Biomedical subjects

O Sheils

Publications and source records attributed to O Sheils.

25 records · Page 2Linked to original sources

PubMed1995

Detection of Epstein-Barr virus DNA in tongue tissues from AIDS autopsies without clinical evidence of oral hairy leukoplakia.

Epstein-Barr virus (EBV) DNA was detected by in situ hybridization at 3 sites of 30 samples taken from clinically normal lateral border of tongue mucosa from 15 AIDS autopsies and in none of 20 samples from 10 controls. The first positive case showed a thin layer of parakeratosis correlated with positive signals for EBV in one area and an adjacent area without obvious parakeratosis was also positive for EBV. These findings were present on both sides of the tongue. The second case was unilaterally positive for EBV and parakeratosis was absent. The hybridization signals were localised to koilocyte-like cells in the stratum spinosum, as in oral hairy leukoplakia (OHL). These observations suggest that the in situ hybridization technique can detect very early or subclinical OHL, and supports the role of EBV in the pathogenesis of this lesion.

Acquired Immunodeficiency Syndrome↗

PubMed1995

Tyrosine phosphorylation in the human duodenum.

Many growth factor receptors including the epidermal growth factor receptor function through tyrosine kinase activity. The aim of this study was to examine the constitutive level of tyrosine phosphorylation in the normal duodenum and in the hyperproliferative coeliac duodenum. A flow cytometric assay was devised using monoclonal antibody to phosphorylated (but not native) tyrosine residues to determine the levels of tyrosine phosphorylation in both CD3 positive intraepithelial lymphocytes and CD3 negative epithelial cells obtained by EDTA treatment of endoscopically obtained duodenal biopsy specimens. In addition, immunohistochemistry was performed on 18 formalin fixed coeliac duodenal biopsy specimens and eight control specimens. Tyrosine phosphorylation could be detected by flow cytometry on duodenal enterocytes and this expression was up regulated by pretreatment with epidermal growth factor. Tyrosine phosphorylation decreased with progression from the villus to the crypt, however, and was virtually undetectable on crypt enterocytes. Immunohistochemistry of the coeliac duodenum showed virtually absent tyrosine phosphorylation in the crypt. Increased tyrosine phosphorylation was detected in the infiltrating T cells. In conclusion, tyrosine phosphorylation in the duodenum is confined to the non-proliferative villous epithelium and is virtually undetectable in the proliferative crypt compartment. These findings suggest that tyrosine kinase activity is not a significant factor in the regulation of crypt cell proliferation in the human duodenum either in normal subjects or in coeliac disease patients.

CD3 Complex↗

PubMed1994

Adenovirus 12 E1A gene detection by polymerase chain reaction in both the normal and coeliac duodenum.

A 12 amino acid sequence from the adenovirus 12 E1B protein is homologous at the protein level with a similar 12-mer derived from the wheat protein A-gliadin. It has been suggested that exposure to Ad 12 could sensitise individuals to gliadins with resultant gluten sensitive enteropathy. In this study, the polymerase chain reaction (PCR) was used to analyse duodenal biopsy tissue from patients with coeliac disease for the presence of Ad 12. The sensitivity of the assay system was at least 1 in 10(5) cells and specificity was confirmed both by probing with an internal oligonucleotide and by direct sequencing. Ad 12 sequences were detected in three of 17 patients with adult coeliac disease and in five of 16 adult controls with normal duodenal biopsies. Since exposure to the virus would be predicted to occur in infancy we also studied patients with childhood coeliac disease diagnosed at less than 1 year of age. Ad 12 was positive in three of 10 childhood coeliac patients and one of seven controls. In addition, we studied a cohort of patients who presented with a diarrhoeal illness and associated anti alpha gliadin antibodies in 1983. These patients had duodenal biopsies performed at this time. One of three patients with abnormal histology had detectable Ad 12 while two of 14 with normal findings were positive for Ad 12. Finally, the potential oncogenic nature of Ad 12 prompted examination of a group of patients with intestinal tumours. Ad 12 DNA was, however, in only two of 19 tumour samples tested. These data indicate that Ad 12 can be successfully detected using PCR on paraffin embedded tissue. Furthermore, Ad 12 was detected at a relatively high level in normal duodenum. The results do not, however, support the hypothesis that prior exposure to Ad 12 is implicated in the pathogenesis of coeliac disease.

Adenocarcinoma↗

PubMed1991

Effect of cyclosporin on immune complex deposition in murine glomerulonephritis.

