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Biomedical subjects

P G Toner

Publications and source records attributed to P G Toner.

At least 19 recordsLinked to original sources
PubMed1996

p53 mutation, allele loss on chromosome 17p, and DNA content in ovarian carcinoma.

The aim of this investigation was to explore the relationships between p53 mutation, DNA aneuploidy, 17p deletions, and clinical stage in ovarian cancer. Nuclear suspensions were obtained by tissue disaggregation, stained with propidium iodide, and analysed on a Coulter EPICS Elite flow cytometer. DNA cell cycle analysis was performed using Multicycle software (Phoenix Flow Systems). DNA extracted from paraffin-embedded archival carcinomas/non-tumour tissue was used as template for PCR amplification of the microsatellite dinucleotide repeat polymorphism D17S513, a locus telomeric to p53 on 17p13.1. Allele loss at D17S513 was detected in 64.5 per cent of carcinomas (20 of 31 informative cases). DNA aneuploidy was detected in 20 of 54 (37 per cent) carcinomas. Eight of ten cases previously shown to harbour p53 mutations showed aneuploid DNA content. Although ten other DNA aneuploid cases had shown no p53 mutations, the results show a statistically significant association between p53 mutation and DNA aneuploidy (P < 0.01). Furthermore, the mean DNA index of the DNA aneuploid cases was significantly higher in p53 mutant cases compared with those showing no p53 mutation (P = 0.02). There was also a significant association between p53 mutations and stage, between ploidy and stage, and between allelic deletions at D17S513 or p53 and stage, but not between these allelic deletions and ploidy. p53 mutations appear to be associated with DNA aneuploidy in ovarian cancer independently of 17p deletions. p53 mutations, DNA aneuploidy, and 17p deletions are associated with late stage.

Alleles↗
PubMed1995

B cell signet-ring cell lymphoma of bone marrow.

A case of signet-ring cell lymphoma affecting the bone marrow and diagnosed by bone marrow trephine biopsy is reported. Normal marrow was replaced totally by cells with large central vacuoles, many of which displaced the nucleus to the periphery of the cell, imparting a signet-ring appearance. Initially, the favoured morphological diagnosis was metastatic signet-ring adenocarcinoma, but on immunocytochemistry the tumour cells were strongly positive for CD45 (leucocyte common antigen) and the B cell marker CD20 (L26). Electron microscopy revealed electron-lucent vacuoles with no discernable internal structure. The tumour was classified as a high grade centroblastic lymphoma using the upgraded Kiel classification. Despite chemotherapeutic treatment, the patient died during an episode of septicaemic shock within two months of presentation.

Aged↗
PubMed1995

Parathyroid cyst of the thymus.

A case is described of primary hyperparathyroidism in a patient with both a parathyroid cyst within the thymus gland and a concomitant parathyroid adenoma. The parathyroid adenoma contained microcystic areas of degeneration, and it is thought that the parathyroid cyst reflected degenerative change in a pre-existing adenoma. Parathyroid cyst should be considered in the differential diagnosis of cystic lesions within the thymus. Fine needle aspiration and parathyroid hormone assay on cyst fluid may provide a preoperative diagnosis.

Adult↗
PubMed1994

p53 expression, mutation, and allelic deletion in ovarian cancer.

The aim of this investigation was to study the prevalence of p53 gene mutations and allelic deletions in ovarian cancer and the relationship between these events and p53 expression. Genomic p53 was amplified by the polymerase chain reaction (PCR) from paraffin-embedded sections of tumour and non-tumour tissue. Exons 5-9 were screened for mutation using non-isotopic single-strand conformation polymorphism (SSCP) analysis. Allelic deletions at a sequence polymorphism in exon 4 were studied for loss of heterozygosity (LOH) by restriction analysis and by SSCP. p53 expression was detected by immunohistochemistry with the p53 antibodies CM1 and Do7. Of 44 cases, ten (23 per cent), including a mucinous tumour of low malignant potential, showed mutations. There was a statistically significant correlation between p53 mutation and expression (P < 0.01) but seven cases showed discordance. Of 18 informative cases, eight (44 per cent) demonstrated LOH. Mutations were identified in three of the informative cases, two of which also had LOH. The remaining case showed mutations in two amplicons. p53 dysfunction, as indicated by mutation, deletion, or increased expression, is common in ovarian cancer. There is an association between these molecular events but the exact mechanisms of p53 inactivation remain to be elucidated.

Alleles↗
PubMed1993

Ultrastructural aspects of tumour invasion in the central nervous system.

Tumour invasion in the central nervous system (CNS) was studied using a mouse melanoma cell model. Attention was concentrated on the third ventricle as this site is distant from any implantation artefact. Transmission electron microscopy (TEM) revealed the formation of tumour cell aggregates within the ventricle. Underlying ependymal cells showed loss of cilia and microvilli. Progressive thinning of the ependymal cells took place until continuity of the ependyma was lost through ependymal retraction. Tumour cells were then in direct contact with sub-ependymal neuroglial processes. Further invasion was then accomplished by penetration between neuropil processes, followed by tumour cell infiltration along the intact basement membrane of cerebral capillaries with displacement of astrocyte foot processes from the capillary basement membrane.

