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Biomedical subjects

N Rooney

Publications and source records attributed to N Rooney.

At least 37 records · Page 2Linked to original sources

Absence of Epstein-Barr virus in testicular germ cell tumours: a study of 21 cases using in situ hybridisation.

Aim-To establish whether testicular germ cell tumours contain Epstein-Barr virus (EBV) and if so to provide further evidence for the hypothesis that EBV plays a direct role in the pathogenesis of testicular germ cell tumours.Method-Paraffin wax embedded tissue blocks from 21 germ cell tumours including 12 teratomas and nine classic seminomas were examined by in situ hybridisation for the expression of the small EBV encoded nuclear RNA transcripts (EBER-1 and -2) using isotopic and nonisotopic probes.Results-There was no EBER specific signal detectable in any of the testicular germ cell tumours examined by in situ hybridisation whilst a strong signal was observed in appropriate control sections.Conclusion-The absence of demonstrable EBER transcripts in testicular germ cell tumours make a direct role for EBV in the pathogenesis of these tumours unlikely. Other explanations for the epidemiological and serological evidence linking EBV with germ cell tumours need to be explored.

Journal Article↗

Primary breast lymphoma with skin involvement arising in lymphocytic lobulitis.

Primary breast lymphoma is a rare tumour which has recently been associated with pre-existing lymphocytic lobulitis. We report a patient with lymphocytic lobulitis in whom the lymphoma recurred in the contra-lateral breast 5 years after the initial presentation, to be followed shortly afterwards by skin involvement. This progression illustrates the relationship between extra-nodal lymphomas and underlying autoimmune disease and the homing of lymphomas to related sites.

Breast Neoplasms↗

Latent Epstein-Barr virus infection in cottontop tamarins. A possible model for Epstein-Barr virus infection in humans.

The association of Epstein-Barr virus (EBV) with a growing number of human malignancies underlines the importance of efforts aimed at preventing the infection with this potential carcinogen and of establishing animal models for human virus-associated tumors. Cottontop tamarins have been used in EBV vaccine studies because virus infection regularly induces lymphomas similar to those seen in human immunocompromised individuals. In recent years, several vaccines based on the gp340/220 envelope protein of EBV have been developed and shown to prevent the development of EBV-associated lymphomas in this model. Using in situ hybridization and immunohistology, we have characterized EBV infection in one nonimmunized and three immunized animals after challenge with a standard tumorigenic dose of EBV. In the nonimmunized animal, EBV-infected lymphoid cells were detected in numerous tissues showing no obvious lymphoma infiltration. Surprisingly, variable numbers of virus-carrying cells were also found in all three immunized animals that were protected against the development of virus-associated lymphoma. This observation demonstrates that vaccination does not induce sterilizing immunity against EBV infection in this model. Double labeling suggested a B cell phenotype of the majority of these cells. EBV infection of nonlymphoid cells was not observed. Analysis of viral gene expression in immunized animals suggested a restricted form of virus latency different from that seen in EBV-driven lymphomas in nonimmunized cottontop tamarins. These results raise the possibility that immunized cottontop tamarins protected against the development of EBV-driven lymphoma or animals exposed to a sublymphomagenic dose of virus may serve as a model for EBV infection in humans.

Animals↗

Overexpression of p53 in Hodgkin's disease: lack of correlation with Epstein-Barr virus infection.