Chronic glomerulonephritis (GN) was induced in N/M mice by daily injections of human serum albumin (HSA). The glomerular lesion was similar to that observed in human membranous GN and was characterized by intense mesangial and capillary loop immunofluorescent staining for HSA, IgG and C3. Electron microscopic examination revealed numerous electron-dense deposits in the mesangium and along the subepithelial side of the glomerular basement membrane, the latter deposits being associated with membranous spikes. Chronically injected mice that had been treated with cyclosporin (CsA) from Day 1 had different patterns of immune complex deposition. Mesangial deposition was apparently unaltered but no subepithelial deposits or spikes were evident. In addition, only two out of 21 HSA-injected mice which began CsA treatment on Day 21 had subepithelial deposits. There was no significant difference in serum levels of HSA-specific IgG between the three groups of mice. CsA treatment would therefore appear to ameliorate the immunopathology of antigen-induced glomerulonephritis in this model without affecting serum antibody levels, and may be of therapeutic value in the treatment of human membranous GN.

Animals↗

PubMed1989

Complement activation within the coeliac small intestine is localised to Brunner's glands.

Complement activation may play an important role in the pathogenesis of coeliac disease. In the present study immunohistochemical localisation of C3 and of a neoantigen exposed only on the terminal C5b-9 complement complex has been performed on small intestinal biopsy sections from newly diagnosed untreated coeliac patients, from coeliac patients on long-term gluten-free diet and from disease controls. Levels of C3 were markedly increased in treated coeliac patients compared with controls. Staining of C3 was concentrated subepithelially and within the centre of the lamina propria. No staining was detected at these sites using antibody to the neoantigen, however, strongly suggesting that the increased levels of C3 seen in the coeliac patients was the result of increased extravasation of serum proteins rather than complement activation. Surprisingly, complement activation was detected within the glands of Brunner. Positive staining using anti-C5b-9 neoantigen was found in all coeliac patients, both treated and untreated. Three of the 13 disease controls also showed reactivity with this antibody. This novel finding suggests that Brunner's glands, hitherto largely neglected structures, may play an important role in the development of coeliac disease.

Antigens↗

PubMedDate not supplied

Colocalisation of human immunodeficiency virus and human cytomegalovirus infection in brain autopsy tissue from AIDS patients.

We have examined 26 human AIDS brains obtained at post mortem for infection by human immunodeficiency virus (HIV) and human cytomegalovirus (HCMV), and for dual infection of cells by both viruses. The techniques used were enzyme-linked immunocytochemistry for HCMV and in situ hybridisation using a cDNA probe for HIV. Using these techniques, HCMV infection was detected in 14 brains, HIV infection in 14 brains, and coinfection with HIV and HCMV in 7 brains. Four case of dual HIV/HCMV infection were found where no colocalisation could be detected. In randomly chosen dually infected areas 19.2% of infected cells were coinfected with both viruses. Although cells identified morphologically as macrophages were the most common infected cell type, astrocytes and neurons were both singly and doubly infected with HIV and HCMV. Complete clinical data were available for 4 of the 7 cases with coinfection and each had AIDS dementia complex.

AIDS-Related Opportunistic Infections↗

PubMedDate not supplied

Genome-wide analysis of deoxyribonucleic acid in endometrial cancer using comparative genomic hybridization microarrays.

The aim of this study was to identify amplified oncogenes in endometrial cancer using array-based comparative genomic hybridization (array CGH). Despite its prevalence, the molecular mechanisms of endometrial carcinogenesis are still poorly understood. The selected array CGH allows the simultaneous examination of 58 oncogenes commonly amplified in human cancers and is capable of achieving increased mapping resolution compared with conventional CGH. A subset of 8 specimens from a bank of 60 malignant and normal specimens was selected for array analysis to identify potential genes of interest. TaqMan polymerase chain reaction was carried out on the 60 specimens to examine if aberrations at the genomic level correlated with gene expression and to compare expression in normal and malignant samples. Oncogenes amplified in the endometrial cancers included AR, PIK3CA, MET, HRAS, NRAS, D17S1670, FGFR1, CTSB, RPS6KB1, LAMC2, MYC, PDGFRA, FGF4/FGF3, PAKI, and FGR. Three genes were examined at the messenger RNA level. AR and PIK3CA were higher in normal specimens, and MET was higher in malignant samples, suggesting a role for MET in endometrial cancer. Newer arrays examining more genes and larger sample numbers are necessary to elucidate the carcinogenic pathway in endometrial cancer.

Adenocarcinoma↗