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Biomedical subjects

A K Foulis

Publications and source records attributed to A K Foulis.

At least 19 recordsLinked to original sources
PubMed1998

Comparison of in situ hybridisation and polymerase chain reaction in the diagnosis of B cell lymphoma.

AIM: To compare the sensitivity of the detection of immunoglobulin light chain messenger RNA (mRNA) restriction by in situ hybridisation (ISH) and clonal immunoglobulin heavy chain gene rearrangements by polymerase chain reaction (PCR) in the diagnosis of B cell lymphoma. METHODS: Analyses were applied to formalin fixed, paraffin wax embedded, routine diagnostic specimens from cases with a provisional diagnosis of reactive lymph node (n = 23), B cell lymphoma (n = 21), and T cell lymphoma (n = 4). Nonisotopic ISH for kappa and lambda immunoglobulin light chain mRNA was performed using both fluorescein and digoxigenin labelled oligodeoxynucleotide probe cocktails. PCR was carried out on DNA extracted from sections using primers to framework 3 (Fr3) of the V segments and to conserved sequences from the J regions of the immunoglobulin heavy chain genes. RESULTS: All reactive lymph nodes showed a polyclonal pattern of light chain mRNA by ISH, although one showed an excess of kappa positive cells. Nineteen of 21 (90%) cases of B cell lymphoma showed light chain restriction, and a further case showed a vast excess of kappa positive cells. By PCR, 20 of 23 reactive nodes (87%) showed a polyclonal pattern. In 13 of 21 B cell lymphomas (62%) a clonal band was detected. CONCLUSION: In the diagnosis of B cell lymphoma in routinely processed diagnostic material ISH for light chain mRNA was more sensitive (90%) than PCR for heavy chain gene rearrangement using Fr3 and J region primers (62%).

Diagnosis, Differential↗
PubMed1997

Demonstration of insulin production and storage in insulinomas by in situ hybridization and immunocytochemistry.

Twelve cases of insulinoma were studied to assess the amount of hormone synthesis and hormone storage by the tumour and to see what effect a hormone-producing tumour has on the adjacent normal islets. This was investigated by performing in situ hybridization, which detects hormone messenger RNA, thus giving an indication of the degree of hormone synthesis by the tumour, and immunocytochemistry, which detects the hormone itself, thus giving an indication of the amount of hormone stored in the tumour cells. It was found that in most cases there was less hormone stored within the tumour cells than in adjacent islet cells. In a minority of cases, this decrease in stored hormone was associated with reduced hormone synthesis, but the majority of cases showed either equivalent or increased levels of hormone mRNA in the tumour cells compared with adjacent islets. In addition, it was noted that, unlike some other endocrine organs, the presence of a hormone-producing tumour within the pancreas did not appear to inhibit hormone synthesis in the adjacent normal tissue.

Aged↗
PubMed1997

A search for evidence of viral infection in pancreases of newly diagnosed patients with IDDM.

Techniques were developed to look for evidence of viral infection in formalin-fixed paraffin-embedded autopsy pancreatic tissues from patients who had died of recent-onset insulin-dependent diabetes mellitus. DNA extracted from 47 pancreases in which good DNA preservation was confirmed was analysed by a polymerase chain reaction for Epstein-Barr virus and by a nested polymerase chain reaction for cytomegalovirus. Histological sections from 29 pancreases in which there was good RNA preservation were tested for the presence of enterovirus and Epstein-Barr virus using in situ hybridization techniques. Seventy-five pancreases were analysed immunohistochemically for the presence of mumps virus. None of these viruses could be detected in any of the diabetic pancreases studied. Control studies suggested that the techniques employed were as sensitive as culture done at the time of autopsy. Pancreas was available for study in 9 infants who had died of myocarditis; enterovirus was demonstrable in islets in 5 of these cases. An acute or persisting infection in the pancreas at the time of clinical onset of insulin-dependent diabetes by any of the 4 virus included in this study seems unlikely.

Adolescent↗
PubMed1996

Expression of the human heat shock protein 60 in thyroid, pancreatic, hepatic and adrenal autoimmunity.

