisms explains the susceptibility of some children with atopic eczema to cutaneous HSV infections. Ten children with eczema herpeticum and 13 with atopic eczema and recurrent HSV infection affecting multiple skin sites were studied, together with relevant control groups. In all children with atopic eczema, in vitro lymphoproliferation in response to stimulation with concanavalin A (Con A) was significantly decreased and natural killer (NK) cells (CD16 + 56) were reduced compared with non-atopic controls. IL-2 receptors, a marker for lymphocyte activation, were decreased during the acute phase of eczema herpeticum, and for 1 month thereafter. A positive stimulation index (> 3) to HSV antigen, and high HSV IgG antibody titres measured by ELISA, Western blotting and neutralization assay, were seen in children with eczema herpeticum by 6 weeks, and also in children with atopic eczema and recurrent HSV infections. No evidence of an HSV-specific immune defect (either cell-mediated or humoral) was found in atopic eczema. Impairment of cell-mediated immunity in atopic eczema was suggested by the reduced response to Con A. It is likely that reduced numbers of circulating NK cells and a decrease in IL-2 receptors during early eczema herpeticum contribute to the susceptibility of children with atopic eczema to cutaneous HSV infections.
Acute Disease↗
Characterization and immunogenicity of a candidate subunit vaccine against varicella-zoster virus.
This study describes the properties of an inactivated subunit antigen preparation from varicella-zoster virus (VZV)-infected MRC-5 cells by treatment with detergent and formaldehyde, ultracentrifugation over sucrose and acetone precipitation. The method preserved the antigenicity of VZV proteins and several VZV-specific glycoproteins, while virus DNA was less than 20 pg/250 micrograms protein--a putative vaccine dose. The vaccine was immunogenic in rabbits and stimulated antibodies to the major capsid protein as well as to glycoproteins; an immunoprecipitin was shared with a known immune human serum. The preparation contained no infectious VZV with no evidence of side effects in a rabbit or in five human vaccinees during a follow-up period of 6-10 years.
Aged↗
Antagonism of the NMDA and non-NMDA receptors in global versus focal brain ischemia.
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Animals↗
The effects of lithium and potassium on macromolecular synthesis in herpes simplex virus-infected cells.
All herpes simplex virus (HSV) infected cell-specific polypeptides (ICSPs) were synthesized in the presence of lithium at a concentration (60 mM) inhibitory to the production of infectious virus. Yields of certain ICSPs were increased and others, in particular glycoprotein C, decreased. HSV DNA synthesis was completely inhibited; synthesis and in vitro activities of HSV DNA polymerase and thymidine kinase were decreased but to a degree insufficient to account for the complete inhibition of HSV DNA synthesis. HSV DNA synthesis was inhibited to an equivalent degree by either incubation with 60 mM-lithium or by potassium starvation; both procedures decreased intracellular potassium by an equivalent amount as adjudged by X-ray microanalysis. We conclude that lithium inhibits HSV DNA synthesis by displacement of potassium from a potassium-dependent biochemical reaction or by other physiological changes brought about by the loss of cellular potassium. The possibility that lithium also directly inhibits a virus replicative event cannot be excluded.
Animals↗
Development of subunit preparations of cytomegalovirus antigen by aqueous extraction for immunization against cytomegalovirus infection.
This study has examined different methods of preparation of a subunit vaccine from cytomegalovirus (CMV)-infected MRC cells in terms of protein and DNA content, antigenicity and immunogenicity. Two preparations have been developed where CMV proteins were obtained by extraction of infected cells with water. Virus particles were removed from the preparations by ultracentrifugation and residual virus was inactivated by formaldehyde in the WUF preparations or by chloroform in the WUCh preparations. The preparations contained CMV proteins which may play a role in protective immune responses, and the preparations were antigenic as determined by immunodiffusion, ELISA and immunoblotting. Immunogenicity as evaluated in rabbits indicated that the preparations stimulated neutralizing and immunoprecipitating antibody. These results suggest that the gentle method of water extraction of viral antigens may be a useful protocol for vaccine preparation.
Animals↗
Sciatic neuropathy associated with persistent sciatic artery.
Persistent sciatic artery is a congenital vascular anomaly of the arterial supply to the lower extremity. Thrombosis, distal embolization, aneurysmal dilatation, and rupture of this vessel with compression of the sciatic nerve have been recorded. Although rare in occurrence, complications of persistent sciatic artery should be included in the differential diagnosis of sciatic neuropathy. We present a case of an acute sciatic neuropathy secondary to pseudoaneurysm formation of a persistent sciatic artery. We demonstrate the diagnostic usefulness of magnetic resonance imaging.
Adult↗
Report of twelve years experience in open study of Skinner herpes simplex vaccine towards prevention of herpes genitalis.
Three hundred and forty-seven subjects at risk for herpes genitalis were vaccinated with Skinner vaccine, NFUAc.HSV1.(S-MRC5), and were followed for an average duration of 2 years representing a total consortship of 664.4 years. Based on survey information obtained during this consortship, there were estimated to be 3076 recurrences which summated to 3.5 years total duration of disease and comprised at least 6794 lesions; there were an estimated 51997 episodes of intercourse including at least 241 episodes of unprotected intercourse in the presence of herpetic lesions. The rate of contraction of herpes genitalis was 6 of 54 consorts (11.1%) who received one vaccination and 7 of 293 (2.4%) who received two, three of four vaccinations. There was no evidence of physical or psychological side effects from vaccination.
Adolescent↗
In vivo model for evaluation of species-specific virus vaccines.