Animals↗
PubMed1993

C-erbB-2 oncogene product expression depends on tumour type and is related to oestrogen receptor and lymph node status in human breast carcinoma.

Although over-expression of the C-erbB-2 oncogene product can be detected on formalin-fixed, paraffin-embedded sections from tumours of the human breast, fixation results in a considerable loss of immunostaining for this protein. In this study, C-erbB-2 expression was studied immunohistochemically on frozen sections in 63 infiltrating carcinomas, 3 phyllodes tumours, 15 fibroadenomas and 16 cases of fibrocystic disease. The value of C-erbB-2 expression as a prognostic indicator in ductal carcinomas was examined by seeking an association with known prognostic indicators. C-erbB-2 over-expression was confined to ductal carcinomas of the breast and was positively correlated with tumour size, grade, oestrogen receptor status and the presence of metastatic deposits in axillary lymph nodes. Only the association with lymph node and oestrogen receptor status were statistically significant. No evidence of a correlation between C-erbB-2 expression and growth fraction (as assessed with the Ki-67 antibody) was demonstrated in the cases studied. Formalin fixation was associated with the loss of immunoreactivity in all cases studied. 75% of cases which were positive on frozen sections were negative in paraffin sections. These results highlight the significance of the method of fixation used in studying C-erbB-2 expression. They confirm the association between C-erbB-2 expression and known prognostic indicators.

Breast Neoplasms↗
PubMed1991

Use of the autopsy in Northern Ireland and its value in perioperative deaths.

A report on the pilot study of the Confidential Enquiry into Perioperative Deaths was published recently in the United Kingdom. The scheme was designed as a specialized form of clinical audit relating to perioperative patient care. Because the report placed little emphasis on autopsy, we have looked at all autopsied perioperative deaths, as defined by the enquiry, over a three-year period (1986-88) in a defined catchment area of Northern Ireland. Class I major discrepancies of diagnosis between clinical and postmortem records were found in 21% of 213 autopsied perioperative deaths. By definition, these represented instances in which an adverse impact on patient survival had resulted from the discrepancy. In an additional 29% of cases, there were Class II major discrepancies, which were discrepancies in the primary diagnosis not relevant to life-saving treatment. In 30% of cases there was a discrepancy in a secondary diagnosis, which might have affected the eventual prognosis, had the patient survived, but which was not related directly to the cause of death; these were termed Class III discrepancies. In 47% of cases, there were Class IV discrepant secondary diagnoses, which were 'incidental' findings and had no bearing on prognosis. To put these findings in context, the autopsy rate in Northern Ireland was 12% in 1987, with a higher rate (23%) in the two main teaching hospitals and a lower rate (8%) in all other hospitals. The rate of coroner's autopsies, 6%, is uniform throughout Northern Ireland. Coroner's autopsies are carried out mostly by the salaried staff of the State Pathologist's department. The observed differences in the rates of hospital autopsies reflect local deficiencies of pathologists in relation to the work load. In a series of consecutive autopsies carried out at one of the main teaching hospitals, the highest autopsy rate (68%) was found for paediatric patients, with rates of 29% for surgical and 23% for medical cases. The proportion of hospital autopsies carried out in perioperative surgical patients was the same as that for medical patients, reflecting the fact that no particular emphasis is placed on use of the autopsy as a form of clinical audit for the perioperative group.

Adolescent↗
PubMed1990

The blood-testis barrier in experimental unilateral cryptorchidism.

Unilateral cryptorchidism was induced in Wistar rat pups within 48 h of birth. After a period of 150 days, the blood-testis barrier was evaluated in the cryptorchid and contralateral scrotal testis, using a lanthanum immersion technique. The barrier was demonstrated to be competent, with tracer confined to the basal and intermediate compartments.

Animals↗
PubMed1990

Value of the necropsy in perioperative deaths.

A series of 213 perioperative deaths was studied out of a total of 1451 consecutive necropsies carried out over three years. Discrepancies between the clinical and the necropsy diagnosis were assessed under four classes of discrepant diagnosis: class I, patient survival affected, treatable; class II, patient survival affected but not treatable; class III, correlated to cause of death but treatable; and class IV, incidental diagnosis which could not have been made before death. Major discrepancies of classes I and II were found in 44 (21%) and 62 (29%) cases, respectively. Minor discrepancies of classes III and IV were found in 63 (30%) and 101 (47%) cases, respectively. No discrepancies were found in 50 (23.5%) cases. These results confirm the continuing value of the necropsy in the assessment of perioperative deaths.

Adolescent↗