Heat shock proteins (hsps) have been proposed to play a role in autoimmune disease. Their highly conserved nature and role as a common antigenic determinant throughout phylogeny has raised the possibility that they may act as cellular targets of an autoimmune response when their expression is altered in stressed tissue cells. Using an antibody to human hsp60 we have demonstrated a wide tissue distribution in normal tissues, including thymus, the degree of staining reflecting the content of mitochondria in the cells, consistent with the known mitochondrial location of this protein. Enhanced staining was also demonstrated in oncocytes (deeply eosinophilic cells which have greatly increased numbers of mitochondria) in both thyroid and adrenal autoimmune disease and also in unrelated conditions where oncocytic change was identified. No enhancement was demonstrated in target cells in organ specific autoimmune diseases where oncocytic change was not seen, for example islet cells in diabetes and bile duct cells in primary biliary cirrhosis. Thus, no alteration of hsp60 expression was demonstrated which was specific to the autoimmune diseases studied.

Adrenal Glands↗
PubMed1996

The pathology of the endocrine pancreas in type 1 (insulin-dependent) diabetes mellitus.

Type 1 diabetes is an organ-specific autoimmune disease in which the insulin-secreting B cell is destroyed. Both genetic factors (linked to class II MHC genes) and environmental agents (viruses, diet) appear to be involved in the aetiology. Study of autopsy pancreases of children who die at presentation of their disease has proved elucidating. In such pancreases islets before, during and after B cell destruction, are all visible. The earliest defined immunological event in the disease process appears to be expression of interferon-alpha by insulin-containing B cells. Secretion of this cytokine is associated with hyperexpression of class I MHC by all the endocrine cells within insulin-containing islets. Another immunological phenomenon which is unique to type I diabetes is the presence of aberrant class II MHC molecule expression by B cells. This may induce autoimmunity by allowing antigen presentation of B cell specific antigens. If the onset of the disease process is marked by interferon-alpha expression by B cells then a search for the presence of a continuing viral infection in these cells may prove profitable, although no viruses have been found in them to date.

Animals↗
PubMed1994

Pancreatic islet cell tumour in a patient with familial adenomatous polyposis.

A case of familial adenomatous polyposis is reported in a 39 year old patient who underwent a Whipple's resection for adenoma of the duodenum. He subsequently developed a pancreatic glucagonoma. Endocrine neoplasia other than papillary carcinoma of thyroid has seldom been reported in association with FAP. The true incidence of islet cell tumours in FAP may be underestimated.

Adenomatous Polyposis Coli↗
PubMed1993

Abnormal expression of MHC class II and ICAM-1 by melanocytes in vitiligo.

The relationship between damage to cutaneous melanocytes and antimelanocyte autoimmunity in vitiligo is unclear. We have demonstrated abnormal expression of MHC class II molecules by perilesional melanocytes in 13/21 patients with vitiligo and a six-fold increase in the number expressing the intercellular adhesion molecule ICAM-1. These molecules have important roles in normal antigen presentation and activation of helper T lymphocytes, and their expression by melanocytes may contribute to the abnormal immune response in vitiligo. MHC class II is not expressed by melanocytes in psoriasis and is unlikely to be induced in vitiligo by cytokines released from activated non-melanocyte-specific T lymphocytes.

Autoimmune Diseases↗
PubMed1992

The distribution and possible function of gamma interferon-immunoreactive cells in normal endometrium and myometrium.

T-lymphocytes are present in normal endometrium, where they may have a role in the control of glandular maturation. T-cell activity could be related to the local secretion of cytokines such as gamma interferon, which has an anti-proliferative effect on endometrial epithelial cells in vitro. We have examined gamma interferon immunoreactivity and T-cell distribution in 24 normal pre-menopausal uteri. Endometrial appearances were representative of all stages of the menstrual cycle. Most cells in the lymphoid aggregates in the stratum basalis were stained by T-cell and gamma interferon antisera. T-lymphocytes were also scattered in glandular epithelium and throughout the stroma of basal and functional layers; immunoreactivity for gamma interferon was less consistent in these cells. There was no alteration in the intensity or distribution of gamma interferon staining in different phases of the menstrual cycle. Endometrial granulocytes (K-cells) present mainly in the late secretory endometria were not reactive with the gamma interferon antiserum. In addition to endometrial staining, T-cells were distributed in all areas of the myometrium in most uteri, and many myometrial lymphocytes were gamma interferon positive. These results support a role for gamma interferon in endometrial physiology, possibly as an inhibitor of epithelial proliferation.