It is difficult to evaluate the protective efficacy of species-specific viruses of humans and expensive companion animals where there is no non-human animal model. This study describes an in vivo model system which allows simultaneous operation of humoral, cell-mediated, interferon-like or other unidentified immunological defence mechanisms. There was evidence of in vivo inactivation of both enveloped and unenveloped DNA and RNA viruses including retrovirus mouse sarcoma virus/mouse leukaemia virus as evaluated by assay of the enzyme reverse transcriptase. This model will allow examination of vaccine efficacy in immunocompetent host animals while avoiding morbidity and/or mortality from virus infection in these animals.
Animals↗
Adult domestic violence.
Adult domestic violence in Leicestershire was reviewed by examining the clinical notes of all patients aged 14 years and over attending the Accident and Emergency Department of the Leicester Royal Infirmary in 1988 with a history of assault. Of the 341 patients so classified, 297 victims were identified. This paper describes the results of the review, including the age and gender of the victims, and the nature and cost of the violence. Suggestions are made to improve the management of adult domestic violence.
Adult↗
Advances in cerebral ischemia: experimental approaches.
Drugs that dissolve clots, such as streptokinase and rTPA, and drugs that promote vasodilation are undergoing clinical testing for the treatment of hyperacute stroke, but an adjuvant therapy that either prolongs temporal thresholds before irreversible injury occurs or actually protects the brain from ischemia would transform these trials. Mild hypothermia, either intraischemically or at the onset of reperfusion, provides us with a gold standard for cytoprotection against which new pharmacologic strategies can be measured. The cytoprotective effects of the voltage-sensitive calcium channel blockers and the NMDA antagonists have been relatively less compelling than more recent findings with non-NMDA or AMPA antagonists. Their ability to inhibit SINN or reduce neocortical infarction is remarkable. Future randomized clinical trials for both resuscitated cardiac arrest victims and patients sustaining embolic stroke are predicted by this major advance in the field of stroke medicine.
Animals↗
Cytomegalovirus surveillance following liver transplantation: does it allow presymptomatic diagnosis of cytomegalovirus disease?
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Adult↗
A virus-particle vaccine prepared from bovine mammillitis virus against herpes genitalis.
A vaccine against herpes genitalis was prepared from the extracellular virus particles from baby hamster kidney cells infected with bovine mammillitis virus (BMV) strain "Allerton". The virus was inactivated by formaldehyde followed by ultracentrifugation to concentrate the virus particles and eliminate formaldehyde to an acceptable concentration for immunisation of human subjects. The vaccine was cross antigenic and cross immunogenic with herpes simplex virus type 1. Thirty-four consorts at high risk of herpes genitalis were immunised with two or three doses each containing 10(9) virus particles equialent to approx. 150 micrograms protein. There has been no evidence of local or general side effect in a follow-up period of over 100 patient years. The immunogenicity and protective efficacy of this vaccine in human subjects will be investigated in a double-blind placebo-controlled trial.
Adult↗
Immune inhibition of virus release from human and nonhuman cells by antibody to viral and host cell determinants.
Immune inhibition of release of the DNA viruses, herpes simplex virus types 1 and 2 and pseudorabies virus by anti-viral and anti-host cell sera occurred while two RNA viruses, influenza and encephalomyocarditis, were inhibited only by anti-viral sera (not anti-host cell sera). Simian virus 40 and surprisingly two herpes viruses, bovine mamillitis and equine abortion, were not inhibited by either anti-viral or anti-host sera. Using the herpes simplex virus model, inhibition of virus release was detected in different cells of human and nonhuman origin with cross-inhibition between cell lines of different origin; thus, this form of immunotherapy may not require antibody to be tissue or organ specific. Evidence of inhibition of virus release from neoplastic and leukemic cell lines suggests possible application of this approach to control of virus-mediated leukoproliferative pathology (e.g. Burkitt's lymphoma or adult T cell leukemia).
Animals↗
The N-methyl-D-aspartate antagonist, MK-801, fails to protect against neuronal damage caused by transient, severe forebrain ischemia in adult rats.
The neuroprotective effects of dizocilipine maleate (MK-801), a noncompetitive antagonist of the N-methyl-D-aspartate (NMDA) receptor/channel, were tested in the 4-vessel occlusion rat model of forebrain ischemia. Adult Wistar rats, treated intraperitoneally with MK-801 or saline using several different treatment paradigms were subjected to 5 (n = 208) or 15 (n = 62) min of severe, transient forebrain ischemia. In saline-treated animals, 15 min of ischemia (n = 13) produced extensive and consistent loss of pyramidal neurons in the CA1 zone of hippocampus. The degree and distribution of cell loss were not reduced by single dose preischemic administration of MK-801 at 1 (n = 7), 2.5 (n = 4), or 5 mg/kg (n = 8). In other animals subjected to 15 min of forebrain ischemia, multiple doses of MK-801 (5, 2.5, and 2.5 mg/kg) given immediately and at approximately 8 and 20 hr after cerebral reperfusion (n = 5) did not alter CA1 injury compared to saline-treated controls (n = 5). Five minutes of forebrain ischemia in saline-treated animals, (n = 82) resulted in significantly fewer (p less than 0.001) dead CA1 pyramidal cells and a greater variance compared to animals subjected to 15 min of ischemia. Power analysis of the preliminary saline-treated animals subjected to 5 min of ischemia (n = 22) indicated that 60 animals per group were necessary to detect a 15% difference between MK-801 and vehicle-treated groups. Multidose treatment with MK-801 (1 mg/kg) given 1 hr prior to 5 min of ischemia (n = 60) and again at approximately 8 and 16 hr after recirculation failed to attenuate hippocampal injury.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