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Biomedical subjects

J Hungerford

Publications and source records attributed to J Hungerford.

At least 19 recordsLinked to original sources

Modelling the field efficacy of a genetically engineered vaccine against the cattle tick, Boophilus microplus.

The cattle tick Boophilus microplus Canestrini (Ixodidae) is an obligate parasite of bovines in the tropics. Vaccination against the tick, using concealed antigens, has previously been demonstrated to give partial protection which can vary under field conditions. In this paper computer modelling is used to evaluate the potential impact of the vaccine on populations of ticks on grazing cattle. The degree and duration of protection required to maintain tick numbers at acceptable levels is investigated. Results of the computer analyses have been used to guide the further development of the vaccine and to support an application for registration of the vaccine for control of the cattle tick in Australia. They demonstrate the contribution that modelling can make in evaluating the novel impacts that new technologies may have on the host-parasite relationship in different ecological environments.

Animals

Commercialisation of a recombinant vaccine against Boophilus microplus.

Increasingly, there is need for methods to control cattle tick (Boophilus microplus) infestations by the use of non-chemical technology. This need is brought about by a mixture of market forces and the failure or inadequacy of existing technology. A recombinant vaccine has now been developed against the tick. This vaccine relies on the uptake with the blood meal of antibody directed against a critical protein in the tick gut. The isolation of the vaccine antigen, Bm86, and its production as a recombinant protein is briefly described. The vaccine has been tested in the field, has been taken through the full registration process and is now in commercial use in Australia. A related development has occurred in Cuba. The potential for improvement of the current vaccine and for the development of similar vaccines against other haematophagous parasites is discussed.

Administration, Oral

Follow-up of retinoblastoma patients having prenatal and perinatal predictions for mutant gene carrier status using intragenic polymorphic probes from the RB1 gene.

We have carried out presymptomatic prediction of mutant gene carrier status in ten individuals with a family history of retinoblastoma. In all cases standard linkage studies were employed using intragenic DNA probes which recognise restriction fragment length polymorphisms. In four cases foetal DNA samples were obtained by chorionic villus sampling, the remaining six were derived from either cord blood samples or venipuncture of neonates. We demonstrated that the mutant gene was inherited by only one of these patients who has subsequently developed bilateral tumours. Six of the other cases have now reached the age beyond which it might have been expected that tumours would develop and are all disease free. It must be concluded that repeated ophthalmological examination of these and future patients shown not to have inherited the mutant gene, is unnecessary.

Base Sequence

Increased expression and mutation of p53 in choroidal melanoma.

Using CM-1 antibody directed against the human p53 protein, high levels of mutant p53 protein expression were found in 12 out of 18 malignant choroidal melanomas. In contrast, we failed to observe elevated p53 expression, indicating the absence of p53 mutation in seven choroidal naevi, a potentially premalignant condition that can progress to form malignant melanoma. For two choroidal melanomas, we demonstrated that high levels of p53 protein were accompanied by exon 7 mutations. The mutations were found at codon 238, TGT-->TTT and codon 253, ACC-->AGC. These observations suggest that acquisition of abnormalities of the p53 gene may be an important step in the development of malignant melanoma.

Animals

Early diagnosis of the retinopathy of incontinentia pigmenti: successful treatment by cryotherapy.

Prospective examination of the ocular fundi was carried out in the newborn female sibling of a girl with incontinentia pigmenti and bilateral retinopathy. At age 3 months the new baby's peripheral retina was found to be avascular in both eyes. At age 2 years progressive vascular proliferation at the watershed area between normal and abnormal retina led to bilateral vitreous haemorrhage. The new vessel tufts promptly regressed when the avascular area in each eye was treated by single-freeze cryotherapy and the blood in the vitreous absorbed. Cicatricial retinopathy was thereby prevented. Prospective retinal examination of newborn female siblings of children with incontinentia pigmenti is advised, with early cryotherapy recommended if progressive neovascularisation is detected.

Child

Electrophoretic assessment of aqueous and serum neurone-specific enolase in retinoblastoma and ocular malignant melanoma.

The isoenzyme pattern of enolase was examined in the aqueous humour and serum of patients with retinoblastoma (10 aqueous, 8 sera), malignant melanoma (4 aqueous, 25 sera), and normal subjects undergoing cataract surgery (25 aqueous, 30 sera). The assay we used allowed assessment of all three major isoenzymes, including the gamma gamma isoenzyme (neurone-specific enolase). No enolase was detectable in normal aqueous; alpha alpha isoenzyme was present in the aqueous of one patient with malignant melanoma, while aqueous from all patients with retinoblastoma contained both alpha alpha and gamma gamma. Normal serum contained only an alpha alpha band, while serum from patients with retinoblastoma contained alpha alpha, alpha gamma, and gamma gamma bands (7 sera, 87.5%), or alpha alpha only (1 patient, 12.5%). All sera from patients with malignant melanoma contained the alpha alpha band, with low levels of gamma gamma in 16 (60%). In a single patient with Coats's disease alpha alpha was present in the serum, but no enolase was detected in aqueous. Increased amounts of gamma-containing isoenzymes of enolase are found in both serum and aqueous from patients with retinoblastoma. In malignant melanoma there is often an increase in serum gamma gamma enolase. The assessment of aqueous and serum enolase patterns may be of value in the diagnosis of retinoblastoma and malignant melanoma.

