Biomedical subjects
Publications and source records attributed to J A Deans.
Schwannomas, arising from the Schwann cells of the nerve sheath, occur very rarely in the sino-nasal tract and histological diagnosis can, sometimes, be difficult. We describe a case of schwannoma of the sphenoidal sinus occurring in a 71-year-old man, who underwent complete excision of the tumour endoscopically. To our knowledge, this is the third case of sphenoid sinus schwannoma reported in the English literature.
This study assessed the effect of needle electrode position on the human cochlear summating potential (SP) obtained by transtympanic electrocochleography (ECochG). Electrocochleography was performed on 10 subjects with large central tympanic membrane perforations with good cochlear function, and in whom a needle electrode could be accurately placed in a series of five pre-determined positions in the middle ear. A comparison of the electrocochleograms revealed a wide scatter of results between different positions in the same patient and between similar positions in different patients. Only when the needle was repositioned at an almost identical recording site in the same subject, was good reproducibility achieved. Such a wide and unpredictable variation in results would suggest great caution is needed when comparing traces obtained using a transtympanic technique which precludes a view of the electrode tip.
Aneurysm of the intrapetrous carotid artery is an extremely rare and potentially serious occurrence that presents diagnostic and therapeutic difficulties. Such aneurysms may follow trauma, atherosclerosis, mastoid surgery or most commonly can represent a developmental abnormality. We present the case of an 18-year-old female with a short history of recurrent left-sided otalgia and epistaxis who underwent successful endovascular balloon entrapment of a left intrapetrous carotid aneurysm.
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The use of diathermy to achieve haemostasis after tonsillectomy remains controversial. We have reviewed the English language literature, and found no convicting evidence that diathermy is any more likely to cause post-operative haemorrhage than the use of ligatures. The results of a prospective, randomized study of 1036 consecutive tonsillectomies are presented. No significant difference was found in post-operative haemorrhage rates when either diathermy or ligatures were used. Diathermy was found to reduce operating time compared to ligatures. The possibilities for day-case tonsillectomy are discussed.
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The views of the membership of the Association of Otolaryngologists in Training (all current UK Senior Registrars and Consultants in their first year of post) were sought on topical aspects of Higher Surgical Training. 80 members (72.3%) participated. The main points to emerge were that the intercollegiate exam is unpopular. 66% feel it is neither well suited to the developing career structure nor a good assessor of trainees, 80% of Senior Registrars for whom the exam is voluntary say they will not sit it, 66% have doubts about the confidentiality of the Specialist Advisory Committee (SAC) interview and 73% felt the need for a separate faculty for Otolaryngology at the Royal College of Surgeons.
A histological study was performed of biopsies taken from jejunal free grafts used in pharyngeal reconstruction. The main findings were a decreased crypt/villi ratio and a mild chronic inflammatory infiltrate. There was no evidence of metaplastic or dysplastic transformation.
A case of acute isolated sphenoid sinusitis is described in a twelve year old boy who presented with ophthalmic complications. The literature is reviewed to emphasize the potential dangers of this condition.
The 66-kDa merozoite surface antigen (PK66) of Plasmodium knowlesi, a simian malaria, possesses vaccine-related properties that are thought to originate from a receptor-like role in parasite invasion of erythrocytes. We report the complete sequence of PK66 which allowed the demonstration that highly conserved analogues exist throughout Plasmodium including a recently reported gene from P. falciparum (Peterson, M. G., Marshall, V. M., Smythe, J. A., Crewther, P. E., Lew, A., Silva, A., Anders, R. F., and Kemp, D. J. (1989) Mol. Cell. Biol. 9, 3151-3155). These analogues are highly promising vaccination candidates. The distribution of PK66 changes after schizont rupture in a coordinate manner associated with merozoite invasion. The protein is concentrated at the apical end prior to rupture, following which it can distribute itself entirely across the surface of the free merozoite. During invasion, immunofluorescence studies suggest that, PK66 is excluded from the erythrocyte at, and behind, the invasion interface.
Auditory brainstem responses are an established technique in the diagnosis of acoustic neuroma. In several reports abnormalities are shown to occur in the contralateral ear. That these abnormalities recover has been demonstrated, but only in terms of changes in inter-peak latency. In only one case has the waveform trace showing this been published. We present a case in which a highly abnormal wave form was obtained from the ear contralateral to a large acoustic neuroma. Following excision of the lesion, the waveform reverted to a normal pattern. The literature on the subject is reviewed.
We report a case in which a squamous cell carcinoma was found to have arisen from a delto-pectoral skin flap used in pharyngeal reconstruction. The flap had been forming a neo-pharynx for 24 years. No other signs of recurrent disease had developed in this period. This raises the possibility of tumour induction in heterotopic skin used for oropharyngeal reconstruction.
A minor Plasmodium knowlesi 66 kD antigen, which plays an essential role in merozoite invasion, has been shown to be stable in distinct variants and strains of the parasite, and in the face of a specific immune response from the host. Parasites were unable to produce novel molecule(s) to replace it functionally, even in the presence of specific immune pressure. Rhesus monkeys immunized with the purified 66 kD antigen, with saponin as adjuvant, produced antibody which inhibited merozoite invasion of red cells in vitro. Four out of six immunized rhesus monkeys demonstrated clinically effective immunity when challenged at a time of known or presumed high inhibitory antibody titre. When immunization failed to protect, it was ascribed to insufficient levels of specific antibody attributable either to a suboptimal dose of antigen or the use of an inadequate adjuvant.
