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R Allibone

Publications and source records attributed to R Allibone.

7 recordsLinked to original sources

Genetic abnormalities detected in ependymomas by comparative genomic hybridisation.

Using comparative genomic hybridisation, we have analysed genetic imbalance in a series of 86 ependymomas from children and adults. Tumours were derived from intracranial and spinal sites, and classified histologically as classic, anaplastic or myxopapillary. Ependymomas showing a balanced profile were significantly (P<0.0005) more frequent in children than adults. Profiles suggesting intermediate ploidy were common (44% of all tumours), and found more often (P<0.0005) in tumours from adults and the spinal region. Loss of 22q was the most common specific abnormality, occurring in 50% of spinal (medullary) ependymomas and 26% of tumours overall. Genetic profiles combining loss of 22q with other specific abnormalities--gain of 1q, loss of 6q, loss of 10q/10, loss of 13, loss of 14q/14--varied according to site and histology. In particular, we showed that classic ependymomas from within the cranium and spine have distinct genetic profiles. Classic and anaplastic ependymomas with gain of 1q tended to occur in the posterior fossa of children and to behave aggressively. Our extensive data on ependymomas demonstrate significant associations between genetic aberrations and clinicopathological variables, and represent a starting point for further biological and clinical studies.

Adolescent↗

Novel ERBB4 juxtamembrane splice variants are frequently expressed in childhood medulloblastoma.

We recently reported a significant relationship between tumor cell expression of the ERBB4 receptor, the most recently described member of the epidermal growth factor receptor family, and aggressive tumor phenotype in childhood medulloblastoma. Two alternative juxtamembrane (JM) isoforms of the ERBB4 receptor have been described. Termed JMa and JMb, these variants possess different receptor processing and ligand-binding characteristics. In the current study, we employed an RT-PCR and sequencing strategy to determine the pattern of ERBB4 JM isoform expression in a large (n = 78) series of pediatric medulloblastomas. JMa and JMb transcript expression was detected in 53% and 28% of tumor samples, respectively. In addition, two novel ERBB4 JM isoforms, which we have termed JMc and JMd, were isolated from 10% and 36% of tumors, respectively. Sequence analysis revealed the JMc transcript to contain a deletion of the entire JM region. In contrast, JMd includes an extended coding region, retaining both the JMa and JMb sequences. Neither of these novel isoforms was detected in normal human adult cerebellum, but expression of JMd was observed in developing fetal cerebellum, suggesting that this later isoform may represent an ERBB4 transcript restricted to primitive neuroectoderm-derived tissue. To confirm that the four ERBB4 JM isoforms arise by alternative RNA splicing, we sequenced the intron-exon junctions of the human ERBB4 gene within the JM region. This demonstrated the four ERBB4 JM variants to be encoded by two short exons containing the JMb and JMa sequences positioned in the order 5' to 3' and separated by a 121 bp intron.

Alternative Splicing↗

Primary cerebral non-Hodgkin's lymphoma: problems with diagnosis and development of a protocol for management.

The prognosis for primary cerebral non-Hodgkin's lymphoma has improved markedly in the under-70 age group with the introduction of combined chemotherapy and radiotherapy. A review of our patients has revealed difficulty in obtaining definitive histology initially in 21% (9/43). We investigated the role of corticosteroids in these patients and found an idiosyncratic response in that there was no significance either of the cumulative dose (p > 0.424) or the length of treatment (p > 0.453) with the observed regression of lymphoma with corticosteroids. In order to avoid indiscriminate corticosteroid administration we have formulated a management protocol the entry point for which is a patient with enhanced computered tomography appearances of primary cerebral lymphoma.

Adult↗

Extraction and protein sequencing of immunoglobulin light chain from formalin-fixed cerebrovascular amyloid deposits.

Substantial amounts of a single protein have been extracted into electrophoresis sample buffer from archived formalin-fixed brain blood vessels, taken from a case of cerebral amyloidosis. Cyanogen bromide cleavage and tryptic digestion of the protein on Western blots allowed amino acid sequences from three resultant peptides to be determined. Comparison of these peptides with database sequences identified the extracted protein as being derived from an immunoglobulin light chain. This is the first demonstration of amino acid sequencing of a polypeptide extracted from formalin-fixed tissue. This case also appears to be unique, since primary cerebrovascular amyloidosis involving immunoglobulin light chains has not been previously described. The amyloid protein had clearly resisted formalin fixation; it is possible that this resistance occurred because the protein was deposited in large amounts as insoluble densely packed aggregates, which may exclude infiltration of the formalin. This technique may therefore have applications in the post-mortem diagnosis of amyloidoses and in the purification of other amyloids.

Adult↗

Topographical variation in the calcified zone of upper femoral articular cartilage.

A series of 27 adult human femoral heads has been examined for topographical variation in 'remodelling' and other histological features of the calcified zone at the base of the articular cartilage. The specimens were obtained from necropsies; hip joints with osteoarthritic bone exposure were excluded. A tissue sample from the inferomedial aspect was compared with one from the femoral zenith, using a standard length along the articular contour at each site. Histological sections were cut in a plane vertical to that of the articular surface. A study was made of the various patterns seen within cartilage tidemarks when these were examined at high magnification in paraffin sections stained with Ehrlich's haematoxylin and eosin. Special attention was paid to the identification of tidemark segments which stained faintly and were not readily apparent. The tidemarks were mapped on a photomicrographic montage from each of the tissue samples. When a sample showed evidence of one or more extra phases of cartilage calcification, as indicated by the presence of more than one tidemark, the spatial extent of the extra calcification was quantified by linear measurement and by point counting on the photomicrographic montage. The mean of the results for the spatial extent of extra-phase calcification of the cartilage was greater for the inferomedial than for the zenith samples. However, it was also greater for samples where the articular surface showed minimal fibrillation than for samples where the surface was still intact, and it was noted that surface fibrillation was much more common in the inferomedial than in the zenith samples. Where there was more than one tidemark, the lowest sometimes showed gaps where it had been breached by an advance of ossification into the calcified cartilage. The mean value of the tangential extent of such gaps was similar at the two sites sampled. Focal contacts, where the uncalcified articular cartilage was in contiguity with calcified zone 'defects' containing tissue other than calcified hyaline cartilage, were more numerous at the femoral zenith than inferomedial to the fovea. Counts were also made of tangential shearing splits at the interface of the calcified and uncalcified cartilage. Subject to the reservation that genuine splitting may be difficult to distinguish from technical artifact, the mean number was closely similar at the two sites sampled. The interpretation of the findings is discussed in relation to remodelling changes in the cartilage base and to degenerative changes in the overlying articular cartilage.

Adult↗