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Biomedical subjects

A Buchan

Publications and source records attributed to A Buchan.

At least 73 records · Page 4Linked to original sources

Intraluminal thrombus of the internal carotid arteries: angiographic demonstration of resolution with anticoagulant therapy alone.

Fourteen patients with angiographically demonstrated thrombus in the cerebral vessels were treated immediately with anticoagulant or antiplatelet medication. Follow-up angiograms, obtained in eight cases, showed resolution of the thrombus in seven. In no patient did the thrombus progress to occlude the vessel completely, and no new distal emboli were identified on the follow-up angiograms. There were no new permanent neurologic events in these 14 patients while they were undergoing medical therapy. Six patients subsequently underwent delayed endarterectomy to treat underlying stenoses. Our experience indicates that the presence of intraluminal thrombus may not be a surgical emergency.

Adult↗

Control of herpes simplex virus infections of the genital tract by vaccination.

The apparent increasing incidence of herpes simplex virus infections of the genital tract has focused attention on the efficacy of vaccination in preventing infection or modifying established disease. Results of an 'open trial' using a DNA-free inactivated virus subunit vaccine have shown that vaccination of subjects at risk of contracting infection from their sexual partner reduced the transmission rate from 34% in unvaccinated controls to 0.5%. In a separate study, vaccination of patients who had experienced their first overt attack of herpes genitalis (the initial clinical episode) had significantly fewer recurrences over the follow-up period of 12 months than the unvaccinated control group. The results, we feel, justify a placebo controlled trial.

Adolescent↗

The relative infrequency and low levels of neutralising and immunoprecipitating antibody to herpes simplex viruses types 1 and 2 in patients with a history of recurrent herpes genitalis.

Twenty-seven per cent of 70 patients with a history of recurrent herpes genitalis but no concomitant history of recurrent oral or peri-genital disease, had no detectable neutralising antibody against type 1 or type 2 herpes simplex virus; the prevalence and levels of neutralising antibody were similar to 53 patients with no history of herpetic disease and significantly lower than 67 patients with a history of recurrent herpes genitalis in association with oral or peri-genital disease all of whom had neutralising antibody against both virus types. There were similar differences between groups for immunoprecipitating antibody where 80% of patients were herpes genitalis alone had no detectable immunoprecipitating antibody. The results indicate that the failure to detect immunising and immunoprecipitating antibody in an individual's serum is compatible with a long and even severe history of recurrent herpes genitalis and consequently that the development of neutralising antibody does not necessarily indicate an episode of primary herpetic disease.

Antibodies, Viral↗

Efficacy of vaccine Ac NFU1 (S-) MRC 5 given after an initial clinical episode in the prevention of herpes genitalis.

A subunit antigenoid vaccine, Ac NFU1 (S-) MRC 5, was used in patients who had had a clinical episode of herpes genitalis. The rate of recurrence was compared with that in unvaccinated patients to determine the efficacy of vaccination in preventing recurrence and spread of the virus in the community. Seven of 22 (31%) vaccinated patients had eight recurrences after the initial clinical episode; in contrast there were 51 recurrences in 17 of 20 (85%) unvaccinated patients. Although further studies are needed, the results indicate that the vaccine may prevent recurrent episodes of herpes genitalis and thereby reduce the dissemination of this virus in the population.

Adolescent↗

Expression of cloned herpesvirus genes. I. Detection of nuclear antigens from herpes simplex virus type 2 inverted repeat regions in transfected mouse cells.

Three different recombinant plasmids containing the entire 15-kilobase L and S inverted repeat sequence of herpes simplex virus type 2 DNA have been introduced into cultured Ltk- or BSC cells by both the calcium and DEAE-dextran transfection procedures. In each case, after 24 h approximately 1% of the cells gave strongly positive nuclear staining when assayed by immunofluorescence with hyperimmune antisera made against early and immediate-early infected-cell polypeptides. The nuclear fluorescence pattern and intensity mimicked that observed within 2 to 3 h after infection of Ltk- cells with either herpes simplex virus type 1 or type 2 wild-type virus. Herpes simplex virus type 1 (KOStsB2)-infected Ltk- cells under nonpermissive conditions did not express these antigens in the nucleus. Therefore, we conclude that either one or both of the 185,000- and 110,000-molecular-weight immediate early proteins, or some other as yet unknown gene product encoded entirely within the inverted repeats, can be transiently expressed in large amounts in transfected cells in the absence of other viral genes or accompanying virion components. Permanent mouse cell lines derived from transfection with these plasmids by using the thymidine kinase coselection procedure did not express sufficient nuclear antigen to be detectable by immunofluorescence.

Animals↗

Preparation and immunogenicity of vaccine Ac NFU1 (S-) MRC towards the prevention of herpes genitalis.