Recent work has shown that p53 gene mutations are frequently found in Epstein-Barr virus (EBV)-positive and EBV-negative cases of Burkitt's lymphoma but not in EBV-associated undifferentiated nasopharyngeal carcinomas (NPCs). Similar viral gene expression patterns are observed in undifferentiated NPCs and in EBV-positive cases of Hodgkin's disease (HD), suggesting that the contribution of the virus to the pathogenesis of these malignancies may also be similar. We have analysed 116 cases of HD for EBV association and for immunohistologically detectable overexpression of p53. p53 overexpression was detected in the tumour cell population of 37 (32 per cent) of the cases. Fifteen cases showed p53-specific labelling of more than 40 per cent of tumour cells; in six of these, virtually all tumour cells were stained. In eight cases, between 5 and 40 per cent of tumour cells were labelled, and in another 14 cases, less than 5 per cent of tumour cells expressed detectable amounts of p53. EBV-positive HD cases were found in all groups with different levels of p53 overexpression as well as amongst p53-negative cases. While a more detailed analysis of the p53 gene in HD is required, these data show that overexpression of p53 in HD is heterogeneous and that there is no simple correlation between EBV infection and p53 overexpression.

Gene Expression↗

Lymphomas of the head and neck. 1: Nasofacial T-cell lymphoma.

Nasofacial T-cell lymphoma includes diseases otherwise called "lethal midline granuloma" and "necrosis with atypical cells". It is characterised by relentless destruction of nose and palate in particular but the lymphoma remains localised to the head and neck. The age of onset ranges from 10 to 87 and the survival ranges from a few months to several years. The histological appearances are of a polymorphic infiltrate but including atypical T cells in a background of macrophages. There is a strong association with Epstein-Barr virus infection.

Facial Neoplasms↗

Epidermal growth factor receptor determination on tumour imprints.

Epidermal growth factor receptor (EGFR) is a sensitive prognostic indicator in women with breast cancer. A new technique for the detection of EGFR on breast cancer imprints is described and evaluated in relation to immunohistochemistry on frozen sections. The standard streptavidin-biotin method using the R1 antibody on frozen sections was modified for use on tumour imprints. In the first group (group 1 imprints) 43 tumours were assessed by frozen section and imprint staining. The group 1 imprint method had a sensitivity of 50% and a specificity of 89% compared with the frozen sections. Further modifications were made for the following 32 tumours (group 2) and this method had a much improved sensitivity of 94% while specificity was preserved. This method is simple and could be performed in any hospital histopathology department.

Bacterial Proteins↗

A single human colonic adenoma cell line can be converted in vitro to both a colorectal adenocarcinoma and a mucinous carcinoma.

In a previous study, using a chemical carcinogen, we converted in vitro a non-tumorigenic cell line derived from a human colorectal diploid adenoma, designated PC/AA, into a tumorigenic cell line which, when inoculated into athymic nude mice, produced progressively growing adenocarcinomas. We now report that continuous in vitro passage of the PC/AA adenoma cell line resulted in its spontaneous transformation to a mucinous carcinoma with a modal karyotype of 51, XY, +i(Iq), +8, +9, +13, +i(13q), -21, +mar. These studies show that a single adenoma can be converted along 2 independent pathways, giving rise to either a mucinous carcinoma or an adenocarcinoma, and provide further experimental evidence for the adenoma-carcinoma sequence. Cytogenetic changes which occur along both pathways to tumorigenicity include abnormalities of chromosome I and multiple copies of chromosome 13. These abnormalities may be important in tumour development and progression in colorectal carcinogenesis.

Adenocarcinoma↗

An inter-observer and intra-observer variability study on the diagnosis of lymph node biopsy specimens.

One hundred lymph node biopsy specimens were examined on two separate occasions by seven pathologists differing in experience in lymphoreticular pathology. Neither history nor immunohistochemistry was provided and the study, therefore, focused on morphological interpretation alone. The participants evaluated each case using a constructed response form in which the confidence with which they entered each response was also entered. Agreement on various points, between pathologists, between the two rounds, and with the referring centre was assessed. Whilst there was a high level of agreement over a diagnosis of benign vs. malignant and non-Hodgkin lymphoma vs. Hodgkin's disease, there was considerably less agreement over both T vs. B cell phenotype and high vs. low grade. The lack of agreement over grade, an evaluation which is usually made independent of immunohistochemistry, is particularly important, because of the relevance to selection of treatment. Proliferation markers may be more appropriate determinants of treatment choice.

