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Biomedical subjects

G Dunn

Publications and source records attributed to G Dunn.

At least 109 records · Page 6Linked to original sources
PubMed1991

Outcome following resective surgery for temporal lobe epilepsy: a prospective follow up study of 102 consecutive cases.

The long term outcome has been assessed in a consecutive series of 102 cases undergoing resective temporal lobe surgery because of medically intractable epilepsy. Patients were followed prospectively for a median of 61 months. Actuarial statistics were used to measure the temporal patterns of remission and stability of outcome over prolonged periods of observation. The probability of achieving one year remission was 57% by one year, 70% by two years, and 77% by seven years. Once a patient was in one year remission the probability of remaining seizure free was 90%. This rose to 94% after two consecutive years of being seizure free. The majority of patients who remit following surgery have done so by two years of follow up. Outcome at the end of the second post operative year is a good predictor of long term prognosis.

Adolescent↗
PubMed1990

Virus excretion and mutation by infants following primary vaccination with live oral poliovaccine from two sources.

The excretion of virus by 30 children was followed over a period of 28 days after their first vaccination with live oral poliovaccine. The type 1 and type 2 strains were isolated at similar high frequencies throughout this period, while the type 3 strain was not excreted by most children after day 2 post vaccination. Mutations in the 5' non-coding region associated with the attenuated phenotype reverted most rapidly for type 3 and least rapidly for type 1. The data are consistent with different degrees of selection against the attenuating mutations in the three serotypes in the gut, but imply that reversion is required for prolonged excretion. The findings also provide a possible explanation for the reported distribution of the rarely occurring vaccine associated cases between recipients and contacts for the three serotypes. A statistically significant difference was not observed between vaccine from the two main suppliers to the UK market.

Cells, Cultured↗
PubMed1990

Conservation of the breast using two different radiotherapy techniques: interim report of a clinical trial.

Patients with a clinically palpable breast carcinoma, 4 cm or less in diameter, and with no palpable nodes in the axilla were prospectively entered into a randomized clinical trial. A total of 713 patients were registered between November 1982 and December 1987, of whom 708 are evaluable at a median follow-up of 37 months. Following excision of the primary tumour, patients were randomly allocated either to have radiotherapy to the affected quadrant only (LF group) or to the whole breast and regional lymph node areas (WF group). No adjuvant hormone or chemotherapy was prescribed. The primary tumour was reported as completely excised histologically in 80% of cases, incompletely excised in 10%, and no estimate was possible in 10%. At six years from first randomization, 96% of the WF group and 92% of the LF group have remained free of breast recurrence (94% and 87% actuarial breast recurrence-free survival at 5 years). Part of the difference may be explained by the 20% recurrence rate in the breast for lobular carcinomas treated within the LF group. Of the WF group 14 patients (4%) developed recurrent disease in the axilla, compared to 50 patients (14%) in the LF group (95% and 86% actuarial axillary recurrent-free survival at 5 years). Patients with primary tumours histologically 1 cm or less in diameter had a 98% actuarial 5-year survival compared with 74% for those with tumours measuring 2 cm or more in diameter (P = 0.003). Continued follow-up of these patients will provide further information on the factors governing local/regional recurrence.

Breast Neoplasms↗
PubMed1990

Antigenic structure of chimeras of type 1 and type 3 poliovirus involving antigenic site 1.

Chimeric polioviruses have been prepared in which part of the antigenic site 1-encoding sequence of the Sabin strain of type 1 poliovirus has been replaced by sequences based on those found in the homologous region of the Sabin type 3 strain. The chimeras were analysed for their reaction with polyclonal and monoclonal antibodies raised against type 1 and type 3 viruses, and with polyclonal antipeptide sera, as well as for their immunogenicity in animals. The effectiveness with which the type 3 site was presented antigenically varied in ways which were partially predictable, based on the behaviour of type 3 mutants with monoclonal antibodies. However, other factors were implicated which may include conformational effects and other components of the site in addition to those altered in the chimeras. The ability of the chimeras to induce antibodies reacting with type 3 polioviruses paralleled their antigenic reactivity, and evidence is presented for the induction of strain-specific antibodies.

Animals↗
PubMed1990

Molecular biology and the control of viral vaccines.