A subunit antigenoid vaccine, Ac NFU1 (S-) MRC, was used to prevent primary herpes genitalis in 60 subjects considered to be at risk of this infection. There was no evidence of serious local or general side effects. Neutralising antibody responses were detected in 59% and 90% of subjects receiving the low and high doses of vaccine respectively; immunoprecipitating antibody was detected at a lower frequency, namely in 23% and 43% of subjects receiving the low and high doses respectively. After a mean follow-up period of 18 months none of the vaccinated subjects contracted herpes genitalis after completing the vaccination course.

Adult↗

Early experience with "antigenoid" vaccine Ac NFU1(S-) MRC towards prevention or modification of herpes genitalis.

The preparation and early clinical experience with "antigenoid" vaccine Ac NFU1(S-) MRC is described. A neutralising antibody response against both type 1 and type 2 herpes simplex virus was stimulated in 19 of 21 and 25 of 60 patients who received the high and low dosage of vaccine, respectively: immunoprecipitating antibody against type-common virus antigen "band II", a virus antigen of major importance in neutralization of herpes simplex virus, was detected in 12 of 19 and 2 of consorts who received the high and low dosage vaccine, respectively. To date, after a mean follow-up period of one year, none of the 42 consorts have contracted herpes genitalis: following a mean follow-up period of 6 months, only 1 patient vaccinated after the initial clinical episode has reported a recurrence of herpetic disease. These results compare favourably with the rates of consort transmission and first year recurrences in unvaccinated subjects. Seventeen of 24 patients with recurrent herpetic disease reported an "improvement" in terms of modification of the frequency, severity or extent of herpetic lesions. There were no important side-effects from vaccination: most patients experienced a degree of minor local reaction at the vaccination site for 24-72 hours and 3 patients reported a mild transient "flu-like" syndrome which disappeared within 48 hours of vaccination. It is intended to subject these data to the scrutiny of a placebo-controlled trial with an objective system of clinical assessment.

Animals↗

Synthesis of immunoglobulins by human endocervix in organ culture.

The synthesis of immunoglobulins by the uterine cervix was investigated in an endocervical organ-culture system. Using Ouchterlony immunodiffusion gels immunoglobulin G, immunoglobulin A and secretory piece were detected in washings of endocervical explants and in explant incubation medium. Synthesis of immunoglobulin in the organ-culture system was investigated by polyacrylamide-gel electrophoresis of radiolabelled polypeptides; 2 polypeptides co-migrated with the heavy and light chains of a reference polyclonal immunoglobulin G and were confirmed, by use of anti-human globulin and iodinated staphylococcal protein A, to be the heavy and light chains of immunoglobulin G. This experimental system will provide a useful model in future investigations of the efficacy of a local vaccine in human subjects.

Adult↗

Molecular genetics of herpes simplex virus. VI. Characterization of a temperature-sensitive mutant defective in the expression of all early viral gene products.

The herpes simplex virus 1 (HFEM) mutant tsB7 failed to express any detectable viral polypeptides and did not significantly inhibit host cell protein synthesis in infected cells maintained at the nonpermissive temperature. The mutant could complement the growth of a coinfecting temperature-sensitive mutant virus differing in plaque phenotype and thus appeared capable of penetrating doubly infected cells. The yield of tsB7 was enhanced by the coinfecting virus but not to the extent that the coinfecting virus was enhanced. Coinfection studies suggested that the tsB7 defect was complemented in trans, but poorly, by the wild-type parent and other viruses. Marker rescue of tsB7 by transfection with herpes simplex virus 2 XbaI DNA fragments mapped the mutation between 0.45 and 0.70 map units. Analysis of the DNA structure of the ts(+) intertypic recombinants generated by this rescue showed that the herpes simplex virus 2 DNA substitutions all contained the region between 0.46 and 0.52 map units, thus further defining the map position of the mutation. Analyses of the polypeptides expressed by these intertypic recombinants defined the genome location of the genes specifying polypeptides 2, 6, 10, 32, 43, and 44 and indicated that the mutation maps in or near genes coding for virion structural polypeptides. This region of the genome is represented as stable transcripts and cytoplasmic mRNA only after viral DNA replication (P. C. Jones and B. Roizman, J. Virol. 31:299-314, 1979), and thus this gene appears to be a late function. These results are consistent with the ts mutation in tsB7 being in a gene coding for a virion component which functions before expression of the alpha genes early in infection. The most likely explanation is that the mutant is blocked at a stage of uncoating and the defect is complemented, although poorly, by a coinfecting virus gene product.

Animals↗

Septal elicitation of hippocampal theta rhythm after localized de-afferentation of serotoninergic fibers.