Biopsy↗

Coeliac disease and malignancy of the duodenum: diagnosis by endoscopy, successful treatment of the malignancy, and response to a gluten free diet.

A patient presented with subtotal villous atrophy and a malignant duodenal tumour of uncertain histogenesis. He was successfully treated by resection and chemotherapy and the small bowel mucosa recovered on a gluten free diet. The tumour was diagnosed at upper gastrointestinal endoscopy when barium studies and abdominal computed tomography were normal, thus making this one of the earliest coeliac malignancies diagnosed.

Antineoplastic Combined Chemotherapy Protocols↗

Haemolytic uraemic syndrome and pseudomembranous colitis.

Two cases of haemolytic uraemic syndrome (HUS) associated with pseudomembranous colitis (PMC) are described. The toxin of Clostridium difficile was detected post mortem in the stool of one patient and the other patient showed a good therapeutic response to oral vancomycin, an antibiotic with established efficacy in the management of PMC. When associated with HUS, PMC is probably an independent specific disease that, in common with many other infections, may activate HUS.

Bacterial Proteins↗

Immunophenotype of the lymphoid cell infiltrates in breast carcinomas of low oestrogen receptor content.

Several studies of breast tumour histology and oestrogen receptor (ER) contents report an inverse correlation between the density of the stromal lymphoid cell infiltrate and the presence or concentration of ER. Using monoclonal antibodies to lymphoid cell surface markers we have examined the immunophenotype of the infiltrating lymphoid cells and related this to the tumour ER content. There is a significant inverse correlation between the presence of Leu7-positive cells, which includes a subpopulation of natural killer (NK) cells, and tumour ER content; this is possibly superimposed on the dilutional effect of macrophages and other infiltrating cells.

Adenocarcinoma↗

Giant vascular eccrine spiradenomas: a report of two cases with histology, immunohistology and electron microscopy.

Two examples of a variant of benign spiradenoma are reported, both characterized by their large size and high degree of vascularity. The results of studies using light microscopy, transmission electron microscopy and immunohistology are described. The relationship of this unusual variant to other spiradenomas and their eccrine sweat gland origin is discussed. The possible misdiagnosis of this rare type of spiradenoma is emphasized.

Adenoma, Sweat Gland↗

The lymph node in mycosis fungoides: a light and electron microscopy and immunohistological study supporting the Langerhans' cell-retrovirus hypothesis.

This paper describes the light and electron microscopy and monoclonal antibody findings in the lymph nodes of nine patients with mycosis fungoides. Four cases showed dermatopathic change characterized by close association between small convoluted T4 lymphocytes and T6 antigen-presenting cells (Langerhans' and indeterminate dendritic cells) in the sinuses and paracortical zones. The T4:T8 ratio was between 3 and 5:1. One case showed dermatopathic change but included large convoluted T4 lymphocytes and occasional T10 lymphocytes. The T4:T8 ratio was 4:1. The antigen-presenting cells were mostly T6 negative (interdigitating reticulum cells). One case showed extensive paracortical expansion by small and large convoluted T4 lymphocytes. The T4:T8 ratio was 20:1. Few B lymphocytes and antigen-presenting cells were present. Two cases showed partial and one case total effacement by atypical lymphoid tissue. This included small and large convoluted T4 lymphocytes and T4 immunoblasts. The T4:T8 ratios were between 30 and 40:1. The changes in their antigen-presenting cell population were complex. Langerhans' cells in one case generally failed to express T6 antigen and in two displayed histiocyte features. In one case, both immature and budding type C retrovirus-like particles were identified in Langerhans cells. One extracellular mature type C virus-like particle was identified in another case. No ultrastructural distinction could be made between similarly sized primary lysosomes and possible intracytoplasmic mature type C retrovirus particles. These findings support the hypothesis that mycosis fungoides may represent an altered dermatonodal cycle resulting from an interaction between retrovirus, Langerhans' cells and lymphocytes.

Adult↗