The live attenuated vaccines against poliomyelitis developed by Sabin are among the safest and most effective antiviral vaccines in current use and have eliminated poliomyelitis as a public health problem in many countries. They form the main basis of the WHO intention to eliminate poliomyelitis from the world by the year 2000, and the molecular basis of their attenuated phenotype and some of its virological consequences are increasingly clear. Nonetheless, the data reviewed here show how poorly understood their mechanism of action is in use. Our studies raise the possibility of in vitro neurovirulence tests and may help to identify features of particular importance in the attenuation of the virus for human rather than simian recipients. On the other hand it is clear that when a live virus is used as a vaccine it is not possible to control it in the same way that genetically engineered products may be controlled in so far as replication in the recipient makes it possible for the live vaccine strain to alter in ways which may or may not be undesirable.

Base Sequence↗
PubMed1990

Alcoholism: a follow-up study of participants in an alcohol treatment programme.

One hundred and twelve alcoholic patients treated by an intensive one-month residential programme were followed up for one year. As a group, they were socially disadvantaged and highly dependent on alcohol. Outcome of treatment was assessed at six months and one year following discharge by multiple measures which included assessments of drinking behaviour, measurements of social stability, neuroticism and self-esteem, and self-ratings of satisfaction with important aspects of day-to-day living. During the first six months following treatment, 37% were abstinent or drinking in controlled fashion; during the second six months, 53% achieved this status. Improvement in drinking status was positively related to improvements in all other outcome variables.

Adult↗
PubMed1990

Transvaginal sonographic evaluation of the retrodisplaced uterus.

To determine the clinical value of transvaginal sonography in the assessment of retrodisplaced uteri, the authors reviewed, retrospectively, 500 consecutive transvaginal (TV) and transabdominal (TA) sonograms. Of the 494 patients examined, 27 had a retrodisplaced uterus. Transvaginal sonography was superior to TA sonography in 25 patients, providing improved visualization of the endometrial canal, myometrium, adnexa and cul-de-sac. In 7 of these 25 patients, the findings that suggested the diagnosis were only seen on TV scanning. These findings included intrauterine pregnancy (three patients), fluid collection in the cul-de-sac (two patients), fluid collection in the endometrial canal (one patient) and an embedded intrauterine contraceptive device (one patient). The two techniques yielded the same information in two other patients. In no patient was TA sonography more informative than TV sonography. The authors, therefore, conclude that TV sonography is the procedure of choice in assessing a retrodisplaced uterus and that additional examination with TV sonography is advisable whenever a retrodisplaced uterus is suspected.

Female↗
PubMed1989

New model for the secondary structure of the 5' non-coding RNA of poliovirus is supported by biochemical and genetic data that also show that RNA secondary structure is important in neurovirulence.

A secondary structure model for the 5' non-coding RNA of poliovirus has been derived by comparing computer-generated folding patterns of equivalent sequences from a number of related enteroviruses and rhinoviruses and identifying compensating mutations that suggest conservation of a common secondary structure. Although certain elements are similar, the new model differs considerably from a previously published minimal energy structure and is consistent with the observed sensitivity of in vitro RNA transcripts of infectious poliovirus cDNA to RNases and modifying chemicals. The sequence of a neurovirulent revertant of an attenuated mutant provides additional evidence for an interaction between a region known to be important for neurovirulence, sequence 471-483, and nucleotides 528 to 538.

Animals↗
PubMed1989

The temperature sensitivity of the Sabin type 3 vaccine strain of poliovirus: molecular and structural effects of a mutation in the capsid protein VP3.

The growth of the Sabin strain of type 3 poliovirus is reduced at high temperatures compared to that of its virulent precursor strain Leon. Recombinant viruses have been generated from infectious cDNA clones and demonstrate that the temperature-sensitive (ts) phenotype is mainly attributable to a difference in residue 91 of the virion protein VP3. Examination of non-ts mutants derived in vitro or in vivo reveals the existence of second site mutations some of which are clearly able to suppress the ts phenotype. The location of residue 91 of VP3, and of a number of candidate suppressor mutations, in the atomic structure of the virion suggests that the ts phenotype may result in destabilization of the particle and that the suppressors may function by stabilizing specific interfaces. It is not yet clear whether the ts phenotype is expressed at the level of the particle or in the form of defects in assembly or uncoating of the virion, or all three.

Amino Acid Sequence↗
PubMed1989

Nucleotide sequence of a neurovirulent variant of the type 2 oral poliovirus vaccine.