Previous experiments using serotonin antagonists and electrolytic raphe lesions suggest that the serotonergic input to the hippocampus inhibits low frequencey (< Hz) theta rhythm in the rat, whereas experiments using raphe stimulation suggest facilitation. The present experiments employed neurotoxic lesions of the serotonergic input to the hippocampus in an attempt to reproduce the effects of systemically administered antagonists. If the septal area is stimulated at frequencies between 6 and 10 Hz in the rat, the threshold current for driving hippocampal theta is minimum at 7.7 Hz. Systemic blockage of serotonergic synapses has been shown to shift this minimum to 6.9 Hz. In the present experiments, neurotoxic lesions were made with injections of 5,7-dihydroxytryptamine into the cingulum bundle, fornix or both. The observed effect depended on the loss of serotonin in the hippocampus, rather than the site of injection, and extensive depletion shifted the minimum to 6.9 Hz. These results indicate that the fornix and cingulum serotonergic inputs to the hippocampus are functionally homogenous, at least with respect to this response; and that the effects of systemic manipulation of serotonin systems on the septal elicitation of hippocampal theta rhythm may be attributed to changes in these two inputs.

Afferent Pathways↗

The effect of lithium chloride on the replication of herpes simplex virus.

Lithium chloride inhibited the replication of type 1 and type 2 Herpes simplex virus at concentrations which permitted host cell replication. Virus polypeptide and antigen synthesis were unaffected while viral DNA synthesis was inhibited. The replication of two other DNA viruses, pseudorabies and vaccinia virus, was inhibited but there was no inhibition of two RNA viruses, namely, EMC and influenze virus.

Antigens, Viral↗

The preparation, efficacy and safety of 'antigenoid' vaccine NFU1 (S-L+) MRC toward prevention of herpes simplex virus infections in human subjects.

Vaccine NFU1 (S-L+) MRC was prepared by high multiplicity infection of serum-deprived human embryonic lung (MRC 5) cells with type 1 Herpes simplex virus. The preparative process removed inoculum virus particles and virus DNA while virus particle and DNA synthesis was inhibited by the presence of lithium chloride in the cell culture medium. The vaccine stimulated neutralising antibody in vaccinated mice and provided long-term protection against intra-vaginal challenge with type 2 herpes virus. The safety of the vaccine was confirmed by inoculation into newborn mice and cell lines of human, mammalian, and rodent origin. There was no evidence of cell transformation in vitro or of oncogenicity or teratogenicity in rodent species. It is intended to investigate the efficiency of this vaccine in human subjects.

Animals↗

Recombination and linkage between structural and regulatory genes of herpes simplex virus type 1: study of the functional organization of the genome.

Phenotypic and genetic properties of 12 markers in structural and regulatory functions of herpes simplex virus type 1 were characterized, and their recombination and segregation behavior was investigated and interpreted with reference to available information on their physical locations. The markers were: (i) ts markers in a structural glycoprotein (tsB5) and in alpha (immediate early; tsLB2, tsc75) or beta (early, delayed early; tsB1) functions with regulatory effects; together with (ii) plaque morphology (syn), phosphonoacetate resistance (Pr), and thymidine kinase (TK) phenotypes; and (iii) electrophoretically distinct variants of glycosylated (glycoprotein C, gpC; ICP10) and non-glycosylated [VP(13-14), VP23] structural and nonstructural [ICP(47-48)] polypeptides. Mean two-factor recombination frequencies ranged from 2% (for noncomplementing mutants tsLB2 and tsc75) to 35 to 40% (for unlinked markers) and were influenced by the relative contributions of parental viruses to the mixed infection. Even with control of this variable, standard deviations of mean measures of recombination frequency ranged from a minimum of 14% (with n greater than or equal to 10) to 65% (with n = 3) of mean values; no recombination frequencies higher than 55% were observed. Differences in mean two-factor recombination frequencies between a small number of loosely linked markers were, therefore, not reliable measures of real differences in linkage. Measurements of the segregation of unselected markers among recombinant progeny were, therefore, used as measures of linkage. These experiments (i) established a linkage group for markers in the long unique region of the genome additional to, but consistent with, existing physical data, i.e., TK-syn-tsB5-(tsB1.Pr)-[gpC.VP(13-14)]; (II) identified markers, e.g., ICP(47-48), linked to regulatory mutations (tsLB2, tsc75) in redundant DNA sequences; and (iii) used the segregation of these regulatory mutations and linked markers among unselected progeny to demonstrate the linkage groups: Pr-syn-TK-tsc75-ICP(47-48), [VP(13-14).gpC]-Pr-syn-TK, and TK-tsc75-[VP(13-14).gpC]. These results were most simply explained if bi- or intermolecular recombination occurred between circular molecules or molecules catenated "head-to-tail" and were incompatible with intermolecular recombination as the mechanism of isomerization of herpes simplex virus DNA.

Genes↗