Two monoclonal antibodies, which prevent merozoites attaching to or invading erythrocytes, react with the same or closely apposed epitopes on a minor 66 kDa Plasmodium knowlesi antigen. The antigen is processed, at the time of schizont rupture and merozoite release, to 44 and 42 kDa molecules which are present on the merozoite surface [Deans, J. A. et al. (1984) Mol. Biochem. Parasitol. 11, 189-204]. The monoclonal antibody-defined epitope, which is expressed only once on the 66 kDa molecule, is formed by a tertiary folding of the polypeptide chain (minimum size 42 kDa). The conformation of the epitope is maintained by weak intramolecular forces of attraction, rendering the epitope extremely labile; it is completely destroyed by treatment with sodium dodecyl sulphate (SDS). Polyclonal monospecific antiserum raised against SDS-treated antigen did not inhibit parasite proliferation whereas a polyclonal antiserum raised against native antigen was inhibitory. It is postulated that the monoclonal antibody-defined antigenic determinant is crucial for merozoite invasion.
The simian malaria Plasmodium knowlesi provides many favourable features as an experimental model; it can be grown in vivo or in vitro. Parasites of defined variant specificity and stage of development are readily obtained and both the natural host and a highly susceptible host are available for experimental infection and vaccination trials. Proteins synthesized by erythrocytic P. knowlesi parasites are characteristic of the developmental stage, as are the alterations that the parasite induces in the red cell surface. Erythrocytic merozoites are anatomically and biochemically complex, their surface alone is covered by at least eight distinct polypeptides. Immune serum from merozoite-immunized rhesus recognizes many parasite components, especially those synthesized by schizonts. All of the merozoite surface components and some of the schizont-infected red cell surface antigens are recognized by such immune sera. Rhesus monkeys rendered immune by repeated infection may by contrast recognize comparatively few antigens; a positive correlation was established for these 'naturally' immunized monkeys between protection and antibody directed against a 74 000 molecular mass antigen. Immunization with this purified antigen confers partial protection. Other putative protective antigens have been identified by monoclonal antibodies that inhibit merozoite invasion of red cells in vitro. The antigens recognized by inhibitory monoclonal antibodies are synthesized exclusively by schizonts and are processed, at the time of schizont rupture and merozoite release, to smaller molecules that are present on the merozoite surface. The multiplicity of protective antigens is clearly demonstrated by the fact that seven distinct merozoite surface antigens are recognized by three different inhibitory monoclonals. None of the protective antigens identified are variant or strain specific.
A putative protective Plasmodium knowlesi antigen, recognized by two monoclonal antibodies which prevent invasion of erythrocytes by merozoites in vitro, is synthesised only by schizonts with 7 or more nuclei, during the last 1.5-2 h of the 24 h erythrocytic cycle of parasite development. The 66 000 MW antigen, which constitutes a minor parasite protein, is processed at the time of schizont rupture and merozoite release, to give rise to two smaller molecules of 44 000 and 42 000 MW. The 44 000 and 42 000 MW antigens and traces of the 66 000 MW antigen are present on the surface of isolated merozoites and the smaller antigens are readily shed. The antigens which are shed are soluble in culture medium and are not readily degraded further. None of the molecules can be detected in newly invaded ring stage parasites, indicating that they are either excluded when the merozoite invades, or if internalised, they rapidly undergo further structural alteration since newly parasitised red cells no longer contain epitopes which react with the inhibitory monoclonal antibodies. This antigen is distinct from other putative protective antigens described in bloodstage malaria parasites.
Two rat monoclonal antibodies (both IgG2a isotype and having closely related specificities) and a pool of rhesus immune IgG, all of which inhibit Plasmodium knowlesi merozoite invasion of rhesus erythrocytes, have been studied before and after proteolytic digestion. The F(ab')2 and Fab fragments of both rat monoclonal antibodies show considerably enhanced inhibition of merozoite invasion as compared with the intact IgG. Inhibition by monovalent fragments indicates that these antibodies are not dependent upon merozoite agglutination and may act by blocking merozoite attachment to the specific red cell receptor. The fact that the inhibitory activities of F(ab')2 and Fab are equally enhanced on a weight basis, as compared with IgG, suggests that the removal of Fc may reduce electrostatic repulsion between antibody and merozoite surface, both of which are negatively charged at neutral pH. By contrast, papain digestion of polyclonal IgG derived from an immunised rhesus pool markedly reduces its inhibitory activity. This suggests that much of the inhibition mediated by polyclonal IgG results from merozoite agglutination and that the specificity of the rat inhibitory monoclonal antibodies is poorly represented in the immune pool. The P. knowlesi antigen reactive with the inhibitory monoclonal antibodies is known to be synthesized as a minor 66 kDa polypeptide during the last 1.5 h. of schizont development and is processed to smaller products (44 and 42 kDa) present on the merozoite surface. The present results suggest that this antigen may have particular interest as a vaccine against P. knowlesi malaria.
P. knowlesi parasites with a maximum age distribution of 3 h were metabolically labelled with [35S]methionine during 9 sequential non-overlapping intervals, from young rings to mature segmented schizonts. The proteins synthesised at the different stages were compared using sodium dodecyl sulphate-polyacrylamide gel electrophoresis; more than 40 polypeptides (Mr 20 000 to over 200 000) were identified in the different parasite preparations. The major polypeptides synthesised by rings and trophozoites of different ages were similar, but differences in minor polypeptides could always be recognised. At the onset of schizogony ring and trophozoite specific proteins ceased to be synthesised and proteins specific to schizogony emerged. In general, schizont-specific proteins were of higher molecular weight than ring stage proteins. Details of the morphological changes which occurred during the metabolic labelling episode permits correlation between parasite structure and synthesis of particular polypeptides. Comparison of parasite components metabolically labelled with [3H]glucosamine during defined periods of development also revealed stage-specific synthesis of glycoproteins. The extent to which proteins are altered after synthesis has been investigated by pulse-chase experiments.