Infectious cDNAs of the Sabin type 2 poliovirus vaccine virus and a vaccine-derived neurovirulent type 2 strain (P2/117) have been cloned in Escherichia coli. Nucleotide sequence analysis revealed that P2/117 differs from the vaccine strain by just 23 point mutations. Three occur in the 5' noncoding region. The remainder result in a total of 5 coding changes located in VP1, VP4, 2B, and 3D. The likely role of these mutations in the evolution to neurovirulence is discussed.

Animals↗
PubMed1989

Genetic basis of attenuation of the Sabin type 3 oral poliovirus vaccine.

The poliovirus type 3 Sabin oral poliovirus vaccine strain P3/Leon/12a1b differs in nucleotide sequence from its neurovirulent progenitor P3/Leon/37 by just 10 point mutations. The contribution of each mutation to the attenuation phenotype of the vaccine strain was determined by the construction of a series of recombinant viruses from infectious cDNA clones. The neurovirulence testing of recombinant viruses indicated that the attenuation phenotype is determined by just two point mutations: a C to U in the noncoding region at position 472 and a C to U at nucleotide 2034 which results in a serine-to-phenylalanine amino acid substitution in the structural protein VP3.

Amino Acid Sequence↗
PubMed1988

Antigen chimaeras of poliovirus as potential new vaccines.

Polioviruses occur as three distinct serotypes, 1, 2 and 3, and are composed of a single-stranded positive-sense RNA genome of approximately 7,450 nucleotides enclosed in an icosahedral particle of diameter 27 nm. The three-dimensional crystallographic structure of poliovirus type 1 has been determined at 2.9 A resolution, providing a detailed knowledge of the folding and arrangement of the individual virus proteins, VP1-VP4. From this and the characterization of monoclonal antibody-resistant mutants, the amino acids contributing to antigenic sites have been identified and located on the surface of the virus particle. Here we describe the construction and characterization of a poliovirus chimaera having a defined region of type 3 inserted into type 1. This virus has composite antigenicity and the substitute site is immunogenic in small animals and primates. The ability to construct such viruses has implications for the design of improved poliovirus vaccine strains or vaccines against other picornaviruses, such as hepatitis A.

Animals↗
PubMed1988

'Optimal' designs for drug, neurotransmitter and hormone receptor assays.

The present paper reports the use of computer simulations of ligand-receptor interactions to evaluate the robustness of D-optimal designs for receptor assays when these designs are based on unrealistic models for ligand binding. Particular attention is paid to the assumed distribution of the measurement errors together with complications caused by 'non-specific' binding of a radioligand to a tissue or cell preparation. It is the latter factor which suggests that an optimal design for estimation of the parameters of a simple hyperbolic dose-response curve is nowhere near to being optimal in practice.

Computer Simulation↗
PubMed1988

Chronic antidepressant drug regimes and food and water intake in rats.

Food and water consumption were measured in rats prior to and during a course of antidepressant drug administration. Desmethylimipramine (DMI, 10 mg/kg/day), clorgyline (1.0 mg/kg/day) or saline were injected IP for 30 days. Food and water intake in the DMI- and clorgyline-treated rats was initially and significantly decreased but progressively returned towards pretreatment levels over the course of the drug administration. The effects of these antidepressant drug treatments on food and water intake appeared to consist of two components: (a) a rapid suppressive effect, possibly associated with an acute central action of these drugs (and perhaps a slight initial stress effect related to the drug administration) and (b) an adaptive effect over the course of the treatment which may involve changes in monoaminergic neurotransmitters or receptor status in those brain regions associated with feeding behavior. The similarities of the results of these treatments and those seen with chronic stress are discussed.

Animals↗
PubMed1988

Circadian studies of 5HT2 receptors: effects of clorgyline administration.

This paper demonstrates the application of an assay design that is particularly valuable for estimating receptor number (Bmax values) and affinity (Kd values) in many small samples of tissue. It is illustrated by its application to a study of possible circadian rhythms in the numbers of 5HT2 receptors in the rat cerebral cortex. The assay design involves the use of only two radioligand concentrations, the lower one being close to Kd (estimated from pilot studies) and the upper one close to 4 times this concentration. The results show that chronic clorgyline (1 mg/kg/day/28 days) administration to rats results in an 18% decrease in the number of cortical 5HT2 receptors (as measured by specific [3H]ketanserin binding). There is no significant circadian rhythm in receptor number in either the control or the MAOI-treated group. There is however, evidence of co-variation between the pairs of control animals housed in the same cage, and interestingly, that this effect is abolished by treatment with the MAOI.

Animals↗