Aqueous Humor

Detection of ocular malignancies.

The case notes of new patients attending the oncology clinic at Moorfields Eye Hospital during the first 5 months of 1988 were analysed retrospectively with regard to the origin of the primary referral, the presence of symptoms, the diagnosis and management. Sixty-eight of 94 new patients were diagnosed as having malignant ocular lesions. Of these 68, 47% were first seen and referred by an optician. Half of these patients were asymptomatic at the time of detection.

Adolescent

Mesectodermal leiomyoma of the ciliary body: case report.

The clinical, light microscopical, and electron microscopical features of a mesectodermal leiomyoma of the ciliary body are presented. This exceptionally rare and apparently benign tumour is considered to be of neural crest origin. In the case described the tumour cells were seen to contain thin filaments with focal densities and conspicuous numbers of mitochondria, and smooth muscle protein was demonstrated by immunohistochemical means.

Adult

Local extraocular extension of retinoblastoma following intraocular surgery.

Three cases of local extraocular extension of retinoblastoma following intraocular surgery via a transscleral approach have been seen in one centre during a 12-month period. This number represents a significant increase on the previous incidence of this serious complication, which may be related to more widespread use of vitrectomy techniques. Orbital and local lymph node recurrence of retinoblastoma have been associated with a very poor survival rate in the past, and steps must be taken to limit the chance of this happening should an intraocular surgical procedure be performed inadvertently on an eye containing a retinoblastoma. Early enucleation without implant is advised, and adjuvant orbital radiotherapy is strongly recommended, even when there is no histopathological evidence of local extraocular tumour spread.

Child

Demonstration of bias in series of retinoblastoma.

A register of retinoblastoma is being compiled with the aim of complete ascertainment of all cases with a recorded diagnosis of retinoblastoma in the United Kingdom. Sources of ascertainment include patients seen at St Bartholomew's and Moorfields Eye Hospitals, cases recorded in regional cancer registries, and pathology reports. Ascertainment of the Hospital series is complete, but that of the rest of the country is still incomplete. Comparison between the proportions of bilateral and unilateral cases in an age cohort in the Hospital series and the country as a whole shows that the Hospital series is biased towards an excess of bilateral cases.

Eye Neoplasms

Genetic and cytogenetic analysis of patients showing reduced esterase-D levels and mental retardation from a survey of 500 individuals with retinoblastoma.

The authors have analysed the esterase-D levels in 500 retinoblastoma patients of whom 15 showed red cell enzyme activities of approximately 50% that of normal controls. Chromosome analysis of these 15 patients confirmed the presence of a deletion involving region 13q14 in all cases. Seven of the 15 cases had not previously been diagnosed and all of these showed sub-band deletions within 13q14. None of these seven patients were mentally retarded although the remaining eight who showed larger chromosome deletions demonstrated the full spectrum of psychomotor abnormalities associated with 13q deletions. Two other mentally retarded retinoblastoma patients with normal esterase-D activity showed no karyotypic abnormality, demonstrating that mental retardation cannot be taken to indicate a chromosome deletion in all cases. Eight of the 15 deletion cases were only unilaterally affected. The data presented in this article suggest that esterase-D quantitation could provide the primary means of detection of chromosome deletions in retinoblastoma patients.

Adult

Deletion of chromosome region 13q14 is transmissible and does not always predispose to retinoblastoma.

During routine screening of retinoblastoma patients for esterase D activity in red blood cell lysates a patient was identified with only 50% of normal enzyme activity. Chromosome analysis showed that this patient had a small deletion within chromosome region 13q14. Parental studies showed that, whereas the father had normal enzyme levels, the mother had esterase D levels which were also 50% of normal and a similar small 13q14 deletion. Ophthalmological examination failed to demonstrate any retinal abnormality in either parent. Thus we present the first case not only of the direct transmission of a 13q14 deletion within a family but also of an individual in whom the deletion has not predisposed to tumour formation.

Cell Line

Medulloepithelioma (diktyoma).

Sixteen cases of medulloepithelioma are described. Clinical data and follow-up were available on 15. Four patients underwent iridocyclectomy initially; all later needed enucleation and one had an orbital recurrence. The remaining 12 patients underwent primary enucleation. All 15 patients with follow-up are alive with no evidence of tumour recurrence. It is suggested that enucleation be performed for all but the most localised tumour. Rubeosis was noted in 13 of the 16 eyes, and this may assist in making the diagnosis. The World Health Organisation histological classification of medulloepithelioma was applied, but some problems were encountered, particularly where the presence of heteroplastic brain tissue was used as a criterion for teratoid tumour and where rosettes were used as a criterion for malignancy.

Adolescent