Adult↗
PubMed1992

Characterization of the inflammatory infiltrate in ovarian dysgerminoma: an immunocytochemical study.

The inflammatory infiltrate has been characterized in 10 cases of ovarian dysgerminoma using a panel of antisera to T-cells, B-cells and macrophages. The expression of Class II major histocompatibility complex (MHC) antigens and the distribution of interferons alpha and gamma were also examined. T-lymphocytes were present in all tumours, often closely admixed with neoplastic elements. T-cells in most areas were immunoreactive with gamma interferon. B-cells were generally scanty although germinal centres were present in three tumours. Immunocytochemistry revealed greater numbers of macrophages than had been appreciated on routinely stained sections. Macrophages were closely related to both lymphoid and tumour cells, and many macrophages were immunoreactive for alpha interferon. Class II MHC expression was mainly restricted to macrophages and B-cell areas although occasional T-cells were also stained. Dysgerminoma cells did not express Class II MHC antigens.

Biomarkers↗
PubMed1992

The distribution of immunoreactive interferon-gamma-containing cells in normal human tissues.

An immunohistochemical technique has been used to study the distribution of lymphocytes expressing interferon-gamma in normal adult tissues. The greatest concentrations of these cells were seen in mucosal sites exposed to a resident microflora. It is proposed that such organisms, by eliciting immune responses, provide the stimulus for the production of 'physiological' interferon-gamma. This in turn may act to preserve the 'tone' or readiness of the immune system.

Adult↗
PubMed1991

Insulitis in type 1 (insulin-dependent) diabetes mellitus in man--macrophages, lymphocytes, and interferon-gamma containing cells.

This study sought to determine, firstly, the relative frequency of lymphocytes and macrophages and, secondly, the percentage of lymphocytes containing interferon-gamma in inflamed islets (insulitis) of patients with type 1 (insulin-dependent) diabetes. Autopsy pancreases of 12 patients who had died of recent-onset type 1 diabetes and one pre-diabetic patient who had died of cardiomyopathy were examined immunohistochemically. In the 87 islets that were studied, the lymphocyte macrophage ratio was 9.7:1 and approximately 40 per cent of the lymphocytes contained interferon-gamma. Interferon-gamma release in the insulitis process may be involved in the pathogenesis of type 1 diabetes.

Adolescent↗
PubMed1991

Spatial correlation between thyroid epithelial cells expressing class II MHC molecules and interferon-gamma-containing lymphocytes in human thyroid autoimmune disease.

In this immunohistochemical study we addressed the question whether aberrant class II MHC expression by thyroid epithelial cells (thyrocytes) in established thyroid autoimmune disease is the result of release of interferon-gamma (IFN-gamma) by adjacent lymphocytes. Thyroids from eight cases of Hashimoto's thyroiditis, 13 cases of Graves' disease and 10 cases of focal thyroiditis were studied. Both thyrocytes expressing class II MHC and lymphocytes containing immunoreactive IFN-gamma were found in all 31 autoimmune thyroids. In a serial section study of these thyroids, IFN-gamma-expressing lymphocytes were found within 50 microns of class II MHC-positive thyrocytes in 89% of 282 randomly selected fields. Conversely, class II MHC-positive thyrocytes were found within 50 micron of aggregates of IFN-gamma-positive lymphocytes in 82% of 272 randomly selected fields. These findings support the view that in established thyroid autoimmune disease expression of class II MHC by thyrocytes is the result of local release of IFN-gamma.

Autoimmune Diseases↗